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AtaxiaThe basic anatomy of cerebellum (CB):

The CB occupies the posterior cranial fossa and covered by thetentorium cerebelli. It consists of 2 hemispheres joined by a medianvermis. The cerebellar cortex is divided into 3 lobes by 2 deeptransverse fissures

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Functional divisions of the CB

Vestibulocerebellum

(archicerebellum)

Spinocerebellum

(paleocerebellum)

Cerebro-

cerebellum

(neo-

cerebellum)

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Connections of the cerebellum

Aference copy

Afference copy

Corrective signals

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CEREBELLAR DYSFUNCTION

Cerebellar lesion Signs

Posterior(Flocculo-nodular lobe;Archicerebellum)Eye movement disorders: Nystagmus;Vestibulo-ocular reflex (VOR)Postural and gait dysfunction

Midline(Vermis; paleocerebellum) Truncal & gait ataxia

Hemisphere(Neocerebellum)Limb ataxia: Dysmetria, Dysdiadochokinesis,"intention" tremorDysarthriaHypotonia

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AtaxiasThe word ataxia simply means lack of co-ordination. So ataxias are disorders in which the

nervous system (including the cerebellum) is

affected, causing unsteadiness and lack of co-ordination. 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.

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Ataxia is

either

sensoryor motor.

Type Sensory ataxia Motor ataxia

Most common

cause

Tabes dorsalis Cerebellar

disease

Gait high steppage

(stamping)

Staggering

Romberg signs Positive Negative

Effect of vision Corrected by

vision

Not affected by

vision

Deep sensations Impaired or lost Normal

Tremors Absent Kinetic tremorpresent

Nystagmus Absent Present

Speech Normal Scanning orstaccato

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Causes & classification of ataxias

Some types of ataxia are inherited and some are not

Developmental

Chiari malfaormation

Dandy walker syndromeCerebellar aplasia

Basilar impression

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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)]

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Autosomal recessive:

Friedreichs ataxia

Ataxia telangiectasia

Ataxia with ocular motor apraxia

Ataxia with Isolated Vitamin E deficiency

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Disease Name PopulationFrequencyOnset(Range inYears)

Duration(Years) Distinguishing Features

Friedreich ataxia(FRDA) 1-2/50,0001st - 2nddecade(4-40) 10 - 30

Hyporeflexia,Babinski responses,sensory loss,cardiomyopathy

Ataxia-telangiectasia(A-T)1/40,000to1/100,000 1st decade 10 - 20

Telangiectasia,immune deficiency, cancer, chromosomalinstability, increased alpha-fetoprotein

Ataxia with vitamin Edeficiency(AVED) Rare2-52 years,usually

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Ataxia with identified biochemical defect

AbetalipoproteinemiaCerebrotedinous Xanthomatosis

Nieman pick disease

Refsum diseseWilson disese

Leukodystrophies

Ceroid lipofuscinosisHexosaminidase deficiency

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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

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Non-inherited ataxiasAutoimmuneMiller-Fisher

Multiple sclerosis

Paraneoplastic

Infections:Viral encephalitis,

Bacterial

Fungal

Parasites

Creutzfeldt-Jakob

Vascular

Infarction

Haemorrhage

Vascular

malformation

Vasculitidis

Systemic

Amyloid

EndocrineHypoparathyroidism Hypothyroidism

GI disorders

Celiac disease; Sprue

Vitamin E malabsorption

Whipples diseaseMultiple system atrophy

Mass lesion

Abscess

NeoplasmSarcoid

Toxins & Drugs

Anticonvulsants

Chemotherapeutic

agentsHeavy metals

Alcohol

Trauma

Vestibular

(labrynthytis)

http://www.neuro.wustl.edu/neuromuscular/ataxia/recatax.htmlhttp://www.neuro.wustl.edu/neuromuscular/ataxia/recatax.html

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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 tendonreflexes in the legs, and extensor plantar responses.

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PathophysiologyFRDA 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 offree radicals in tissues.

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The major pathophysiologic finding in FA is a

"dying back phenomena" of axons, and a

secondary gliosis. The primary sites of thesechanges are the spinal cord and spinal roots.

Myocardial muscle fibers also show degeneration

and are replaced by macrophages and fibroblasts.

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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 typicallypresents in children aged 8-15 years and almost

always presents before age 20 years.

Cli i l f

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Clinical features:

Onset of FA is early, with gait ataxia being theusual 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.

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The cardinal features of FA are as follows:

Progressive limb and gait ataxia develops beforethe 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 commoncharacteristics.

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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 haveabnormal ECG findings. Genetic testing for GAA

expansion is positive in 95% of the homozygous

form.

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Treatment

There is currently no cure available for themajority of the cerebellar ataxias. Antioxident

therapy including coenzyme Q10 and vitamin E

are being evaluated. Supportive treatmentincludes physical therapy, speech therapy,

psychological support and treatment of associated

cardiac disease and diabetes. Genetic counseling

should be offered.