Neuro

Passmedicine Neurology note 2021
Prepared by
Medicalstudyzone.com
This PDF was created and uploaded by
www.medicalstudyzone.com which is one the
biggest free resources platform for medical
students and healthcare professionals. You can
access all medical Video Lectures, Books in PDF
Format or kindle Edition, Paid Medical Apps and
Softwares, Qbanks, Audio Lectures And Much
More Absolutely for Free By visiting our Website
https://medicalstudyzone.com all stuff are free
with no cost at all.
Furthermore You can also request a specific
Book In PDF Format OR Medical Video Lectures.
PASSMEDICINE NEUROLOGY NOTE 2021
5-HT3 antagonists
5-HT3 antagonists are antiemetics used mainly in the management of chemotherapy-

related nausea. They mainly act in the chemoreceptor trigger zone area of the medulla
oblongata.
Examples
• ondansetron
• granisetron
Adverse effects
• constipation is common
• prolonged QT interval
Absence seizures
Absence seizures (petit mal) are a form of generalised epilepsy that is mostly seen in children.
The typical age of onset of 3-10 years old and girls are affected twice as commonly as boys
Features
• absences last a few seconds and are associated with a quick recovery
• seizures may be provoked by hyperventilation or stress
• the child is usually unaware of the seizure
• they may occur many times a day
• EEG: bilateral, symmetrical 3Hz spike and wave pattern
Management
• sodium valproate and ethosuximide are first-line treatment

• good prognosis - 90-95% become seizure free in adolescence
2
Absent ankle jerks, extensor plantars
Typically caused by lesion producing both upper motor neuron (extensor plantars) and lower
motor neuron (absent ankle jerk) signs
Causes
• subacute combined degeneration of the cord

• motor neuron disease
• Friedreich's ataxia
• syringomyelia
• taboparesis (syphilis)
• conus medullaris lesion
Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease of the

central nervous system. It may also be termed post-infectious encephalomyelitis. The aetiology
is not fully understood and it can occur following infection with a bacterial or viral pathogen.
Common infections include measles, mumps, rubella and varicella, however this list is not
exhaustive.
After a lag time of between a few days to 2 months, there is an acute onset of multifocal
neurological symptoms with rapid deterioration. Non-specific signs such as headache, fever,
nausea and vomiting may also accompany the onset of illness. Motor and sensory deficits are
frequent and there may also be brainstem involvement including oculomotor defects.
There are no specific biomarkers for the diagnosis of ADEM. MRI imaging may show areas of
supra and infra-tentorial demyelination. Management involves intravenous glucocorticoids and
the consideration of IVIG where this fails.
Anti-NMDA receptor encephalitis
Anti-NMDA receptor encephalitis is a paraneoplastic syndrome, presenting as prominent

psychiatric features including agitation, hallucinations, delusions and disordered thinking;
seizures, insomnia, dyskinesias and autonomic instability. Ovarian teratomas are detected in up
to half of all female adult patients, particularly prevalent in Afro-Caribbean patients. MRI head
can be normal but abnormalities can be visualised on FLAIR sequences in the deep subcortical
limbic structures. CSF may demonstrate pleocytosis but can be normal initially. Anti-MuSK is an
autoantibody specific to muscle kinase in myasthenia gravis with no evidence of a thymoma
and without antibodies to acetylcholine receptors. Anti-GM1 is an autoantibody specific to
3
acute inflammatory demyelinating polyneuropathy (AIDP) variant of Guillain-Barre syndrome.
Treatment of anti-NMDA encephalitis is based of immunosuppression with intravenous

steroids, immunoglobulins, rituximab, cyclophosphamide or plasma exchange, alone or in
combination. Resection of teratoma is also therapeutic.
Aphasia
The table below lists the major types of aphasia. Remember that dysarthria is different and
refers to a motor speech disorder.
Type of aphasia Notes
Wernicke's Due to a lesion of the superior temporal gyrus. It is typically supplied

(receptive) by the inferior division of the left MCA
aphasia
This area 'forms' the speech before 'sending it' to Broca's area.
Lesions result in sentences that make no sense, word substitution and
neologisms but speech remains fluent - 'word salad'
Comprehension is impaired
Broca's Due to a lesion of the inferior frontal gyrus. It is typically supplied by

(expressive) the superior division of the left MCA
aphasia
Speech is non-fluent, laboured, and halting. Repetition is impaired
Comprehension is normal
Conduction Classically due to a stroke affecting the arcuate fasiculus - the

aphasia connection between Wernicke's and Broca's area
Speech is fluent but repetition is poor. Aware of the errors they are
making
Comprehension is normal
Global aphasia Large lesion affecting all 3 of the above areas resulting in severe
expressive and receptive aphasia
May still be able to communicate using gestures
4
Diagram showing the main types of aphasia
Arnold-Chiari malformation
Arnold-Chiari malformation describes the downward displacement, or herniation, of the

cerebellar tonsils through the foramen magnum. Malformations may be congenital or acquired
through trauma.
Features
• non-communicating hydrocephalus may develop as a result of obstruction of

cerebrospinal fluid (CSF) outflow
• headache
• syringomyelia
Ataxia telangiectasia
Ataxia telangiectasia is an autosomal recessive disorder caused by a defect in the ATM gene
which encodes for DNA repair enzymes. It is one of the inherited combined immunodeficiency
disorders. It typically presents in early childhood with abnormal movements.
Features
• cerebellar ataxia
• telangiectasia (spider angiomas)
• IgA deficiency resulting in recurrent chest infections
5
• 10% risk of developing malignancy, lymphoma or leukaemia, but also non-lymphoid

tumours
Comparison of Friedreich's ataxia and ataxia telangiectasia. Note in particular how ataxia
telangiectasia tends to present much earlier, often at the age of 1-2 years
Autonomic neuropathy
Features
• impotence, inability to sweat, postural hypotension

• postural hypotension e.g. drop of 30/15 mmHg
• loss of decrease in heart rate following deep breathing
• pupils: dilates following adrenaline instillation
Causes
• diabetes
• Guillain-Barre syndrome
• multisystem atrophy (MSA), Shy-Drager syndrome
• Parkinson's
6
• infections: HIV, Chagas' disease, neurosyphilis

• drugs: antihypertensives, tricyclics
• craniopharyngioma
Baclofen
Baclofen is used to treat muscle spasticity in conditions such as multiple sclerosis, cerebral palsy
and spinal cord injuries.
Mechanism of action
• agonist of GABA receptors

• acts in the central nervous system (brain and spinal cord)
Bell's palsy
Bell's palsy may be defined as an acute, unilateral, idiopathic, facial nerve paralysis. The
aetiology is unknown although the role of the herpes simplex virus has been investigated
previously. The peak incidence is 20-40 years and the condition is more common in pregnant
women.
Features
• lower motor neuron facial nerve palsy - forehead affected*

• patients may also notice post-auricular pain (may precede paralysis), altered taste, dry
eyes, hyperacusis
Management
• in the past a variety of treatment options have been proposed including no treatment,
prednisolone only and a combination of antivirals and prednisolone
• there is consensus that all patients should receive oral prednisolone within 72 hours of
onset of Bell's palsy
• there is an ongoing debate as to the value of adding in antiviral medications
o NICE Clinical Knowledge Summaries state: 'Antiviral treatments alone are not
recommended.
Antiviral treatment in combination with a corticosteroid may be of small benefit, but seek
specialist advice if this is being considered.'
7
• UpToDate recommends the addition of antivirals for severe facial palsy
eye care is important - prescription of artificial tears and eye lubricants should be considered
Prognosis
• if untreated around 15% of patients have permanent moderate to severe weakness
*upper motor neuron lesion 'spares' upper face

Benign paroxysmal positional vertigo
Benign paroxysmal positional vertigo (BPPV) is one of the most common causes of vertigo
encountered. It is characterised by the sudden onset of dizziness and vertigo triggered by
changes in head position. The average age of onset is 55 years and it is less common in younger
patients.
Features
• vertigo triggered by change in head position (e.g. rolling over in bed or gazing upwards)
• may be associated with nausea
• each episode typically lasts 10-20 seconds
• positive Dix-Hallpike manoeuvre
BPPV has a good prognosis and usually resolves spontaneously after a few weeks to months.
Symptomatic relief may be gained by:
• Epley manoeuvre (successful in around 80% of cases)

• teaching the patient exercises they can do themselves at home, termed vestibular
rehabilitation, for example Brandt-Daroff exercises
Medication is often prescribed (e.g. Betahistine) but it tends to be of limited value.
Around half of people with BPPV will have a recurrence of symptoms 3–5 years after their
diagnosis
Brachial neuritis
8
Brachial neuritis is characterized by acute onset of unilateral (occasionally bilateral) severe pain,
followed by shoulder and scapular weakness several days later. Sensory changes are usually
minimal. There may be subsequent rapid wasting of the arm muscles in accordance to which
nerve is involved. Precipitating factors include recent trauma, infection, surgery, or even
vaccination. Rarely it may be hereditary. The prognosis is usually good except when the phrenic
nerve is involved since this can result in significant breathlessness.
Brachial plexus injuries
Erb-Duchenne paralysis
• damage to C5,6 roots

• winged scapula
• may be caused by a breech presentation
Klumpke's paralysis
• damage to T1
• loss of intrinsic hand muscles
• due to traction
Brain abscess
Brain abscesses may result from a number of causes including, extension of sepsis from middle
ear or sinuses, trauma or surgery to the scalp, penetrating head injuries and embolic events
from endocarditis
The presenting symptoms will depend upon the site of the abscess (those in critical areas e.g.
motor cortex) will present earlier. Abscesses have a considerable mass effect in the brain and
raised intracranial pressure is common.
• headache
o often dull, persistent
• fever
o may be absent and usually not the swinging pyrexia seen with abscesses at other
sites
• focal neurology
o e.g. oculomotor nerve palsy or abducens nerve palsy secondary to raised
intracranial pressure
9
• other features consistent with raised intracranial pressure

o nausea
o papilloedema
o seizures
Investigations
• Assessment of the patient includes imaging with CT scanning
Management
• surgery
o a craniotomy is performed and the abscess cavity debrided
o the abscess may reform because the head is closed following abscess drainage.
• IV antibiotics: IV 3rd-generation cephalosporin + metronidazole
• intracranial pressure management: e.g. dexamethasone
Brain lesions
The following neurological disorders/features may allow localisation of a brain lesion:
Gross anatomy
Parietal lobe lesions
• sensory inattention
• apraxias
• astereognosis (tactile agnosia)
• inferior homonymous quadrantanopia
• Gerstmann's syndrome (lesion of dominant parietal): alexia, acalculia, finger agnosia and
right-left disorientation
Occipital lobe lesions
10
• homonymous hemianopia (with macula sparing)

• cortical blindness
• visual agnosia
Temporal lobe lesion
• Wernicke's aphasia: this area 'forms' the speech before 'sending it' to Brocas
area. Lesions result in word substituion, neologisms but speech remains fluent
• superior homonymous quadrantanopia
• auditory agnosia
• prosopagnosia (difficulty recognising faces)
Frontal lobes lesions
• expressive (Broca's) aphasia: located on the posterior aspect of the frontal lobe, in the
inferior frontal gyrus. Speech is non-fluent, laboured, and halting
• disinhibition
• perseveration
• anosmia
• inability to generate a list
Cerebellum lesions
• midline lesions: gait and truncal ataxia

• hemisphere lesions: intention tremor, past pointing, dysdiadokinesis, nystagmus
More specific areas
Area Associated conditions
Medial thalamus and mammillary bodies Wernicke and Korsakoff syndrome

of the hypothalamus
Subthalamic nucleus of the basal ganglia Hemiballism
11
Area Associated conditions
Striatum (caudate nucleus) of the basal Huntington chorea

ganglia
Substantia nigra of the basal ganglia Parkinson's disease
Amygdala Kluver-Bucy syndrome (hypersexuality, hyperorality,

hyperphagia, visual agnosia
Brown-Sequard syndrome
Overview
• caused by lateral hemisection of the spinal cord
Features
• ipsilateral weakness below lesion

• ipsilateral loss of proprioception and vibration sensation
• contralateral loss of pain and temperature sensation
CADASIL
Overview
• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and

Leukoencephalopathy (CADASIL)
• rare cause of multi-infarct dementia
• patients often present with migraine
Carbamazepine
Carbamazepine is chemically similar to the tricyclic antidepressant drugs. It is most commonly

used in the treatment of epilepsy, particularly partial seizures, where carbamazepine remains a
first-line medication. Other uses include
• trigeminal neuralgia
12
• bipolar disorder
Mechanism of action
• binds to sodium channels increases their refractory period
Adverse effects
• P450 enzyme inducer

• dizziness and ataxia
• drowsiness
• headache
• visual disturbances (especially diplopia)
• Steven-Johnson syndrome
• leucopenia and agranulocytosis
• hyponatraemia secondary to syndrome of inappropriate ADH secretion
Carbamazepine is known to exhibit autoinduction, hence when patients start carbamazepine

they may see a return of seizures after 3-4 weeks of treatment.
Cataplexy
Cataplexy describes the sudden and transient loss of muscular tone caused by strong
emotion (e.g. laughter, being frightened). Around two-thirds of patients with narcolepsy have
cataplexy.
Features range from buckling knees to collapse.
Cerebellar syndrome
Unilateral cerebellar lesions cause ipsilateral signs.
Useful and well-known mnemonic to remember symptoms of cerebellar disease is DANISH:
• D - Dysdiadochokinesia, Dysmetria (past-pointing), patients may appear 'Drunk'

• A - Ataxia (limb, truncal)
• N - Nystamus (horizontal = ipsilateral hemisphere)
• I - Intention tremour
13
• S - Slurred staccato speech, Scanning dysarthria

• H - Hypotonia
Causes
• Friedreich's ataxia, ataxic telangiectasia

• neoplastic: cerebellar haemangioma
• stroke
• alcohol
• multiple sclerosis
• hypothyroidism
• drugs: phenytoin, lead poisoning
• paraneoplastic e.g. secondary to lung cancer
Cerebrospinal fluid: raised lymphocytes
Normal values of cerebrospinal fluid (CSF) are as follows:
• pressure = 60-150 mm (patient recumbent)

• protein = 0.2-0.4 g/l
• glucose = > 2/3 blood glucose
• cells: red cells = 0, white cells < 5/mm³
The following conditions are associated with raised lymphocytes
• viral meningitis/encephalitis
• TB meningitis
• partially treated bacterial meningitis
• Lyme disease
• Behcet's, SLE
• lymphoma, leukaemia
Cerebrospinal fluid: raised protein
Normal values of cerebrospinal fluid (CSF) are as follows:
• pressure = 60-150 mm (patient recumbent)
14
• protein = 0.2-0.4 g/l

• glucose = > 2/3 blood glucose
• cells: red cells = 0, white cells < 5/mm³
The following conditions are associated with raised protein levels
• tuberculous, fungal and bacterial meningitis
• Froin's syndrome*
• viral encephalitis
*describes an increase in CSF protein below a spinal canal blockage (e.g. tumour, disc, infection)
Cervical spondylitic myelopathy
Cervical spondylosis is a degenerative condition affecting the cervical spine, essentially

osteoarthritis of the cervical vertebral bodies. If the spinal canal is narrowed due to this process
it can press on the spinal cord resulting in neurological dysfunction. Myelopathy is thought to
occur in around 5-10% of patients who have cervical spondylosis.
Features
• a variety of motor weakness, sensory loss and bladder/bowel dysfunction may be seen
• neck pain
• wide-based, ataxic or spastic gait
• upper motor neuron weakness in the lower legs - increased reflexes, increased tone and
upgoing plantars
• bladder dysfunction e.g. urgency, retention
Charcot-Marie-Tooth disease
Charcot-Marie-Tooth Disease is the most common hereditary peripheral neuropathy. It results

in a predominantly motor loss. There is no cure, and management is focused on physical and
occupational therapy.
Features:
15
• There may be a history of frequently sprained ankles

• Foot drop
• High-arched feet (pes cavus)
• Hammer toes
• Distal muscle weakness
• Distal muscle atrophy
• Hyporeflexia
• Stork leg deformity
Chorea
Chorea describes involuntary, rapid, jerky movements which often move from one part of the
body to another. Slower, sinuous movement of the limbs is termed athetosis. Chorea is caused
by damage to the basal ganglia, especially the caudate nucleus.
Causes of chorea
• Huntington's disease, Wilson's disease, ataxic telangiectasia

• SLE, anti-phospholipid syndrome
• rheumatic fever: Sydenham's chorea
• drugs: oral contraceptive pill, L-dopa, antipsychotics
• neuroacanthocytosis
• pregnancy: chorea gravidarum
• thyrotoxicosis
• polycythaemia rubra vera
• carbon monoxide poisoning
• cerebrovascular disease
Cluster headache
Cluster headaches are known to be one of the most painful conditions that patients can have
the misfortune to suffer. The name relates to the pattern of the headaches - they typically
occur in clusters lasting several weeks, with the clusters themselves typically once a year.
Cluster headaches are more common in men (3:1) and smokers. Alcohol may trigger an
attack and there also appears to be a relation to nocturnal sleep.
Features
16
• pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours
• clusters typically last 4-12 weeks
• intense sharp, stabbing pain around one eye (recurrent attacks 'always' affect same
side)
• patient is restless and agitated during an attack
• accompanied by redness, lacrimation, lid swelling
• nasal stuffiness
• miosis and ptosis in a minority
Management
• acute: 100% oxygen (80% response rate within 15 minutes), subcutaneous triptan (75%
response rate within 15 minutes)
• prophylaxis: verapamil is the drug of choice. There is also some evidence to support a
tapering dose of prednisolone
• NICE recommend seeking specialist advice from a neurologist if a patient develops
cluster headaches with respect to neuroimaging
Some neurologists use the term trigeminal autonomic cephalgia to group a number of
conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral
neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended
such patients are referred for specialist assessment as specific treatment may be required, for
example it is known paroxysmal hemicrania responds very well to indomethacin
Common peroneal nerve lesion
The sciatic nerve divides into the tibial and common peroneal nerves. Injury often occurs at the
neck of the fibula
The most characteristic feature of a common peroneal nerve lesion is foot drop.
Other features include:
• weakness of foot dorsiflexion

• weakness of foot eversion
• weakness of extensor hallucis longus
• sensory loss over the dorsum of the foot and the lower lateral part of the leg
• wasting of the anterior tibial and peroneal muscles
17
Complex regional pain syndrome
Complex regional pain syndrome (CRPS) is the modern, umbrella term for a number of
conditions such as reflex sympathetic dystrophy and causalgia. It describes a number of
neurological and related symptoms which typically occur following surgery or a minor injury.
CRPS is 3 times more common in women.
There are two types of CRPS:
• type I (most common): there is no demonstrable lesion to a major nerve

• type II: there is a lesion to a major nerve
Features
• progressive, disproportionate symptoms to the original injury/surgery

• allodynia
• temperature and skin colour changes
• oedema and sweating
• motor dysfunction
• the Budapest Diagnostic Criteria are commonly used in the UK
Management
• early physiotherapy is important

• neuropathic analgesia in-line with NICE guidelines
• specialist management (e.g. Pain team) is required
Creutzfeldt-Jakob disease
Creutzfeldt-Jakob disease (CJD) is rapidly progressive neurological condition caused by prion

proteins. These proteins induce the formation of amyloid folds resulting in tightly packed beta-
pleated sheets resistant to proteases.
Features
18
• dementia (rapid onset)

• myoclonus
Investigation
• CSF is usually normal

• EEG: biphasic, high amplitude sharp waves (only in sporadic CJD)
• MRI: hyperintense signals in the basal ganglia and thalamus
Sporadic CJD
• accounts for 85% of cases

• 10-15% of cases are familial
• mean age of onset is 65 years
New variant CJD
• younger patients (average age of onset = 25 years)

• psychological symptoms such as anxiety, withdrawal and dysphonia are the most
common presenting features
• the 'prion protein' is encoded on chromosome 20 - it's role is not yet understood
• methionine homozygosity at codon 129 of the prion protein is a risk factor for
developing CJD - all patients who have so far died have had this
• median survival = 13 months
Other prion diseases
• kuru
• fatal familial insomnia
• Gerstmann Straussler-Scheinker disease
Degenerative cervical myelopathy
Degenerative cervical myelopathy (DCM) has a number of risk factors, which include smoking
19
due to its effects on the intervertebral discs, genetics and occupation - those exposing patients
to high axial loading [1].
The presentation of DCM is very variable. Early symptoms are often subtle and can vary in
severity day to day, making the disease difficult to detect initially. However as a progressive
condition, worsening, deteriorating or new symptoms should be a warning sign.
DCM symptoms can include any combination of [1]:
• Pain (affecting the neck, upper or lower limbs)

• Loss of motor function (loss of digital dexterity, preventing simple tasks such as holding
a fork or doing up their shirt buttons, arm or leg weakness/stiffness leading to impaired
gait and imbalance
• Loss of sensory function causing numbness
• Loss of autonomic function (urinary or faecal incontinence and/or impotence) - these
can occur and do not necessarily suggest cauda equina syndrome in the absence of
other hallmarks of that condition
• Hoffman's sign: is a reflex test to assess for cervical myelopathy. It is performed by
gently flicking one finger on a patient's hand. A positive test results in reflex twitching of
the other fingers on the same hand in response to the flick.
The most common symptoms at presentation of DCM are unknown, but in one series 50% of
patients were initially incorrectly diagnosed and sometimes treated for carpal tunnel syndrome
[2].
An MRI of the cervical spine is the gold standard test where cervical myelopathy is suspected. It
may reveal disc degeneration and ligament hypertrophy, with accompanying cord signal
change.
All patients with degenerative cervical myelopathy should be urgently referred for assessment
by specialist spinal services (neurosurgery or orthopaedic spinal surgery). This is due to the
importance of early treatment. The timing of surgery is important, as any existing spinal cord
damage can be permanent. Early treatment (within 6 months of diagnosis) offers the best
chance of a full recovery but at present, most patients are presenting too late. In one study,
patients averaged over 5 appointments before diagnosis, representing >2 years.
Currently, decompressive surgery is the only effective treatment. It has been shown to prevent
disease progression. Close observation is an option for mild stable disease, but anything
progressive or more severe requires surgery to prevent further deterioration. Physiotherapy
should only be initiated by specialist services, as manipulation can cause more spinal cord
damage.
20
References
1. Baron EM, Young WF. Cervical spondylotic myelopathy: a brief review of its pathophysiology,
clinical course, and diagnosis. Neurosurgery. 2007 Jan;60(1 Supp1 1):S35-41.
2. Behrbalk E, Salame K, Regev GJ, Keynan O, Boszczyk B, Lidar Z. Delayed diagnosis of cervical
spondylotic myelopathy by primary care physicians. Neurosurg Focus. 2013 Jul;35(1):E1.
Drugs causing peripheral neuropathy
Drugs causing a peripheral neuropathy
• amiodarone
• isoniazid
• vincristine
• nitrofurantoin
• metronidazole
DVLA: neurological disorders
The guidelines below relate to car/motorcycle use unless specifically stated. For obvious
reasons, the rules relating to drivers of heavy goods vehicles tend to be much stricter
Epilepsy/seizures - all patient must not drive and must inform the DVLA
• first unprovoked/isolated seizure: 6 months off if there are no relevant structural

abnormalities on brain imaging and no definite epileptiform activity on EEG. If these
conditions are not met then this is increased to 12 months
• for patients with established epilepsy or those with multiple unprovoked seizures:
o may qualify for a driving licence if they have been free from any seizure for 12
months
o if there have been no seizures for 5 years (with medication if necessary) a ’til 70
licence is usually restored
• withdrawawl of epilepsy medication: should not drive whilst anti-epilepsy medication is
being withdrawn and for 6 months after the last dose
Syncope
• simple faint: no restriction

• single episode, explained and treated: 4 weeks off
21
• single episode, unexplained: 6 months off

• two or more episodes: 12 months off
Other conditions
• stroke or TIA: 1 month off driving, may not need to inform DVLA if no residual
neurological deficit
• multiple TIAs over short period of times: 3 months off driving and inform DVLA
• craniotomy e.g. For meningioma: 1 year off driving*
• pituitary tumour: craniotomy: 6 months; trans-sphenoidal surgery 'can drive when there
is no debarring residual impairment likely to affect safe driving'
• narcolepsy/cataplexy: cease driving on diagnosis, can restart once 'satisfactory control
of symptoms'
• chronic neurological disorders e.g. multiple sclerosis, motor neuron disease: DVLA
should be informed, complete PK1 form (application for driving licence holders state of
health)
*if the tumour is a benign meningioma and there is no seizure history, licence can be
reconsidered 6 months after surgery if remains seizure free
Dystrophinopathies
Overview
• X-linked recessive
• due to mutation in the gene encoding dystrophin, dystrophin gene on Xp21
• dystrophin is part of a large membrane associated protein in muscle which connects the
muscle membrane to actin, part of the muscle cytoskeleton
• in Duchenne muscular dystrophy there is a frameshift mutation resulting in one or both
of the binding sites are lost leading to a severe form
• in Becker muscular dystrophy there is a non-frameshift insertion in the dystrophin gene
resulting in both binding sites being preserved leading to a milder form
Duchenne muscular dystrophy
• progressive proximal muscle weakness from 5 years

• calf pseudohypertrophy
22
• Gower's sign: child uses arms to stand up from a squatted position

• 30% of patients have intellectual impairment
Becker muscular dystrophy
• develops after the age of 10 years

• intellectual impairment much less common
Epilepsy in children: syndromes
Infantile spasms (West's syndrome)
• brief spasms beginning in first few (4-6) months of life; M>F

• 1. Flexion of head, trunk, limbs → extension of arms (Salaam attack); last 1-2 secs,
repeat up to 50 times
• 2. Progressive mental handicap
• 3. EEG: hypsarrhythmia
• usually 2nd to serious neurological abnormality (e.g. TS, encephalitis, birth asphyxia) or
may be cryptogenic
• poor prognosis
• vigabatrin/steroids
Typical (petit mal) absence seizures
• onset 4-8 yrs

• duration few-30 secs; no warning, quick recovery; often many per day
• EEG: 3Hz generalized, symmetrical
• sodium valproate, ethosuximide
• good prognosis: 90-95% become seizure free in adolescence
Lennox-Gastaut syndrome
• may be extension of infantile spasms (50% have hx)

• onset 1-5 yrs
• atypical absences, falls, jerks
• 90% moderate-severe mental handicap
23
• EEG: slow spike

• ketogenic diet may help
Benign rolandic epilepsy
• most common in childhood, M>F

• paraesthesia (e.g. unilateral face), usually on waking up
Juvenile myoclonic epilepsy (Janz syndrome)
• onset: teens; F:M = 2:1

• 1. Infrequent generalized seizures, often in morning//following sleep deprivation
• 2. Daytime absences
• 3. Sudden, shock like myoclonic seizure (these may develop before seizures)
• usually good response to sodium valproate
Neonatal period - try vitamin B6
• 2nd: hypoglycaemia, meningitis, head trauma

• pyridoxine dependency (AR, IV B6)
• benign familial neonatal seizures (AD)
• benign neonatal convulsions (5th day)
Epilepsy: classification
The basic classification of epilepsy has changed in recent years. The new basic seizure
classification is based on 3 key features:
• 1. Where seizures begin in the brain

• 2. Level of awareness during a seizure (important as can affect safety during seizure)
• 3. Other features of seizures
Focal seizures
24
• previously termed partial seizures

• these start in a specific area, on one side of the brain
• the level of awareness can vary in focal seizures. The terms focal aware (previously
termed 'simple partial'), focal impaired awareness (previously termed 'complex partial')
and awareness unknown are used to further describe focal seizures
• further to this, focal seizures can be classified as being motor (e.g. Jacksonian march),
non-motor (e.g. déjà vu, jamais vu; ) or having other features such as aura
Generalised
• these engage or involve networks on both sides of the brain at the onset
• consciousness lost immediately. The level of awareness in the above classification is
therefore not needed, as all patients lose consciousness
• generalised seizures can be further subdivided into motor (e.g. tonic-clonic) and non-
motor (e.g. absence)
• specific types include:
o tonic-clonic (grand mal)
o tonic
o clonic
o typical absence (petit mal)
o atonic
Unknown onset
• this termed is reserved for when the origin of the seizure is unknown
Focal to bilateral seizure
• starts on one side of the brain in a specific area before spreading to both lobes
• previously termed secondary generalized seizures
Epilepsy: localising features of focal seizures
25
Location Typical seizure type
Temporal lobe Hallucinations (auditory/gustatory/olfactory), Epigastric rising/Emotional,

(HEAD) Automatisms (lip smacking/grabbing/plucking), Deja vu/Dysphasia post-ictal)
Frontal lobe Head/leg movements, posturing, post-ictal weakness, Jacksonian march

(motor)
Parietal lobe Paraesthesia

(sensory)
Occipital lobe Floaters/flashes

(visual)
Epilepsy: pregnancy and breast feeding
The risks of uncontrolled epilepsy during pregnancy generally outweigh the risks of medication
to the fetus. All women thinking about becoming pregnant should be advised to take folic acid
5mg per day well before pregnancy to minimise the risk of neural tube defects. Around 1-2% of
newborns born to non-epileptic mothers have congenital defects. This rises to 3-4% if the
mother takes antiepileptic medication.
Other points
• aim for monotherapy

• there is no indication to monitor antiepileptic drug levels
• sodium valproate: associated with neural tube defects
• carbamazepine: often considered the least teratogenic of the older antiepileptics
• phenytoin: associated with cleft palate
• lamotrigine: studies to date suggest the rate of congenital malformations may be low.
The dose of lamotrigine may need to be increased in pregnancy
Breast feeding is generally considered safe for mothers taking antiepileptics with the possible
exception of the barbiturates
It is advised that pregnant women taking phenytoin are given vitamin K in the last month of
pregnancy to prevent clotting disorders in the newborn
26
Sodium valproate
The November 2013 issue of the Drug Safety Update also carried a warning about new evidence
showing a significant risk of neurodevelopmental delay in children following maternal use of
sodium valproate.
The update concludes that sodium valproate should not be used during pregnancy and in
women of childbearing age unless clearly necessary. Women of childbearing age should not
start treatment without specialist neurological or psychiatric advice.
Epilepsy: treatment
Most neurologists now start antiepileptics following a second epileptic seizure. NICE guidelines
suggest starting antiepileptics after the first seizure if any of the following are present:
• the patient has a neurological deficit

• brain imaging shows a structural abnormality
• the EEG shows unequivocal epileptic activity
• the patient or their family or carers consider the risk of having a further seizure
unacceptable
It should be remembered that the following are only general guidelines. For example, maternal
use of sodium valproate is associated with a significant risk of neurodevelopmental delay in
children. Guidance is now clear that sodium valproate should not be used during pregnancy
and in women of childbearing age unless clearly necessary.
Sodium valproate is considered the first line treatment for patients with generalised seizures
with carbamazepine used for focal seizures.
Generalised tonic-clonic seizures
• sodium valproate
• second line: lamotrigine, carbamazepine
Absence seizures* (Petit mal)
• sodium valproate or ethosuximide

• sodium valproate particularly effective if co-existent tonic-clonic seizures in primary
27
generalised epilepsy
Myoclonic seizures**
• sodium valproate
• second line: clonazepam, lamotrigine
Focal seizures
• carbamazepine or lamotrigine
• second line: levetiracetam, oxcarbazepine or sodium valproate
*carbamazepine may exacerbate absence seizures
**carbamazepine may exacerbate myoclonic seizures

Essential tremor
Essential tremor (previously called benign essential tremor) is an autosomal dominant condition
which usually affects both upper limbs
Features
• postural tremor: worse if arms outstretched

• improved by alcohol and rest
• most common cause of titubation (head tremor)
Management
• propranolol is first-line
• primidone is sometimes used
Ethosuximide
Ethosuximide is an antiepileptic that is particularly indicated in patients with absence seizures
28
Mechanism of action
• blocks T-type calcium channels in thalamic neurons
Facial nerve palsy
The facial nerve is the main nerve supplying the structures of the second embryonic branchial
arch. It is predominantly an efferent nerve to the muscles of facial expression, digastric muscle
and also to many glandular structures. It contains a few afferent fibres which originate in the
cells of its genicular ganglion and are concerned with taste.
Supply - 'face, ear, taste, tear'
• face: muscles of facial expression

• ear: nerve to stapedius
• taste: supplies anterior two-thirds of tongue
• tear: parasympathetic fibres to lacrimal glands, also salivary glands
Causes of bilateral facial nerve palsy
• sarcoidosis
• Lyme disease
• bilateral acoustic neuromas (as in neurofibromatosis type 2)
• as Bell's palsy is relatively common it accounts for up to 25% of cases f bilateral palsy,
but this represents only 1% of total Bell's palsy cases
Causes of unilateral facial nerve palsy - as above plus
29
Lower motor neuron
• Bell's palsy
• Ramsay-Hunt syndrome (due to herpes zoster)
• acoustic neuroma
• parotid tumours Upper motor neuron
• HIV
• multiple sclerosis*
• diabetes mellitus • stroke
LMN vs. UMN
• upper motor neuron lesion 'spares' upper face i.e. forehead

• lower motor neuron lesion affects all facial muscles
*may also cause an UMN palsy
Path
Subarachnoid path
• Origin: motor- pons, sensory- nervus intermedius

• Pass through the petrous temporal bone into the internal auditory meatus with the
vestibulocochlear nerve. Here they combine to become the facial nerve.
Facial canal path
• The canal passes superior to the vestibule of the inner ear

• At the medial aspect of the middle ear, it becomes wider and contains the geniculate
ganglion.
- 3 branches:
• 1. greater petrosal nerve
30
• 2. nerve to stapedius
• 3. chorda tympani
Stylomastoid foramen
• Passes through the stylomastoid foramen (tympanic cavity anterior and mastoid antrum
posteriorly)
• Posterior auricular nerve and branch to posterior belly of digastric and stylohyoid
muscle
Facioscapulohumeral muscular dystrophy
Facioscapulohumeral muscular dystrophy (FSHMD) is an autosomal dominant form of muscular

dystrophy. As the name suggests it stypically affects the face, scapula and upper arms first.
Symptoms typically presents by the age of 20 years.
Foot drop
Foot drop is a result of weakness of the foot dorsiflexors.
Possible causes include:
• common peroneal nerve lesion - the most common cause

• L5 radiculopathy
• sciatic nerve lesion
• superficial or deep peroneal nerve lesion
• other possible includes central nerve lesions (e.g. stroke) but other features are usually
present
A common peroneal nerve lesion is the most common cause . This is often secondary to
compression at the neck of the fibula. This may be caused by certain positions such as leg
crossing, squatting or kneeling. Prolonged confinement, recent weight loss, Baker's cysts and
plaster casts to the lower leg are also known to be precipitating factors.
Examination
• if the patient has an isolated peroneal neuropathy there will be weakness of foot
dorsiflexion and eversion. Reflexes will be normal
31
• weakness of hip abduction is suggestive of a L5 radiculopathy
Bilateral symptoms, fasiculations or other abnormal neurological findings (e.g. hyperreflexia)

are indications for specialist referral.
If the examination suggests a peroneal neuropathy then conservative management is

appropriate. Leg crossing, squatting and kneeling should be avoided. Symptoms typically
improve over 2-3 months.*
*BMJ 2015;350:h1736 - Foot drop

Fourth nerve palsy
Overview
• supplies superior oblique (depresses eye, moves inward)
Features
• vertical diplopia
o classically noticed when reading a book or going downstairs
• subjective tilting of objects (torsional diplopia)
• the patient may develop a head tilt, which they may or may not be aware of
• when looking straight ahead, the affected eye appears to deviate upwards and is
rotated outwards
Friedreich's ataxia
Friedreich's ataxia is the most common of the early-onset hereditary ataxias. It is an autosomal
recessive, trinucleotide repeat disorder characterised by a GAA repeat in the X25 gene on
chromosome 9 (frataxin). Friedreich's ataxia is unusual amongst trinucleotide repeat disorders
in not demonstrating the phenomenon of anticipation.
The typical age of onset is 10-15 years old. Gait ataxia and kyphoscoliosis are the most common
presenting features.
Neurological features
• absent ankle jerks/extensor plantars
32
• cerebellar ataxia
• optic atrophy
• spinocerebellar tract degeneration
Other features
• hypertrophic obstructive cardiomyopathy (90%, most common cause of death)

• diabetes mellitus (10-20%)
• high-arched palate
Comparison of Friedreich's ataxia and ataxic telangiectasia. Note in particular how ataxic
telangiectasia tends to present much earlier, often at the age of 1-2 years
Gingival hyperplasia
Drug causes of gingival hyperplasia
• phenytoin
• ciclosporin
• calcium channel blockers (especially nifedipine)
Other causes of gingival hyperplasia include
33
• acute myeloid leukaemia (myelomonocytic and monocytic types)
Guillain-Barre syndrome
Guillain-Barre syndrome describes an immune-mediated demyelination of the peripheral

nervous system often triggered by an infection (classically Campylobacter jejuni)
Pathogenesis
• cross-reaction of antibodies with gangliosides in the peripheral nervous system

• correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has
been demonstrated
• anti-GM1 antibodies in 25% of patients
Miller Fisher syndrome
• variant of Guillain-Barre syndrome

• associated with ophthalmoplegia, areflexia and ataxia. The eye muscles are typically
affected first
• usually presents as a descending paralysis rather than ascending as seen in other forms
of Guillain-Barre syndrome
• anti-GQ1b antibodies are present in 90% of cases
Guillain-Barre syndrome: features
Guillain-Barre syndrome describes an immune-mediated demyelination of the peripheral

nervous system often triggered by an infection (classically Campylobacter jejuni).
Initial symptoms
• around 65% of patients experience back/leg pain in the initial stages of the illness
The characteristic features of Guillain-Barre syndrome is progressive, symmetrical weakness of

all the limbs.
• the weakness is classically ascending i.e. the legs are affected first
• proximal muscles (e.g. hips/shoulders) are usually affected before than the distal ones
34
(e.g. feet/hands)
• reflexes are reduced or absent
• sensory symptoms tend to be mild (e.g. distal paraesthesia) with very few sensory signs
Other features
• there may be a history of gastroenteritis

• respiratory muscle weakness
• cranial nerve involvement
o diplopia
o bilateral facial nerve palsy
o oropharyngeal weakness is common
• autonomic involvement
o urinary retention
o diarrhoea
Less common findings
• papilloedema: thought to be secondary to reduced CSF resorption
Investigations
• lumbar puncture
o rise in protein with a normal white blood cell count (albuminocytologic
dissociation) - found in 66%
• nerve condution studies may be performed
Guillain-Barre syndrome: management
Guillain-Barre syndrome describes an immune mediated demyelination of the peripheral

nervous system often triggered by an infection (classically Campylobacter jejuni).
Management
• plasma exchange
• IV immunoglobulins (IVIG): as effective as plasma exchange. No benefit in combining
35
both treatments. IVIG may be easier to administer and tends to have fewer side-effects
• steroids and immunosuppressants have not been shown to be beneficial
• FVC regularly to monitor respiratory function
Prognosis
• severe motor problems persist in about 15%

• around 5% die
Guillain-Barre syndrome: prognosis
Guillain-Barre syndrome (GBS) describes an immune mediated demyelination of the peripheral

nervous system often triggered by an infection (classically Campylobacter jejuni)
Poor prognostic features
• age > 40 years

• poor upper extremity muscle strength
• previous history of a diarrhoeal illness (specifically Campylobacter jejuni)
• high anti-GM1 antibody titre
• need for ventilatory support
There is currently contradictory evidence as to whether a gradual or rapid onset of GBS is

associated with a poor outcome
Head injury: NICE guidance on investigation
NICE has strict and clear guidance regarding which adult patients are safe to discharge and
which need further CT head imaging. The latter group are also divided into two further cohorts,
those who require an immediate CT head and those requiring CT head within 8 hours of injury:
CT head immediately
• GCS < 13 on initial assessment

• GCS < 15 at 2 hours post-injury
• suspected open or depressed skull fracture.
• any sign of basal skull fracture (haemotympanum, 'panda' eyes, cerebrospinal fluid
leakage from the ear or nose, Battle's sign).
• post-traumatic seizure.
36
• focal neurological deficit.

• more than 1 episode of vomiting
CT head scan within 8 hours of the head injury - for adults with any of the following risk factors
who have experienced some loss of consciousness or amnesia since the injury:
• age 65 years or older

• any history of bleeding or clotting disorders
• dangerous mechanism of injury (a pedestrian or cyclist struck by a motor vehicle, an
occupant ejected from a motor vehicle or a fall from a height of greater than 1 metre or
5 stairs)
• more than 30 minutes' retrograde amnesia of events immediately before the head
injury
If a patient is on warfarin who have sustained a head injury with no other indications for a CT
head scan, perform a CT head scan within 8 hours of the injury.
Head injury: types of traumatic brain injury
Basics
• primary brain injury may be focal (contusion/haematoma) or diffuse (diffuse axonal

injury)
• diffuse axonal injury occurs as a result of mechanical shearing following deceleration,
causing disruption and tearing of axons
• intra-cranial haematomas can be extradural, subdural or intracerebral, while contusions
may occur adjacent to (coup) or contralateral (contre-coup) to the side of impact
• secondary brain injury occurs when cerebral oedema, ischaemia, infection, tonsillar or
tentorial herniation exacerbates the original injury. The normal cerebral auto regulatory
processes are disrupted following trauma rendering the brain more susceptible to blood
flow changes and hypoxia
• the Cushings reflex (hypertension and bradycardia) often occurs late and is usually a pre
terminal event
Type of injury Notes
37
Type of injury Notes
Extradural Bleeding into the space between the dura mater and the skull. Often results
(epidural) from acceleration-deceleration trauma or a blow to the side of the head. The
haematoma majority of epidural haematomas occur in the temporal region where skull
fractures cause a rupture of the middle meningeal artery.
Features
• features of raised intracranial pressure

• some patients may exhibit a lucid interval
Subdural Bleeding into the outermost meningeal layer. Most commonly occur around
haematoma the frontal and parietal lobes.
Risk factors include old age, alcoholism and anticoagulation.
Slower onset of symptoms than a epidural haematoma. There may

be fluctuating confusion/consciousness
Subarachnoid Classically causes a sudden occipital headache. Usually occurs spontaneously in

haemorrhage the context of a ruptured cerebral aneurysm but may be seen in association
with other injuries when a patient has sustained a traumatic brain injury
Intracerebral An intracerebral (or intraparenchymal) haemorrhage is a collection of blood

haematoma within the substance of the brain.
Causes / risk factors include: hypertension, vascular lesion (e.g. aneurysm or

arteriovenous malformation), cerebral amyloid angiopathy, trauma, brain
tumour or infarct (particularly in stroke patients undergoing thrombolysis).
Patients will present similarly to an ischaemic stroke (which is why it is crucial

to obtain a CT in head in all stroke patients prior to thrombolysis) or with a
decrease in consciousness.
CT imaging will show a hyperdensity (bright lesion) within the substance of the
brain.
Treatment is often conservative under the care of stroke physicians, but large
clots in patients with impaired consciousness may warrant surgical evacuation.
38
Image gallery
Extradural (epidural) haematoma:
Subdural haematoma:
39
Subarachnoid haemorrhage:
Headache
Headache accounts for a large proportion of medical consultations. The table below
summarises the main characteristics of common or important causes:
Condition Notes
Migraine Recurrent, severe headache which is usually unilateral and

throbbing in nature
May be be associated with aura, nausea and photosensitivity
Aggravated by, or causes avoidance of, routine activities of daily
living. Patients often describe 'going to bed'.
In women may be associated with menstruation
40
Condition Notes
Tension headache Recurrent, non-disabling, bilateral headache, often described as

a 'tight-band'
Not aggravated by routine activities of daily living
Cluster headache* Pain typical occurs once or twice a day, each episode lasting 15
mins - 2 hours with clusters typically lasting 4-12 weeks
Intense pain around one eye (recurrent attacks 'always' affect
same side)
Patient is restless during an attack
Accompanied by redness, lacrimation, lid swelling
More common in men and smokers
Temporal arteritis Typically patient > 60 years old

Usually rapid onset (e.g. < 1 month) of unilateral headache
Jaw claudication (65%)
Tender, palpable temporal artery
Raised ESR
Medication overuse Present for 15 days or more per month

headache Developed or worsened whilst taking regular symptomatic
medication
Patients using opioids and triptans are at most risk
May be psychiatric co-morbidity
Other causes of headache
Acute single episode
• meningitis
• encephalitis
• subarachnoid haemorrhage
• head injury
• sinusitis
• glaucoma (acute closed-angle)
• tropical illness e.g. Malaria
Chronic headache
41
• chronically raised ICP

• Paget's disease
• psychological
*some neurologists use the term trigeminal autonomic cephalgia to group a number of
conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral
neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended
such patients are referred for specialist assessment as specific treatment may be required, for
example it is known paroxysmal hemicrania responds very well to indomethacin
Hemiballism
Hemiballism occurs following damage to the subthalamic nucleus. Ballisic movements

are involuntary, sudden, jerking movements which occur contralateral to the side of the lesion.
The ballisic movements primarily affect the proximal limb musculature whilst the distal muscles
may display more choreiform-like movements
Symptoms may decrease whilst the patient is asleep.
Antidopaminergic agents (e.g. Haloperidol) are the mainstay of treatment
Herpes simplex encephalitis
Herpes simplex (HSV) encephalitis is a common topic in the exam. The virus characteristically
affects the temporal lobes - questions may give the result of imaging or describe temporal lobe
signs e.g. aphasia.
Features
• fever, headache, psychiatric symptoms, seizures, vomiting

• focal features e.g. aphasia
• peripheral lesions (e.g. cold sores) have no relation to presence of HSV encephalitis
Pathophysiology
• HSV-1 responsible for 95% of cases in adults

• typically affects temporal and inferior frontal lobes
42
Investigation
• CSF: lymphocytosis, elevated protein

• PCR for HSV
• CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal
in one-third of patients
• MRI is better
• EEG pattern: lateralised periodic discharges at 2 Hz
Treatment
• intravenous aciclovir
The prognosis is dependent on whether aciclovir is commenced early. If treatment is started

promptly the mortality is 10-20%. Left untreated the mortality approaches 80%
© Image used on license from Radiopaedia

MRI of a patient with HSV encephalitis. There is hyperintensity of the affected white matter and
cortex in the medial temporal lobes and insular cortex.
HSMN
Hereditary sensorimotor neuropathy (HSMN) is a relatively new term which encompasses

Charcot-Marie-Tooth disease (also known as peroneal muscular atrophy). Over 7 types have
been characterised - however only 2 are common to clinical practice
43
• HSMN type I: primarily due to demyelinating pathology

• HSMN type II: primarily due to axonal pathology
HSMN type I
• autosomal dominant
• due to defect in PMP-22 gene (which codes for myelin)
• features often start at puberty
• motor symptoms predominate
• distal muscle wasting, pes cavus, clawed toes
• foot drop, leg weakness often first features
Huntington's disease
Huntington's disease is an inherited neurodegenerative condition. It is a progressive and

incurable condition that typically results in death 20 years after the initial symptoms develop.
Genetics
• trinucleotide repeat disorder: repeat expansion of CAG
o as Huntington's disease is a trinucleotide repeat disorder, the phenomenon of
anticipation may be seen, where the disease is presents at an earlier age in
successive generations
• results in degeneration of cholinergic and GABAergic neurons in the striatum of the
basal ganglia
• due to defect in huntingtin gene on chromosome 4
Features typical develop after 35 years of age
• chorea
• personality changes (e.g. irritability, apathy, depression) and intellectual impairment
• dystonia
• saccadic eye movements
44
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension (also known as pseudotumour cerebri and formerly benign
intracranial hypertension) is a condition classically seen in young, overweight females.
Risk factors
• obesity
• female sex
• pregnancy
• drugs*: oral contraceptive pill, steroids, tetracycline, vitamin A, lithium
Features
• headache
• blurred vision
• papilloedema (usually present)
• enlarged blind spot
• sixth nerve palsy may be present
Management
• weight loss
• diuretics e.g. acetazolamide
• topiramate is also used, and has the added benefit of causing weight loss in most
patients
• repeated lumbar puncture
• surgery: optic nerve sheath decompression and fenestration may be needed to prevent
damage to the optic nerve. A lumboperitoneal or ventriculoperitoneal shunt may also
be performed to reduce intracranial pressure
*if intracranial hypertension is thought to occur secondary to a known causes (e.g. Medication)
then it is of course not idiopathic
Internuclear ophthalmoplegia
Overview
45
• a cause of horizontal disconjugate eye movement

• due to a lesion in the medial longitudinal fasciculus (MLF)
o controls horizontal eye movements by interconnecting the IIIrd, IVth and VIth
cranial nuclei
o located in the paramedian area of the midbrain and pons
Features
• impaired adduction of the eye on the same side as the lesion

• horizontal nystagmus of the abducting eye on the contralateral side
Causes
• vascular disease
Intracranial venous thrombosis
Overview
• can cause cerebral infarction, much lesson common than arterial causes
• 50% of patients have isolated sagittal sinus thromboses - the remainder have coexistent
lateral sinus thromboses and cavernous sinus thromboses
Features
• headache (may be sudden onset)

• nausea & vomiting
Sagittal sinus thrombosis
• may present with seizures and hemiplegia

• parasagittal biparietal or bifrontal haemorrhagic infarctions are sometimes seen
Cavernous sinus thrombosis
46
• other causes of cavernous sinus syndrome: local infection (e.g. sinusitis), neoplasia,
trauma
• periorbital oedema
• ophthalmoplegia: 6th nerve damage typically occurs before 3rd & 4th
• trigeminal nerve involvement may lead to hyperaesthesia of upper face and eye pain
• central retinal vein thrombosis
Lateral sinus thrombosis
• 6th and 7th cranial nerve palsies

CT with contrast demonstrating a superior sagittal sinus thrombosis showing the typical empty
delta sign. Look at the 'bottom' of the scan for the triangular shaped dural sinus. This should
normally be white due to it being filled with contrast. The empty delta sign occurs when the
thrombus fails to enhance within the dural sinus and is outlined by enhanced collateral
channels in the falx. This sign is seen in only about 25%-30% of cases but is highly diagnostic for
sagittal sinus thrombosis
Lambert-Eaton syndrome
Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer and to a
lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune
disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against
presynaptic voltage-gated calcium channel in the peripheral nervous system.
Features
• repeated muscle contractions lead to increased muscle strength (in contrast to
47
myasthenia gravis)
o in reality, this is seen in only 50% of patients and following prolonged muscle use
muscle strength will eventually decrease
• limb-girdle weakness (affects lower limbs first)
• hyporeflexia
• autonomic symptoms: dry mouth, impotence, difficulty micturating
• ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
EMG
• incremental response to repetitive electrical stimulation
Management
• treatment of underlying cancer

• immunosuppression, for example with prednisolone and/or azathioprine
• 3,4-diaminopyridine is currently being trialled
o works by blocking potassium channel efflux in the nerve terminal so that the
action potential duration is increased. Calcium channels can then be open for a
longer time and allow greater acetylcholine release to the stimulate muscle at
the end plate
• intravenous immunoglobulin therapy and plasma exchange may be beneficial
Lamotrigine
Lamotrigine is an antiepileptic used second-line for a variety of generalised and partial seizures.
Mechanism of action
• sodium channel blocker
Adverse effects
• Stevens-Johnson syndrome
48
Lateral medullary syndrome
Lateral medullary syndrome, also known as Wallenberg's syndrome, occurs following occlusion
of the posterior inferior cerebellar artery.
Cerebellar features
• ataxia
• nystagmus
Brainstem features
• ipsilateral: dysphagia, facial numbness, cranial nerve palsy e.g. Horner's

• contralateral: limb sensory loss
Levodopa
Overview
• usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to

prevent peripheral metabolism of L-dopa to dopamine
• reduced effectiveness with time (usually by 2 years)
• no use in neuroleptic induced parkinsonism
Adverse effects
• dyskinesia
• 'on-off' effect
• postural hypotension
• cardiac arrhythmias
• nausea & vomiting
• psychosis
• reddish discolouration of urine upon standing
Macroglossia
49
Causes
• hypothyroidism
• acromegaly
• amyloidosis
• Duchenne muscular dystrophy
• mucopolysaccharidosis (e.g. Hurler syndrome)
Patients with Down's syndrome are now thought to have apparent macroglossia due to a
combination of mid-face hypoplasia and hypotonia
Medication overuse headache
Medication overuse headache is one of the most common causes of chronic daily headache. It
may affect up to 1 in 50 people
Features
• present for 15 days or more per month

• developed or worsened whilst taking regular symptomatic medication
• patients using opioids and triptans are at most risk
• may be psychiatric co-morbidity
Management (from 2008 SIGN guidelines)
• simple analgesics and triptans should be withdrawn abruptly (may initially worsen
headaches)
• opioid analgesics should be gradually withdrawn
Withdrawal symptoms such as vomiting, hypotension, tachycardia, restlessness, sleep

disturbances and anxiety may occur when medication is stopped
Meniere's disease
Meniere's disease is a disorder of the inner ear of unknown cause. It is characterised by

excessive pressure and progressive dilation of the endolymphatic system. It is more common in
middle-aged adults but may be seen at any age. Meniere's disease has a similar prevalence in
both men and women.
50
Features
• recurrent episodes of vertigo, tinnitus and hearing loss (sensorineural). Vertigo is usually
the prominent symptom
• a sensation of aural fullness or pressure is now recognised as being common
• other features include nystagmus and a positive Romberg test
• episodes last minutes to hours
• typically symptoms are unilateral but bilateral symptoms may develop after a number of
years
Natural history
• symptoms resolve in the majority of patients after 5-10 years

• the majority of patients will be left with a degree of hearing loss
• psychological distress is common
Management
• ENT assessment is required to confirm the diagnosis

• patients should inform the DVLA. The current advice is to cease driving until satisfactory
control of symptoms is achieved
• acute attacks: buccal or intramuscular prochlorperazine. Admission is sometimes
required
• prevention: betahistine and vestibular rehabilitation exercises may be of benefit
Meningitis
Most common adult cause (mortality)
• meningococcus (10%)
• pneumococcus (25%)
Diagnosis
51
• if partially treated with antibiotics, negative CSF culture, but glucose, protein and white
cells unchanged
Neurological sequalae
• sensorineural hearing loss (most common)

• other neurological: epilepsy, paralysis
• infective: sepsis, intracerebral abscess
• pressure: brain herniation, hydrocephalus
Migraine
Migraine is a common type of primary headache. It is characterised typically by:
• a severe, unilateral, throbbing headache

• associated with nausea, photophobia and phonophobia
• attacks may last up to 72 hours
• patients characteristically go to a darkened, quiet room during an attack
• 'classic' migraine attacks are precipitated by an aura. These occur in around one-third of
migraine patients
• typical aura are visual, progressive, last 5-60 minutes and are characterised by transient
hemianopic disturbance or a spreading scintillating scotoma
• formal diagnostic criteria are produced by the International Headache Society (see
below)
Epidemiology
• 3 times more common in women

• prevalence in men is around 6%, in women 18%
Common triggers for a migraine attack
• tiredness, stress
• alcohol
• combined oral contraceptive pill
• lack of food or dehydration
52
• cheese, chocolate, red wines, citrus fruits

• menstruation
• bright lights
Migraine diagnostic criteria
A At least 5 attacks fulfilling criteria B-D

B Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated)
C Headache has at least two of the following characteristics:
• 1. unilateral location*
• 2. pulsating quality (i.e., varying with the heartbeat)
• 3. moderate or severe pain intensity
• 4. aggravation by or causing avoidance of routine physical activity (e.g.,
walking or climbing stairs)
D During headache at least one of the following:
• 1. nausea and/or vomiting*

• 2. photophobia and phonophobia
E Not attributed to another disorder (history and examination do not suggest a

secondary headache disorder or, if they do, it is ruled out by appropriate
investigations or headache attacks do not occur for the first time in close temporal
relation to the other disorder)
*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and
gastrointestinal disturbance is more prominent.
Migraine: diagnostic criteria
The International Headache Society has produced the following diagnostic criteria for migraine
without aura:
Point Criteria
A At least 5 attacks fulfilling criteria B-D
B Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated)
53
Point Criteria
C Headache has at least two of the following characteristics:
• 1. unilateral location*
• 2. pulsating quality (i.e., varying with the heartbeat)
• 3. moderate or severe pain intensity
• 4. aggravation by or causing avoidance of routine physical activity (e.g.,
walking or climbing stairs)
D During headache at least one of the following:
• 1. nausea and/or vomiting*

• 2. photophobia and phonophobia
E Not attributed to another disorder (history and examination do not suggest a

secondary headache disorder or, if they do, it is ruled out by appropriate
investigations or headache attacks do not occur for the first time in close
temporal relation to the other disorder)
*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and
gastrointestinal disturbance is more prominent.
Migraine with aura (seen in around 25% of migraine patients) tends to be easier to diagnose
with a typical aura being progressive in nature and may occur hours prior to the headache.
Typical aura include a transient hemianopic disturbance or a spreading scintillating scotoma
('jagged crescent'). Sensory symptoms may also occur
If we compare these guidelines to the NICE criteria the following points are noted:
• NICE suggests migraines may be unilateral or bilateral

• NICE also give more detail about typical auras:
Auras may occur with or without headache and:
• are fully reversible

• develop over at least 5 minutes
• last 5-60 minutes
54
The following aura symptoms are atypical and may prompt further investigation/referral;
• motor weakness
• double vision
• visual symptoms affecting only one eye
• poor balance
• decreased level of consciousness.
Migraine: management
It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment
of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines
in 2012 on the management of headache, including migraines.
Acute treatment
• first-line: offer combination therapy with an oral triptan and an NSAID, or an oral triptan
and paracetamol
• for young people aged 12-17 years consider a nasal triptan in preference to an oral
triptan
• if the above measures are not effective or not tolerated offer a non-oral preparation of
metoclopramide* or prochlorperazine and consider adding a non-oral NSAID or triptan
Prophylaxis
• prophylaxis should be given if patients are experiencing 2 or more attacks per month.
Modern treatment is effective in about 60% of patients.
• NICE advise either topiramate or propranolol 'according to the person's preference,
comorbidities and risk of adverse events'. Propranolol should be used in preference to
topiramate in women of child bearing age as it may be teratogenic and it can reduce the
effectiveness of hormonal contraceptives
• if these measures fail NICE recommend 'a course of up to 10 sessions of acupuncture
over 5-8 weeks'
• NICE recommend: 'Advise people with migraine that riboflavin (400 mg once a day) may
be effective in reducing migraine frequency and intensity for some people'
• for women with predictable menstrual migraine treatment NICE recommend either
frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a
type of 'mini-prophylaxis'
55
• pizotifen is no longer recommend. Adverse effects such as weight gain & drowsiness are
common
*caution should be exercised with young patients as acute dystonic reactions may develop
Migraine: pregnancy, contraception and other hormonal factors
SIGN produced guidelines in 2008 on the management of migraine, the following is selected
highlights:
Migraine during pregnancy
• paracetamol 1g is first-line
• NSAIDs can be used second-line in the first and second trimester
• avoid aspirin and opioids such as codeine during pregnancy
Migraine and the combined oral contraceptive (COC) pill
• if patients have migraine with aura then the COC is absolutely contraindicated due to an
increased risk of stroke (relative risk 8.72)
Migraine and menstruation
• many women find that the frequency and severity of migraines increase around the
time of menstruation
• SIGN recommends that women are treated with mefanamic acid or a combination of
aspirin, paracetamol and caffeine. Triptans are also recommended in the acute situation
Migraine and hormone replacement therapy (HRT)
• safe to prescribe HRT for patients with a history of migraine but it may make migraines
worse
Miosis
56
Causes of miosis (small pupil)
• Horner's syndrome
• Argyll-Robertson pupil
• senile miosis
• pontine haemorrhage
• congenital
Drugs causes
• opiates
• parasympathomimetics: pilocarpine
• organophosphate toxicity
Motor neuron disease: features
Motor neuron disease is a neurological condition of unknown cause which can present with
both upper and lower motor neuron signs. It rarely presents before 40 years and various
patterns of disease are recognised including amyotrophic lateral sclerosis, progressive muscular
atrophy and bulbar palsy.
There are a number of clues which point towards a diagnosis of motor neuron disease:
• fasciculations
• the absence of sensory signs/symptoms*
• the mixture of lower motor neuron and upper motor neuron signs
• wasting of the small hand muscles/tibialis anterior is common
Other features
• doesn't affect external ocular muscles

• no cerebellar signs
• abdominal reflexes are usually preserved and sphincter dysfunction if present is a late
feature
The diagnosis of motor neuron disease is clinical, but nerve conduction studies will
show normal motor conduction and can help exclude a neuropathy. Electromyography shows a
reduced number of action potentials with increased amplitude. MRI is usually performed to
exclude the differential diagnosis of cervical cord compression and myelopathy
57
*vague sensory symptoms may occur early in the disease (e.g. limb pain) but 'never' sensory
signs
Motor neuron disease: management
patterns of disease are recognised including amyotrophic lateral sclerosis, progressive muscular
atrophy and bulbar palsy
Riluzole
• prevents stimulation of glutamate receptors

• used mainly in amyotrophic lateral sclerosis
• prolongs life by about 3 months
Respiratory care
• non-invasive ventilation (usually BIPAP) is used at night

• studies have shown a survival benefit of around 7 months
Prognosis
• poor: 50% of patients die within 3 years
Motor neuron disease: types
patterns of disease are recognised including amyotrophic lateral sclerosis, primary lateral
sclerosis, progressive muscular atrophy and progressive bulbar palsy. In some patients
however, there is a combination of clinical patterns
Amyotrophic lateral sclerosis (50% of patients)
• typically LMN signs in arms and UMN signs in legs

• in familial cases the gene responsible lies on chromosome 21 and codes for superoxide
dismutase
Primary lateral sclerosis
58
• UMN signs only
Progressive muscular atrophy
• LMN signs only

• affects distal muscles before proximal
• carries best prognosis
Progressive bulbar palsy
• palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of
function of brainstem motor nuclei
• carries worst prognosis
Multiple sclerosis
Multiple sclerosis is chronic cell-mediated autoimmune disorder characterised by

demyelination in the central nervous system.
Epidemiology
• 3 times more common in women

• most commonly diagnosed in people aged 20-40 years
• much more common at higher latitudes (5 times more common than in tropics)
Genetics
• monozygotic twin concordance = 30%

• dizygotic twin concordance = 2%
A variety of subtypes have been identified:
Relapsing-remitting disease
• most common form, accounts for around 85% of patients

• acute attacks (e.g. last 1-2 months) followed by periods of remission
Secondary progressive disease
59
• describes relapsing-remitting patients who have deteriorated and have developed

neurological signs and symptoms between relapses
• around 65% of patients with relapsing-remitting disease go on to develop secondary
progressive disease within 15 years of diagnosis
• gait and bladder disorders are generally seen
Primary progressive disease
• accounts for 10% of patients

• progressive deterioration from onset
• more common in older people
Multiple sclerosis: features
Patient's with multiple sclerosis (MS) may present with non-specific features, for example
around 75% of patients have significant lethargy.
Diagnosis can be made on the basis of two or more relapses and either objective clinical
evidence of two or more lesions or objective clinical evidence of one lesion together with
reasonable historical evidence of a previous relapse.
Visual
• optic neuritis: common presenting feature

• optic atrophy
• Uhthoff's phenomenon: worsening of vision following rise in body temperature
• internuclear ophthalmoplegia
Sensory
• pins/needles
• numbness
• Lhermitte's syndrome: paraesthesiae in limbs on neck flexion
Motor
• spastic weakness: most commonly seen in the legs
Cerebellar
60
• ataxia: more often seen during an acute relapse than as a presenting symptom
• tremor
Others
• urinary incontinence
• sexual dysfunction
• intellectual deterioration
Multiple sclerosis: investigation
Diagnosis requires demonstration of lesions disseminated in time and space
MRI
• high signal T2 lesions

• periventricular plaques
• Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the
corpus callosum
CSF
• oligoclonal bands (and not in serum)

• increased intrathecal synthesis of IgG
Visual evoked potentials
• delayed, but well preserved waveform
61

MRI showing multiple white matter plaques penpendicular to the corpus callosum giving the
appearance of Dawson fingers

MRI from a young patient with multiple sclerosis. Widespread periventricular, juxtacortical,
post fossa and upper cervical cord high T2 regions are noted. Note the difference in the lesions
with varying degrees of contrast enhancement and restricted diffusion indicating active/recent
demyelination. This satisfies the diagnostic criteria in terms of separation in terms of time
space.
62

MRI FLAIR from the same patient as above. The numerous lesions are more easily identified
than in the above T2 image.
Multiple sclerosis: management
Treatment in multiple sclerosis is focused at reducing the frequency and duration of relapses.
There is no cure.
Acute relapse
High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the
length of an acute relapse. It should be noted that steroids shorten the duration of a relapse
and do not alter the degree of recovery (i.e. whether a patient returns to baseline function)
Disease modifying drugs
Beta-interferon has been shown to reduce the relapse rate by up to 30%. Certain criteria have
to be met before it is used:
• relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided

• secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or
unaided)
• reduces number of relapses and MRI changes, however doesn't reduce overall disability
Other drugs used in the management of multiple sclerosis include:
• glatiramer acetate: immunomodulating drug - acts as an 'immune decoy'
63
• natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-

integrin found on the surface of leucocytes, thus inhibiting migration of leucocytes
across the endothelium across the blood-brain barrier
• fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from
leaving lymph nodes. An oral formulation is available
Some specific problems
Fatigue
• once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE
recommend a trial of amantadine
• other options include mindfulness training and CBT
Spasticity
• baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and
tizanidine
• physiotherapy is important
• cannabis and botox are undergoing evalulation
Bladder dysfunction
• may take the form of urgency, incontinence, overflow etc

• guidelines stress the importance of getting an ultrasound first to assess bladder
emptying - anticholinergics may worsen symptoms in some patients
• if significant residual volume → intermittent self-catheterisation
• if no significant residual volume → anticholinergics may improve urinary frequency
Oscillopsia (visual fields apper to oscillate)
• gabapentin is first-line
Multiple sclerosis: prognostic features
Good prognosis features
• female sex
64
• young age of onset (i.e. 20s or 30s)

• relapsing-remitting disease
• sensory symptoms only
• long interval between first two relapses
• complete recovery between relapses
Ways of remembering prognostic features
• the typical patient carries a better prognosis than an atypical presentation
Multiple system atrophy
There are 2 predominant types of multiple system atrophy
• 1) MSA-P - Predominant Parkinsonian features

• 2) MSA-C - Predominant Cerebellar features
Shy-Drager syndrome is a type of multiple system atrophy.
Features
• parkinsonism
• autonomic disturbance
o erectile dysfunction: often an early feature
o postural hypotension
o atonic bladder
• cerebellar signs
Myasthenia gravis
Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine

receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases*. Myasthenia is
more common in women (2:1)
The key feature is muscle fatigability - muscles become progressively weaker during periods of
activity and slowly improve after periods of rest:
• extraocular muscle weakness: diplopia

• proximal muscle weakness: face, neck, limb girdle
65
• ptosis
• dysphagia
Associations
• thymomas in 15%
• autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders,
rheumatoid, SLE
• thymic hyperplasia in 50-70%
Investigations
• single fibre electromyography: high sensitivity (92-100%)

• CT thorax to exclude thymoma
• CK normal
• autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors.
In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine
kinase antibodies
• Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly
used any more due to the risk of cardiac arrhythmia
Management
• long-acting acetylcholinesterase inhibitors

o pyridostigmine is first-line
• immunosuppression:
o prednisolone initially
o azathioprine, cyclosporine, mycophenolate mofetil may also be used
• thymectomy
Management of myasthenic crisis
• plasmapheresis
• intravenous immunoglobulins
*antibodies are less commonly seen in disease limited to the ocular muscles
Myasthenia gravis: exacerbating factors
66
The most common exacerbating factor is exertion resulting in fatigability, which is the hallmark
feature of myasthenia gravis . Symptoms become more marked during the day
The following drugs may exacerbate myasthenia:
• penicillamine
• quinidine, procainamide
• beta-blockers
• lithium
• phenytoin
• antibiotics: gentamicin, macrolides, quinolones, tetracyclines
Myotonic dystrophy
Myotonic dystrophy (also called dystrophia myotonica) is an inherited myopathy with features
developing at around 20-30 years old. It affects skeletal, cardiac and smooth muscle. There are
two main types of myotonic dystrophy, DM1 and DM2.
Genetics
• a trinucleotide repeat disorder
• DM1 is caused by a CTG repeat at the end of the DMPK (Dystrophia Myotonica-Protein
Kinase) gene on chromosome 19
• DM2 is caused by a repeat expansion of the ZNF9 gene on chromosome 3
The key differences are listed in table below:
DM1 DM2
- DMPK gene on chromosome 19 - ZNF9 gene on chromosome 3
- Distal weakness more prominent - Proximal weakness more prominent
- Severe congenital form not seen
General features
• myotonic facies (long, 'haggard' appearance)

• frontal balding
• bilateral ptosis
• cataracts
• dysarthria
67
Other features
• myotonia (tonic spasm of muscle)

• weakness of arms and legs (distal initially)
• mild mental impairment
• diabetes mellitus
• testicular atrophy
• cardiac involvement: heart block, cardiomyopathy
• dysphagia
•
Narcolepsy
Overview
• associated with HLA-DR2

• it is associated with low levels of orexin (hypocretin), a protein which is responsible for
controlling appetite and sleep patterns
• early onset of REM sleep
Features
• typical onset in teenage years

• hypersomnolence
• cataplexy (sudden loss of muscle tone often triggered by emotion)
• sleep paralysis
• vivid hallucinations on going to sleep or waking up
Investigation
• multiple sleep latency EEG
Management
• daytime stimulants (e.g. modafinil) and nighttime sodium oxybate
Neck lumps
The table below gives characteristic exam question features for conditions causing neck lumps:
68
Condition Notes
Reactive By far the most common cause of neck swellings. There may be a
lymphadenopathy history of local infection or a generalised viral illness
Lymphoma Rubbery, painless lymphadenopathy

The phenomenon of pain whilst drinking alcohol is very uncommon
There may be associated night sweats and splenomegaly
Thyroid swelling May be hypo-, eu- or hyperthyroid symptomatically

Moves upwards on swallowing
Thyroglossal cyst More common in patients < 20 years old

Usually midline, between the isthmus of the thyroid and the hyoid
bone
Moves upwards with protrusion of the tongue
May be painful if infected
Pharyngeal pouch More common in older men

Represents a posteromedial herniation between thyropharyngeus and
cricopharyngeus muscles
Usually not seen but if large then a midline lump in the neck that
gurgles on palpation
Typical symptoms are dysphagia, regurgitation, aspiration and chronic
cough
Cystic hygroma A congenital lymphatic lesion (lymphangioma) typically found in the

neck, classically on the left side
Most are evident at birth, around 90% present before 2 years of age
Branchial cyst An oval, mobile cystic mass that develops between the
sternocleidomastoid muscle and the pharynx
Develop due to failure of obliteration of the second branchial cleft in
embryonic development
Usually present in early adulthood
Cervical rib More common in adult females

Around 10% develop thoracic outlet syndrome
Carotid aneurysm Pulsatile lateral neck mass which doesn't move on swallowing
69
Nerve conduction studies
Nerve conduction studies (NCS) are useful in determining between axonal and demyelinating
pathology
Axonal
• normal conduction velocity

• reduced amplitude
Demyelinating
• reduced conduction velocity

• normal amplitude
•
Neurofibromatosis
There are two types of neurofibromatosis, NF1 and NF2. Both are inherited in an autosomal
dominant fashion
NF1 is also known as von Recklinghausen's syndrome. It is caused by a gene mutation

on chromosome 17 which encodes neurofibromin and affects around 1 in 4,000
NF2 is caused by gene mutation on chromosome 22 and affects around 1 in 100,000
Features
NF1 NF2
Café-au-lait spots (>= 6, 15 mm in Bilateral vestibular schwannomas

diameter) Multiple intracranial schwannomas, mengiomas and
Axillary/groin freckles ependymomas
Peripheral neurofibromas
Iris hamatomas (Lisch nodules) in >
90%
Scoliosis
Pheochromocytomas
70
Comparison of neurofibromatosis and tuberous sclerosis. Note that whilst they are both
autosomal dominant neurocutaneous disorders there is little overlap otherwise
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a rare but dangerous condition seen in patients

taking antipsychotic medication. It carries a mortality of up to 10% and can also occur with
atypical antipsychotics. It may also occur with dopaminergic drugs (such as levodopa) for
Parkinson's disease, usually when the drug is suddenly stopped or the dose reduced.
The pathophysiology is unknown but one theory is that the dopamine blockade induced by
antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle
damage.
It occurs within hours to days of starting an antipsychotic (antipsychotics are also known as
neuroleptics, hence the name) and the typical features are:
• pyrexia
• muscle rigidity
• autonomic lability: typical features include hypertension, tachycardia and tachypnoea
• agitated delirium with confusion
A raised creatine kinase is present in most cases. Acute kidney injury (secondary to
rhabdomyolysis) may develop in severe cases. A leukocytosis may also be seen
Management
71
• stop antipsychotic
• patients should be transferred to a medical ward if they are on a psychiatric ward and
often they are nursed in intensive care units
• IV fluids to prevent renal failure
• dantrolene may be useful in selected cases
o thought to work by decreasing excitation-contraction coupling in skeletal muscle
by binding to the ryanodine receptor, and decreasing the release of calcium from
the sarcoplasmic reticulum
• bromocriptine, dopamine agonist, may also be used
Venn diagram showing contrasting serotonin syndrome with neuroleptic malignant syndrome.
Note that both conditions can cause a raised creatine kinase (CK) but it tends to be more
associated with NMS.
Neuromyelitis optica
Neuromyelitis optica (NMO) is monophasic or relapsing-remitting demyelinating CNS disorder

Although previously thought to be a variant of multiple sclerosis, it is now recognised to be a
distinct disease, particularly prevalent in Asian populations. It typically involves the optic nerves
and cervical spine, with imaging of the brain frequently normal. Vomiting is also a common
presenting complaint.
Diagnosis is requires bilateral optic neuritis, myelitis and 2 of the follow 3 criteria:
• 1. Spinal cord lesion involving 3 or more spinal levels

• 2. Initially normal MRI brain
72
• 3. Aquaporin 4 positive serum antibody
Neuropathic pain
Neuropathic pain may be defined as pain which arises following damage or disruption of the
nervous system. It is often difficult to treat and responds poorly to standard analgesia.
Examples include:
• diabetic neuropathy
• post-herpetic neuralgia
• prolapsed intervertebral disc
NICE updated their guidance on the management of neuropathic pain in 2013:
• first-line treatment*: amitriptyline, duloxetine, gabapentin or pregabalin

o if the first-line drug treatment does not work try one of the other 3 drugs
o in contrast to standard analgesics, drugs for neuropathic pain are typically used
as monotherapy, i.e. if not working then drugs should be switched, not added
• tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain
• topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic
neuralgia)
• pain management clinics may be useful in patients with resistant problems
*please note that for some specific conditions the guidance may vary. For example
carbamazepine is used first-line for trigeminal neuralgia
Normal pressure hydrocephalus
Normal pressure hydrocephalus is a reversible cause of dementia seen in elderly patients. It is

thought to be secondary to reduced CSF absorption at the arachnoid villi. These changes may
be secondary to head injury, subarachnoid haemorrhage or meningitis.
A classical triad of features is seen
• urinary incontinence
• dementia and bradyphrenia
• gait abnormality (may be similar to Parkinson's disease)
73
It is thought around 60% of patients will have all 3 features at the time of diagnosis. Symptoms
typically develop over a few months.
Imaging
• hydrocephalus with an enlarged fourth ventricle

• in addition to the ventriculomegaly there is typically an absence of substantial sulcal
atrophy
Management
• ventriculoperitoneal shunting
• around 10% of patients who have shunts experience significant complications such as
seizures, infection and intracerebral haemorrhages
Nystagmus
Upbeat nystagmus
• cerebellar vermis lesions
Downbeat nystagmus - foramen magnum lesions
• Arnold-Chiari malformation
Image sourced from Wikipedia

Horizontal optokinetic nystagmus, a normal (physiological) form of nystagmus
Otitis externa
Otitis externa is a common reason for primary care attendance in the UK.
Causes of otitis externa include:
74
• infection: bacterial (Staphylococcus aureus, Pseudomonas aeruginosa) or fungal

• seborrhoeic dermatitis
• contact dermatitis (allergic and irritant)
Features
• ear pain, itch, discharge

• otoscopy: red, swollen, or eczematous canal
The recommended initial management of otitis externa is:
• topical antibiotic or a combined topical antibiotic with a steroid

• if the tympanic membrane is perforated aminoglycosides are traditionally not used*
• if there is canal debris then consider removal
• if the canal is extensively swollen then an ear wick is sometimes inserted
Second-line options include
• consider contact dermatitis secondary to neomycin

• oral antibiotics (flucloxacillin) if the infection is spreading
• taking a swab inside the ear canal
• empirical use of an antifungal agent
If a patient fails to respond to topical antibiotics then the patient should be referred to ENT.
Malignant otitis externa is more common in elderly diabetics. In this condition, there is
extension of infection into the bony ear canal and the soft tissues deep to the bony canal.
Intravenous antibiotics may be required.
*many ENT doctors disagree with this and feel that concerns about ototoxicity are unfounded
Otosclerosis
Otosclerosis describes the replacement of normal bone by vascular spongy bone. It causes a
progressive conductive deafness due to fixation of the stapes at the oval window. Otosclerosis
is autosomal dominant and typically affects young adults
Onset is usually at 20-40 years - features include:
75
• conductive deafness
• tinnitus
• normal tympanic membrane*
• positive family history
Management
• hearing aid
• stapedectomy
*10% of patients may have a 'flamingo tinge', caused by hyperaemia
Paraneoplastic syndromes affecting nervous system
Lambert-Eaton myasthenic syndrome
• associated with small cell lung cancer (also breast and ovarian)
• antibody directed against pre-synaptic voltage gated calcium channel in the peripheral
nervous system
• can also occur independently as autoimmune disorder
Anti-Hu
• associated with small cell lung carcinoma and neuroblastomas

• sensory neuropathy - may be painful
• cerebellar syndrome
• encephalomyelitis
Anti-Yo
• associated with ovarian and breast cancer

• cerebellar syndrome
Anti-GAD antibody
• associated with breast, colorectal and small cell lung carcinoma

• stiff person's syndrome or diffuse hypertonia
76
Anti-Ri
• associated with breast and small cell lung carcinoma

• ocular opsoclonus-myoclonus
Purkinje cell antibody

- peripheral neuropathy in breast cancer
Parkinson's disease: features
Parkinson's disease is a progressive neurodegenerative condition caused by degeneration of

dopaminergic neurons in the substantia nigra. This results in a classic triad of features:
bradykinesia, tremor and rigidity. The symptoms of Parkinson's disease are characteristically
asymmetrical.
Epidemiology
• around twice as common in men

• mean age of diagnosis is 65 years
Bradykinesia
• poverty of movement also seen, sometimes referred to as hypokinesia

• short, shuffling steps with reduced arm swinging
• difficulty in initiating movement
Tremor
• most marked at rest, 3-5 Hz

• worse when stressed or tired, improves with voluntary movement
• typically 'pill-rolling', i.e. in the thumb and index finger
Rigidity
• lead pipe
• cogwheel: due to superimposed tremor
Other characteristic features

77
• mask-like facies
• flexed posture
• micrographia
• drooling of saliva
• psychiatric features: depression is the most common feature (affects about 40%);
dementia, psychosis and sleep disturbances may also occur
• impaired olfaction
• REM sleep behaviour disorder
• fatigue
• autonomic dysfunction:
o postural hypotension
Drug-induced parkinsonism has slightly different features to Parkinson's disease:
• motor symptoms are generally rapid onset and bilateral

• rigidity and rest tremor are uncommon
Diagnosis is usually clinical. However, if there is difficulty differentiating between essential

tremor and Parkinson's disease NICE recommend considering 123I-FP-CIT single photon emission
computed tomography (SPECT).
A Lewy body (stained brown) in a brain cell of the substantia nigra in Parkinson's disease. The
brown colour is positive immunohistochemistry staining for alpha-synuclein.
78
Discoloration of the substantia nigra due to loss of pigmented nerve cells.
Parkinson's disease: management
Parkinsons disease should only be diagnosed, and management initiated, by a specialist with
expertise in movement disorders. However, it is important for all doctors to be aware of the
medications used in Parkinson's given the prevalence of this condition. NICE published
guidelines in 2017 regarding the management of Parkinson's disease.
For first-line treatment:
• if the motor symptoms are affecting the patient's quality of life: levodopa
• if the motor symptoms are not affecting the patient's quality of life: dopamine agonist
(non-ergot derived), levodopa or monoamine oxidase B (MAO-B) inhibitor
Whilst all drugs used to treat Parkinson's can cause a wide variety of side-effects NICE produced
tables to help with decision making:
Levodopa Dopamine agonists MAO-B inhibitors
Motor symptoms More improvement in Less improvement in Less improvement in

motor symptoms motor symptoms motor symptoms
Activities of daily More improvement in Less improvement in Less improvement in

living activities of daily living activities of daily living activities of daily living
Motor More motor complications Fewer motor Fewer motor

complications complications complications
Adverse events Fewer specified adverse More specified adverse Fewer specified adverse
events* events* events*
* excessive sleepiness, hallucinations and impulse control disorders
79
If a patient continues to have symptoms despite optimal levodopa treatment or has developed
dyskinesia then NICE recommend the addition of a dopamine agonist, MAO-B inhibitor or
catechol-O-methyl transferase (COMT) inhibitor as an adjunct. Again, NICE summarise the main
points in terms of decision making:
Dopamine
agonists MAO-B inhibitors COMT inhibitors Amantadine
Motor Improvement in Improvement in Improvement in No evidence of

symptoms motor symptoms motor symptoms motor symptoms improvement in
motor symptoms
Activities of Improvement in Improvement in Improvement in No evidence of

daily living activities of daily activities of daily activities of daily improvement in
living living living activities of daily
living
Off time More off-time Off-time reduction Off-time reduction No studies reporting
reduction this outcome
Adverse events Intermediate risk Fewer adverse More adverse No studies reporting
of adverse events events events this outcome
Hallucinations More risk of Lower risk of Lower risk of No studies reporting

hallucinations hallucinations hallucinations this outcome
Specific points regarding Parkinson's medication
NICE reminds us of the risk of acute akinesia or neuroleptic malignant syndrome if medication is
not taken/absorbed (for example due to gastroenteritis) and advise against giving patients a
'drug holiday' for the same reason.
Impulse control disorders have become a significant issue in recent years. These can occur with
any dopaminergic therapy but are more common with:
• dopamine agonist therapy

• a history of previous impulsive behaviours
• a history of alcohol consumption and/or smoking
If excessive daytime sleepiness develops then patients should not drive. Medication should be
80
adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.
If orthostatic hypotension develops then a medication review looking at potential causes should
be done. If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to
increase arterial resistance) can be considered.
Consider glycopyrronium bromide to manage drooling of saliva in people with Parkinson's

disease.
Further information regarding specific anti-Parkinson's medication
Levodopa
• usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to

prevent peripheral metabolism of levodopa to dopamine
• reduced effectiveness with time (usually by 2 years)
• unwanted effects: dyskinesia (involuntary writhing movements), 'on-off' effect, dry
mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness
• no use in neuroleptic induced parkinsonism
• it is important not to acutely stop levodopa, for example if a patient is admitted to
hospital. If a patient with Parkinson's disease cannot take levodopa orally, they can be
given a dopamine agonist patch as rescue medication to prevent acute dystonia
Dopamine receptor agonists
• e.g. bromocriptine, ropinirole, cabergoline, apomorphine

• ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been
associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on
Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray
should be obtained prior to treatment and patients should be closely monitored
• patients should be warned about the potential for dopamine receptor agonists to cause
impulse control disorders and excessive daytime somnolence
• more likely than levodopa to cause hallucinations in older patients. Nasal congestion
and postural hypotension are also seen in some patients
MAO-B (Monoamine Oxidase-B) inhibitors
• e.g. selegiline
• inhibits the breakdown of dopamine secreted by the dopaminergic neurons
81
Amantadine
• mechanism is not fully understood, probably increases dopamine release and inhibits its
uptake at dopaminergic synapses
• side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis
COMT (Catechol-O-Methyl Transferase) inhibitors
• e.g. entacapone, tolcapone

• COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as
an adjunct to levodopa therapy
• used in conjunction with levodopa in patients with established PD
Antimuscarinics
• block cholinergic receptors

• now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson's
disease
• help tremor and rigidity
• e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)
Parkinsonism
Causes of Parkinsonism
• Parkinson's disease
• drug-induced e.g. antipsychotics, metoclopramide*
• progressive supranuclear palsy
• multiple system atrophy
• Wilson's disease
• post-encephalitis
• dementia pugilistica (secondary to chronic head trauma e.g. boxing)
• toxins: carbon monoxide, MPTP
*Domperidone does not cross the blood-brain barrier and therefore does not cause extra-
pyramidal side-effects.
82
Peripheral neuropathy
Peripheral neuropathy may be divided into conditions which predominately cause a motor or
sensory loss
Predominately motor loss
• porphyria
• lead poisoning
• hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth
• chronic inflammatory demyelinating polyneuropathy (CIDP)
• diphtheria
Predominately sensory loss
• diabetes
• uraemia
• leprosy
• alcoholism
• vitamin B12 deficiency
• amyloidosis
Alcoholic neuropathy
• secondary to both direct toxic effects and reduced absorption of B vitamins

• sensory symptoms typically present prior to motor symptoms
Vitamin B12 deficiency
• subacute combined degeneration of spinal cord

• dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia
Peripheral neuropathy: demyelinating vs. axonal
Demyelinating pathology
• chronic inflammatory demyelinating polyneuropathy (CIDP)
• amiodarone
83
• hereditary sensorimotor neuropathies (HSMN) type I

• paraprotein neuropathy
Axonal pathology
• alcohol
• diabetes mellitus*
• vasculitis
• vitamin B12 deficiency*
• hereditary sensorimotor neuropathies (HSMN) type II
* may also cause a demyelinating picture
Phenytoin
Phenytoin is used in the management of seizures.
Mechanism of action
• binds to sodium channels increasing their refractory period
Adverse effects
Phenytoin is associated with a large number of adverse effects. These may be divided into
acute, chronic, idiosyncratic and teratogenic. Phenytoin is also an inducer of the P450 system.
Acute
• initially: dizziness, diplopia, nystagmus, slurred speech, ataxia

• later: confusion, seizures
Chronic
• common: gingival hyperplasia (secondary to increased expression of platelet derived

growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness
• megaloblastic anaemia (secondary to altered folate metabolism)
• peripheral neuropathy
• enhanced vitamin D metabolism causing osteomalacia
• lymphadenopathy
• dyskinesia
84
Idiosyncratic
• fever
• rashes, including severe reactions such as toxic epidermal necrolysis
• hepatitis
• Dupuytren's contracture*
• aplastic anaemia
• drug-induced lupus
Teratogenic
• associated with cleft palate and congenital heart disease
Monitoring
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before
dose should be checked if:
• adjustment of phenytoin dose

• suspected toxicity
• detection of non-adherence to the prescribed medication
*although not listed in the BNF
Pituitary apoplexy
Sudden enlargement of pituitary tumour secondary to haemorrhage or infarction.
Features
• sudden onset headache similar to that seen in subarachnoid haemorrhage

• vomiting
• neck stiffness
• visual field defects: classically bitemporal superior quadrantic defect
• extraocular nerve palsies
• features of pituitary insufficiency e.g. Hypotension secondary to hypoadrenalism
Post-lumbar puncture headache
Headache following lumbar puncture (LP) occurs in approximately one-third of patients. The
85
pathophysiology of is unclear but may relate to a 'leak' of CSF following dural puncture. Post-LP
headaches are more common in young females with a low body mass index
Typical features
• usually develops within 24-48 hours following LP but may occur up to one week later
• may last several days
• worsens with upright position
• improves with recumbent position
Factors which may contribute to Factors which do not contribute to

headache headache
Increased needle size Increased volume of CSF removed
Direction of bevel Bed rest following procedure
Not replacing the stylet Increased fluid intake post procedure
Increased number of LP attempts Opening pressure of CSF
Position of patient
Management
• supportive initially (analgesia, rest)

• if pain continues for more than 72 hours then specific treatment is indicated, to prevent
subdural haematoma
• treatment options include: blood patch, epidural saline and intravenous caffeine
Progressive supranuclear palsy
Overview
• aka Steele-Richardson-Olszewski syndrome

• a 'Parkinson Plus' syndrome
Features
• postural instability and falls

o patients tend to have a stiff, broad-based gait
• impairment of vertical gaze (down gaze worse than up gaze - patients may complain of
difficultly reading or descending stairs)
• parkinsonism
o bradykinesia is prominent
• cognitive impairment
86
o primarily frontal lobe dysfunction
Management
• poor response to L-dopa
Ramsay Hunt syndrome
Ramsay Hunt syndrome (herpes zoster oticus) is caused by the reactivation of the varicella
zoster virus in the geniculate ganglion of the seventh cranial nerve.
Features
• auricular pain is often the first feature

• facial nerve palsy
• vesicular rash around the ear
• other features include vertigo and tinnitus
Management
• oral aciclovir and corticosteroids are usually given
Restless legs syndrome
Restless legs syndrome (RLS) is a syndrome of spontaneous, continuous lower limb movements
that may be associated with paraesthesia. It is extremely common, affecting between 2-10% of
the general population. Males and females are equally affected and a family history may be
present
Clinical features
• uncontrollable urge to move legs (akathisia). Symptoms initially occur at night but as
condition progresses may occur during the day. Symptoms are worse at rest
• paraesthesias e.g. 'crawling' or 'throbbing' sensations
• movements during sleep may be noted by the partner - periodic limb movements of
sleeps (PLMS)
Causes and association
87
• there is a positive family history in 50% of patients with idiopathic RLS

• iron deficiency anaemia
• uraemia
• pregnancy
The diagnosis is clinical although bloods such as ferritin to exclude iron deficiency anaemia may
be appropriate
Management
• simple measures: walking, stretching, massaging affected limbs

• treat any iron deficiency
• dopamine agonists are first-line treatment (e.g. Pramipexole, ropinirole)
• benzodiazepines
• gabapentin
Reye's syndrome
Reye's syndrome is a severe, progressive encephalopathy affecting children that is

accompanied by fatty infiltration of the liver, kidneys and pancreas. The aetiology of Reye's
syndrome is not fully understood although there is a known association with aspirin use and a
viral cause has been postulated
The peak incidence is 2 years of age, features include:
• there may be a history of preceding viral illness

• encephalopathy: confusion, seizures, cerebral oedema, coma
• fatty infiltration of the liver, kidneys and pancreas
• hypoglycaemia
Management is supportive
Although the prognosis has improved over recent years there is still a mortality rate of 15-25%.
Rinne's and Weber's test
Performing both Rinne's and Weber's test allows differentiation of conductive and
sensorineural deafness.
88
Rinne's test
• tuning fork is placed over the mastoid process until the sound is no longer heard,
followed by repositioning just over external acoustic meatus
• 'positive test': air conduction (AC) is normally better than bone conduction (BC)
• 'negative test': if BC > AC then conductive deafness
Weber's test
• tuning fork is placed in the middle of the forehead equidistant from the patient's ears
• the patient is then asked which side is loudest
• in unilateral sensorineural deafness, sound is localised to the unaffected side
• in unilateral conductive deafness, sound is localised to the affected side
Interpretation of Rinne and Weber tests
Rinne result Weber result
Normal Air conduction > bone conduction Midline

bilaterally
Conductive hearing Bone conduction > air conduction in Lateralises to affected

loss affected ear ear
Air conduction > bone conduction in
unaffected ear
Sensorineural hearing Air conduction > bone conduction Lateralises to

loss bilaterally unaffected ear
Sodium valproate
Sodium valproate is used in the management of epilepsy and is first-line therapy for generalised
seizures. It works by increasing GABA activity.
Adverse effects
• teratogenic
o maternal use of sodium valproate is associated with a significant risk of
neurodevelopmental delay in children
89
o guidance is now clear that sodium valproate should not be used during
pregnancy and in women of childbearing age unless clearly necessary. Women of
childbearing age should not start treatment without specialist neurological or
psychiatric advice.
• P450 inhibitor
• gastrointestinal: nausea
• increased appetite and weight gain
• alopecia: regrowth may be curly
• ataxia
• tremor
• hepatotoxicity
• pancreatitis
• thrombocytopaenia
• hyponatraemia
• hyperammonemic encephalopathy: L-carnitine may be used as treatment if this
develops
Spastic paraparesis
Spastic paraparesis describes a upper motor neuron pattern of weakness in the lower limbs
Causes
• demyelination e.g. multiple sclerosis

• cord compression: trauma, tumour
• parasagittal meningioma
• tropical spastic paraparesis
• transverse myelitis e.g. HIV
• syringomyelia
• hereditary spastic paraplegia
• osteoarthritis of the cervical spine
Spinal cord lesions
The diagram belows shows cross-section view of the spinal cord:
90
Motor lesions
Amyotrophic lateral sclerosis (motor neuron disease)
• affects both upper (corticospinal tracts) and lower motor neurons

• results in a combination of upper and lower motor neuron signs
Poliomyelitis
• affects anterior horns resulting in lower motor neuron signs
Combined motor and sensory lesions
Disorder Tracts affected Clinical notes
91
Brown-Sequard 1. Lateral corticospinal tract 1. Ipsilateral spastic paresis

syndrome (spinal cord 2. Dorsal columns below lesion
hemisection) 3. Lateral spinothalamic tract 2. Ipsilateral loss of
proprioception and vibration
sensation
3. Contralateral loss of pain
and temperature sensation
Subacute combined 1. Lateral corticospinal tracts 1. Bilateral spastic paresis

degeneration of the spinal cord 2. Dorsal columns 2. Bilateral loss of
(vitamin B12 & E deficiency) 3. Spinocerebellar tracts proprioception and vibration
sensation
3. Bilateral limb ataxia
Friedrich's ataxia Same as subacute combined Same as subacute combined

degeneration of the spinal degeneration of the spinal
cord (see above) cord (see above)
In addition cerebellar ataxia

→ other features e.g.
intention tremor
Anterior spinal artery occlusion 1. Lateral corticospinal tracts 1. Bilateral spastic paresis
2. Lateral spinothalamic tracts 2. Bilateral loss of pain and
temperature sensation
Syringomyelia 1. Ventral horns 1. Flacid paresis (typically

2. Lateral spinothalamic tract affecting the intrinsic hand
muscles)
2. Loss of pain and
temperature sensation
Multiple sclerosis Asymmetrical, varying spinal Combination of motor,

tracts involved sensory and ataxia symptoms
Sensory lesions
92
Neurosyphilis (tabes 1. Dorsal 1. Loss of proprioception and vibration

dorsalis) columns sensation
Status epilepticus
Status epilepticus is defined as:
• a single seizure lasting >5 minutes, or

• >= 2 seizures within a 5-minute period without the person returning to normal between
them
This is a medical emergency. The priority is the termination of seizure activity, which if
prolonged will lead to irreversible brain damage.
Management
• ABC
o airway adjunct
o oxygen
o check blood glucose
• First-line drugs are benzodiazepines such as diazepam or lorazepam
o in the prehospital setting diazepam may be given rectally
o in hospital IV lorazepam is generally used. This may be repeated once after 10-20
minutes
• If ongoing (or 'established') status it is appropriate to start a second-line agent such
as phenytoin or phenobarbital infusion
• If no response ('refractory status') within 45 minutes from onset, then the best way to
achieve rapid control of seizure activity is induction of general anaesthesia.
Stroke by anatomy
Site of the lesion Associated effects

Anterior cerebral artery Contralateral hemiparesis and
sensory loss, lower extremity > upper
93
Site of the lesion Associated effects

Middle cerebral artery Contralateral hemiparesis and
sensory loss, upper extremity > lower
Contralateral homonymous
hemianopia
Aphasia
Posterior cerebral artery Contralateral homonymous
hemianopia with macular sparing
Visual agnosia
Weber's syndrome (branches of the posterior Ipsilateral CN III palsy
cerebral artery that supply the midbrain) Contralateral weakness of upper and
lower extremity
Posterior inferior cerebellar artery (lateral Ipsilateral: facial pain and
medullary syndrome, Wallenberg syndrome) temperature loss
Contralateral: limb/torso pain and
temperature loss
Ataxia, nystagmus
Anterior inferior cerebellar artery (lateral Symptoms are similar to
pontine syndrome) Wallenberg's (see above), but:
Ipsilateral: facial paralysis and
deafness
Retinal/ophthalmic artery Amaurosis fugax
Basilar artery 'Locked-in' syndrome
Lacunar strokes
• present with either isolated hemiparesis, hemisensory loss or hemiparesis with limb
ataxia
• strong association with hypertension
• common sites include the basal ganglia, thalamus and internal capsule
Stroke management: other issues
This background note focuses on other issues in acute stroke management, particularly
management of fluids, glycaemic control, blood pressure management, feeding
assessment/management and disability scales.
94
Fluid management
• As in all patients in hospital, regular assessment for fluid status must be undertaken to
ensure patients remain normovolaemic
• The NICE guidelines recommend assessing the hydration of all patients with acute stroke
on admission, with regular review during their stay
• Greater than 80% of patients who cannot swallow post stroke will recover within 2-4
weeks
• However, it is important to manage fluids in this immediate post-event period as
hypovolaemia can worsen the ischaemic penumbra, as well as increase risk of other
complications such as infection, deep vein thrombosis, constipation and delirium
• Conversely, over-hydration can also complicate matters by leading to cerebral oedema,
cardiac failure and hyponatraemia, therefore it is important to regularly review fluid
status in these patients
• Recommendations for management:
o Oral hydration is preferable in all patients who are able to safely swallow
o Intravenous hydration may be necessary otherwise, and although studies have
remained contentious regarding choice of intravenous fluid, UptoDate currently
recommend isotonic saline without dextrose as the agent of choice in most
patients
o Other factors to take into consideration when choosing fluid agent include
electrolyte disturbances and/or cardiovascular status
Glycaemic control
• It is important to closely monitor and control blood sugar, particularly if they are nil by
mouth due to concerns regarding swallowing safety post stroke, and/or in diabetics
• Post stroke, patients with hyperglycaemia have increased mortality independent from
their age and the severity of stroke
o This is likely due to increased tissue acidosis from anaerobic metabolism, free
radical generation, and increased blood brain barrier permeability post injury
• The NICE guidelines recommend maintaining a blood sugar level between 4 and 11
mmol/L in people with acute stroke
• Diabetic patients
o It is important to provide intensive management for diabetics post acute stroke
o The NICE guidelines suggest optimising insulin treatment using intravenous
insulin and glucose infusions
o Hypoglycaemia also needs to be managed appropriately, as alone it can cause
neuronal injury as well as mimic stroke-related neurological deficits
Blood pressure management
95
• Use of anti-hypertensive medications should only be used for blood pressure control in
patients post ischaemic stroke if there is a hypertensive emergency with one or more of
the following serious concomitant medical issues (according to the NICE guidelines):
o Hypertensive encephalopathy
o Hypertensive nephropathy
o Hypertensive cardiac failure/myocardial infarction
o Aortic dissection
o Pre-eclampsia/eclampsia
• This is because lowering blood pressure too much can potentially compromise collateral
blood flow to the affected region, and possibly hasten the time to complete and
irreversible tissue infarction
• If if treatment is indicated, UptoDate recommend cautious lowering of blood pressure
by approximately 15% in the first 24-hours after stroke onset
• UptoDate suggest using intravenous labetalol, nicardipine and clevidipine as first-line
agents, due to the possibility for rapid and safe titration to control blood pressure
• However, in patients who are candidates for thrombolytic therapy for acute stroke,
blood pressure should be reduced to 185/110mmHg or lower
o Elevated BP can affect thrombolytic eligibility and delay treatment
o Timely management of elevated BP is crucial when patients are otherwise
eligible for intravenous thrombolysis
o After thrombolytic therapy, UptoDate recommend ensuring that the blood
pressure is stabilised and maintained at or below 180/105mmHg for at least 24
hours after treatment
Feeding assessment and management
• All patients presenting with acute stroke must be screened for safe swallowing function
prior to further oral intake, as dysphagia is common after stroke
o This is to reduce the risk of aspiration and subsequent complications
o This includes prior to any oral intake of food, fluids, and/or medications
• If there are any concerns regarding swallowing, the NICE guidelines recommend
specialist assessment of swallowing
o This should preferably within 24 hours of admission and not greater than 72
hours after
o Prior to assessment is undertaken, a patient should remain nil by mouth to
prevent complications
• Recommendations for patients deemed unsafe for oral intake:
o Patients should receive nasogastric tube feeding, ideally within 24 hours of
admission, unless they have had thrombolytic therapy
o If nasogastric tube feeding is not tolerated, patients should be considered for a
nasal bridle tube/gastrostomy instead
o Medications need to be assessed to determine if formulations are available for
96
nasogastric feeding, or if conversion to subcutaneous or intravenous forms are

required
• Nutritional support may be required for patients at risk of malnutrition post stroke,
whether a result from dysphagia, poor oral health or reduced ability to self-feed due to
weakness or paralysis
Disability scales
• Stroke can result in a number of complications and subsequent disability, therefore

disability scales are often used as a measure of functional decline post event and
subsequent improvement after medical intervention
• Disability, often measured in terms of functional status (notably, basic activities of daily
living), is often the leading cause of morbidity after stroke
• After a patient is medically stabilised after a stroke, they may require transfer to a
rehabilitation team for ongoing treatment depending on their level of disability
• Disability is most commonly measured using the Barthel index (BI), an outcome measure
for stroke
o Describes 10 tasks, and is scored according to amount of time or assistance
required by the patient for each given task
o Tasks: feeding, moving from wheelchair to bed, personal toileting, getting on/off
toilet, bathing, walking on level surface, ascending/descending stairs, dressing,
controlling bowels and controlling bladder
o The total score is from 0 to 100, with 0 being completely dependent, and 100
being completely independent
• This index should be used to assess the functional status of a patient post stroke, and to
monitor their improvement with ongoing rehabilitation to regain independence after
the event
Stroke: assessment
Whilst the diagnosis of stroke may sometimes be obvious in many cases the presenting
symptoms may be vague and accurate assessment difficult.
The FAST screening tool (Face/Arms/Speech/Time) is widely known by the general public
following a publicity campaign. It has a positive predictive value of 78%.
A variant of FAST called the ROSIER score is useful for medical professionals. It is validated tool
recommended by the Royal College of Physicians.
97
ROSIER score
Exclude hypoglycaemia first, then assess the following:
Assessment Scoring
Loss of consciousness or syncope - 1 point
Seizure activity - 1 point
New, acute onset of:
• asymmetric facial weakness + 1 point
• asymmetric arm weakness + 1 point
• asymmetric leg weakness + 1 point
• speech disturbance + 1 point
• visual field defect + 1 point
A stroke is likely if > 0.
Investigations
A non-contrast CT head scan is the first line radiological investigation for suspected stroke
Stroke: management
The Royal College of Physicians (RCP) published guidelines on the diagnosis and management of
patients following a stroke in 2004. NICE updated their stroke guidelines in 2019.
Selected points relating to the management of acute stroke include:
• blood glucose, hydration, oxygen saturation and temperature should be maintained

within normal limits
• blood pressure should not be lowered in the acute phase unless there are complications
e.g. Hypertensive encephalopathy*
• aspirin 300mg orally or rectally should be given as soon as possible if a haemorrhagic
stroke has been excluded
• with regards to atrial fibrillation, the RCP state: 'anticoagulants should not be started
until brain imaging has excluded haemorrhage, and usually not until 14 days have
passed from the onset of an ischaemic stroke'
98
• if the cholesterol is > 3.5 mmol/l patients should be commenced on a statin. Many
physicians will delay treatment until after at least 48 hours due to the risk of
haemorrhagic transformation
Thrombolysis for acute ischaemic stroke
Thrombolysis with alteplase should only be given if:
• it is administered within 4.5 hours of onset of stroke symptoms (unless as part of a

clinical trial)
• haemorrhage has been definitively excluded (i.e. Imaging has been performed)
Contraindications to thrombolysis:
Absolute Relative
- Previous intracranial haemorrhage - Concurrent anticoagulation (INR >1.7)

- Seizure at onset of stroke - Haemorrhagic diathesis
- Intracranial neoplasm - Active diabetic haemorrhagic
- Suspected subarachnoid haemorrhage retinopathy
- Stroke or traumatic brain injury in - Suspected intracardiac thrombus
preceding 3 months - Major surgery / trauma in the
- Lumbar puncture in preceding 7 days preceding 2 weeks
- Gastrointestinal haemorrhage in preceding
3 weeks
- Active bleeding
- Pregnancy
- Oesophageal varices
- Uncontrolled hypertension
>200/120mmHg
Thrombectomy for acute ischaemic stroke
Mechanical thrombectomy is an exciting new treatment option for patients with an acute
ischaemic stroke. NICE incorporated recommendations into their 2019 guidelines. It is
important to remember the significant resources and senior personnel to provide such a service
99
24 hours a day. NICE recommend that all decisions about thrombectomy take into account a
patient's overall clinical status:
• NICE recommend a pre-stroke functional status of less than 3 on the modified Rankin
scale and a score of more than 5 on the National Institutes of Health Stroke Scale
(NIHSS)
Offer thrombectomy as soon as possible and within 6 hours of symptom onset, together with
intravenous thrombolysis (if within 4.5 hours), to people who have:
acute ischaemic stroke and
• confirmed occlusion of the proximal anterior circulation demonstrated by computed

tomographic angiography (CTA) or magnetic resonance angiography (MRA)
Offer thrombectomy as soon as possible to people who were last known to be well between 6
hours and 24 hours previously (including wake-up strokes):
• confirmed occlusion of the proximal anterior circulation demonstrated by CTA or MRA

and
• if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion
or diffusion-weighted MRI sequences showing limited infarct core volume
Consider thrombectomy together with intravenous thrombolysis (if within 4.5 hours) as soon as
possible for people last known to be well up to 24 hours previously (including wake-up strokes):
• who have acute ischaemic stroke and confirmed occlusion of the proximal posterior
circulation (that is, basilar or posterior cerebral artery) demonstrated by CTA or MRA
and
• if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion
or diffusion-weighted MRI sequences showing limited infarct core volume
Secondary prevention
NICE also published a technology appraisal in 2010 on the use of clopidogrel and dipyridamole
Recommendations from NICE include:
• clopidogrel is now recommended by NICE ahead of combination use of aspirin plus
100
modified-release (MR) dipyridamole in people who have had an ischaemic stroke

• aspirin plus MR dipyridamole is now recommended after an ischaemic stroke only if
clopidogrel is contraindicated or not tolerated, but treatment is no longer limited to 2
years' duration
• MR dipyridamole alone is recommended after an ischaemic stroke only if aspirin or
clopidogrel are contraindicated or not tolerated, again with no limit on duration of
treatment
With regards to carotid artery endarterectomy:
• recommend if patient has suffered stroke or TIA in the carotid territory and are not
severely disabled
• should only be considered if carotid stenosis > 70% according ECST** criteria or > 50%
according to NASCET*** criteria
*the 2009 Controlling hypertension and hypotension immediately post-stroke (CHHIPS) trial
may change thinking on this but guidelines have yet to change to reflect this
**European Carotid Surgery Trialists' Collaborative Group
***North American Symptomatic Carotid Endarterectomy Trial
Stroke: types
The Oxford Stroke Classification (also known as the Bamford Classification) classifies strokes
based on the initial symptoms. A summary is as follows:
The following criteria should be assessed:

1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
• 2. homonymous hemianopia
• 3. higher cognitive dysfunction e.g. dysphasia
Total anterior circulation infarcts (TACI, c. 15%)
• involves middle and anterior cerebral arteries

• all 3 of the above criteria are present
Partial anterior circulation infarcts (PACI, c. 25%)
• involves smaller arteries of anterior circulation e.g. upper or lower division of middle
101
cerebral artery
• 2 of the above criteria are present
Lacunar infarcts (LACI, c. 25%)
• involves perforating arteries around the internal capsule, thalamus and basal ganglia
• presents with 1 of the following:
• 1. unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three.
• 2. pure sensory stroke.
• 3. ataxic hemiparesis
Posterior circulation infarcts (POCI, c. 25%)
• involves vertebrobasilar arteries

• presents with 1 of the following:
• 1. cerebellar or brainstem syndromes
• 2. loss of consciousness
• 3. isolated homonymous hemianopia
Other recognised patterns of stroke:
Lateral medullary syndrome (posterior inferior cerebellar artery)
• aka Wallenberg's syndrome

• ipsilateral: ataxia, nystagmus, dysphagia, facial numbness, cranial nerve palsy e.g.
Horner's
• contralateral: limb sensory loss
Weber's syndrome
• ipsilateral III palsy

• contralateral weakness
Subacute combined degeneration of spinal cord
Basics
102
• due to vitamin B12 deficiency

• dorsal + lateral columns affected
• joint position and vibration sense lost first then distal paraesthesia
• upper motor neuron signs typically develop in the legs, classically extensor plantars,
brisk knee reflexes, absent ankle jerks
• if untreated stiffness and weakness persist
Subarachnoid haemorrhage
A subarachnoid haemorrhage (SAH) is an intracranial haemorrhage that is defined as the

presence of blood within the subarachnoid space, i.e. deep to the subarachnoid layer of the
meninges.
The most common cause of SAH is head injury and this is called traumatic SAH . In the absence
of trauma, SAH is termed spontaneous SAH . The rest of this note focuses on spontaneous SAH.
Causes of spontaneous SAH include:
• Intracranial aneurysm* (saccular ‘berry’ aneurysms): this accounts for around 85% of
cases. Conditions associated with berry aneurysms include adult polycystic kidney
disease, Ehlers-Danlos syndrome and coarctation of the aorta
• Arteriovenous malformation
• Pituitary apoplexy
• Arterial dissection
• Mycotic (infective) aneurysms
• Perimesencephalic (an idiopathic venous bleed)
Classical presenting features include:
• Headache: typically sudden-onset (‘thunderclap’ or ‘baseball bat’), severe (‘worst of my

life’) and occipital
• Nausea and vomiting
• Meningism (photophobia, neck stiffness)
• Coma
• Seizures
• Sudden death
• ECG changes including ST elevation may be seen
Confirmation of SAH:
103
• Computed tomography (CT) head

o Acute blood (hyperdense/bright on CT) is typically distributed in the basal
cisterns, sulci and in severe cases the ventricular system.
o CT is negative for SAH (no blood seen) in 7% of cases.
• Lumbar puncture (LP)
o Used to confirm SAH if CT is negative.
o LP is performed at least 12 hours following the onset of symptoms to allow the
development of xanthochromia (the result of red blood cell breakdown).
o Xanthochromia helps to distinguish true SAH from a ‘traumatic tap’ (blood
introduced by the LP procedure).
o As well as xanthochromia, CSF findings consistent with subarachnoid
haemorrhage include a normal or raised opening pressure
• Referral to neurosurgery to be made as soon as SAH is confirmed
After spontaneous SAH is confirmed, the aim of investigation is to identify a causative

pathology that needs urgent treatment:
• CT intracranial angiogram (to identify a vascular lesion e.g. aneurysm or AVM)

• +/- digital subtraction angiogram (catheter angiogram)
Treatment
• The treatment in spontaneous SAH is in accordance with the causative pathology

• Intracranial aneurysms are at risk of rebleeding and therefore require prompt
intervention, preferably within 24 hours
• Most intracranial aneurysms are now treated with a coil by interventional
neuroradiologists, but a minority require a craniotomy and clipping by a neurosurgeon
• Until the aneurysm is treated, the patient should be kept on strict bed rest, well-
controlled blood pressure and should avoid straining in order to prevent a re-bleed of
the aneurysm
• Vasospasm is prevented using a 21-day course of nimodipine (a calcium channel
inhibitor targeting the brain vasculature) and treated with hypervolaemia, induced-
hypertension and haemodilution**
• Hydrocephalus is temporarily treated with an external ventricular drain (CSF diverted
into a bag at the bedside) or, if required, a long-term ventriculo-peritoneal shunt
Complications of aneurysmal SAH:
• Re-bleeding
o happens in around 10% of cases and most common in the first 12 hours
o if rebleeding is suspected (e.g. sudden worsening of neurological symptoms)
104
then a repeat CT should be arranged

o associated with a high mortality (up to 70%)
• Vasospasm (also termed delayed cerebral ischaemia), typically 7-14 days after onset
• Hyponatraemia (most typically due to syndrome inappropriate anti-diuretic hormone
(SIADH))
• Seizures
• Hydrocephalus
• Death
Important predictive factors in SAH:
• conscious level on admission

• age
• amount of blood visible on CT head
CT image shows diffuse subarachnoid haemorrhage in all basal cisterns, bilateral sylvian fissures
and the inter-hemispheric fissure. This case demonstrates the typical distribution that takes the
blood into the subarachnoid space in a subarachnoid hemorrhage.
*this may be secondary to either autonomic neural stimulation from the hypothalamus or
elevated levels of circulating catecholamines
**the way nimodipine works in subarachnoid haemorrhage is not fully understood. It has been
previously postulated that it reduces cerebral vasospasm (hence maintaining cerebral
105
perfusion) but this has not been demonstrated in studies
Subdural haemorrhage
A subdural haematoma is a collection of blood deep to the dural layer of the meninges. The
blood is not within the substance of the brain and is therefore called an ‘extra-axial’ or
‘extrinsic’ lesion. They can be unilateral or bilateral.
Subdural haematomas can be classified in terms of their age:
• Acute
• Subacute
• Chronic
Although the collection of blood is within the same anatomical compartment, acute and chronic
subdurals have important differences in terms of their mechanisms, associated clinical features
and management:
Acute subdural haematoma
An acute subdural haematoma is a collection of fresh blood within the subdural space and is
most commonly caused by high-impact trauma. Since it is associated with high-impact injuries,
there is often other brain underlying brain injuries.
There is a spectrum of severity of symptoms and presentation depending on the size of the
compressive acute subdural haematoma and the associated injuries. Presentation ranges from
an incidental finding in trauma to severe coma and coning due to herniation.
CT imaging is the first-line investigation and will show a crescentic collection, not limited by
suture lines. They will appear hyperdense (bright) in comparison to the brain. Large acute
subdural haematomas will push on the brain (‘mass effect’) and cause midline shift or
herniation.
Small or incidental acute subdurals can be observed conservatively. Surgical options include
monitoring of intracranial pressure and decompressive craniectomy.
Chronic subdural haematoma
106
A chronic subdural haematoma is a collection of blood within the subdural space that has been
present for weeks to months.
Rupture of the small bridging veins within the subdural space rupture and cause slow bleeding.
Elderly and alcoholic patients are particularly at risk of subdural haematomas since they have
brain atrophy and therefore fragile or taut bridging veins.
Presentation is typically a several week to month progressive history of either confusion,

reduced consciousness or neurological deficit.
Infants also have fragile bridging veins and can rupture in shaken baby syndrome.
On CT imaging they similarly are crescentic in shape, not restricted by suture lines and
compress the brain (‘mass effect’). In contrast to acute subdurals, chronic subdurals
are hypodense (dark) compared to the substance of the brain.
If the chronic subdural is an incidental finding or if it is small in size with no associated

neurological deficit then it can be managed conservatively with the hope that it will dissolve
with time. If the patient is confused, has an associated neurological deficit or has severe
imaging findings then surgical decompression with burr holes is required.
Syringomyelia
Syringomyelia (‘syrinx’ for short) describes a collection of cerebrospinal fluid within the spinal
cord.
Syringobulbia is a similar phenomenon in which there is a fluid-filled cavity within the medulla
of the brainstem. This is often an extension of the syringomyelia but in rare cases can be an
isolated finding.
Causes include:
• a Chiari malformation: strong association

• trauma
• tumours
• idiopathic
The classical presentation of a syrinx is a patient who has a ‘cape-like’ (neck and arms) loss of
sensation to temperature but preservation of light touch, proprioception and vibration. Classic
examples are of patients who accidentally burn their hands without realising. This is due to the
crossing spinothalamic tracts in the anterior commissure of the spinal cord being the first tracts
to be affected. Other symptoms and signs include spastic weakness (predominantly of the
upper limbs), paraesthesia, neuropathic pain, upgoing plantars and bowel and bladder
107
dysfunction. Scoliosis will occur over a matter of years if the syrinx is not treated. It may cause a
Horner’s syndrome due to compression of the sympathetic chain, but this is rare.
Investigation requires a full spine MRI with contrast to exclude a tumour or tethered cord. A
brain MRI is also needed to exclude a Chiari malformation.
Treatment will be directed at treating the cause of the syrinx. In patients with a persistent or
symptomatic syrinx, a shunt into the syrinx can be placed.
Third nerve palsy
Features
• eye is deviated 'down and out'

• ptosis
• pupil may be dilated (sometimes called a 'surgical' third nerve palsy)
Causes
• vasculitis e.g. temporal arteritis, SLE
• false localizing sign* due to uncal herniation through tentorium if raised ICP
• posterior communicating artery aneurysm
o pupil dilated
o often associated pain
• cavernous sinus thrombosis
• Weber's syndrome: ipsilateral third nerve palsy with contralateral hemiplegia -caused by
midbrain strokes
• other possible causes: amyloid, multiple sclerosis
*this term is usually associated with sixth nerve palsies but it may be used for a variety of
neurological presentations
Thyroglossal cyst
The key to understanding thyroglossal cysts is to think about the name; thyro (thyroid) and
glossal (tongue).
Embryology
108
The thyroid develops from the floor of the pharynx and descends into the neck during its
development. It is connected to the tongue by the thyroglossal duct. The foramen cecum is the
point of attachment of the thyroglossal duct to the tongue. The thyroglossal duct normally
atrophies but in some people may persist and give rise to a thyroglossal duct cyst.
Presentations
More common in patients < 20 years old.
Features
• usually midline, between the isthmus of the thyroid and the hyoid bone
• moves upwards with protrusion of the tongue
• may be painful if infected
Tinnitus
Tinnitus is the perception of sounds in the ears or head that do not come from an outside
source. Around 1 in 10 people will experience an episode of tinnitus at some point in their life.
Although sometimes considered a 'minor' symptom of 'ringing in the ears' it can be distressing
to patients and may occasionally be a sign of a serious underlying condition.
Causes of tinnitus include:
An underlying cause will not be found

Idiopathic in the majority of patients.
Meniere's disease Associated with hearing loss, vertigo,
tinnitus and sensation of fullness or
pressure in one or both ears
Otosclerosis Onset is usually at 20-40 years
Conductive deafness
Tinnitus
Normal tympanic membrane although
10% of patients may have a 'flamingo
tinge', caused by hyperaemia
Positive family history
109
An underlying cause will not be found

Idiopathic in the majority of patients.
Sudden onset Around 80% of Hearing loss, vertigo,
sensorineural hearing Acoustic neuroma tinnitus
loss (SSNHL) Absent corneal reflex is
important sign
Associated with
neurofibromatosis type
2
Hearing loss Causes include excessive loud noise and
presbycusis
Drugs Aspirin/NSAIDs
Aminoglycosides
Loop diuretics
Quinine
Impacted ear wax Usually obvious on otoscopy
Assessment
• audiological assessment
o detect underlying hearing loss
• imaging
o not all patients will require imaging. Generally, non-pulsatile tinnitus does not
require imaging unless it is unilateral or there are other neurological or
ontological signs. MRI of the internal auditory meatuses (IAM) is first-line
o pulsatile tinnitus generally requires imaging as there may be an underlying
vascular cause. Magnetic resonance angiography (MRA) is often used to
investigate pulsatile tinnitus
Management
• investigate and treat any underlying cause

• amplification devices
o more beneficial if associated hearing loss
• psychological therapy may help a limited group of patients
o examples include cognitive behavioural therapy
• tinnitus support groups
110
Topiramate
Topiramate was developed as an antiepileptic and is used alone or as adjunctive treatment in

generalised tonic-clonic seizures.
There appear to be multiple mechanisms of action:
• blocks voltage-gated Na+ channels

• increases GABA action
• carbonic anhydrase inhibition: this results in a decrease in urinary citrate excretion and
formation of alkaline urine that favours the creation of calcium phosphate stone
Topiramate is an inducer of the P450 enzyme CYP3A4. This may result in hormonal
contraception being less effective. As a result, the Faculty of Sexual and Reproductive Health
(FSRH) suggests the following for patients taking topiramate:
• combined oral contraceptive pill and progestogen-only pill: UKMEC 3 (disadvantages

outweigh advantages):
• implant: UKMEC 2 (advantages generally outweigh the disadvantages)
The injection (Depo-Provera) and intrauterine system are not affected by topiramate.
Adverse effects of topiramate include:
• reduced appetite and weight loss

• dizziness
• paraesthesia
• lethargy and poor concentration
• rare but important: acute myopia and secondary angle-closure glaucoma
Topiramate is associated with a risk of foetal malformations.
Transient global amnesia
Overview
• presents with transient loss of memory function

• patients may appear anxious and repeatedly ask the same question
• patients have no recall of events after the attack
111
• aetiology is unknown, thought to be due to transient ischaemia to the thalamus (in

particular the amygdala and hippocampus)
Transient ischaemic attack
The original definition of a transient ischaemic attack (TIA) was time-based: a sudden onset of a
focal neurologic symptom and/or sign lasting less than 24 hours, brought on by a transient
decrease in blood flow. However, this has now changed as it is recognised that even short
periods of ischaemia can result in pathological changes to the brain. Therefore, a new 'tissue-
based' definition is now used: a transient episode of neurologic dysfunction caused by focal
brain, spinal cord, or retinal ischaemia, without acute infarction.
Patients often use the term 'mini-stroke' for TIAs.
Assessment and referral
The ABCD2 prognostic score has previously been used to risk stratify patients who present with
a suspected TIA. However, data from studies have suggested it performs poorly and it is
therefore no longer recommended by NICE Clinical Knowledge Summaries. Instead, NICE
recommend:
Immediate antithrombotic therapy:
• give aspirin 300 mg immediately, unless

• 1. the patient has a bleeding disorder or is taking an anticoagulant (needs immediate
admission for imaging to exclude a haemorrhage)
• 2. the patient is already taking low-dose aspirin regularly: continue the current dose of
aspirin until reviewed by a specialist
• 3. Aspirin is contraindicated: discuss management urgently with the specialist team
If the patient has had more than 1 TIA ('crescendo TIA') or has a suspected cardioembolic
source or severe carotid stenosis:
• discuss the need for admission or observation urgently with a stroke specialist
If the patient has had a suspected TIA in the last 7 days:
• arrange urgent assessment (within 24 hours) by a specialist stroke physician
112
If the patient has had a suspected TIA which occurred more than a week previously:
• refer for specialist assessment as soon as possible within 7 days
Advise the person not to drive until they have been seen by a specialist.
Further management
Antithrombotic therapy
• clopidogrel is recommended first-line (as for patients who've had a stroke)

• aspirin + dipyridamole should be given to patients who cannot tolerate clopidogrel
• these recommendations follow the 2012 Royal College of Physicians National clinical
guideline for stroke. Please see the link for more details (section 5.5)
• these guidelines may change following the CHANCE study (NEJM 2013;369:11). This
study looked at giving high-risk TIA patients aspirin + clopidogrel for the first 90 days
compared to aspirin alone. 11.7% of aspirin only patients had a stroke over 90 days
compared to 8.2% of dual antiplatelet patients
With regards to carotid artery endarterectomy:
• recommend if patient has suffered stroke or TIA in the carotid territory and are not
severely disabled
• should only be considered if carotid stenosis > 70% according ECST* criteria or > 50%
according to NASCET** criteria
*European Carotid Surgery Trialists' Collaborative Group

**North American Symptomatic Carotid Endarterectomy Trial
Transverse myelitis
Causes of transverse myelitis
• viral infections: varicella-zoster, herpes simplex, cytomegalovirus, Epstein-Barr,

influenza, echovirus, human immunodeficiency virus
• bacterial infections: syphilis, Lyme disease
• post-infectious (immune mediated)
113
• first symptom of multiple sclerosis (MS) or neuromyelitis optica (NMO)
Trigeminal neuralgia
Trigeminal neuralgia is a pain syndrome characterised by severe unilateral pain. The vast
majority of cases are idiopathic but compression of the trigeminal roots by tumours or vascular
problems may occur.
The International Headache Society defines trigeminal neuralgia as:
• a unilateral disorder characterised by brief electric shock-like pains, abrupt in onset and
termination, limited to one or more divisions of the trigeminal nerve
• the pain is commonly evoked by light touch, including washing, shaving, smoking,
talking, and brushing the teeth (trigger factors), and frequently occurs spontaneously
• small areas in the nasolabial fold or chin may be particularly susceptible to the
precipitation of pain (trigger areas)
• the pains usually remit for variable periods
NICE Clinical Knowledge Summaries list the following as red flag symptoms and signs suggesting
a serious underlying cause:
• Sensory changes
• Deafness or other ear problems
• History of skin or oral lesions that could spread perineurally
• Pain only in the ophthalmic division of the trigeminal nerve (eye socket, forehead, and
nose), or bilaterally
• Optic neuritis
• A family history of multiple sclerosis
• Age of onset before 40 years
Management
• carbamazepine is first-line
• failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt
referral to neurology
Triptans
Triptans are specific 5-HT1B and 5-HT1D agonists used in the acute treatment of migraine. They
114
are generally used first-line in combination therapy with an NSAID or paracetamol.
Prescribing points
• should be taken as soon as possible after the onset of headache, rather than at onset of
aura
• oral, orodispersible, nasal spray and subcutaneous injections are available
Adverse effects
• 'triptan sensations' - tingling, heat, tightness (e.g. throat and chest), heaviness, pressure
Contraindications
• patients with a history of, or significant risk factors for, ischaemic heart disease or
cerebrovascular disease
Tuberous sclerosis
Tuberous sclerosis (TS) is a genetic condition of autosomal dominant inheritance. Like

neurofibromatosis, the majority of features seen in TS are neurocutaneous.
Cutaneous features
• depigmented 'ash-leaf' spots which fluoresce under UV light

• roughened patches of skin over lumbar spine (Shagreen patches)
• adenoma sebaceum (angiofibromas): butterfly distribution over nose
• fibromata beneath nails (subungual fibromata)
• café-au-lait spots* may be seen
Neurological features
• developmental delay
• epilepsy (infantile spasms or partial)
• intellectual impairment
Also
• retinal hamartomas: dense white areas on retina (phakomata)

• rhabdomyomas of the heart
115
• gliomatous changes can occur in the brain lesions

• polycystic kidneys, renal angiomyolipomata
• lymphangioleiomyomatosis: multiple lung cysts
Comparison of neurofibromatosis and tuberous sclerosis. Note that whilst they are both
autosomal dominant neurocutaneous disorders there is little overlap otherwise
*these of course are more commonly associated with neurofibromatosis. However a 1998
study of 106 children with TS found café-au-lait spots in 28% of patients
Vertigo
Vertigo may be defined as the false sensation that the body or environment is moving.
The table below lists the main characteristics of the most important causes of vertigo
Disorder Notes
Viral labyrinthitis Recent viral infection
Sudden onset
Nausea and vomiting
Hearing may be affected
Vestibular neuronitis Recent viral infection
Recurrent vertigo attacks lasting hours or days
No hearing loss
Benign paroxysmal Gradual onset
positional vertigo Triggered by change in head position
Each episode lasts 10-20 seconds
116
Disorder Notes
Meniere's disease Associated with hearing loss, tinnitus and sensation of
fullness or pressure in one or both ears
Vertebrobasilar ischaemia Elderly patient
Dizziness on extension of neck
Acoustic neuroma Hearing loss, vertigo, tinnitus
Absent corneal reflex is important sign
Associated with neurofibromatosis type 2
Other causes of vertigo include
• posterior circulation stroke

• trauma
• ototoxicity e.g. gentamicin
Vestibular neuronitis
Vestibular neuronitis is a cause of vertigo that often develops following a viral infection.
Features
• recurrent vertigo attacks lasting hours or days

• nausea and vomiting may be present
• horizontal nystagmus is usually present
• no hearing loss or tinnitus
Differential diagnosis
• viral labyrinthitis
• posterior circulation stroke: the HiNTs exam can be used to distinguish vestibular
neuronitis from posterior circulation stroke
Management
• vestibular rehabilitation exercises are the preferred treatment for patients who
experience chronic symptoms
• buccal or intramuscular prochlorperazine is often used to provide rapid relief for severe
cases
• a short oral course of prochlorperazine, or an antihistamine (cinnarizine, cyclizine, or
117
promethazine) may be used to alleviate less severe cases
Vestibular schwannoma (acoustic neuroma)
Vestibular schwannomas (sometimes referred to as acoustic neuromas) account for

approximately 5% of intracranial tumours and 90% of cerebellopontine angle tumours.
The classical history of vestibular schwannoma includes a combination of vertigo, hearing loss,
tinnitus and an absent corneal reflex. Features can be predicted by the affected cranial nerves:
• cranial nerve VIII: vertigo, unilateral sensorineural hearing loss, unilateral tinnitus
• cranial nerve V: absent corneal reflex
• cranial nerve VII: facial palsy
Bilateral vestibular schwannomas are seen in neurofibromatosis type 2.
Patients with a suspected vestibular schwannoma should be referred urgently to ENT. It should
be noted though that the tumours are often slow growing, benign and often observed initially.
MRI of the cerebellopontine angle is the investigation of choice. Audiometry is also important
as only 5% of patients will have a normal audiogram.
Management is with either surgery, radiotherapy or observation.
Vigabatrin
Key points
• 40% of patients develop visual field defects, which may be irreversible

• visual fields should be checked every 6 months
Visual field defects
The main points for the exam are:
• left homonymous hemianopia means visual field defect to the left, i.e. Lesion of right
optic tract
• homonymous quadrantanopias: PITS (Parietal-Inferior, Temporal-Superior)
• incongruous defects = optic tract lesion; congruous defects = optic radiation lesion or
occipital cortex
118
A congruous defect simply means complete or symmetrical visual field loss and conversely an
incongruous defect is incomplete or asymmetric. Please see the link for an excellent diagram.
Homonymous hemianopia
• incongruous defects: lesion of optic tract

• congruous defects: lesion of optic radiation or occipital cortex
• macula sparing: lesion of occipital cortex
Homonymous quadrantanopias*
• superior: lesion of the inferior optic radiations in the temporal lobe (Meyer's loop)
• inferior: lesion of the superior optic radiations in the parietal lobe
• mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
Bitemporal hemianopia
• lesion of optic chiasm

• upper quadrant defect > lower quadrant defect = inferior chiasmal compression,
commonly a pituitary tumour
• lower quadrant defect > upper quadrant defect = superior chiasmal compression,
commonly a craniopharyngioma
*this is very much the 'exam answer'. Actual studies suggest that the majority of
quadrantanopias are caused by occipital lobe lesions. Please see the link for more details.
Von Hippel-Lindau syndrome
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant condition predisposing to

neoplasia. It is due to an abnormality in the VHL gene located on short arm of chromosome 3
Features
• cerebellar haemangiomas: these can cause subarachnoid haemorrhages

• retinal haemangiomas: vitreous haemorrhage
• renal cysts (premalignant)
• phaeochromocytoma
• extra-renal cysts: epididymal, pancreatic, hepatic
• endolymphatic sac tumours
119
• clear-cell renal cell carcinoma
CT scan showing a cerebellar haemangioma in a patient with Von Hippel-Lindau syndrome.
MRI showing renal cysts in patient with known Von Hippel-Lindau syndrome.
120
Wernicke's encephalopathy
Wernicke's encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which

is most commonly seen in alcoholics. Rarer causes include: persistent vomiting, stomach
cancer, dietary deficiency. A classic triad of ophthalmoplegia/nystagmus, ataxia and confusion
may occur. In Wernicke's encephalopathy petechial haemorrhages occur in a variety of
structures in the brain including the mamillary bodies and ventricle walls.
Features
• nystagmus (the most common ocular sign)

• ophthalmoplegia
• ataxia
• confusion, altered GCS
• peripheral sensory neuropathy
Investigations
• decreased red cell transketolase

• MRI
Treatment is with urgent replacement of thiamine
Relationship with Korsakoff syndrome
If not treated Korsakoff's syndrome may develop as well. This is termed Wernicke-Korsakoff
syndrome and is characterised by the addition of antero- and retrograde amnesia and
confabulation in addition to the above symptoms.
121
Diagram showing the mechanism of action of Parkinson's drugs
122

Neuro

Uploaded by

Copyright:

Available Formats

Neuro

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Neuro

Uploaded by

Copyright:

Available Formats

Passmedicine Neurology note 2021

5-HT3 antagonists are antiemetics used mainly in the management of chemotherapy-

• sodium valproate and ethosuximide are first-line treatment

Absent ankle jerks, extensor plantars

• subacute combined degeneration of the cord

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease of the

Anti-NMDA receptor encephalitis

Anti-NMDA receptor encephalitis is a paraneoplastic syndrome, presenting as prominent

acute inflammatory demyelinating polyneuropathy (AIDP) variant of Guillain-Barre syndrome.

Treatment of anti-NMDA encephalitis is based of immunosuppression with intravenous

Type of aphasia Notes

Wernicke's Due to a lesion of the superior temporal gyrus. It is typically supplied

Broca's Due to a lesion of the inferior frontal gyrus. It is typically supplied by

Conduction Classically due to a stroke affecting the arcuate fasiculus - the

May still be able to communicate using gestures

Diagram showing the main types of aphasia

Arnold-Chiari malformation describes the downward displacement, or herniation, of the

• non-communicating hydrocephalus may develop as a result of obstruction of

• 10% risk of developing malignancy, lymphoma or leukaemia, but also non-lymphoid

• impotence, inability to sweat, postural hypotension

• infections: HIV, Chagas' disease, neurosyphilis

• agonist of GABA receptors

• lower motor neuron facial nerve palsy - forehead affected*

• UpToDate recommends the addition of antivirals for severe facial palsy

• if untreated around 15% of patients have permanent moderate to severe weakness

*upper motor neuron lesion 'spares' upper face

• Epley manoeuvre (successful in around 80% of cases)

Medication is often prescribed (e.g. Betahistine) but it tends to be of limited value.

Brachial plexus injuries

• damage to C5,6 roots

• other features consistent with raised intracranial pressure

• Assessment of the patient includes imaging with CT scanning

The following neurological disorders/features may allow localisation of a brain lesion:

Parietal lobe lesions

Occipital lobe lesions

• homonymous hemianopia (with macula sparing)

Temporal lobe lesion

Frontal lobes lesions

• midline lesions: gait and truncal ataxia

More specific areas

Area Associated conditions

Medial thalamus and mammillary bodies Wernicke and Korsakoff syndrome

Subthalamic nucleus of the basal ganglia Hemiballism

Area Associated conditions

Striatum (caudate nucleus) of the basal Huntington chorea

Substantia nigra of the basal ganglia Parkinson's disease

Amygdala Kluver-Bucy syndrome (hypersexuality, hyperorality,

• caused by lateral hemisection of the spinal cord

• ipsilateral weakness below lesion

• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and

Carbamazepine is chemically similar to the tricyclic antidepressant drugs. It is most commonly

• binds to sodium channels increases their refractory period

• P450 enzyme inducer

Carbamazepine is known to exhibit autoinduction, hence when patients start carbamazepine

Features range from buckling knees to collapse.

Unilateral cerebellar lesions cause ipsilateral signs.

Useful and well-known mnemonic to remember symptoms of cerebellar disease is DANISH:

• D - Dysdiadochokinesia, Dysmetria (past-pointing), patients may appear 'Drunk'

• S - Slurred staccato speech, Scanning dysarthria