Hallervorden Spatz disease is a neurodegenerative hereditary pathology caused by the deposition of iron in the basal ganglia of the brain. It is manifested by Parkinsonism syndrome, intellectual and mental disorders, hyperkinesis, visual disorders. The main diagnostic value is the detection of the “tiger’s eye” pattern in the area of the pale globe during MRI of cerebral structures. Symptomatic treatment: dopamine agonists, valproates, anticonvulsants, neuroleptics, antidepressants. The prognosis is unfavorable.
G23.0 Gallervorden Spatz disease
Hallervorden Spatz disease was described in 1922 by German morphologists, after whom it got its name. The most typical clinical markers of this pathology include hyperkinesis, Parkinsonism syndrome, intellectual decline, optic nerve atrophy, retinopathy pigmentosa.Hallervorden Spatz disease is extremely rare. Depending on the time of its manifestation, there are children’s, juvenile (adolescent) and adult forms. Previously, the disease was diagnosed only posthumously according to autopsy data. After the introduction of MRI into practical neurology, a lifetime diagnosis became possible. A breakthrough in the study of etiology was made in 2001, when it was found that the basis of the disease is a genetic defect that causes disorders in the synthesis of the enzyme pantothenate kinase. After that, Hallervorden Spatz disease was officially renamed pantothenate kinase-associated neurodegeneration.
Hallervorden Spatz disease is a genetic pathology of both familial and sporadic nature, inherited by autosomal recessive pathway. The genetic substrate is aberrations in the pantothenate kinase gene (locus 20p12.3–p13 of the 20th chromosome). In total, more than 50 mutations are known. The result of the genetic defect is a decrease in the production of pantothenate kinase, which leads to the accumulation of cysteine in the basal structures. The latter forms stable chemical compounds with iron ions, which adversely affect proteins and trigger the process of peroxidation, leading to apoptosis of neurons. In place of necrotized neurons, glial tissue grows.
The described pathological process mainly affects the pale ball and the black substance (nigra substance), where extracellular iron deposits with brown pigmentation are morphologically detected. In addition, there are spheroidal periaxonal formations located in the white cerebral substance, cerebral cortex, spinal cord and peripheral nerve trunks.
The classic variant of Hallervorden Spatz disease is considered to be an early childhood form with clinical manifestation in the period from 4 to 10 years (usually after the age of 5). In 90% of cases, the first sign of the disease is torsion dystonia, affecting the leg muscles. The leading complaint is difficulty walking. Then, as a rule, the generalization of the process occurs with its spread to the muscles of the pharynx, face, trunk. Along with generalized variants, a multifocal or segmental type of dystonia may be noted. Writing spasm, blepharospasm, facial paraspasm, spastic torticollis are most often observed. A third of patients have signs of parkinsonism: muscle rigidity and hypokinesia. In some cases, epileptic seizures occur.
Hallervorden Spatz disease is characterized by cognitive disorders in the form of a decrease in mindfulness and memory with the gradual development of oligophrenia; mental changes with a predominance of aggressiveness and antisocial behavior. Dysarthria is noted. Most patients have visual acuity disorders. In 68% of cases, they are caused by atrophy of the optic nerves, in 29% of cases — retinopathy pigmentosa. For the childhood form of Hallervorden Spatz disease, rapid progression is typical with a complete loss of the ability to move within 10-15 years.
The adolescent variant of Hallervorden Spatz disease manifests itself at the age of 10 to 18 years and is characterized by a slower course. Debuts with manifestations of focal torsion dystonia, most often in the muscles of the extremities or the orthomandibular region. It is accompanied by mental, intellectual and behavioral disorders.
The adult form of Hallervorden Spatz disease debuts after the age of 18. In most patients, it proceeds in the form of Parkinsonism syndrome. Impoverishment of active movements (hypokinesia), generalized muscle rigidity (a symptom of a “gear wheel”), postural tremor and instability (ataxia) are characteristic. Evaluation of the latter is possible with the help of the Tavenard test — attempts to bring the patient out of balance in a standing position, by pushing him by the shoulders forward and to the sides. The main feature is the combination of Parkinsonism with various hyperkineses (myoclonia, focal torsion dystonia, athetosis, hemibalism). The degree of cognitive impairment can vary from complete preservation to progressive dementia. Emotional lability, depression, aggressiveness, epiprimes are possible.
Due to the polymorphism of symptoms, the diagnosis of Hallervorden Spatz disease is a difficult task for neurologists. The main criteria of the disease are considered to be a debut at the age of 30, extrapyramidal disorders, steady progression of symptoms, the presence of a typical MRI picture. Additional signs include the presence of pyramidal signs, progressive intellectual decline, epiprimes, optic nerve atrophy, retinal pigment atrophy, autosomal inheritance by recessive type.
The diagnosis is based on the data of neurological status and electroencephalography. In case of visual impairment, an ophthalmologist is consulted, visiometry, ophthalmoscopy is performed. The geneticist determines the type of inheritance by compiling a family tree. DNA diagnostics is possible (search for mutations in the pantothenate kinase gene). When conducting a PET of the brain, it is possible to detect a reduced metabolism in the pallidum zone. The reason for excluding Hallervorden Spatz disease is the presence of symptoms of another pathology, within which the existing clinical picture can fit: Wilson’s disease, Huntington’s chorea, neuroacanthocytosis, Machado-Joseph disease.
The fundamental method of diagnosing Hallervorden Spatz disease is MRI. In all typical variants of pathology in the T2 mode, an oval hyperintensive zone located in the area of the pale globe, surrounded by an even larger hypointensive zone, is determined on the MRI of the brain. Such an MRI picture is pathognomonic and is called the “eye of the tiger”. The hypointensive zone is the “eye”, and the hyperintensive zone is its “pupil”. The time of appearance of this sign on tomograms is still being debated. According to some authors, the “eye of the tiger” may appear even before the clinical manifestation of the disease, according to others — a few years after the debut of clinical symptoms.
Currently, Hallervorden Spatz disease has no effective treatment methods. Attempts at therapy with chelated compounds (deferoxamine) and antioxidants that prevent the accumulation of iron were unsuccessful. In this regard, symptomatic treatment is used. Parkinsonism syndrome serves as an indication for the appointment of dopamine agonists (piribedil, pramipexol) or amantadine derivatives. However, with this disease, it is usually resistant to the treatment.
With hyperkinesis, valproates, benzodiazepines (diazepam, clonazepam) are used. Muscle relaxants (baclofen, tolperizone hydrochloride) are recommended for spasticity, topiramate or valproates for epiprimes, ipidacrine and choline alfoscerate for cognitive disorders, neuroleptics (risperidone, quetiapine, clonazepam), 3rd generation antidepressants (venlafaxine, citalopram, dapoxetine) for mental disorders.
Symptomatic therapy of Hallervorden Spatz disease makes it possible to reduce the manifestation of clinical symptoms, prolong the ability of patients to self-care. At the same time, the development of new methods of treatment continues. The effectiveness of the use of pantothenic acid is investigated. Data on the positive effect of magnetic stimulation of the pale globe on the course of the disease were obtained.
The prognosis depends on the form of the disease. The most unfavorable course has an early form, in which complete disability occurs in the interval from 10 to 15 years from the moment of the onset of symptoms. The adult option is more favorable, especially in cases where dementia is poorly expressed. Its average duration is more than 20 years.