Bilateral Basal Ganglia Calcification: Fahr's Disease

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.


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.

Case Presentation
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 progressive visual blurring, and left-sided hearing loss. However, there was no associated weakness or numbness of the extremities. The patient had a history of hypertension and hyperlipidaemia and had not been taking his antihypertensive agent, statins, or aspirin.
On physical examination, the patient was afebrile, hypertensive with a blood pressure reading of 191/90, a pulse rate of 82 beats per minute, and oxygen saturation of 100% on room air. No focal motor or sensory deficits were detected at the time of presentation. There were no  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.

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.

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

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

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

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

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][12][13][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. Symptomatic treatment is most helpful. Symptomatic treatment can be pharmacological in nature. Table 5 below summarizes the drugs commonly used [16][17][18].

Symptoms Treatment
Urinary   [16][17][18] This case was slightly different from the published cases as the clinical presentation was nonspecific, 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.