Alexander's disease (Alexander leukodystrophy) is a rare, autosomal recessive demyelinating disorder. It can progress quickly, leading to death within a few months. What are the causes and symptoms of Alexander's disease?

Alexander's disease(Alexander leukodystrophy, fibrinoid leukodystrophy, fibrinoid white matter degeneration, Alexander megalencephalic leukodystrophy, dysmyelinogenic leukodystrophy) is a leukodystrophy of unknown etiology in which inherited demyelination is in the brain is connected with the presence of Rosenthal fibrinoids.

Alexander's disease can occur at any age, but its frequency is unknown due to its rarity.

It usually occurs sporadically, and its characteristic features are: abnormal dynamics of head circumference growth leading to macrocephaly and thinning of white matter in the frontal lobes of the central nervous system. The disease can progress rapidly, leading to death within a few months. The pathological picture of the deceased shows an increase in the mass of the brain, the presence of softening foci and diffuse demyelination.

Alexander's disease: causes

Despite the significant development of genetics, cytochemical, histochemical and enzymatic studies, the etiopathogenesis of Alexander's disease has not been elucidated so far. It is now believed to be a consequence of a primary abnormal metabolism confined to the astrocyte population, which is characterized by filamentous degeneration with widespread Rosenthal fibers, resulting in abnormal myelination of axons. Oligodendrocytes have also been shown to be morphologically normal, but need the "support" of normal astrocytes to undergo the myelination process. For this reason, in Alexander disease, filamentous degeneration is accompanied by diffuse demyelination, mainly in the frontal lobes.

The disease process involves astrocytes in which filamentous degeneration occurs, with a massive presence of Rosenthal fibers. They are located in the sublingual, subdural and perivascular regions and are scattered throughout the white matter of the brain and cortex. Their main components are alpha B-crystallin and low molecular weight proteinstress HSP 27.

Another characteristic element is the presence of diffuse demyelination, mainly affecting the frontal lobes or appearing focally in the form of islets.

Alexander's disease: symptoms

There are 3 clinical forms of Alexander's disease, the symptomatology of which depends on the age. It is infant, adolescent and adult.The infant formis predominantly male and the mean survival from onset is approximately 2 to 2.5 years. The disease usually progresses from birth or early childhood and is characterized by the presence of macrocephaly as a result of an increase in the mass of the brain, less often hydrocephalus, and symptoms of intracranial hypertension. In addition, inhibition and / or regression in psychomotor development, epilepsy, atrophy of the optic nerves and a progressive pyramidal syndrome leading to post-cerebral stiffness are observed.Juvenile formoccurs in both boys and girls, a appears between the ages of 7 and 14. Its average duration is 8 years. Characteristic for this form are the presence of pyramidal symptoms, bulbar and pseudo-follicular paralysis, relatively rarer mental retardation and no epilepsy and macrocephaly. Two subgroups are distinguished withinof adult figures . The first one appears most often between the ages of 19 and 43, usually lasts about a year, and more often affects women than men. In its course, there are no neurological disorders that make up a neurological syndrome. The second subgroup appears most often between the ages of 32 and 44, lasts a long time - even over a dozen years, and equally often applies to women and men. It is characterized by an intermittent course in terms of neurology, and its clinical picture may resemble multiple sclerosis or Parkinson's disease.

Alexander's disease: research

The diagnosis of Alexander's disease is made on the basis of the clinical picture and the characteristic picture of the brain in neuroradiological examinations, such as trans-glandular ultrasound, computed tomography and magnetic resonance imaging. There are no specific biochemical markers to confirm the diagnosis. Only in the cerebrospinal fluid may the increased concentration of protein be found. Transtratian ultrasound of the brain shows an increase in the mass of the brain with a significant flattening of its furrows. Cerebral furrows can be so obliterated that even the interhemispheric fissure is difficult to find. The brain tissue is relatively homogeneous with the abnormal white matter structure resembling in appearance"frosted glass". Its reduced echogenicity can also be observed. Already in the very early stages of Alexander's disease, narrow chambers of the brain are noticeable.

Other progressive macrocephalic encephalopathies, hydrocephalus, and brain tumors should be considered in the differential diagnosis.

Computed tomography of the brain shows the presence of hypodense areas. After contrast administration, changes are visible near the anterior horns of the lateral ventricles, as well as around the thalamus and caudate nuclei. The anterior branches of the inner capsule and arcuate subcortical fibers are also involved. MRI images of the brain are characterized by the presence of symmetrically occurring areas in both hemispheres of increased signal intensity. The lesions are usually located in the frontal lobes, occupy the arcuate fibers and spread in the fronto-occipital direction. The white matter of the occipital lobes and the knee of the corpus callosum are relatively well preserved. Usually, the disease process does not involve the cerebellum and the brainstem.

Alexander's disease: treatment

Unfortunately, there is no causal treatment for Alexander's leukodystrophy. Due to the unknown metabolic defect of this disease, prenatal testing does not answer whether the developing fetus has the disease or not. Keep in mind that in a family where a child was born with Alexander's disease, there is an approximately 25% risk of a recurrence in another child.

Category:

Neurology