Ataxia

Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum.

Types

Ataxia can be due to dysfunction of cerebellum,disorder of sensory nerve,vestibular(inner ear) dysfunction or a combination of above.

Cerebellar

The term cerebellar ataxia is used to indicate ataxia that is due to dysfunction of the cerebellum. The cerebellum is responsible for integrating a significant amount of neural information that is used to coordinate smoothly ongoing movements and to participate in motor planning. People with cerebellar ataxia may have trouble regulating the force, range, direction, velocity and rhythm of muscle contractions.These deficits can vary depending on which cerebellar structures have been damaged, and whether the lesion is bilateral or unilateral.
People with cerebellar ataxia may initially present with poor balance, which could be demonstrated as an inability to stand on one leg or perform tandem gait. As the condition progresses, walking is characterized by a widened base and high stepping, as well as staggering and lurching from side to side. Turning is also problematic and could result in falls. There may also be slurring of speech, tremor of the voice. Cerebellar ataxia could result with incoordination of movement, particularly in the extremitiesThere may also be tremor of the head and trunk (titubation) in individuals with cerebellar ataxia.

Sensory

AThe term sensory ataxia is employed to indicate ataxia due to loss of proprioception, the loss of sensitivity to the positions of joint and body parts. This is generally caused by dysfunction of the dorsal columns of the spinal cord, because they carry proprioceptive information up to the brain.Sensory ataxia presents itself with an unsteady “stomping” gait with heavy heel strikes, as well as a postural instability that is usually worsened when the lack of proprioceptive input cannot be compensated for by visual input, such as in poorly lit environments.
Physicians can find evidence of sensory ataxia during physical examination by having the patient stand with his/her feet together and eyes shut. In affected patients, this will cause the instability to worsen markedly, producing wide oscillations and possibly a fall. This is called a positive Romberg’s test.

Vestibular

The term vestibular ataxia is employed to indicate ataxia due to dysfunction of the vestibular system, which in acute and unilateral cases is associated with prominent vertigo, nausea and vomiting. In slow-onset, chronic bilateral cases of vestibular dysfunction, these characteristic manifestations may be absent, and dysequilibrium may be the sole presentation.

Causes

Etiology of Cerebellar Ataxia
Symmetric and Progressive Signs Focal and Ipsilateral Cerebellar Signs
Acute (Hours to Days) Subacute (Days to Weeks) Chronic (Months to Years) Acute (Hours to Days) Subacute (Days to Weeks) Chronic (Months to Years)
Intoxication: alcohol, lithium, phenytoin, barbiturates (positive history and toxicology screen) Intoxication: mercury, solvents, gasoline, glue; cytotoxic chemotherapeutic, hemotherapeutic drugs Paraneoplastic syndrome Anti-gliadin antibody syndrome Hypothyroidism Vascular: cerebellar infarction, hemorrhage, or subdural hematoma
Infectious: cerebellar abscess (mass lesion on MRI/CT, history in support of lesion)
Neoplastic: cerebellar glioma or metastatic tumor (positive for neoplasm on MRI/CT)
Demyelinating: multiple sclerosis (history, CSF, and MRI are consistent)
Stable gliosis secondary to vascular lesion or demyelinating plaque (stable lesion on MRI/CT older than several months)
Acute viral cerebellitis (CSF supportive of acute viral infection)
Postinfection syndrome
Alcoholic-nutritional (vitamin B1 and B12 deficiency)
Lyme disease
Inherited diseases
Tabes dorsalis (tertiary syphilis)
Phenytoin toxicity
Amiodarone
AIDS-related multifocal leukoencephalopathy (positive HIV test and CD4+ cell count for AIDS) Congenital lesion: Chiari or Dandy-Walker malformations (malformation noted on MRI/CT)

Abbreviations:

: CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging
The three types of ataxia have overlapping causes, and therefore can either coexist or occur in isolation.

Focal lesions

Any type of focal lesion of the central nervous system (such as stroke, brain tumour, multiple sclerosis) will cause the type of ataxia corresponding to the site of the lesion: cerebellar if in the cerebellum, sensory if in the dorsal spinal cord (and rarely in the thalamus or parietal lobe), vestibular if in the vestibular system (including the vestibular areas of the cerebral cortex).

Exogenous substances

Exogenous substances that cause ataxia mainly do so because they have a depressant effect on central nervous system function. The most common example is alcohol, which is capable of causing reversible cerebellar and vestibular ataxia. Other examples include various prescription drugs (e.g. most antiepileptic drugshave cerebellar ataxia as a possible adverse effect), Lithium, cannabis ingestion and various other recreational drugs (e.g. ketamine, PCPor dextromethorphan )A further class of pharmaceuticals which can cause short term ataxia, especially in high doses are the benzodiazepines. Exposure to high levels of methylmercury, through consumption of fish with high mercury concentrations, is also a known cause of ataxia and other neurological disorders.

Radiation poisoning

Ataxia can be induced as a result of severe acute radiation poisoning with an absorbed dose of more than 30 Grays.

Vitamin B12 deficiency

Vitamin B12 deficiency may cause, among several neurological abnormalities, overlapping cerebellar and sensory ataxia.

Hypothyroidism

Symptoms of neurological dysfunction may be the presenting feature in some patients with hypothyroidism. These include reversible cerebellar ataxia, dementia,peripheral neuropathy, psychosis and coma. Most of the neurological complications improve completely after thyroid hormone replacement therapy.

Causes of isolated sensory ataxia

Peripheral neuropathies may cause generalised or localised sensory ataxia (e.g. a limb only) depending on the extent of the neuropathic involvement. Spinal disorders of various types may cause sensory ataxia from the lesioned level below, when they involve the dorsal columns

Non-hereditary cerebellar degeneration

Non-hereditary causes of cerebellar degeneration include chronic ethanol abuse, head injury, paraneoplastic cerebellar degeneration, high altitude cerebral oedema, coeliac disease, normal pressure hydrocephalus and cerebellitis.

Hereditary ataxias

Ataxia may depend on hereditary disorders consisting of degeneration of the cerebellum and/or of the spine; most cases feature both to some extent, and therefore present with overlapping cerebellar and sensory ataxia, even though one is often more evident than the other. Hereditary disorders causing ataxia include autosomal dominant ones such as spinocerebellar ataxia, episodic ataxia, and dentatorubropallidoluysian atrophy, as well as autosomal recessivedisorders such as Friedreich’s ataxia (sensory and cerebellar, with the former predominating) and Niemann Pick disease, ataxia-telangiectasia (sensory and cerebellar, with the latter predominating), and abetalipoproteinaemia. An example of X-linked ataxic condition is the rare fragile X-associated tremor/ataxia syndrome.

Genetic Defects Associated with Hereditary Spinocerebellar Ataxia (SCA)

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Notation Gene Genetics Age of Onset Clinical and Miscellaneous Features in Addition to Ataxia
Dentatorubropallidoluysian atrophy Atrophin ADa Childhood Chorea, dystonia, seizures, dementia
SCA1 Ataxin-1 ADa Variable 10–25% of dominant ataxias; spasticity, polyneuropathy, ophthalmoparesis, dementia
SCA2 Ataxin-2 ADa Teens Neuropathy, ophthalmoparesis, extrapyramidal features
SCA3 (Machado-Joseph) Ataxin-3 ADa Teens Neuropathy, ophthalmoparesis, extrapyramidal features
SCA6 alpha1A calcium channel ADa Adult 20% of dominant ataxias; dysarthria, nystagmus,
SCA7 Ataxin-7 ADa Late teens Retinal degeneration, hearing loss, ophthalmoplegia, spasticity
Infantile Fulminant, with large CAG expansion
SCA8 CTG repeat (noncoding) AD Adult Sensory neuropathy, spasticity; there is rapid infantile variant
SCA10 ATTCT repeat (ataxin-10) AD Teens–adult Seizures, personality change
SCA11 TTBK2 AD Adult Mild phenotype
SCA12 PPP2R2B, CAG repeat AD Adult Head and hand tremor
SCA13 KCNC3 CAG repeat AD Childhood Mental retardation
SCA14 Protein kinase C gamma AD Teens–adult Myoclonus, tremor
SCA16 ITPR1 AD Varies Head and hand tremor
SCA17 TATA box binding protein ADa Variable Cognitive decline, seizures, extrapyramidal features
SCA with tremor Fibroblast growth factor 14 AD Childhood Tremor, cognitive defects, facial dyskinesia
Friedreich ataxia Frataxin AR Teens Spinocerebellar ataxia, neuropathy, cardiomyopathy, arrhythmia
Friedreich ataxia variant Vitamin E transport protein AR Childhood Spinocerebellar ataxia, neuropathy, cardiomyopathy, arrhythmia
Episodic
Episodic ataxia with myokymia KCNA AD Teens Limb stiffness, dizziness, visual blurring
Paroxysmal episodic ataxia alpha1A calcium channel AD Teens Nystagmus, vertigo, weakness

Arnold-Chiari malformation

Arnold-Chiari malformation is a malformation of the brain. It consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of cerebrospinal fluid outflow.

Wilson’s disease

Wilson’s disease is an autosomal-recessive gene disorder whereby an alteration of the ATP7B gene results in an inability to properly excrete copper from the body. Copper accumulates in the nervous system and liver and can cause ataxia as well as other neurological and organ impairments.

Gluten ataxia

Gluten ataxia is defined as sporadic cerebellar ataxia associated with the presence circulating antigliadin antibodies and in the absence of an alternative etiologyfor ataxia.

Sodium-potassium pump

Misfunction of the sodium-potassium pump may be a factor in some ataxias. The Na+-k+ pump has been shown to control and set the intrinsic activity mode o of cerebellar Purkinje neurons. This suggests that the pump might not simply be a homeostatic, “housekeeping” molecule for ionic gradients; but could be a computational element in the cerebellum and the brain.

Treatment

The treatment of ataxia and its effectiveness depend on the underlying cause. Treatment may limit or reduce the effects of ataxia, but it is unlikely to eliminate them entirely. Recovery tends to be better in individuals with a single focal injury (such as stroke or a benign tumour), compared to those who have a neurological degenerative condition. The movement disorders associated with ataxia can be managed by pharmacological treatments and through physical therapy and occupational therapy to reduce disability. Some drug treatments that have been used to control ataxia include: 5-hydroxytryptophan (5-HTP), idebenone, amantadine, physostigmine, L-carnitine or derivatives, trimethoprim–sulfamethoxazole, vigabatrin, phosphatidylcholine, acetazolamide, 4-aminopyridine, buspirone, and a combination ofcoenzyme Q10 and vitamin E