Fahr’s disease is idiopathic symmetrical calcification of cerebral structures: subcortical ganglia, cerebral cortex, cerebellum. It can be asymptomatic, clinically manifested by extrapyramidal disorders (hyperkinesis, parkinsonism), cerebellar disorders, intellectual decline. It is diagnosed according to cerebral CT with the exclusion of the secondary nature of calcified foci according to the results of biochemical, ultrasound, PCR studies. Treatment is symptomatic with the use of agents that improve tissue metabolism, cytoprotectors, levodopa preparations, anticonvulsants.
ICD 10
G23.8 Other specified degenerative diseases of the basal ganglia
General information
Fahr’s disease includes cases of primary idiopathic calcium deposition in brain structures, secondary forms of cerebral calcification are not considered in this pathology. The first detailed descriptions of the disease were made in 1930 by the German neurologist K.T. Fahr. Fahr’s disease is a rare nosology, the prevalence is less than 1 case per 1 million population. Gender differences in morbidity are expressed by the ratio of men and women 2:1. Pathology manifests itself in any age period, more often in 30-60 years. In vivo, it is detected only in 1-2% of cases, which is explained by the presence of asymptomatic variants of the course, the diagnosis of the disease under the guise of other neurodegenerative processes (Parkinson’s disease, senile chorea).
Causes
The etiological factors leading to the occurrence of the disease are not precisely established. It is assumed that the genetic nature of the pathology with localization of disorders in the fourteenth (locus 14q13), second (locus 2q37) chromosomes, chromosomal region q21.1-q11.23 of the eighth chromosome. The study of family cases revealed genetic heterogeneity. Variants have been established when the disease was inherited in an autosomal dominant and X-linked way. Sporadic cases are described in which the family nature of the pathology is not traced. It is known that clinical manifestation occurs when the total volume of calcifications reaches a critical value – 3.9 cm3.
Pathogenesis
The pathogenetic mechanisms that form the disease have not been definitively determined. It is assumed that genetically determined shifts in cerebral metabolism, which cause the deposition of excess calcium in brain tissues. Pronounced calcification of subcortical formations causes disorganization of the frontal-subcortical system, which regulates voluntary movements and provides cognitive functions (memory, thinking, attention).
Morphologically, calcifications are found symmetrically in various structures: the cerebral cortex, white matter, subcortical ganglia, inner capsule, cerebellum, walls of small arteries, rarely veins. The presence of perivascular small calcium conglomerates is characteristic. The most massive calcification is detected in the subcortical sections. Microscopically, calcifications differ in a typical structure, represented by threads with a thickness of 140-400 microns. They often contain mineral complexes with inclusions of iron, copper, aluminum, phosphorus, lead, zinc, cobalt.
Classification
In practical neurology, Fahr’s disease is divided into two clinical forms, differing in the age of manifestation, the type of predominant symptoms:
- Juvenile form — the debut of the disease occurs in childhood or adolescence. Extrapyramidal disorders in the form of athetosis, chorea, and muscular dystonia are characteristic. Pathology may be accompanied by oligophrenia. As they grow older, there is a change of hyperkinesis with Parkinsonian symptoms.
- Senile form — manifests in the elderly and middle age. The clinical picture is characterized by the dominance of Parkinsonism symptoms in combination with cognitive disorders. Progressive dementia is typical.
Symptoms
In typical cases, the disease debuts with the appearance of fatigue, clumsiness of movements, unsteadiness of walking, speech changes, involuntary motor acts or nocturnal muscle spasms. The basis of clinical manifestations are extrapyramidal disorders. At a young age, these are various hyperkineses: athetosis — involuntary worm—like movements in the fingers of the hands, choreoathetosis — a combination of athetosis with rapid violent movements in the limbs, torsion dystonia – tonic muscle spasms that give the body unnatural poses. In adults, secondary Parkinsonism is observed: facial amymia, bradykinesia, slow constrained movements, shuffling gait, postural tremor.
The symptoms of Parkinsonism are often combined with cerebellar ataxia (discoordination, disproportion of movements, nystagmus), pyramidal insufficiency (weakness in the extremities, increased tendon reflexes, pathological stop signs). Dysarthria, dysphagia, urinary incontinence are possible. Epileptic paroxysms are more characteristic of the juvenile form of the disease, may occur in adults.
The cognitive impairments accompanying Fahr’s disease are characterized by a decrease in memory for current and past events, slow thinking, unstable attention, and the fading of the ability to analytical and synthetic intellectual activity. The progression of cognitive disorders in children leads to oligophrenia, in adulthood — to the development of cortical-subcortical dementia with elements of agnosia, apraxia, alexia. However, some patients with juvenile form remain intellectually preserved.
Diagnostics
The main diagnostic method that allows a neurologist to reliably determine the presence of foci of calcification in brain tissues is a CT scan of the brain. The intensity of foci on tomograms reflects the level of calcium concentration. MRI of the brain is much worse at visualizing calcifications, but it allows you to assess the associated degenerative processes. In order to confirm the idiopathic nature of the pathology, a number of additional examinations are carried out:
- Blood test. Blood electrolytes are determined: calcium, phosphorus, iron, sodium. The absence of significant deviations makes it possible to exclude general metabolic disorders in the body that lead to calcium deposition.
- Determination of the parathyroid hormone level. Normal levels of hormone concentration in the blood exclude the presence of hypoparathyroidism, pseudohypoparathyroidism, as the most common causes of calcification.
- Ultrasound of the thyroid and parathyroid glands. In patients with Fahr’s disease, the echoscopic picture remains within the normal range, which excludes hormonal and metabolic disorders associated with the lesion of these glands.
- PCR studies. They are aimed at identifying toxoplasma, cytomegalovirus and other infectious agents capable of causing inflammatory changes in brain tissues with the formation of calcifications.
The diagnosis of Fahr’s disease is valid after excluding the secondary nature of cerebral calcification observed in endocrine (hypoparathyroidism, pseudohypoparathyroidism, hypothyroidism), vascular (atherosclerosis, vascular amyloidosis), infectious (rubella, cysticercosis, toxoplasmosis, cytomegaly) diseases. Differential diagnosis is also carried out with Gallervorden-Spatz disease, tuberous sclerosis.
Treatment
Since the pathogenesis of the disease remains unclear, therapy is mainly symptomatic. In order to improve metabolic processes, stimulators of tissue metabolism (acetylcarnitine, glutamic acid, L-citrulline + malate complex, nicotinamide), cytoprotectors (riboflavin, succinic acid, meldonium) are used. With symptoms of parkinsonism, it is preferable to prescribe levodopa pharmaceuticals, with hyperkinesis — cholinolytics, benzodiazepines. The presence of epileptic seizures is an indication for treatment with modern anticonvulsants (levetiracetam). In complex therapy, physical therapy, hydrotherapy, cognitive training are used.
Prognosis and prevention
Clinically manifested Fahr’s disease is considered as a chronic neurodegenerative disease. The prognosis of recovery is unfavorable, however, with the proper level of supportive symptomatic therapy, the condition of patients remains satisfactory for a long time. The subclinical variant does not affect the health and cognitive abilities of the patient, it may be an accidental finding during computed tomography. Specific measures to prevent the development of the disease have not been developed.
