Peripheral Neuropathy

Faisal Althekair FRCPC

Assistant Professor at KSAU-HS
Consultant Neurologist at KAMC
2/3/2016 HEMA-312 Lecture: Introduction to Autoimmunity 2
 Objectives:

At the end of the lecture you will be able to:

• Identify the clinical presentation of radiculopathy, plexopathy,

mononeuropathy, an polyneuropathy
• Identify the appropriate investigations and management for patients
present with peripheral nerve disease
• Diagnose and manage patients with acute inflammatory peripheral
neuropathy
• Identify the peripheral nervous system complications of diabetes
mellitus
Central and peripheral nervous system
Outline
• Definitions and neuroanatomy
• Journey through the peripheral nervous system and clinical
correlation
• Acute and chronic peripheral neuropathy

Blumenfield,clinical neuroanatomy
Classification of peripheral Nerve Disease

Bradley, Clinical Neurology

 Neuroanatomy:
Roots: Radiculopathy

• Dorsal root>>sensory dorsal root

ganglion contains cells bodies of large
fibers which carry vibration and
position sense

• Temperature and pain small fibers

synapse at the dorsal horn

• Ventral Root>> Motor, sympathetic

efferent (thoracolumbar). What
about parasympathetic
Plexus
• Brachial

• Lumbosacral
Upper limb mononeuropathy:
Remember the dermatomes
Structural classification of neuropathy

• Demyelinating: This occurs by compression or chronic nerve

entrapment and in immune-mediated demyelinating neuropathies
and hereditary disorders of Schwann cell/myelin metabolism

• Axonal: vasculitis, diabetes

Approach to peripheral Neuropathy
• Is it Neurological condition?. Sensory symptoms are subjective

• Localization, are the symptoms in 1 limb (mono neuropathy,

plexopathy, radiculopathy) or caused by CNS lesion. Are the
symptoms in 2 limbs. Is it proximal (favor demyelinating or distal
(favor axonal). Are the symptoms pure motor, sensory or mixed.

• Think about the cause by asking about the timeline of the symptoms
Acute ex (GBS), subacute, or chronic (CIDP)
Points in History:
Sensory symptoms: Differentiate between pins and needles (acquired
neuropathy) and numbness (loss of sensation: Hereditary neuropathy)
Pain history can direct us ( distal pain in both legs>>small fiber
neuropathy vs radiating pain (radiculopathy, sciatica, plexopathy)

Motor: Ask about daily functions, getting out of the car, up from the
chair or toilet (favor a proximal weakness, demyelinating disease or
myopathy). Difficulty going down the stairs, pushing the puddles while
driving the car favor a distal weakness (axonal neuropathy)

Don’t forget to ask autonomic symptoms

Duration of symptoms gives an
idea about the cause

Bradley, Clinical Neurology

Nerve fibers types
• Large fiber>>>>. Vibration and position sense, reflexes

• Small fibers: pain and temperature, normal reflexes

 Small- Fiber Neuropathy

• Reflexes are
normal why?
 Sensory Neuronopathy

• Where is the
lesion ?
• Common peripheral Neuropathies
Mononeuropathy
Introduction
 This may result from compression, traction, laceration, thermal, or chemical
injury
 The pathologic response to a lesion include axon loss, demyelination, or a
combination of both.
 peripheral nerve injury into three classes:
 Neurapraxia
 Axonotmesis
 and neurotmesis
 Neurapraxia (First-Degree Nerve Injury):
 Neurapraxia usually results from brief or mild compression on the nerve that distorts
the myelin, resulting in segmental demyelination but leaving the axons intact.
 With this injury, recovery is usually complete following remyelination that occurs
within 1 to 3 months if the offending cause (such as a compression) is removed.
 Introduction
Axonotmesis :
 Axonotmesis injury is characterized by axonal damage that results in wallerian
degeneration distal to the injury and the end-organs become denervated.

 Its divided into three further subtypes based on the disruptions of the supporting
structures (endoneurium, perineurium, and epineurium).
 SECOND-DEGREE NERVE INJURY
 The axonal loss is associated with intact endoneurial tubes as well as intact
perineurium and epineurium.
 These lesions have fairly good prognosis, since nerve regeneration between the site
of nerve injury and the target organs is well guided by the intact endoneurial tubes.
 THIRD-DEGREE NERVE INJURY
 The axons and endoneurium are damaged while leaving the perineurium and
epineurium intact.
 These lesions have fair prognosis and may require surgical intervention, mostly
because of axonal misdirection and formation of neuromas.
 Introduction
 FOURTH-DEGREE NERVE INJURY
 The axons, endoneurium, and perineurium are disrupted, but the epineurium is intact.
 These lesions have poor prognosis and often require surgical repair.

Neurotmesis (Fifth-Degree Nerve Injury):

 is the most severe type of nerve injury.
 It involves complete disruption of the nerve and all supporting structures (the
nerve is transected completely.
N.Al-Bustani ;-)
INFLAMMATORY DEMYELINATING
POLYRADICULONEUROPATHIES:
GUILLAIN-BARRÉ SYNDROME (Acute demyelinating inflammatory
polyradiculopathy)

• In 1916, Guillain, Barré, and Strohl emphasized the main clinical

features of GBS:

• Motor weakness
• Areflexia
• Paresthesias with minor sensory loss, and
• Increased protein in CSF without pleocytosis (albuminocytological
dissociation).
GUILLAIN-BARRÉ SYNDROME
• Clinical Features
• Patients may present initially with weakness with or without paresthetic
sensory symptoms, often worse in the hands and fingers.

• Symmetrical weakness of LE ascends proximally over hours – several days and

may subsequently involve arm, facial, and oropharyngeal muscles, and in
severe cases, respiratory muscles.

• Hyporeflexia or areflexia may be absent early in the course of the disease.

GUILLAIN-BARRÉ SYNDROME
• Cranial n. involvement = 45 – 75%.

• Facial weakness = at least ½ of cases.

• Respiratory failure = up to 30% require ventilation.

• Facial myokymia – may develop.

• Pseudotumor cerebri – rare complication.

• Sensory loss is not a prominent feature and is frequently limited to distal

impairment of vibration sense.
GUILLAIN-BARRÉ SYNDROME
• Autonomic dysfunction – in approximately 65% : orthostatic hypotension,
urinary retention, gastrointestinal atony, iridoplegia, episodic or sustained
hypertension, sinus tachycardia, tachyarrhythmias, anhidrosis or episodic
diaphoresis, and acral vasoconstriction.

• Moderate – severe pain in the extremities, interscapular area, or back occurs

in ~ 70% of patients during the acute phase of illness, and may persist for a
year in a third of those affected.

• Dysesthetic pain, described as burning or tingling of the limbs, or joint

stiffness are less common.
GUILLAIN-BARRÉ SYNDROME
 GBS Subtypes & Variants:

Acute sensory and motor axonal neuropathy (AMSAN):

 Patients develop an acute and rapidly progressive course leading to a
maximum deficit in less than 7 days.
 Profound quadriparesis with severe muscle wasting and requiring prolonged
ventilatory support.
 Carries a poor prognosis for recovery.

Axonal>> poor prognosis>> nerve conduction study

GUILLAIN-BARRÉ SYNDROME
Acute motor axonal neuropathy (AMAN):
 Antecedent Campylobacter jejuni infection is detected by using serological
tests in 76% of AMAN patients from northern China.

Miller-Fischer Syndrome:
 Accounts for ~5% of cases.
 Characterized by the triad of ophthalmoplegia, ataxia, and areflexia,
(preserved motor strength).
 Patients present with diplopia followed by gait and limb ataxia.
 Ocular signs: dilated unreactive pupils, ophthalmoparesis with/without ptosis.
 GUILLAIN-BARRÉ SYNDROME
Investigations:

 Most patients have increased CSF protein without pleocytosis 1 week

after the onset.

 Brain MRI is usually normal, though rarely the MRI may show
brainstem lesions or gadolinium enhancement of ocular motor nerves.

 Serum IgG antibodies to the ganglioside, GQ1b, are detected in acute-

phase sera of up to 90% of patients. In patients with MFS.
GUILLAIN-BARRÉ SYNDROME
Diagnostic Studies:
 LFT = mild elevation in 1/3 of patients.

 Hyponatremia : secondary to SIADH.

 CSF protein = may be normal then become elevated >> may remain
normal in 10% of cases throughout the illness.

 Moderate CSF pleocytosis (usually >50 cells) is a distinctive feature of

GBS associated with HIV infection.
GUILLAIN-BARRÉ SYNDROME
EDX Studies:
 Abnormalities found in ~ 90% of cases during the course of illness.

 Most common abnormalities seen in 1st 2 weeks of illness:

 Abnormal F waves in the presence of normal conduction velocity and distal

latency are more specific findings, since they suggest proximal demyelination.
Differential diagnosis for
acute subacute weakness
Pathogenesis of
GBS
GUILLAIN-BARRÉ SYNDROME
Treatment:
 Immunotherapy.

 Respiratory Mx.

 Pain Mx.

 Cardiovascular Mx.

 DVT Prophylaxis.
GUILLAIN-BARRÉ SYNDROME
•Immunotherapy:
• IVIg : 0.4g/kg/day for 5 days( or 2 g/Kg over 3-5 days) , given in the 1st 2
weeks of symptom onset.
• PLEX : 50 ml/kg over 7 – 14 days >> to be started within 2 weeks of
symptoms onset.
• Both have been shown to be equally efficacious.
• Steroids cannot be recommended because two RCT , one using conventional
doses of prednisolone and the other using high-dose IV methylprednisolone,
have found no benefit.
GUILLAIN-BARRÉ SYNDROME
 Respiratory Mx: IMPORTANT

 20/30/40 Rule >> aid for decision for elective intubation:

 Vital capacity (VC) < 20 mL/kg.

 Maximal inspiratory pressure (MIP) is less than -30 cmH2O (negative inspiratory force).

 Maximal expiratory pressure (MEP) < +40 cmH2O.

 Vital capacity, maximal inspiratory pressure, or maximal expiratory pressure is reduced by

30% from baseline initial measurement.
GUILLAIN-BARRÉ SYNDROME
DVT Prophylaxis:
 Immobility and hypercoagulability from treatments such as IVIG can increase the
risk of DVT in these patients.

 There are no studies evaluating efficiency of DVT prophylaxis specifically.

 SC heparin or enoxaparin and support stockings are recommended for non-

ambulatory patients until they are able to walk independently.
GUILLAIN-BARRÉ SYNDROME
Pain Mx:
 Gabapentin or carbamazepine in the ICU for the acute phase is recommended.

 Adjuvant therapy with tricyclic antidepressants, tramadol, gabapentin,

carbamazepine, or mexiletine may be helpful for long-term management of
neuropathic pain.
 GUILLAIN-BARRÉ SYNDROME: Course & Prognosis:

• Patients reach their maximum deficit within 4 weeks of onset; if the disease
progresses for longer, it is classified as subacute (less than 2 months) or CIDP (more
than 2 months).

• About 2% of patients initially diagnosed with GBS develop a more protracted course
similar to CIDP >> acute-onset CIDP (should be considered if GBS patients
deteriorate after 8 weeks or have ≥ 2 treatment-related fluctuations).
GUILLAIN-BARRÉ SYNDROME
• 30% develop respiratory insufficiency requiring assisted ventilation.

• 2 – 5 % die of complication.

• After progression stops, patients enter a plateau phase lasting 2 – 4 weeks or longer
before recovery begins.

• Most patients recover functionally, 20% still have residual motor weakness 1 year later.

• ~ 70% of patients complete their recovery in 12 months and 82% in 24 months.

• Up to 5% of patients may have a recurrence following recovery.

Chronic Inflammatory Demyelinating
Polyradiculoneuropathy (CIDP)
Many similarities between CIDP & AIDP.

The major differences between the two conditions are in the time
course and their response to corticosteroids.

CIDP:
 Has more protracted clinical course,
 Rarely associated with preceding infections,
 Responds to corticosteroid therapy.
 CIDP
2 patterns of temporal evolution seen:

 > 60% of patients show a continuous or stepwise progressive course over

months to years.

 One-third have a relapsing course with partial or complete recovery between

recurrences.
 CIDP
• Clinical Features:
• Peak incidence 5th – 6th decade.

• Most patients have symmetrical motor and sensory involvement, although

occasional cases with predominantly motor involvement may be seen.

• Weakness must be present for at least 2 months.

• Proximal limb weakness is almost as severe as distal limb weakness,

indicating a non–length-dependent neuropathy.
 CIDP
 Muscle wasting is rarely pronounced.

 Both UE & LE are affected, although the legs are often more severely involved.

 Generalized hyporeflexia or areflexia is the rule.

 Sensory symptoms in a stocking-glove distribution (numbness or tingling)

implicating large-fiber involvement occur frequently, whereas pain occurs less
frequently.
 CIDP
 Additional findings in decreasing order of frequency:
 Postural tremor of the hands,
 Enlargement of peripheral nerves,
 papilledema,
 Facial or bulbar weakness.

 Rarely, respiratory failure requiring mechanical ventilation or autonomic

dysfunction may be seen.

 Occasionally, may be associated with a relapsing multifocal demyelinating

CNS disorder resembling MS, with CNS demyelination confirmed by abnormal
VEP + SEP and brain MRI.
Concomitant Diseases Associated with CIDP
i.e. Causes :
 DM.
 HIV-1 infection.
 SLE.
 Monoclonal gammopathy of undetermined significance (MGUS)
 Plasma cell dyscrasias (macroglobulinemia, osteosclerotic myeloma, POEMS
syndrome, Castleman disease).
 Chronic active hepatitis.
 Inflammatory bowel disease.
 Hodgkin lymphoma.
 Malignant melanoma.
 CIDP
CSF:
CSF protein > 45 mg/dL are found in 95% of cases, and levels
above 100 mg/dL are common.
Pleocytosis is rare except in HIV-associated CIDP.

MRI:
May demonstrate gadolinium enhancement of lumbar roots +
hypertrophy of roots : providing radiological evidence of an
abnormal blood-nerve barrier.
 CIDP
Treatment
 Prednisone: oral (60-80mg/d) or pulse solumedrol (1 RCT shows good
response, improvement within 2-3 months)
 Plasmapheresis: effective within days, 70% relapse w/in 14d of stopping 
may need PLEX for mths-yrs
 IVIG: beneficial w/in a few days, max benefit at 6 weeks
 Other immunosuppressants do not have proven benefit
Prognosis
 Most respond (if not, revise dx)
 However, many will relapse and disability higher than in GBS
Diabetic Neuropathy
Distal Symmetrical Polyneuropathy:

• Most common form of diabetic neuropathies.

• Subclassified into large & small fiber neuropathy.

• Sensory deficits predominate, and autonomic symptoms usually correlate with

the severity of the neuropathy.

• Most patients will develop only a minor motor involvement affecting the distal
muscles of the lower extremities.
• Sensory symptoms:

o Have a stocking-glove distribution following a length-dependent pattern.

o Early sensory manifestations begin in the toes, gradually spreading
proximally; when these reach above knee level, the fingers and hands
become affected.
o In advanced cases:
 Sensation becomes impaired over the anterior chest and abdomen,
producing a truncal wedge-shaped area of sensory loss.
• Large – fiber neuropathy:
o Presents with painless paresthesias beginning at the toes and feet,
o Impairment of vibration and joint position sense,
o Diminished muscle stretch reflexes.
o Advanced cases:
 Significant ataxia may develop secondary to sensory deafferentation.
o Often asymptomatic, but sensory deficit may be detected by careful examination.

• Small – fiber neuropathy:

o Presents with pain of a deep, burning, stinging, aching character, often associated with
spontaneous shooting pains and allodynia to light touch.
o Pain and temperature modalities are impaired, with relative preservation of vibration and
joint position sensation and muscle stretch reflexes.
o Often accompanied by autonomic neuropathy.
Diabetic Autonomic Neuropathy (DAN):
Cont. DAN:
Approach to peripheral Neuropathy
• Is it Neurological condition?. Sensory symptoms are subjective

• Localization, are the symptoms in 1 limb (mono neuropathy,

plexopathy, radiculopathy) or caused by CNS lesion. Are the
symptoms in 2 limbs. Is it proximal (favor demyelinating or distal
(favor axonal). Are the symptoms pure motor, sensory or mixed.

• Think about the cause by asking about the timeline of the symptoms
Acute ex (GBS), subacute, or chronic (CIDP)
Thank You