Classification of Ataxias
(Cerebellar and Spinocerebellar Degenerations)
05 November 2004
Idiopathic cerebellar degeneration
Paraneoplastic cerebellar degeneration
Classification of inherited ataxias
Spinocerebellar ataxia with retained tendon reflexes
Spinocerebellar ataxia with isolated Vitamin E deficiency
Other rare recessive ataxias
Hypogonadotrophic hypogonadism (Matthews – Rundle syn)
Learning disability, optic atrophy, spasticity (Behr’s syn)
Learning disability, cataracts, short stature, myopathy (Marinesco Sjogren syn)
Deafness with neuropathy
Autosomal Dominant Cerebellar ataxia (ADCA / Harding’s Classification)
Harding A.E. Classification of the hereditary ataxias and paraplegias. Lancet1983: 1151-55.
Harding A.E The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of “the Drew family of Walworth”. Brain 1982; 105: 1-28.
Pure cerebellar syndrome plus cognitive impairment, slow saccades, ophthalmoplegia, optic atrophy, facial fasciculation, bulbar weakness, chorea, dystonia, Parkinsonism, pyramidal signs, peripheral neuropathy, amyotrophy.
SCA 1: normal 19-36 CAG on Chr 6p, abnormal 42-81 (ataxin )
SCA2: CAG expansion on Chr 12q
SCA3 (Machado – Joseph, Groote Eylandt Disease): CAG rpt on Chr 14q; commonest spinocerebellar ataxia
SCA4: Chr 16q
SCA5: Chr 11centromere
SCA6: CAG expansion on Chr 19p with close relationship to familial hemiplegic migraine, episodic ataxia type 2, responsive to acetazolamide.
ADCA II / SCA7
Ataxia with retinal degeneration
Pure cerebellar syndrome after age 50.
Probable mitochondrial encephalopathy (ataxia, myoclonus, deafness, dementia, optic atrophy, myopathy, neuropathy)
DRPLA (Dentatorubropallidoluysian atrophy)
CAG expansion on Chr 12p
Mostly Japanese population
Ddx is Huntington’s
Ataxia, chorea, myoclonic epilepsy, dementia.
Episodic Ataxia (EA)
EA 1: ataxia for seconds or minutes
Provoked by startle or exercise
Persistent myokymia in hand and face
Missense point mutation for K channel on Chr 12p
EA 2: ataxia for hours or days
Progressive cerebellar syn
Familial hemiplegic migraine, CADASIL as possible allelic variants
Differentiation of SCA 1, 2, 3.
Pyramidal tract signs, pale discs, dysphagia: SCA 1> SCA2,3
VEP, MEP: SCA 1> SCA2,3
SSEP: abnormal in SCA 1,2, 3
Abnormal NCS: abnormal in SCA 1,2, 3
56% SCA1,2 reduced saccade velocity cf SCA3
MRI in SCA2:
Mendelian autosomal dominant pattern
Trinucleotide sequence repeats
Anticipation: increase triplet expansion size with each successive generation
Increase triplet expansion size results in earlier clinical manifestation and worse prognosis.
Poorer outcome if inherited from father
Within ADCA I much clinical, pathological heterogeneity; marked intrafamilial variability.
Genetic diagnosis is important for : Formal diagnosis
Diseases with Trinucleotide Sequence Repeats
Friedreich’s ataxia (AR)
Fragile X syndrome
Huntington’s disease / Westphal variant
Clinical features that can indicate specific spinocerebellar ataxia (SCA) genotypes