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Fahr Syndrome - Abstract, Etiology, Diagnosis, Symptoms | HealthInfi

Fahr Syndrome – Abstract, Etiology, Diagnosis, Symptoms

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Fahr Syndrome

Fahr syndrome, also known as bilateral striatopallidodentatecalcinosis, is characterized by abnormal vascular calcium deposition, particularly in the basal ganglia, cerebellar dentate nuclei, and white matter, with subsequent atrophy.

It can be either primary (usually autosomal dominant) or secondary to a large number of underlying illnesses or metabolic disturbances.

Fahr Disease is a rare degenerative neurological disorder characterized by the presence of abnormal calcium deposition and associated cell loss in the areas of the brain that control movement, including basal ganglia and cerebral cortex. 

Primary familial brain calcification (PFBC), also known as familial idiopathic basal ganglia calcification (FIBGC) and Fahr’s disease, is a rare, genetically dominant, inherited neurological disorder characterized by abnormal deposits of calcium in areas of the brain that control movement. 

Through the use of CT scans, calcifications are seen primarily in the basal ganglia and other areas such as the cerebral cortex.

The condition was first described by Fahr in 1930. According to reports in medical literature, Fahr Disease is often familial. 

It is believed to have autosomal dominant inheritance but a few cases have been reported to have autosomal recessive inheritance and even some sporadic cases have been reported in the literature. 

The association between the abnormal phenotypes and abnormal genes remains unclear despite the recent mapping to chromosome 14q of a susceptible locus for Fahr Disease.

Fahr’s syndrome is also known as Fahr’s disease, familial idiopathic basal ganglia calcification, and primary familial brain calcification. It is a rare neurological disorder characterized by bilateral calcifications of areas in the brain including.

  • Basal ganglia (most commonly the globuspallidus)
  • Cerebellum (most commonly the dentate nucleus)
  • Thalamus
  • Hippocampus
  • Cerebral cortex

Calcifications are hypothesized to be due to lipid deposition and demyelination. The presentation of an individual with Fahr’s disease can vary greatly with some remaining asymptomatic despite receiving imaging confirmation of calcification. In more severe cases individuals will present first and most prominently with extrapyramidal symptoms.

Further symptoms may include progressive psychosis, cognitive impairment, dementia, gait disturbance, and sensory changes. Fahr’s syndrome can present at any age but is typically first diagnosed in individuals between 40-60 years old.

Abstract

Fahr’s disease or Fahr’s syndrome is a rare, neurological disorder characterized by abnormal calcified deposits in the basal ganglia and cerebral cortex. 

Calcified deposits are made up of calcium carbonate and calcium phosphate, and are commonly located in the Basal Ganglia, Thalamus, Hippocampus, Cerebral cortex, Cerebellar Subcortical white matter, and Dentate Nucleus. 

Molecular genetics of this disease hasn’t been studied extensively; hence evidence at the molecular and genetic level is limited.

Fahr’s disease commonly affects young to middle-aged adults. The etiology of this syndrome does not identify a specific agent but associations with some conditions have been noted; most common of which are endocrine disorders, mitochondrial myopathies, dermatological abnormalities, and infectious diseases. 

Clinical manifestations of this disease incorporate a wide variety of symptoms, ranging from neurological symptoms of the extrapyramidal system to neuropsychiatric abnormalities of memory and concentration to movement disorders including Parkinsonism, chorea, and tremors amongst others.

Diagnostic criteria for this disease has been formulated after modifications from previous evidence and can be stated briefly, it consists of bilateral calcification of basal ganglia, progressive neurologic dysfunction, absence of biochemical abnormalities, absence of an infectious, traumatic, or toxic cause, and significant family history. Imaging modalities for the diagnosis include CT, MRI, and plain radiography of the skull. 

Other investigations include blood and urine testing for hematologic and biochemical indices.

The disease is as yet incurable but management and treatment strategies mainly focus on symptomatic relief and eradication of causative factors; however certain evidence is present to suggest that early diagnosis and treatment can reverse the calcification process leading to complete recovery of mental functions. 

Families with a known history of Fahr’s disease should be counseled before conception so that the birth of affected babies can be prevented. This review was written to remark on the current substantial evidence surrounding this disease.

Etiology

Fahr’s syndrome is familial and inherited, with autosomal dominant cases making up 60% of diagnoses. Some research has shown that fewer cases may be inherited in an autosomal recessive fashion. Several other factors could lead to brain calcification which includes: endocrinopathies, vasculitis, mitochondrial disorders, infections, other inherited disorders, radiation, chemotherapy, and carbon monoxide poisoning.

Diagnosis

In addition to the usual routine hematologic and biochemical investigations, the serum calcium, phosphorus, magnesium, alkaline phosphatase, calcitonin, and parathyroid hormone should also be measured. The cerebrospinal fluid (CSF) should be examined to exclude bacteria, viruses, and parasites. 

The Ellsworth Howard test (a 10-20 fold increase of urinary cyclic AMP excretion following stimulation with 200 micromoles of parathyroid hormone) may be worth doing also Serology for toxoplasmosis is also indicated.

A brain CT scan is a preferred method of localizing and assessing the extent of cerebral calcifications.

Elevated levels of copper, iron, magnesium, and zinc but not calcium have been reported in the CSF but the significance of this finding if any is not known.

The diagnosis requires the following criteria be met:

  1. the presence of bilateral calcification of the basal ganglia
  2. the presence of progressive neurologic dysfunction
  3. the absence of an alternative metabolic, infectious, toxic, or traumatic cause
  4. a family history consistent with autosomal dominant inheritance

The calcification is usually identified on a CT scan but may be visible on plain films of the skull.

Differential diagnosis

Symmetrical calcification of the basal ganglia occurs in a variety of familial and non-familial conditions; hence it doesn’t necessarily direct us towards a definitive diagnosis of Fahr’s syndrome.

  • Congenital or early-onset finding along with intellectual disability or presence of systemic involvement should alert one to the possibility of an alternative diagnosis.
  • When latent Tetany and myopathic changes occur with changes in somatosensory, visual, and brain stem auditory responses, then parathyroid dysfunction, mitochondrial disease, or other disease associated with brain calcification may be considered.
  • Basal ganglia calcification, discovered in infancy along with ophthalmologic abnormality should prompt the consideration of infectious disease.

Signs and symptoms

Symptoms of this disease include deterioration of motor functions and speech, seizures, and other involuntary movements. Other symptoms are headaches, dementia, and vision impairment. Characteristics of Parkinson’s disease are also similar to PFBC.

The disease usually manifests itself in the third to fifth decade of life but may appear in childhood or later in life. It usually presents with clumsiness, fatigability, unsteady gait, slow or slurred speech, difficulty swallowing, involuntary movements, or muscle cramping.

Seizures of various types are common. 

Neuropsychiatric symptoms, which may be the first or the most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia.

Neuropsychiatric and Other Symptoms

Due to the heterogeneity of brain calcifications and associated impairments, it is common to see a wide variety of symptoms other than movement disorders. These include epileptic seizures, dysarthria, mood disorders, and problems with cognition (memory and concentration), behavior/personality changes, psychosis, and dementia. 

While some of these symptoms may not be directly treatable with physiotherapy interventions, they do affect treatment considerations and are important to keep in mind when planning for patient care. 

Included below are links to resources within Physiopedia and external sources that provide more information regarding these symptoms?

Methodology

Available literature concerning Fahr syndrome was analyzed. A literature search was conducted using the following databases: Pub med, Google Scholar, and Google. 

Keywords used for searching were Fahr syndrome, Fahr disease, and bilateral basal ganglia calcification. Using the word “Fahr’s syndrome” in Pub med, 64 articles were found from 1954–2013, the term “Fahr’s disease” turned up 218 articles from 1951–2013, and the word “bilateral basal ganglia calcification” unearthed 172 articles from 1951–2013. Clinical data and diagnostic information were collected from abstracts or full-text articles. 

Only articles written in the English language and case reports which had a definitive diagnosis of Fahr syndrome were included. Articles irrelevant to our study objectives were excluded.

It is differentiated from calcified angiomas, infections, encephalitides, and Addison’s disease by its severity and characteristic distribution.

Prognosis

Prognosis differs from person to person and thus is hard to predict. Fahr’s syndrome is a progressive disease with no known cure and no specific treatments at this time. Due to Fahr’s progressive and degenerative features, individuals will often lose previously acquired skills and motor control, which can lead to death. 

There is no direct correlation between the number of calcium deposits that are seen in the brain and the degree of neurological impairments displayed by an individual with the disease.

Clinical Presentation

Lesions in the basal ganglia can cause patients to present with different motor deficits. These include slowness of movement, involuntary extra movement, and alterations in posture and muscle tone. 

Therefore patients with basal ganglia involvement can present on a continuum of motor behavior from severely limited as seen in the final stages of Parkinson’s disease to excessive movements apparent in Huntington’s disease. In “Fahr’s Disease Registry”, the most common symptoms were movement disorders, in particular Parkinsonism, which affects more than half of patients.

Neuroimaging

CT – used to assess the location and severity of cerebral calcification.

MRI – generally less useful than CT, may be used to locate calcification in the brain, but appearance varies depending on the stage of the disease and the amount of calcification.

X-ray – may be used to locate symmetrical calcium clusters lateral to the midline.

Case report        

A 36-year-old woman presented with progressive deterioration of mentality and motor functions, extrapyramidal signs, dysarthria, ataxia, athetosis. Plain radiographs of the skull demonstrated irregular calcifications in the bilateral frontoparietal region of the skull. 

A contrast-enhanced CT scan head was done in Spiral CT scanner Wipro GE which revealed bilaterally symmetrical non-enhancing hyperdense ( HU + 234) lesions s/o calcification, involving globuspallidus, putamen, caudate nucleus, internal capsule, thalami, dentate nucleus, cerebellum, and subcortical white matter.

Blood chemistry revealed normal serum levels of calcium, phosphorus, and alkaline phosphatase. The CT Scan findings when correlated with typical clinical history and normal blood chemistry was suggestive of Fahr Disease.

Neurology was consulted given 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.

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