Figure 1
Teaching Case
SectionNeuroradiology
Case TypeClinical Cases
AuthorsMuhammad Asim Rana1, Ahmed F. Mady1, Omar E. Ramadan1, Intekhab Ahmed1, Waleed T. Hashim1, Abdulrehman Alharthy1, Mostafa Yaseen1, Tarik M. Alsaqat 2, Ahmed F. Farakha2, Dina M. Khalil2
Connected authors
19 years, male
The patient was admitted via ER in status epilepticus and developed cardio-respiratory arrest because of hypoxia, 15 minutes CPR was done. History of abnormal movements started a few months before and he had suffered seizures for the past two weeks. Family history revealed abnormal movements in his brother who had died five years before undiagnosed. No previous investigations were available.
Fahr's Syndrome with incidental finding of congenital cavum variants
Idiopathic calcification as in aging
Toxic calcification as in lead poisoning and mineralizing microangiopathy
Calcifications from infections like TORCH
CNS Tuberculosis
AIDS
Neurocysticercosis
Inherited like mitochondrial diseases e.g. MELAS
Cockayne syndrome
Non-enhanced CT brain showing extensive bilateral calcifications involving the basal ganglia, thalami and subcortical white matter of both cerebral and cerebellar hemispheres in symmetric fashion, compatible with Fahr's disease.
Cavum variants, "cavum septum pellucidum" and "cavum vergae" are also seen.
Infarct involving the right and left occipital lobes and right cerebellar hemisphere are seen. The area of involvement corresponds to the posterior circulation territory.
No signs of intracranial haemorrhage are seen.
The ventricular size is prominent for the patient's age without any mid-line shift. Basal cisterns appear normal. Mastoid air cells are sclerotic bilaterally.
Cavum variants, "cavum septum pellucidum" and "cavum vergae" are also seen.
Infarct involving the right and left occipital lobes and right cerebellar hemisphere are seen. The area of involvement corresponds to the posterior circulation territory.
No signs of intracranial haemorrhage are seen.
The ventricular size is prominent for the patient's age without any mid-line shift. Basal cisterns appear normal. Mastoid air cells are sclerotic bilaterally.
Fahr’s disease, also called idiopathic basal ganglia calcification, is a rare inherited disorder characterized by abnormal deposits of calcium (carbonate and phosphate) in movement-controlling areas of the brain. It was first described by the German neurologist Karl Theodor Fahr in 1930 [1].
Genetic heterogeneity is suggested in this disease [2] as latest research has identified a locus at 14q [3], second on chromosome 8 [4] and third on chromosome 2 [5]. A mutation in the gene encoding the type 3 sodium-dependent phosphate transporter 2 (SLC20A2) located on chromosome 8 has been reported suggesting that phosphate transport is involved. [6]
Basal ganglia calcification may occur in several other known conditions [7-10].
The disease usually manifests in 3rd to 5th decade but may appear earlier. It usually presents with gait ataxia, slurred speech, involuntary movements, and seizures. Neuropsychiatric symptoms range from changes in personality to psychosis and dementia [11].
Calcification commonly affects lenticular nucleus, especially globuspallidus, but caudate, dentae, putamen, and thalami are also involved (Fig. 1d, 2a). Sometimes it may predominate regions outside the basal ganglia (see Fig. 2b, 2c). Classification seems to be progressive and can involve cerebellar gyri, brain stem, and subcortical white matter (Fig. 3b, 3c).
Diagnosis requires the following criteria:
1) Bilateral basal ganglia calcification
2) Progressive neurologic dysfunction
3) Absence of an alternative cause (metabolic, infectious, toxic, or traumatic)
4) A positive family history consistent with autosomal dominant inheritance.
The diagnosis is usually made on CT but calcification may be visible on plain X-ray films of the skull.
All these criteria were met in our case. The work up to search for an alternative cause including investigations like calcium, phosphorus, magnesium, alkaline phosphatase, calcitonin and parathyroid hormone were normal. The infarcts found in the CT were probably related to hypoxic ischaemic event i.e. long CPR.
There is currently neither a known cure nor a standard course of treatment for Fahr’s syndrome except symptomatic control. Some data suggests that haloperidol or lithium carbonate may help with psychotic symptoms [12] and some improvement was shown with bisphosphonate [13].
Genetic counselling may help to avoid passing on this disease to future generations.
The prognosis of this disease is variable and cannot be predicted easily because there is no reliable correlation among age, extent of calcium deposits in the brain, and neurologic deficit. A CT can be negative in a gene carrier.
Progressive neurological deterioration results in disability and death.
Additional incidental findings in our case were presence of cavum variants, cavum septum pellucidum (Fig. 2b, c) and cavum vergae (Fig. 3a, b, c).
Genetic heterogeneity is suggested in this disease [2] as latest research has identified a locus at 14q [3], second on chromosome 8 [4] and third on chromosome 2 [5]. A mutation in the gene encoding the type 3 sodium-dependent phosphate transporter 2 (SLC20A2) located on chromosome 8 has been reported suggesting that phosphate transport is involved. [6]
Basal ganglia calcification may occur in several other known conditions [7-10].
The disease usually manifests in 3rd to 5th decade but may appear earlier. It usually presents with gait ataxia, slurred speech, involuntary movements, and seizures. Neuropsychiatric symptoms range from changes in personality to psychosis and dementia [11].
Calcification commonly affects lenticular nucleus, especially globuspallidus, but caudate, dentae, putamen, and thalami are also involved (Fig. 1d, 2a). Sometimes it may predominate regions outside the basal ganglia (see Fig. 2b, 2c). Classification seems to be progressive and can involve cerebellar gyri, brain stem, and subcortical white matter (Fig. 3b, 3c).
Diagnosis requires the following criteria:
1) Bilateral basal ganglia calcification
2) Progressive neurologic dysfunction
3) Absence of an alternative cause (metabolic, infectious, toxic, or traumatic)
4) A positive family history consistent with autosomal dominant inheritance.
The diagnosis is usually made on CT but calcification may be visible on plain X-ray films of the skull.
All these criteria were met in our case. The work up to search for an alternative cause including investigations like calcium, phosphorus, magnesium, alkaline phosphatase, calcitonin and parathyroid hormone were normal. The infarcts found in the CT were probably related to hypoxic ischaemic event i.e. long CPR.
There is currently neither a known cure nor a standard course of treatment for Fahr’s syndrome except symptomatic control. Some data suggests that haloperidol or lithium carbonate may help with psychotic symptoms [12] and some improvement was shown with bisphosphonate [13].
Genetic counselling may help to avoid passing on this disease to future generations.
The prognosis of this disease is variable and cannot be predicted easily because there is no reliable correlation among age, extent of calcium deposits in the brain, and neurologic deficit. A CT can be negative in a gene carrier.
Progressive neurological deterioration results in disability and death.
Additional incidental findings in our case were presence of cavum variants, cavum septum pellucidum (Fig. 2b, c) and cavum vergae (Fig. 3a, b, c).
References
[1] Fahr, T. (1930) IdiopathischeVerkalkung der Hirngefässe. ZentralblattfürallgemeinePathologie und pathologische Anatomie 50: 129–133.
[2] 2) Oliveira JR, Spiteri E, Sobrido MJ, et al. (2004) Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease). Neurology Neurology63 (11): 2165–7. (PMID: 15596772)
[3] Geschwind DH, Loginov M, Stern JM (1999) Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am. J. Hum. Genet 65(3):764–772. (PMID: 10441584)
[4] Dai X, Gao Y, Xu Z, et al. (2010) Identification of a novel genetic locus on chromosome 8p21.1-q11.23 for idiopathic basal ganglia calcification. Am. J. Med. Genet. B Neuropsychiatr.Genet 153B (7): 1305–10. (PMID: 20552677)
[5] Volpato CB, De Grandi A, Buffone E, et al. (2009) 2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family. J. Mol. Neurosci 39 (3): 346–53. (PMID: 19757205)
[6] Wang C, Li Y, Shi L, et al. (2012) Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat. Genet 44 (3): 254–6. (PMID: 22327515)
[7] Niwa A, Naito Y, Kuzuhara S (2008) \"Severe cerebral calcification in a case of LEOPARD syndrome\". Intern. Med 47 (21): 1925–9. (PMID: 18981639)
[8] Preusser M, Kitzwoegerer M, Budka H, Brugger S (2007) Bilateral striopallidodentate calcification (Fahr\'s syndrome) and multiple system atrophy in a patient with longstanding hypoparathyroidism. Neuropathology 27 (5): 453–6. (PMID: 18018479)
[9] Saito Y, Shibuya M, Hayashi M, et al. (2005) Cerebellopontine calcification: a new entity of idiopathic intracranial calcification?. ActaNeuropathol 110 (1): 77–83. (PMID: 15959794)
[10] Tojyo K, Hattori T, Sekijima Y, Yoshida K, Ikeda S (2001) A case of idiopathic brain calcification associated with dyschromatosissymmetricahereditaria, aplasia of dental root, and aortic valve sclerosis. RinshoShinkeigaku 41 (6): 299–305 (PMID: 11771159)
[11] Chiu HF, Lam LC, Shum PP, Li KW (1993) Idiopathic calcification of the basal ganglia. Postgrad Med J 69 (807): 68–70. (PMID: 8446558)
[12] Munir KM. (1986) The treatment of psychotic symptoms in Fahr\'s disease with lithium carbonate. J ClinPsychopharmacol 6 (1): 36–8. (PMID: 3081601)
[13] Loeb JA (1998) Functional improvement in a patient with cerebral calcinosis using a bisphosphonate. Mov.Disord 13 (2): 345–9. (PMID: 9539353)
Case information
| URL: | https://www.eurorad.org/case/11853 |
| DOI: | 10.1594/EURORAD/CASE.11853 |
| ISSN: | 1563-4086 |
