Fahr disease, also known as familial cerebral ferrocalcinosis, is a congenital disorder characterised 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.
Onset is age-dependent, and CT may be negative in patients under 55 years old.
Initially patients can be asymptomatic. Severe forms can later present with progressive psychosis, cognitive impairment, dementia, movement disorders, and parkinsonian symptoms.
- autosomal dominant inheritance with positive family history
- typically presents in fourth or fifth decade (can be earlier)
- progressive neurological or neuropsychiatric manifestations
- typical calcification (see radiographic features)
- 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.
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, aluminium, 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.
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.
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.
- 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
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 4.
History and etymology
It was first noted in 1930 by Karl Theodor Fahr, a German neurologist.
The differential of basal ganglia calcification is relatively long and includes a number of broad categories:
For a more comprehensive list please refer to the article basal ganglia calcification.
Toxic and metabolic encephalopathies
- overview by region
- white matter
- grey matter
- by agent/substance
- by systemic illness
- overview by region
- by substance
- Wernicke encephalopathy (vitamin B1)
- by substance
- Kearns-Sayre syndrome
- Leigh syndrome
- mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)
- myoclonus epilepsy with ragged red fibres (MERRF)
- mitochondrial deletion syndromes
- progressive cerebral poliodystrophy (also known as Alpers syndrome)
- trichopoliodystrophy (also known as Menkes disease)
- 1. Grossman RI, Yousem DM. Neuroradiology, the requisites. Mosby Inc. (2003) ISBN:032300508X. Read it at Google Books - Find it at Amazon
- 2. Shenoy AM, Volpe D, Ensrud ER. Fahr's disease. Pract Neurol. 2009;9 (2): 100-1. doi:10.1136/jnnp.2008.166157 - Pubmed citation
- 3. LazăR M, Ion DA, Streinu-Cercel A et-al. Fahr's syndrome: diagnosis issues in patients with unknown family history of disease. Rom J Morphol Embryol. 2009;50 (3): 425-8. Pubmed citation
- 4. Avrahami E, Cohn DF, Feibel M et-al. MRI demonstration and CT correlation of the brain in patients with idiopathic intracerebral calcification. J. Neurol. 1994;241 (6): 381-4. Pubmed citation