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Bilateral Basal Ganglia Calcification: Fahr's Disease

Article in Cureus · June 2019

DOI: 10.7759/cureus.4797

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 Open Access Case
Report DOI: 10.7759/cureus.4797

Bilateral Basal Ganglia Calcification: Fahr's

Disease
Hsein Wei Ooi 1 , Chaozer Er 2 , Ikram Hussain 2 , Navin Kuthiah 3 , Veeraraghavan Meyyur
Aravamudan 2

1. Miscellaneous, Ministry of Health Holdings, Singapore, SGP 2. Internal Medicine, Woodlands Health
Campus, Singapore, SGP 3. General Medicine, Woodlands Health Campus, Singapore, SGP

 Corresponding author: Hsein Wei Ooi, [email protected]

Disclosures can be found in Additional Information at the end of the article

Abstract
Fahr’s disease/syndrome is a condition defined as bilateral striato-pallido-dentate calcinosis, a
neurodegenerative disease with radiological findings of symmetrical and bilateral idiopathic
calcifications of the cerebellum, periventricular white matter, and basal ganglia. Clinical
correlation with radiological and a calcium metabolism panel is crucial in differentiating
between Fahr’s disease and Fahr’s syndrome. We describe a case that presented with the
clinical feature of a cerebrovascular accident and had an incidental radiological finding of Fahr
syndrome. The clinical features, laboratory investigations, and clinical management of Fahr's
disease/syndrome will be discussed in detail in the article.

Categories: Internal Medicine, Neurology, Radiology

Keywords: fahr syndrome, fahr disease

Introduction
Fahr’s disease was described by Karl Theodor Fahr in 1930 as a rare familial (autosomal
dominant) disorder that presented with idiopathic basal ganglia calcification, as seen in the
neuroimaging study [1]. This condition is presented clinically with a broad range of
neuropsychiatric symptoms and extrapyramidal disorders. A post-mortem examination
revealed non-atherosclerotic vascular disease in the centrum semiovale and striatum [2-3].
Herein, we present the case of a male patient who presented with symptoms suggestive of a
cerebrovascular accident and had computed tomography (CT) findings which were suggestive
of Fahr's syndrome. The lab investigations also showed hypocalcaemia which was also a sign of
Fahr's syndrome. This article will emphasize the radiological features, clinical features,
diagnostic criteria, and management of Fahr's syndrome/Fahr's disease.

Received 04/01/2019
Review began 05/11/2019 Case Presentation
Review ended 05/25/2019
Published 06/01/2019 The patient was a 77-year-old Chinese male who presented with the acute onset of
symptomatic non-vertiginous giddiness (vomiting), nocturnal right wrist numbness, chronic
© Copyright 2019
Ooi et al. This is an open access
progressive visual blurring, and left-sided hearing loss. However, there was no associated
article distributed under the terms of weakness or numbness of the extremities. The patient had a history of hypertension and
the Creative Commons Attribution hyperlipidaemia and had not been taking his antihypertensive agent, statins, or aspirin.
License CC-BY 3.0., which permits
unrestricted use, distribution, and
reproduction in any medium, provided On physical examination, the patient was afebrile, hypertensive with a blood pressure reading
the original author and source are of 191/90, a pulse rate of 82 beats per minute, and oxygen saturation of 100% on room air. No
credited. focal motor or sensory deficits were detected at the time of presentation. There were no

How to cite this article

Ooi H, Er C, Hussain I, et al. (June 01, 2019) Bilateral Basal Ganglia Calcification: Fahr's Disease. Cureus
11(6): e4797. DOI 10.7759/cureus.4797
 demonstrable cerebellar signs. Results from the fundoscopic examination were unremarkable.
No goitre was palpated. The cardiac and lung examination results were unremarkable.

Laboratory investigations revealed a hypocalcaemia level of 2.12 mmol/L (normal: 2.25 - 2.5
mmol/L) and serum phosphate level of 0.98 mmol/L (normal: 0.8 - 1.4 mmol/L), although a
serum parathyroid level was not evaluated. The renal panel showed acute renal impairment
with a serum creatine level of 105 umol/L (normal: 80 - 95 umol/L). The serum electrolytes
levels were normal with a sodium of 141 umol/L (normal: 135 - 145 umol/L) and potassium of
3.9 umol/l (3.5 - 4.5 umol/L). There was an incidental note of vitamin D insufficiency of 29.5
ng/mL (normal: 40 - 59 ng/mL), subclinical hypothyroidism (free thyroxine (FT4) of 13.1 (7 - 15
mg/L)), and a thyroid-stimulating hormone (TSH) level of 5.88 (normal: 0.4 - 4.5 U/mL). The
electrocardiogram (ECG) showed sinus rhythm and a normal QTc of 453 ms (normal: 451 - 470
ms). A low-density lipoprotein (LDL) of 5.06 umol/L (normal: < 3.4 umol/L), high-density
lipoprotein (HDL) of 1.03 umol/L (normal: 1 - 1.5 umol/L), and triglyceride level of 1.83 umol/L
(normal: < 2.3 umol/L) were noted in the screening lipid panel.

CT imaging of the brain demonstrated confluent and asymmetrical calcification of the

lentiform nuclei, thalami, corona radiata, and dentate nuclei (Figure 1). There was no evidence
of acute intracranial haemorrhage or established territorial infarction. The patient’s symptoms
resolved after an intramuscular administration of stemetil in the emergency department.
Antihypertensive and statins were reinstituted in view of the clinical presentation of
hypertension urgency, as well as hyperlipidaemia. The patient’s acute renal impairment
resolved after intravenous and oral rehydration in the general ward.

2019 Ooi et al. Cureus 11(6): e4797. DOI 10.7759/cureus.4797 2 of 8

 FIGURE 1: Axial Section of the Brain Shows Symmetrical
Calcifications in the Corona Radiata (arrows).

Neurology was consulted in view of the radiological findings demonstrated in the CT scan of
the brain. The impression of the neurologist was possible Fahr syndrome which could still be
incidental and the current clinical presentation could be due to accelerated hypertension. After
optimal blood pressure control, he had a complete recovery and was discharged with advice on
stroke prevention and blood pressure control.

Discussion
Although both Fahr’s syndrome and Fahr’s disease resemble each other in terms of clinical
signs and symptoms (e.g., neurological and psychiatric manifestations), there is still a clear
distinction regarding the aetiology, location of calcifications, and treatment.

Table 1 is adapted from the diagnostic checklist by Perugula and Lippman to demonstrate the

2019 Ooi et al. Cureus 11(6): e4797. DOI 10.7759/cureus.4797 3 of 8

 distinctions between these conditions [4].

Fahr’s Syndrome Fahr’s Disease

Age of
30 to 40 years old 40 to 60 years old
Onset

Genetic Autosomal dominant

None
Traits or recessive

Coarse, progressive,
bilateral and
Radiological
Symmetrical and bilateral intracranial calcifications. symmetrical striato-
Findings
pallido-dentate
calcifications.

Endocrinopathies: Idiopathic hypoparathyroidism secondary hypoparathyroidism,

Associated pseudo-hypothyroidism, hyperparathyroidism, or presence of any of the following
None
Conditions conditions: Brucellosis infection (intrauterine or perinatal), neuroferritinopathy,
tuberous sclerosis, mitochondrial myopathy, lipoid proteinosis

No specific
remediation, only
Treatment Treatment directed to specific aetiology and adjunctive symptomatic treatment.
symptomatic
treatment.

TABLE 1: Diagnostic Features for Fahr’s Disease and Fahr's Syndrome

Table adapted from the diagnostic checklist by Perugula and Lippman [4]

Prevalence
The exact prevalence of Fahr’s syndrome is uncertain; however, intracranial calcifications
suggestive of Fahr’s syndrome are detected incidentally in approximately 0.3% to 1.2% of CT
imaging of the brain [2].

Clinical features
Clinical features of both Fahr’s disease and Fahr’s syndrome are as listed in Table 2 below [5].

2019 Ooi et al. Cureus 11(6): e4797. DOI 10.7759/cureus.4797 4 of 8

 Neurological Psychiatric

Seizure Cognitive impairment (dementia/delirium/confusion)

Movement disorder Psychotic symptoms (hallucination/delusion)

Pyramidal signs/parkinsonism Catatonia

Gait disorder Irritability/aggression

Sensory changes Personality disorder/personality change

Cerebellar abnormalities (vertigo) Mood disorder

Anxiety/obsessive behaviour

TABLE 2: Clinical Features of Fahr’s Disease and Fahr's Syndrome

Pistacchi et al. [5]

Complications
Other complications or clinical presentations include stroke, orthostatic hypotension, and
syncope.

Diagnostic criteria
Diagnostic criteria for Fahr’s syndrome/disease are listed in Table 3 below [6-10].

Diagnostic Criteria

Neuroimaging characterized by bilateral basal ganglia calcifications

Progressive neurological dysfunction that constitutes a variety of manifestations from motor disorder to neuropsychiatric
presentation

The typical age of onset is thought to be around the fourth or fifth decades of life

In the absence of biochemical abnormalities or somatic features, another diagnosis has to be considered. For instance,
mitochondrial disorders or metabolic conditions have to be excluded

Diagnosis of exclusion after evaluation for infectious, toxic, or traumatic causes

Presence of autosomal dominant familial inheritance disorder

TABLE 3: Diagnostic Criteria of Fahr’s Syndrome and Fahr's Disease

Jaworski et al., Saleem et al., Pourshahid et al., Moskowitz et al., Manyam BV [6-10]

2019 Ooi et al. Cureus 11(6): e4797. DOI 10.7759/cureus.4797 5 of 8

 Biochemical and haematological investigations
Baseline biochemical investigations are indicated to rule out other possible diagnoses (Table 4)
[7-8].

Types of Laboratory Investigations Indication

Serum calcium, magnesium, phosphate, serum To exclude hypocalcaemia, hypomagnesaemia, hyper- or

parathyroid hormones hypoparathyroidism

To exclude vitamin D deficiency and secondary

Serum Vitamin D and calcitonin
hypoparathyroidism.

Ellsworth-Howard test To assess for hypoparathyroidism

Blood and urinary heavy metals level To exclude heavy metal toxicity

CSF evaluation To exclude infection and autoimmune aetiology

TABLE 4: Laboratory Investigations in Diagnosing Fahr’s Disease

Saleem et al. [7]

CSF: cerebrospinal fluid

Genetic testing
Molecular genetic testing is indicated if there is a strong family history of autosomal dominant
inheritance. SLC20A2 sequencing is the first test to be performed. If no identifiable mutation or
deletion of SLC20A2, one must consider PDGFRB sequence analysis [7].

Type of genetic abnormalities

The exact aetiology of Fahr’s syndrome is still unclear. Genetic alteration at chromosome 14
has been suggested as a cause of this condition [3]. It is thought to be autosomal dominant in
transmission. The 14q chromosome is most commonly affected in Fahr's syndrome [11-14].

Radiological findings
Radiological findings are usually detected incidentally in CT imaging for both Fahr’s disease
and Fahr’s syndrome. These are the most important features as indicated in the diagnostic
criteria. Bilateral calcifications of the basal ganglia, gangliocapsular region, and dentate nuclei
are the classical radiological findings. Pathologically, calcifications occur in the vascular walls
and in the perivascular spaces of arterioles, capillaries, and veins [7]. Laser spectroscopy
demonstrated the presence of mucopolysaccharides and other minerals (zinc, phosphorus,
chlorine, iron, aluminum, magnesium, and potassium). An MRI study has no significant role in
imaging for these conditions. In the interest of MR imaging, the basal ganglia calcifications
exhibit a low T2 signal and low to high T1 signal [15].

Management and treatment

Treatment for Fahr’s syndrome is tailored to the underlying associated conditions.

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 Symptomatic treatment is most helpful. Symptomatic treatment can be pharmacological in
nature. Table 5 below summarizes the drugs commonly used [16-18].

Symptoms Treatment

Urinary Incontinence Oxybutynin

Dystonia Clonazepam

Dysparathyroidism-related movement disorders and seizures Corticosteroids and Vitamin D3 supplementation

Depression and mood-related symptoms Atypical antipsychotics

Seizures Anti-epileptics

TABLE 5: Pharmacological Treatment for Each Symptom

Lauterbach et al., Ramos et al., el Maghraoui et al. [16-18]

This case was slightly different from the published cases as the clinical presentation was non-
specific, but the CT scan findings were suggestive of Fahr syndrome.

Conclusions
Fahr’s disease and Fahr’s syndrome have a widespread clinical presentation with radiological
findings of bilateral symmetrical basal ganglia and dentate nuclei calcifications. Therefore, it's
essentially a diagnosis of exclusion after ruling out metabolic disorders. Treatment is tailored
to symptom control for Fahr's disease and correction of underlying metabolic abnormalities.

Additional Information
Disclosures
Human subjects: Consent was obtained by all participants in this study. Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following:
Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared
that they have no financial relationships at present or within the previous three years with any
organizations that might have an interest in the submitted work. Other relationships: All
authors have declared that there are no other relationships or activities that could appear to
have influenced the submitted work.

Acknowledgements
I will like to acknowledge Dr. Chi Long Ho, Sengkang General Hospital (Singapore), Consultant
Radiologist, for sharing other CT scans with features suggestive of Fahr's syndrome/disease.

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