Fahr disease,
also known as familial cerebral ferrocalcinosis,
is a congenital disorder characterized by abnormal calcium deposition with subsequent atrophy involving the basal ganglia, cerebral and cerebellar cortical regions. Both autosomal dominant and autosomal recessive inheritance patterns have been proposed. There is variable expressivity.
is a congenital disorder characterized by abnormal calcium deposition with subsequent atrophy involving the basal ganglia, cerebral and cerebellar cortical regions. Both autosomal dominant and autosomal recessive inheritance patterns have been proposed. There is variable expressivity.
Epidemiology
Onset is age-dependent, and CT may be negative in patients under 55 years old.
Clinical presentation
Initially patients can be asymptomatic. Severe forms can later present with progressive psychosis, cognitive impairment, dementia, movement disorders, and parkinsonian symptoms.
Diagnostic criteria
- autosomal dominant inheritance with positive family history
- typically presents in fourth or fifth decade (can be earlier)
- progressive neurological or neuropsychiatric manifestations
- typical calcification
- other causes excluded
- normal biochemistry (esp calcium/phosphate metabolism)
- no clinical features of systemic illness (e.g. vasculitis)
- no clinical features of mitochondrial disorders
- no infectious or toxic causes identified
Not all criteria need to be met. In the absence of a family history it is still possible to propose the diagnosis provided the other 4 criteria are met.
Pathology
Characterised by deposition of calcium in the walls of the capillaries and larger arteries and veins. Other compounds, such as mucopolysaccharides, and elements, including magnesium, zinc, aluminum, and iron have also been found deposited in the vessels.
Calcification can be found in the globus pallidus, putamen, caudate, thalamus, cerebellum (especially dentate nucleus), corona radiata, and subcortical white matter. There is no abnormality in calcium or phosphate metabolism.
Radiographic features
CT
Calcification is extensive and has a fairly typical distribution 3:
- basal ganglia and thalami
- symmetric involvement of caudate, lentiform nucleus, thalamus, and dentate nuclei
- globus pallidus affected first
- subcortical white matter
Bilateral calcification of the basal ganglia on neuroimaging or other brain regions, although in isolated cases patients from families with FIBGC may not present such findings;
MRI
The MRI appearance varies depending on the degree of calcification and the stage of the disease.
- T1: contrary to expectation, the calcified areas are of high signal, attributed to the surface area of calcium crystals 4.
- T2
- calcified areas demonstrate low to isointense signal
- high signal regions may be identified in the basal ganglia, white matter and internal capsule which are not in the areas of calcification 4
FDG-PET
May show decreased FDG uptake particularly in basal ganglia.
Treatment and prognosis
The disease progresses steadily, and there is no known cure or specific treatment currently. Interestingly there is no direct correlation between the amount of calcification and the degree of neurological impairment, which perhaps correlates to the amount of T2 high signal affected brain .