Ataxia

The basic anatomy of cerebellum (CB): The CB occupies the posterior cranial fossa and covered by the tentorium cerebelli. It consists of 2 hemispheres joined by a median vermis. The cerebellar cortex is divided into 3 lobes by 2 deep transverse fissures

Functional divisions of the CB

Cerebrocerebellum (neocerebellum)

Vestibulocerebellum (archicerebellum)

Spinocerebellum (paleocerebellum)

Connections of the cerebellum

Corrective signals

Aference copy Afference copy

CEREBELLAR DYSFUNCTION
Cerebellar lesion
Posterior (Flocculo-nodular lobe; Archicerebellum) Midline (Vermis; paleocerebellum)

Signs
Eye movement disorders: Nystagmus; Vestibulo-ocular reflex (VOR) Postural and gait dysfunction Truncal & gait ataxia

Hemisphere (Neocerebellum)

Limb ataxia: Dysmetria, Dysdiadochokinesis, "intention" tremor Dysarthria Hypotonia

Ataxias
The word ataxia simply means lack of coordination. So ataxias are disorders in which the nervous system (including the cerebellum) is affected, causing unsteadiness and lack of coordination. Several brain areas, including the cerebellum and the spinocerebellar tracts, thalamus, pons, and cerebral cortex control these functions. Injuries in one or more of these areas or in the spinal cord may lead to some form of ataxia.

Ataxia is either sensory or motor.

Type Most cause Gait Romberg signs Effect of vision Deep sensations Tremors Nystagmus Speech common

Sensory ataxia Tabes dorsalis high steppage (stamping) Positive Corrected vision by

Motor ataxia Cerebellar disease Staggering Negative Not affected by vision Normal Kinetic present Present Scanning staccato or tremor

Impaired or lost Absent Absent Normal

Causes & classification of ataxias

Some types of ataxia are inherited and some are not
Developmental Chiari malfaormation Dandy walker syndrome Cerebellar aplasia Basilar impression

Hereditary
Autosomal dominant: Spinocerebellar ataxias (SCAs) Dentatorubral-pallidoluysian atrophy (DRPLA) Episodic ataxia type 1 (EA-1) Episodic ataxia type 2 (EA-2) Hereditary motor and sensory neuropathy type I [HMSN1 or (CMT1)]

Autosomal recessive: Friedreichs ataxia Ataxia telangiectasia Ataxia with ocular motor apraxia Ataxia with Isolated Vitamin E deficiency

Disease Name

Population Frequency

Onset (Range in Years)

Duratio n (Years)

Distinguishing Features

Friedreich ataxia (FRDA)

1-2/50,000

1st - 2nd decade (4-40)

10 - 30

Hyporeflexia, Babinski responses, sensory loss, cardiomyopathy Telangiectasia, immune deficiency, cancer, chromosomal instability, increased alpha-fetoprotein

Ataxia-telangiectasia (A-T)

1/40,000 to 1/100,000

1st decade

10 - 20

Ataxia with vitamin E deficiency (AVED)

Rare

2-52 years, usually <20

Decade s

Similar to FRDA, head titubation (28%)

Ataxia with oculomotor apraxia type 1 (AOA1)

Unknown

Childhood

Decade s

Oculomotor apraxia, choreoathetosis, mild mental retardation, hypoalbuminemia

Ataxia with oculomotor apraxia type 2 (AOA2)

Unknown

10-22 years

Decade s

Cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia

Ataxia with identified biochemical defect Abetalipoproteinemia Cerebrotedinous Xanthomatosis Nieman pick disease Refsum disese Wilson disese Leukodystrophies Ceroid lipofuscinosis Hexosaminidase deficiency

X-linked ataxias Fragile x-tremor ataxia Ataxia with spasticity with mental retardation with deafness Mitochondrial NARP (neuropathy, ataxia, and retinitis pigmentosa) MELAS (mitochondrial encephalomyopathy, lactic acidosis with stroke-like episodes) Myoclonus epilepsy with ragged red fibres (MERRF) Co-Q10 deficiency

Non-inherited ataxias
Autoimmune Infections: Miller-Fisher Viral encephalitis, Multiple sclerosis Paraneoplastic Bacterial Fungal Parasites Systemic Amyloid Endocrine Hypoparathyroidism Hypothyroidism GI disorders Celiac disease; Sprue Vitamin E malabsorption Whipples disease Multiple system atrophy Mass lesion Abscess Neoplasm Sarcoid Trauma Vestibular (labrynthytis)

Toxins & Drugs

Anticonvulsants Chemotherapeutic agents Heavy metals Alcohol

Creutzfeldt-Jakob
Vascular Infarction

Haemorrhage
Vascular malformation Vasculitidis

Friedreich ataxia (FA, FRDA)

Friedreich ataxia (FA, FRDA) is an autosomal recessive ataxia resulting from a mutation of a gene locus on chromosome 9. It accounts for at least 50% of cases of hereditary ataxias in most large series. Cardinal features include progressive limb and gait ataxia, dysarthria, loss of joint position and vibration senses, absent tendon reflexes in the legs, and extensor plantar responses.

Pathophysiology
FRDA is a result of a mutation of a gene locus on chromosome 9. This mutation is characterized by an excessive number of repeats of the GAA (guanine adenine adenine) trinucleotide DNA sequence. This mutation result in a deficiency of frataxin, which causes defects of mitochondrial oxidative phosphorylation with accumulation of free radicals in tissues.

The major pathophysiologic finding in FA is a "dying back phenomena" of axons, and a secondary gliosis. The primary sites of these changes are the spinal cord and spinal roots. Myocardial muscle fibers also show degeneration and are replaced by macrophages and fibroblasts.

Epidemiology
FA is a relatively common disorder. It is the most common autosomal recessive ataxia, accounting for approximately 50% of all cases of hereditary ataxia. Estimates of incidence range anywhere from 1 in 22,000 to 2 in 100,000. Age: The onset of FA is early; it typically presents in children aged 8-15 years and almost always presents before age 20 years.

Clinical features:
Onset of FA is early, with gait ataxia being the usual presenting symptom. As the disease progresses, ataxia affects the trunk, legs, and arms. Patients with advanced FA may have profound distal weakness of the legs. Eventually, the patient is unable to walk because of the progressive weakness and ataxia.

The cardinal features of FA are as follows: Progressive limb and gait ataxia develops before the age of 30 years. Lower extremity tendon reflexes are absent. Evidence of axonal sensory neuropathy is noted. Extensor plantar responses (90%) Foot deformity, scoliosis, diabetes mellitus, and cardiac involvement are other common characteristics.

Investigations:
Vitamin E levels were normal and no acanthocytes were identified. Magnetic resonance scan shows cervical cord atrophy with preserved cerebellar anatomy. Nerve conduction studies showed evidence of an axonal, mainly sensory, neuropathy. Echocardiography reveals symmetric, concentric ventricular hypertrophy. Approximately 65% of patients with FA have abnormal ECG findings. Genetic testing for GAA expansion is positive in 95% of the homozygous form.

Treatment
There is currently no cure available for the majority of the cerebellar ataxias. Antioxident therapy including coenzyme Q10 and vitamin E are being evaluated. Supportive treatment includes physical therapy, speech therapy, psychological support and treatment of associated cardiac disease and diabetes. Genetic counseling should be offered.