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Fahr's disease

Summary

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  • Rare neurodegenerative disorder characterised by abnormal calcium deposits in basal ganglia and cerebral cortex
  • Presents with movement disorders, cognitive impairment, and psychiatric symptoms
  • Diagnosis based on clinical features and characteristic neuroimaging findings

Pathophysiology

  • Bilateral calcification of basal ganglia, thalamus, and cerebral cortex
  • Disruption of calcium and phosphorus metabolism in the brain
  • Genetic factors implicated, with autosomal dominant inheritance pattern in some cases
  • Associated with mutations in SLC20A2, PDGFRB, and PDGFB genes

Demographics

  • Rare disorder with an estimated prevalence of <1/1,000,000
  • Typically presents in 4th to 6th decades of life
  • No significant gender predilection
  • Higher prevalence in certain geographic regions (e.g., Japan)

Diagnosis

  • Clinical presentation:
    • Movement disorders (e.g., parkinsonism, dystonia, chorea)
    • Cognitive impairment and dementia
    • Psychiatric symptoms (e.g., mood disorders, psychosis)
    • Seizures in some cases
  • Laboratory findings:
    • Normal serum calcium, phosphorus, and parathyroid hormone levels
    • Genetic testing for known mutations
  • Neuroimaging crucial for diagnosis

Imaging

  • CT:
    • Bilateral, symmetric calcifications in basal ganglia, thalamus, and cerebral cortex
    • Hyperdense lesions with Hounsfield units >100
  • MRI:
    • T1-weighted: Hyperintense signal in affected areas
    • T2-weighted: Variable signal intensity (hypo- to hyperintense)
    • Susceptibility-weighted imaging (SWI): Hypointense signal in calcified regions
  • PET:
    • Reduced glucose metabolism in affected brain regions

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  • While asymptomatic, this patient had a strong family history of intracranial calcification.
  • CT showed hazy calcification in the deep grey nuclei and frontal and cerebellar white matter.
  • The calcification in the deep grey nuclei caused both T1 hypointensity (blue arrow) and hyperintensity (red arrow).

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  • A 40-year-old patient undergoing treatment for a meningioma.
  • Incidentally, there were mixed dystrophic/hazy calcification in the striatum, dentate nuclei and peridentate white matter.
  • Fahr's disease was confirmed on genetic testing.

Treatment

  • No specific curative treatment available
  • Management focuses on symptomatic relief:
    • Antipsychotics for psychiatric symptoms
    • Anticonvulsants for seizures
    • Levodopa or dopamine agonists for parkinsonian features
    • Botulinum toxin injections for dystonia
  • Supportive care and rehabilitation:
    • Physical therapy for movement disorders
    • Cognitive rehabilitation for cognitive impairment
    • Psychotherapy and counseling for psychiatric symptoms
  • Genetic counseling for familial cases
  • Experimental treatments under investigation:
    • Calcium chelation therapy
    • Gene therapy targeting identified mutations

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Hypoparathyroidism Identical bilateral symmetric basal ganglia calcification on CT; dentate nuclei and subcortical white matter involvement indistinguishable from Fahr's disease
Wilson's disease T2/FLAIR signal change in putamen and thalami on MRI; no calcification; "face of the giant panda" sign
Mitochondrial disorders (MELAS) Cortical stroke-like lesions not following vascular territories; basal ganglia T2 signal change rather than calcification
Cockayne syndrome Calcifications combined with diffuse white matter signal change and cerebral atrophy; cerebellar atrophy
Aicardi-Goutières syndrome Periventricular and basal ganglia calcifications with white matter T2 signal change; progressive cerebral atrophy
Tuberous sclerosis Cortical tubers; subependymal nodules calcify on CT; very different from symmetric basal ganglia pattern
Carbon monoxide toxicity Bilateral globus pallidus T2 hyperintensity on MRI without calcification; acute onset