Cerebellar ataxia

Cerebellar ataxia is a general term for a movement disorder caused by diseases and damage to the cerebellum and its connections. Cerebellar ataxia is manifested by specific gait disorders (cerebellar dysbasia), balance, movement incoordination in the limbs (ataxia proper), speech disorder (cerebellar dysarthria), various types of cerebellar tremor, muscle hypotonia, as well as oculomotor dysfunction and dizziness. There are a large number of special tests for detecting cerebellar dysfunction and many individual symptoms that it can manifest.

The huge number of diseases capable of affecting the cerebellum and its extensive connections makes it difficult to create a convenient classification of cerebellar ataxias. A unified classification has not yet been created, although there are quite a few such attempts in the literature, and they are all based on different principles.

From the point of view of a practicing physician, it is more convenient to rely on a classification based on one or another important clinical sign. We focused on the classification based on the characteristics of the course of cerebellar ataxia (acute ataxia, subacute, chronic and paroxysmal). This classification is further supplemented by an etiological classification of cerebellar ataxias.

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Classification of cerebellar ataxia

Acute onset ataxia

1. Strokes and volumetric processes with pseudo-stroke course.
2. Multiple sclerosis
3. Guillain-Barre syndrome
4. Encephalitis and postinfectious cerebellitis
5. Intoxication (including drug intoxication: lithium, barbiturates, phenytoin)
6. Metabolic disorders
7. Hyperthermia
8. Obstructive hydrocephalus

Ataxia with subacute onset (over a week or several weeks)

1. Tumors, abscesses and other space-occupying processes in the cerebellum
2. Normal pressure hydrocephalus
3. Toxic and metabolic disorders (including those associated with impaired absorption and nutrition).
4. Paraneoplastic cerebellar degeneration
5. Multiple sclerosis

Chronically progressive ataxias (over several months or years)

1. Spinocerebellar ataxias (usually early onset)

• Friedreich's ataxia
• Early-onset "non-Friedreichian" ataxia with preserved reflexes, hypogonadism, myoclonus, and other abnormalities

2. Cortical cerebellar ataxias

• Holmes' cerebellar cortical atrophy
• Late cerebellar atrophy of Marie-Foix-Alajouanine

3. Cerebellar ataxias with late onset, involving brainstem structures and other formations of the nervous system

• OPTSA
• Dentato-rubro-pallido-Lewis atrophy
• Machado-Joseph disease
• Other degenerations involving the cerebellum
• Cerebellar dysgenesis

Paroxysmal episodic ataxia

In childhood:

• Autosomal dominant hereditary periodic ataxia (type 1 and type 2, differing in the duration of attacks).
• Other ataxias (Hartnup disease; pyruvate dehydrogenase deficiency; maple syrup urine disease)

Episodic ataxia in adults

• Medicinal
• Multiple sclerosis
• Transient ischemic attacks
• Compression processes in the area of the foramen magnum
• Intermittent obstruction of the ventricular system

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Acute onset cerebellar ataxia

Stroke is probably the most common cause of acute ataxia in clinical practice. Lacunar infarctions in the pontine and supratentorial areas may cause ataxia, usually in the picture of ataxic hemiparesis. Ischemia in the area of the thalamus, posterior limb of the internal capsule and corona radiata (area of blood supply from the posterior cerebral artery) may manifest as cerebellar ataxia. At the same time, "silent" lacunar infarctions are often found in the cerebellum. Cerebellar infarction may also manifest as isolated dizziness. Cardiac embolism and atherosclerotic occlusion are the two most common causes of cerebellar stroke.

Hemiataxia with hemihypesthesia is typical for strokes in the thalamus (branch of the posterior cerebral artery). Isolated ataxic gait is sometimes encountered with damage to the penetrating branches of the basilar artery. Hemiataxia with the involvement of certain cranial nerves develops with damage to the upper parts of the pons (superior cerebellar artery), lower lateral parts of the pons and lateral parts of the medulla oblongata (anterior inferior and posterior inferior cerebellar arteries), usually in the picture of brainstem alternating syndromes.

Extensive cerebellar infarctions or hemorrhages are accompanied by the rapid development of generalized ataxia, dizziness and other brainstem and general cerebral manifestations, often in connection with the development of obstructive hydrocephalus.

Cerebellar tumors, abscesses, granulomatous and other volumetric processes sometimes manifest acutely and without severe symptoms (headaches, vomiting, mild ataxia when walking).

Multiple sclerosis sometimes develops acutely and rarely occurs without cerebellar symptoms. There are usually other signs (clinical and neuroimaging) of multifocal damage to the brainstem and other parts of the nervous system.

Guillain-Barré syndrome is a rare form of damage involving cranial nerves and ataxia. But even here, at least mild hyporeflexia and increased protein in the cerebrospinal fluid are detected. Miller Fisher syndrome is acute with the development of ataxia, ophthalmoplegia and areflexia (other symptoms are optional) with subsequent good restoration of impaired functions. These manifestations are very specific and sufficient for clinical diagnosis.

Encephalitis and postinfectious cerebellitis often involve the cerebellum. Cerebellitis in mumps is especially common in children with premorbid cerebellar abnormalities. Chickenpox can cause cerebellitis. Epstein-Barr virus causes infectious mononucleosis with secondary acute cerebellar ataxia. Acute postinfectious ataxia is especially common among the consequences of childhood infections.

Intoxication is another common cause of acute ataxia. As a rule, there is an ataxic gait and nystagmus. If ataxia is detected in the limbs, it is usually symmetrical. The most common causes are: alcohol (including Wernicke's encephalopathy), anticonvulsants, psychotropic drugs.

Metabolic disorders such as insulinoma (hypoglycemia causes acute ataxia and confusional state) are fairly common causes of acute ataxia.

Hyperthermia in the form of prolonged and intense heat stress (high fever, heat stroke, neuroleptic malignant syndrome, malignant hyperthermia, hyperthermia due to lithium intoxication) can affect the cerebellum, especially in the rostral region around the vermis.

Obstructive hydrocephalus, which developed acutely, is manifested by a whole complex of symptoms of intracranial hypertension (headache, drowsiness, confusion, vomiting), among which acute cerebellar ataxia often occurs. With slow development of hydrocephalus, ataxia can manifest itself with minimal general cerebral disorders.

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Ataxia with subacute onset

Tumors (especially medulloblastomas, astrocytomas, ependymomas, hemangioblastomas, meningiomas, and schwannomas (of the cerebellopontine angle), as well as abscesses and other space-occupying lesions in the cerebellum, may present clinically as subacute or chronically progressive ataxias. In addition to progressive cerebellar ataxia, symptoms of involvement of adjacent lesions are not uncommon; signs of increased intracranial pressure appear relatively early. Neuroimaging methods aid in diagnosis.

Normal pressure hydrocephalus (Hakim-Adams syndrome: progressive enlargement of the ventricles with normal cerebrospinal fluid pressure) is clinically manifested by a characteristic triad of symptoms in the form of dysbasia (gait apraxia), urinary incontinence and subcortical dementia, which develop over several weeks or months.

Main causes: consequences of subarachnoid hemorrhage, previous meningitis, craniocerebral trauma with subarachnoid hemorrhage, brain surgery with bleeding. Idiopathic normal-pressure hydrocephalus is also known.

Differential diagnosis is carried out with Alzheimer's disease, Parkinson's disease, Huntington's chorea, and multi-infarct dementia.

Toxic and metabolic disorders (deficiency of vitamin B12, vitamin B1, vitamin E; hypothyroidism, hyperparathyroidism; intoxication with alcohol, thallium, mercury, bismuth; overdose of diphenin or other anticonvulsants, as well as lithium, cyclosporine and some other substances) can lead to progressive cerebellar ataxia.

Paraneoplastic cerebellar degeneration. Malignant neoplasm may be accompanied by subacute (sometimes acute) cerebellar syndrome, often with tremor or myoclonus (and also opsoclonus). Often it is a tumor of the lungs, lymphoid tissue or female genital organs. Paraneoplastic cerebellar degeneration sometimes clinically precedes the immediate manifestations of the tumor itself. Unexplained subacute (or chronic) cerebellar ataxia sometimes requires targeted oncological search.

Multiple sclerosis should be confirmed or excluded in subacute cerebellar ataxia, especially in individuals under 40 years of age. If the clinical picture is atypical or questionable, MRI and evoked potentials of different modalities usually allow this question to be resolved.

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Chronically progressive cerebellar ataxias (over months or years)

In addition to slowly growing tumors and other volumetric processes, this group is characterized by:

Spinocerebellar ataxias (early onset)

Spinocerebellar ataxias are a group of diseases, the list of which is not strictly fixed and includes, according to different authors, various hereditary diseases (especially in childhood).

Friedreich's ataxia (typical symptoms: cerebellar ataxia, sensory ataxia, hyporeflexia, Babinski's sign, scoliosis, Friedreich's foot (pes cavus), cardiomyopathy, diabetes mellitus, axonal polyneuropathy).

Spinocerebellar degenerations of the "non-Friedreich type". Unlike Friedreich's ataxia, this is characterized by an earlier onset of the disease, preserved tendon reflexes, hypogonadism. In some families - lower spastic paraparesis or other signs of predominant spinal cord damage.

Cortical cerebellar ataxias

Holmes' cerebellar cortical atrophy is a hereditary disease of adults, manifested by slowly progressive cerebellar ataxia, dysarthria, tremor, nystagmus and, rarely, other neurological signs (isolated cerebellofugal familial atrophy, heredoataxia type B). On MRI - atrophy of the cerebellar vermis.

Late cerebellar atrophy of Marie-Foix-Alajouanine begins late (mean age 57 years) and progresses very slowly (over 15-20 years), in many ways resembling the previous form (clinically and morphologically), but without a family history (isolated cerebellofugal atrophy of the sporadic type). Similar pathomorphological and clinical manifestations have been described in alcoholic cerebellar degeneration.

Cerebellar ataxias with late onset, involving brainstem structures and other nervous system formations

Olivopontocerebellar atrophy (OPCA)

There are various classifications of OPCA. The sporadic form (Dejerine-Thomas) appears as a clinically "pure" type or as a type with extrapyramidal and vegetative (progressive vegetative failure) manifestations. The latter variant is classified as multiple system atrophy. Hereditary forms (approximately 51%) of OPCA (heredoataxia type A) are pathomorphologically and sometimes clinically (unlike sporadic forms, PVN is not characteristic here) little different from sporadic forms of OPCA and today number seven genetic variants.

The leading manifestation of any form of OPCA is cerebellar ataxia (on average, more than 90% of patients), especially noticeable in walking (more than 70%); dysarthria (scanned speech, dysphagia, bulbar and pseudobulbar disorders); Parkinsonism syndrome occurs in approximately 40-60% of cases; pyramidal signs are no less characteristic. Individual clinical variants include myoclonus, dystonia, choreic hyperkinesis, dementia, oculomotor and visual disorders; rarely - amyotrophy, fasciculations and other (epileptic seizures, eyelid apraxia) symptoms. In recent years, sleep apnea has been increasingly described in OPCA.

CT or MRI reveals atrophy of the cerebellum and brainstem, dilation of the fourth ventricle and the cistern of the cerebellopontine angle. Parameters of auditory brainstem evoked potentials are often impaired.

Differential diagnosis is carried out within various forms of multiple system atrophy (sporadic variant of MSA, Shy-Drager syndrome, striatonigral degeneration). The range of diseases with which MSA has to be differentiated includes such diseases as Parkinson's disease, progressive supranuclear palsy, Huntington's chorea, Machado-Joseph disease, Friedreich's ataxia, ataxia-telangiectasia, Marinesco-Sjogren syndrome, abetalipoproteinemia, CM2 gangliosidosis, Refsum disease, metachromatic leukodystrophy, adrenoleukodystrophy, Creutzfeldt-Jakob disease, paraneplastic cerebellar degeneration and, sometimes, Alzheimer's disease, diffuse Lewy body disease and others.

Dento-rubro-pallido-Lewis atrophy is a rare familial disorder, described mainly in Japan, in which cerebellar ataxia is associated with choreoathetosis and dystonia, and in some cases includes myoclonus, parkinsonism, epilepsy or dementia. Accurate diagnosis is made by molecular genetic DNA analysis.

Machado-Joseph disease (Azores disease) is an autosomal dominant disorder characterized by slowly progressive cerebellar ataxia in adolescence or early adulthood, with hyperreflexia, extrapyramidal rigidity, dystonia, bulbar signs, distal motor weakness, and ophthalmoplegia. Interfamilial variability in individual neurological manifestations is possible. Accurate diagnosis is achieved by genetic DNA analysis.

Other hereditary ataxias involving the cerebellum. There are many descriptions of hereditary cerebellar ataxias with unusual clinical features (cerebellar ataxia with optic atrophy; with retinal pigment degeneration and congenital deafness; retinal degeneration and diabetes mellitus; Friedreich's ataxia with juvenile parkinsonism; etc.).

This group also includes the so-called "ataxia plus" syndromes (Von Hippel-Lindau disease; ataxia-telangiectasia; "cerebellar ataxia plus hypogonadism"; Marinescu-Sjögren syndrome; "cerebellar ataxia plus hearing loss") and diseases with a known biochemical defect (Refsum disease; Bassen-Kornzweig disease), as well as some other rare diseases (Leigh disease; Gerstmann-Straussler disease); Creutzfeldt-Jakob disease; X-linked adrenoleukodystrophy; MERRF syndrome; Tay-Sachs disease; Gaucher disease; Niemann-Pick disease; Sandhof disease).

Cerebellar dysgenesias

Arnold-Chiari malformation is characterized by protrusion of the cerebellar tonsils into the foramen magnum. Type I of this malformation represents the mildest protrusion and is characterized by headache, neck pain, nystagmus (especially downward), ataxic dysbasia, and involvement of the lower cranial nerves and the brainstem conduction systems. Type IV is the most severe and is characterized by cerebellar hypoplasia with cystic dilatation of the fourth ventricle. This type overlaps with Dandy-Walker syndrome, which may include many other brain anomalies.

Such variants of cerebellar dysgenesia as congenital hypoplasia of the granular cell layer and agenesis of the cerebellar vermis have also been described.

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Paroxysmal (episodic) ataxia

In childhood

Familial episodic (paroxysmal) ataxia exists in two forms.

Type I begins at 5-7 years of age and is characterized by short attacks of ataxia or dysarthria, lasting from a few seconds to several minutes. Myokymia is detected in the interictal period, which is usually observed in the orbicularis oculi muscles and hands. Attacks are usually provoked by a startle or physical exertion. In some families, attacks respond to anticonvulsants. Other findings include joint contractures and paroxysmal dyskinesias. EMG shows constant motor unit activity.

Type II episodic ataxia is characterized by attacks lasting up to several days. Attacks are provoked by emotional stress and physical exertion. The disease often begins at school age. In some patients, attacks are accompanied by migraine-like headaches, dizziness and nausea, i.e. a picture that makes it necessary to exclude basilar migraine. In the interictal period, nystagmus, beating downwards, is typical. In some cases, progressive cerebellar ataxia may occur. MRI sometimes shows a picture of selective atrophy of the cerebellar vermis.

Hartnup disease is a rare disorder with an autosomal recessive type of inheritance, consisting of a disorder of tryptophan metabolism. It is characterized by intermittent cerebellar ataxia. Symptoms increase over several days and last from a week to a month. Children with this disease are distinguished by increased photosensitivity of the skin (photodermatosis). Many patients have episodes of cerebellar ataxia, sometimes accompanied by nystagmus. Neurological manifestations are provoked by stress or intercurrent infections, as well as a diet containing tryptophan. The course is favorable. Aminoaciduria is characteristic. Attacks are prevented by oral daily administration of nicotinamide (from 25 to 300 mg per day).

Pyruvate dehydrogenase deficiency. Most patients present with mild developmental delay in early childhood. Attacks of ataxia, dysarthria, and sometimes hypersomnia usually begin after 3 years of age. In more severe forms, episodes of ataxia begin in infancy and are accompanied by generalized weakness and impaired consciousness. Some attacks develop spontaneously; others are provoked by stress or infections. Attacks of cerebellar incoordination recur at irregular intervals and may last from 1 day to several weeks. Lactic acidosis and recurrent polyneuropathy are characteristic. Lactate and pyruvate concentrations always increase during attacks. With per os glucose load, hyperglycemia is prolonged and the concentration of lactate in the blood increases. This test may provoke the appearance of clinical symptoms.

Maple syrup urine disease is an autosomal recessive disorder characterized by a defect in amino acid metabolism. Clinical manifestations become noticeable between the ages of 5 months and 2 years: episodes of ataxia, irritability, and increasing hypersomnia appear. Precipitating factors include infections, surgical interventions, and a high-protein diet. The duration of attacks is variable; most children recover spontaneously, but some die with severe metabolic acidosis. In survivors, psychomotor development remains normal. Diagnosis is based on general clinical data and the detection of a specific sweetish odor in urine. The amino acids leucine, isoleucine, and valine are found in large quantities in the blood serum and urine (they are the ones that give urine this odor). Differential diagnosis includes phenylketonuria and other hereditary abnormalities of amino acid metabolism.

Episodic ataxia in adults

Drug (toxic) ataxia has already been mentioned above. Its occurrence is often caused by the accumulation or overdose of such drugs as diphenin and other anticonvulsants, some psychotropic drugs (lithium) and other drugs. Multiple sclerosis in a remitting course at the time of exacerbations (as well as pseudo-relapses) can manifest itself as periodically occurring ataxia. Transient ischemic attacks, manifested by cerebellar ataxia, are characteristic of damage to the vertebral and basilar arteries (including in the picture of basilar migraine).

Compression processes in the area of the foramen magnum can also manifest as episodes of cerebellar ataxia.

Intermittent obstruction of the ventricular system in some neurosurgical diseases, among other neurological manifestations, also contains episodes of cerebellar ataxia.

The presented syndromic-nosological analysis of cerebellar ataxia concerns the main forms of neurological diseases occurring with ataxia, but it is not and can hardly be absolutely complete. Therefore, we additionally present another classification of cerebellar ataxia, in which the etiology (and not clinical signs) formed the basis of the classification. It contains, first of all, a detailed list of diseases and can serve as an aid to the previous clinical classification in the differential diagnosis of cerebellar ataxia.

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