ataxia د.رشاد عبدالغني
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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.