Makindo Medical Notes

Related Subjects: |Neurological History taking |Causes of Stroke

Fahr Syndrome refers to bilateral basal ganglia (± dentate nucleus, thalami, subcortical white matter) calcifications with neurological/psychiatric features. When due to a pathogenic variant and after excluding metabolic causes, the preferred term is Primary Familial Brain Calcification (PFBC). Presentation ranges from incidental CT findings to movement disorders, seizures, and cognitive/psychiatric syndromes.

🧾 Terminology

• “Fahr’s disease”: historical/primary (genetic) form.
• “Fahr’s syndrome”: secondary calcifications (e.g., hypoparathyroidism).
• PFBC: modern umbrella term for primary (genetic) cases.

📚 Epidemiology & Inheritance

• Rare; true prevalence unknown (incidental CT detection is rising).
• Classically autosomal dominant, but autosomal recessive forms occur.
• Penetrance is age-dependent and variable—even within families.

🧬 Aetiology & Pathophysiology

Concept: disturbed phosphate handling and neurovascular unit integrity → perivascular mineral deposition (calcium phosphate/carbonate) in deep grey matter.

🧠 Clinical Presentation

• Movement disorders: parkinsonism, dystonia, chorea/athetosis, gait/postural instability.
• Seizures (focal/generalised), headaches.
• Cognitive/psychiatric: executive dysfunction, memory issues, depression, anxiety, psychosis.
• Bulbar/speech: dysarthria, dysphagia in advanced cases.
• Onset typically mid-adult (40s–50s), but variable; can be asymptomatic despite heavy calcification.

🆚 Primary vs Secondary Brain Calcification

🖼 Imaging

• CT head: bilateral, symmetric calcifications in globus pallidus, putamen, caudate ± thalami, dentate, subcortical WM. Severity correlates more with age than symptoms.
• MRI: T1/T2 hypointensity; SWI useful; less sensitive than CT for calcification.

🔬 Investigations (UK-oriented)

• Labs: Ca, phosphate, Mg, ALP, vitamin D, PTH; U&E, TFTs, B12/folate; HIV if indicated.
• If metabolic cause found: treat (e.g., hypo-PTH correction) and reassess.
• Neuro: CT head diagnostic; MRI for differentials; EEG if seizures.
• Genetics: PFBC panel after excluding secondary causes; family counselling/testing.

🛠 Management

Principle: Treat reversible causes; otherwise symptomatic, multidisciplinary care.

• Secondary causes: e.g., hypo-PTH → calcium + calcitriol, endocrine review.
• Motor: Levodopa/dopamine agonists variably effective; botox for focal dystonia; physio for falls prevention.
• Seizures: Standard ASMs (levetiracetam common); driving advice (DVLA).
• Psychiatric: Antidepressants/antipsychotics (start low, go slow); monitor EPS.
• Rehab/support: SLT, OT, neuropsychology, falls prevention, carer education.
• Follow-up: periodic cognitive & gait review; osteoporosis prevention if immobile.

📌 OSCE / Viva Tips

• CT basal ganglia calcifications → check Ca/P/Mg/PTH first.
• PFBC: normal labs + family history + typical CT → refer genetics.
• Symptoms do not correlate with calcification load—counsel carefully.
• Management = symptomatic; treat seizures, gait, mood; prevent falls.

🧭 Differential Diagnosis

• Parkinson’s (rest tremor, bradykinesia; normal imaging).
• Huntington’s (FHx; caudate atrophy on MRI).
• Alzheimer’s/vascular dementia (pattern, risk factors, MRI changes).
• Mitochondrial cytopathies (multisystem; lactic acidosis; stroke-like episodes).

📈 Prognosis

• Highly variable: some remain minimally symptomatic; others develop disabling movement/cognitive/psychiatric disease.
• Secondary: treatable → improved outcomes. Primary PFBC: supportive therapy reduces morbidity (falls, aspiration, mood disorder).

📚 References

• Manyam BV. What is and what is not “Fahr’s disease”. Parkinsonism Relat Disord. 2005;11(2):73–80.
• Nicolas G, et al. Primary Familial Brain Calcification. GeneReviews. 2018 (updated).
• Saleem S, Aslam HM, et al. Fahr’s syndrome: literature review. Orphanet J Rare Dis. 2013;8:156.