Bilateral Striopallidodentate Calcinosis

Bilateral striopallidodentate calcinosis (BSPDC, also erroneously called Fahr disease) is characterized by the accumulation of calcium deposits in different brain regions, particularly the basal ganglia and dentate nucleus, and is often associated with neurodegeneration.

Epidemiology

The prevalence of BSPDC is not known, however it is very rare and fewer than 200 cases have been reported. BSPDC is more common in men (male:female ratio 2:1).

Clinical description

BSPCD can be asymptomatic. Symptomatic forms usually manifest in the fourth decade of life, whereas calcification may be found in the second decade. Patients present with progressive movement disorders, including parkinsonism, chorea, tremor, dystonia, athetosis and orofacial dyskinesia, ataxia and neuropsychiatric disorders including difficultly with concentration and memory, personality and/or behavior changes, and dementia. The first manifestations often include clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements or muscle cramping. Seizures occur frequently. Urinary incontinence may occur.

Etiology

The causative gene or genes are not known. Linkage to chromosome 14q has been established in one family. Calcium is the major element deposited on the basal ganglia and accounts for the radiologic appearance of the disease. It is thought that the calcifications observed are a marker of the disease rather than a cause of the clinical symptoms.

Diagnostic methods

Single proton emission computed tomography (SPECT) reveals markedly decreased perfusion to the basal ganglia bilaterally with decreased perfusion to the cerebral cortices. Diagnosis is based on CT or MRI evidence of bilateral, almost symmetric, calcifications of one or more of the following areas: basal ganglia, dentate nuclei, thalamus and cerebral white matter. Diagnosis is further based on normal childhood growth and development and the absence of parathyroid or other known neurologic disorders. Electroencephalogram, nerve conduction studies, and pattern shift visual-evoked potentials studies are usually normal and brainstem auditory-evoked potentials may vary from normal to minor abnormalities.

Differential diagnosis

Differential diagnoses include hypoparathyroidism and pseudohypoparathyroidism, which can usually be excluded by normal serum levels of parathyroid hormone, Kenny-Caffey syndrome type 1, neurodegeneration with iron accumulation, Cockayne syndrome and Aicardi-Goutières syndrome (see these terms).

Antenatal diagnosis

Genetic counseling may be offered.However, there is currently no possibility of antenatal diagnosis.

Genetic counseling

It can be familial or sporadic. Over 30 families with the familial form have been reported. The familial form of idiopathic basal ganglia calcification is inherited in an autosomal dominant manner.

Management and treatment

There is no specific treatment available. Treatment based on amelioration of manifestations, including pharmacologic treatment for anxiety, depression, obsessive-compulsive behaviors and dystonia, may be attempted.

Prognosis

Prognosis is not fully understood due to a lack of longitudinal studies. However, while asymptomatic cases have been observed in individuals younger than 25 years old, it is possible that symptoms may appear with increasing age.