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Olivopontocerebellar Atrophy Workup

  • Author: Christina J Azevedo, MD; Chief Editor: Selim R Benbadis, MD  more...
 
Updated: Nov 11, 2014
 

Laboratory Studies

Anti-Purkinje cell antibodies: Paraneoplastic cerebellar degeneration is an important entity in the differential diagnosis. Ovarian cancer is one of the malignancies associated with this syndrome, and the paraneoplastic syndrome may manifest in the early and curable stage of cancer. Anti-Purkinje cell antibodies are the diagnostic marker for this entity, and an assay for these antibodies is commercially available. If the patient is a female who has not had oophorectomy and if the degenerative disorder is sporadic rather than clearly familial, additional screening for ovarian cancer is appropriate. Small cell cancer of the lung is also associated with this syndrome.

Vitamin E level: Although isolated vitamin E deficiency is exceedingly rare, the serum vitamin E level should be measured as part of the diagnostic workup.

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Imaging Studies

MRI is the imaging study of choice in patients with olivopontocerebellar atrophy (OPCA) because CT scanning does not provide adequate resolution of the pons and cerebellum. MRI typically shows (1) pancerebellar and brainstem atrophy, with flattening of the pons; (2) an enlarged fourth ventricle and cerebellopontine angle; and (3) demyelination of the transverse pontine fibers. This demyelination of the transverse pontine fibers is responsible for the "hot cross bun" sign, which is thought to be highly specific for multiple system atrophy.

In the first year after the onset of cerebellar symptoms in patients with OPCA, MRIs may be normal; therefore, serial MRI examinations are necessary for detecting infratentorial atrophy.

Brain MRI is also useful in patients presenting with spinocerebellar syndromes to exclude the diagnoses of multiple sclerosis, cerebrovascular disease, and malignancy.

MRI also permits visualization of pontine atrophy, which distinguishes OPCA from other forms of genetic ataxias, and presentations of multiple system atrophy that do not yet heavily involve the pons.

MR SPECT has been used in case reports and shows a decreased NAA/Cr ratio consistent with atrophy. The clinical use of this is not yet defined.[112]

Positron emission tomography (PET) scanning shows reduced metabolism in the brain stem and cerebellum. While this finding is of academic interest, PET scanning is not necessary for the diagnostic workup of a patient with OPCA, and the results do not distinguish subtypes of OPCA.

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Other Tests

Table 3 in Causes lists whether genetic tests are available for the particular SCA. At present, commercial tests are available for SCA-1 (OPCA-I and OPCA-IV), SCA-2 (OPCA-2), SCA-3 (Machado-Joseph disease, not an OPCA), SCA-7 (OPCA-III), SCA-8 (an ADCA-1 but not an OPCA), SCA-10 (an ADCA-3, not an OPCA), SCA-12 (not an OPCA), SCA-14 (not an OPCA), SCA-17 (may be OPCA-V), and DRPLA (not an OPCA). In addition, a research test may be available for some others, such as episodic ataxia type 1, which is a dominant ataxia that is not an OPCA. Table 3 also provides the relevant chromosome and literature reference to the gene involved.

Sleep studies reveal lack of rapid eye movement and stage IV sleep in patients with OPCA. Apneic periods have also been observed.

Nerve conduction studies reveal a sensory neuropathy greater than motor neuropathy.

Evoked potentials may be delayed, especially visual evoked potentials.

EEG may show diffuse slowing and background disorganization.

None of the studies mentioned is necessary for the diagnostic workup of every patient with a progressive spinocerebellar syndrome.

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Histologic Findings

Histologic findings vary among the subtypes of OPCA. The cerebellum shows predominant Purkinje cell loss. Sometimes, Purkinje cells are completely obliterated. Purkinje cell axon torpedoes are variably present. The molecular and granular layers are usually thin. The cerebellar white matter is depleted. The pons exhibits loss of transverse pontine fibers and pontine nuclei. Fibrous gliosis exists in the spaces created by the loss of fibers. Preolivary medullary fibers are reduced, and the arcuate nuclei may be so atrophic that they cannot be found. Some patients demonstrate olivary hypertrophy.

Degeneration of the dorsal columns and neuronal loss in the Clarke columns are present. In addition, dorsal root ganglia and anterior horn cells may be reduced.

Argyrophilic oligodendroglial cytoplasmic inclusions, which under light microscopy may resemble neurofibrillary tangles, are present in sporadic forms of OPCA. These typically contain alpha-synuclein.

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Staging

A staging system specific to OPCA is not available.

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Contributor Information and Disclosures
Author

Christina J Azevedo, MD Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center

Christina J Azevedo, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nestor Galvez-Jimenez, MD, MSc, MHA The Pauline M Braathen Endowed Chair in Neurology, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Kalpana Kari, MD; Syed T Arshad, MD; and Yash Mehndiratta, MD to the development and writing of this article.

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Table 1. Most Common OPCAs With Alternative Names
OMIM # OPCA Names Other Names Genetic Pattern Description
#164400 OPCA-1,



OPCA-I,



Menzel type OPCA



SCA-1,



SCA-I,



ADCA-1,



ADCA-I



Gene map locus 6p23 expanded (CAG)n trinucleotide repeat in the ataxin-1 gene (ATXN1; 601556); autosomal dominant; genetic test available Onset 30-40 years; ataxia, spasticity, dysarthria, ophthalmoplegia, slow saccades, nystagmus, optic atrophy, pyramidal tract signs; rare extrapyramidal signs; some have dementia; neuropathy occurs late[15]
#183090 OPCA-2 SCA-2, ADCA-I Gene map locus 12q24 expanded (CAG)n trinucleotide repeat in the gene encoding ataxin-2 (ATXN2; 601517); autosomal dominant; genetic test available Onset in 30s; ataxia, dysarthria, muscle cramps; slow saccades; ophthalmoplegia; peripheral neuropathy; dementia (some); no pyramidal or extrapyramidal features[16]
%258300 OPCA-II, Fickler-Winkler type OPCA Fickler-Winkler Syndrome Gene/biochemistry not known; autosomal recessive Adult-onset; cerebellar ataxia, albinism, impaired intellect; neurological impairments similar to OPCA-I but no involuntary movements or sensory loss[9, 17, 18]
#164500 OPCA-III, OPCA-3, OPCA with retinal degeneration ADCA-II, SCA-7, OPCA with macular degeneration and external ophthalmoplegia Gene locus 3p21.1-p12; expanded trinucleotide repeat in the gene encoding ataxin-7 (ATXN7; 607640); autosomal dominant; genetic test available Onset in mid 20s; initially pigmentary retinal degeneration then ataxia, dysarthria, ophthalmoplegia, slow saccades, pyramidal tract signs[16]
^ 164600 Number now obsolete; considered the same as # 164400 (see first row above) OPCA-IV, Schut-Haymaker type OPCA   Genetics unclear; glutamate dehydrogenase deficiency suspected in some; some cases may be linked to OPCA locus at chromosome 6p; may not be a pure genetic type; now thought to be same as OPCA-I (SCA-1) Adult-onset ataxia with involvement of cranial nerves IX, X, and XII[19]
164700 OPCA-V, OPCA-5, OPCA with dementia and extrapyramidal signs This may be the same as SCA-17 Autosomal dominant; genetic test available for SCA-17, but unclear if this is the same Cerebellar ataxia, rigidity, dementia; neuronal loss in cerebellum, basal ganglia, substantia nigra, olivary nuclei, cerebral cortex[20, 8]
%302500 OPCA-X, OPCA X-linked-1 SCA-X1 (do not confuse this with SAX-1, the locus for hereditary (autosomal dominant) spastic ataxia [%108600]) X-linked, some cases linked to Xp11.21-q21.3; not homogenous; gene(s) not known Onset in first or second decade and often bedbound by 20s; loss of cerebellar Purkinje cells, inferior olivary cells, myelin loss in spinocerebellar tracts, posterior columns, and corticospinal tracts; gait and limb ataxia, intention tremor, dysmetria, dysdiadochokinesia, dysarthria, and nystagmus; some have peripheral neuropathy[21, 22]
Table 2. Extremely Rare Types of OPCAs
OMIM # OPCA Names Other Names Genetic Pattern Description
%607596 Pontocerebellar hypoplasia type 1, PCH-1 Pontocerebellar hypoplasia with infantile spinal muscular atrophy, pontocerebellar hypoplasia with anterior horn cell disease Autosomal recessive Cerebellar hypoplasia plus motor neuron loss; sometimes called a combination of olivopontocerebellar degeneration plus spinal muscular atrophy; present from birth; patients usually die in infancy[23, 24]
%277470 Pontocerebellar hypoplasia type 2, PCH-2 Pontocerebellar hypoplasia with progressive cerebral atrophy, Volendam neurodegenerative disease Autosomal recessive Congenital microcephaly, extrapyramidal findings, epilepsy; autopsy in one case showed that the olivopontocerebellar system was the most heavily involved in degeneration
%608027 Pontocerebellar hypoplasia type, PCH-3, Pontocerebellar hypoplasia with optic atrophy Cerebellar atrophy with progressive microcephaly, CLAM Autosomal recessive; gene map locus 7q11-q21Gene map locus 7q11-q21 Onset in infancy or childhood, cerebellar atrophy with progressive microcephaly; on MRI of small brainstem, small cerebellar vermis and atrophy of the cerebellum and cerebrum; ataxia, truncal hypotonia, and exaggerated deep tendon reflexes; one patient had optic atrophy; seizures common[25]
225753 Pontocerebellar hypoplasia type 4, PCH-4 Fatal infantile encephalopathy with olivopontocerebellar hypoplasia Probably autosomal recessive, possibly autosomal dominant or maternal transmission; biochemical defect and gene locus not known Patients die in infancy; severe olivopontocerebellar hypoplasia on autopsy[26, 27]
610204 Pontocerebellar hypoplasia type 5, PCH-5 Olivopontocerebellar hypoplasia, fetal onset Genetics not clear Pontocerebellar hypoplasia is a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem with significant hypoplasia of the olivae, the pons, and the cerebellum; patients typically die in infancy[27]
#278800 De Sanctis-Cacchione syndrome   Gene map locus 10q11; an excision repair gene named variously ERCC6, CKN2, COFS, and CSB causing Cockayne syndrome type B (CSB; 133540) or genes of xeroderma pigmentosum, usually XPA (ie, complementation group A); 278700 9q22.3 or more rarely, other genes associated with xeroderma pigmentosum; autosomal recessive Xeroderma pigmentosum (severe sun sensitivity), mental retardation, dwarfism, and progressive neurological deterioration; overlaps with known types of xeroderma pigmentosum and Cockayne syndrome, especially XPA and CSB, apparently as allelic variants but other unknown factors may bring out the olivopontocerebellar (and cerebral) atrophy[28, 29, 30]
#212065 Congenital disorder of glycosylation, type Ia   Phosphomannomutase-2 (PMM2; 601785); autosomal recessive Severe congenital psychomotor retardation, generalized hypotonia, hyporeflexia, and trunk ataxia, neonatal-onset OPCA, peripheral neuropathy, retinitis pigmentosa; defects in other systems include heart and musculoskeletal systems; severe neonatal neurodegenerative disease; some patients have olivopontocerebellar phenotype; usually death in infancy or childhood[31, 32]
Table 3. Dominant SCAs with OPCAs Identified
Disease OMIM # Disease Names Locus GeneProduct (OMIM #) Description References
#164400 SCA-1, OPCA-I, OPCA-IV (OPCA-IV same as OPCA-I), ADCA-1 ATXN1, 6p23 CAG expansion repeat in N-terminal coding region of Ataxin-1 (*601556); Onset 30-40 years; ataxia, spasticity, dysarthria, ophthalmoplegia, slow saccades, nystagmus, optic atrophy, pyramidal tract signs; rare extrapyramidal; signs; some have dementia; neuropathy occurs late. Expansion repeat causes toxic gain of function via abnormally long ataxin-1. This worsens in subsequent generations. Menzel, 1891[33] ; Waggoner et al, 1938[34] ; Schut, 1950[35] ; Schut and Haymaker, 1951[19] ; Orr et al, 1993[36]



Donato et al. 2012[37]



#183090 SCA-2, OPCA-2, ADCA-1 ATXN2, 12q24 Ataxin-2 (601517); genetic test available Onset in 30s; ataxia, dysarthria, muscle cramps; slow saccades/ophthalmoplegia; peripheral neuropathy, hyporeflexia, dementia in some; no pyramidal or extrapyramidal features Boller and Segarra, 1969[38] ; Wadia and Swami, 1971[39] ; Ueyama et al, 1998[40]
#109150 SCA-3 or Machado-Joseph disease, ADCA-1 ATXN3, 14q24.3-q31 Machado-Joseph disease protein 1(ATXN3). (607047); genetic test available All have ataxia, dysarthria, ophthalmoplegia; type I onset in mid 20s with facial-lingual myokymia, pyramidal and extrapyramidal features; type II onset in 40s; type III onset in mid 40s with peripheral neuropathy (weakness and atrophy) Nakano et al, 1972[41] ; Kawaguchi et al, 1994[42]
%600223 SCA-4, ADCA-1 Gene unknown, 16q22.1 (same region as #117210 below)   Onset average approximately 40 years (range, 19-72 y); pure ataxia in some cases, most have sensory axonal neuropathy; deafness in some Gardner et al, 1994[43] ; Hellenbroich et al, 2003[44]
#117210 SCA, 16q22-linked ADCA-3 PLEKHG4, 16q22.1 Puratrophin-1 (609526) Typically pure cerebellar ataxia with gait ataxia, cerebellar dysarthria, limb ataxia, decreased muscle tone, horizontal-gaze nystagmus; lacks other feature seen in SCA-4, ADCA-1 (but sometimes called SCA-4) Ishikawa et al, 2005[45]
#600224 SCA-5, ADCA-3 SPTBN2, 11p13 Spectrin beta chain, brain 2 (604985) Onset mid 30s; downbeat nystagmus; ataxia, dysarthria, impaired smooth pursuit, and gaze-evoked nystagmus; slow progression; both vermal and hemispheric cerebellar atrophy, normal life expectancy Ikeda et al, 2006[46]
#183086 SCA-6, ADCA-1 ADCA-3 CACNA1A, 19p13 Voltage-dependent P/Q-type Ca+2 channel alpha-1a subunit (601011); genetic test available Onset 20-40 years; ataxia, dysarthria, nystagmus, distal sensory loss, normal life expectancy Subramony et al, 1996[47] ; Zhuchenko et al, 1997[48]
#164500 SCA-7, OPCA-3 ADCA-2 ATXN7, 3p21.1-p12 Ataxin-7 (607640); genetic test available Onset mid 20s; pigmentary retinal degeneration, ataxia, dysarthria, ophthalmoplegia, slow saccades, pyramidal tract signs David et al, 1997[49] ; Harding, 1982[7]
#608768 SCA-8, ADCA-2 KLHL1AS, 13q21 Genetic test available Onset 20s to 70s; ataxia, dysarthria, nystagmus, impaired smooth pursuit Koob et al, 1999[50] ; Ikeda et al, 2000[51] ; Factor et al, 2005[52] (Factor et al case was actually consistent with MSA)
  SCA-9 Unassigned category   Unassigned category Unassigned category
+603516 SCA-10 ADCA-3 ATXN10, 22q13 Ataxin-10; genetic test available Onset in 20s; ataxia, dysarthria, nystagmus, epileptic seizures; to date only found in Mexican families Grewal et al, 1998[53] ; Zu et al, 1999[54] ; Grewal et al, 2002[55]
%604432 SCA-11 SCA11, 15q14-q21.3 Tau-tubulin kinase 2 Onset at 20-40 years; ataxia, dysarthria, nystagmus Worth et al, 1999[56]
#604326 SCA-12 PPP2R2B, 5q31-q33 Serine/threonine protein phosphatase 2A, 55-kd regulatory subunit B, beta isoform; genetic test available Onset at 8-55 years, commonly 30s; upper extremity and head tremor, gait ataxia, ophthalmoplegia, hyperreflexia, bradykinesia, dementia Holmes et al, 1999[57] ; Fujigasaki et al, 2001[58]
#605259 SCA-13 KCNC3, 19q13.3-q13.4 Voltage-gated K+ channel, subfamily C member 3 Onset in childhood; ataxia, dysarthria, mental retardation; slow progression Waters et al, 2006[59]
#605361 SCA-14 PRKCG, 19q13.4 Kinase C, gamma type; genetic test available Onset mostly in most those older than 39 years; ataxia, dysarthria, nystagmus; younger patients (< 27 y) also had intermittent axial myoclonus prior to ataxia Yamashita et al 2000[60] ; Brkanac, Bylenok et al 2002[61] ; Chen, Brkanac et al 2003[62] ; Yabe et al 2003[63]
%606658 SCA-15 Gene unknown, 3p26.1-p25.3 Inositol 1,4,5-triphosphate receptor type 1 Similar to SCA-6 and SCA-8; MRI-proven cerebellar atrophy; onset at 10-50 years; slowly progressive pure cerebellar ataxia, ataxic dysarthria, tremor; may have head titubation, nystagmus, oculovestibular reflex abnormalities, mild hyperreflexia (no spasticity or Babinski signs) Storey et al, 2001[64] ; Knight et al, 2003[65] ; Hara et al, 2004[66]
%606364 SCA-16 SCA16, 8q22.1-q24.1 Contactin-4 MRI-proven cerebellar atrophy without brainstem involvement; onset at 20-66 years; pure cerebellar ataxia, some with head tremor, slow progression Miyoshi et al, 2001[67]
#607136 SCA-17, may be OPCA-5 TBP, 6q27 TATA-box–binding protein; genetic test available Onset at 3-55 years; ataxia and involvement of pyramidal, extrapyramidal, and, possibly autonomic system; intellectual impairment, dementia, psychosis, chorea; presentation similar to Huntington disease; degeneration of caudate, putamen, thalamus, frontal cortex, temporal cortex, and cerebellum Nakamura et al, 2001[68] ; Rolfs et al, 2003[69] ; Maltecca et al, 2003[70]
%607458 SCA-18 SCA18 7q22-q32   Onset in teens, 20s, and 30s; sensorimotor neuropathy with ataxia; gait abnormality, dysmetria, hyporeflexia, muscle weakness and atrophy, axonal neuropathy, decreased vibratory and proprioceptive sense Brkanac et al, 2002[71]
%607346 SCA-19 1p21-q21   Onset at 12-40 years; gait and limb ataxia, hyporeflexia, dysphagia, dysarthria, and gaze-evoked horizontal nystagmus; cerebellar atrophy on MRIs Schelhaas et al, 2001[72] ; Verbeek et al, 2002[73] ; Chung et al, 2003[74] ; Schelhaas et al, 2004[75]
%608687 SCA-20 SCA20, 11p13-q11   Onset at 19-64 years; dysarthria, gait ataxia, upper limb, slow progression; more variable features are mild pyramidal signs, hypermetric saccades, nystagmus, palatal tremor, slow cognitive decline; CT scan shows dentate calcification Knight et al, 2004[76]
%607454 SCA-21 SCA21, 7p21-15   Onset at 6-30 years; cerebellar ataxia, limb ataxia and akinesia, dysarthria, dysgraphia, hyporeflexia, postural tremor, resting tremor, rigidity, cognitive impairment, cerebellar atrophy Devos et al, 2001[77] ; Vuillaume et al, 2002[78]
%607346 SCA-22 1p21-q21   Now believed to be identical to SCA-19 (Schelhaas et al, 2004[75] ) though Chung et al (2004)[74] dispute this Schelhaas et al, 2001[72] ; Verbeek et al, 2002[73] ; Chung et al, 2004[74] ; Schelhaas et al, 2004[75]
%610245 SCA-23 20p13-12.3   Onset at 40s and 50s; slow progression; gait and limb ataxia, dysarthria (varies), slow saccades and ocular dysmetria, decreased vibratory sense; severe cerebellar atrophy Verbeek, et al, 2004[79]
%608703 SCA-25 SCA25, 2p21-p13   Onset in childhood; invariable features are cerebellar ataxia; variable features are lower limb areflexia, peripheral sensory neuropathy, nystagmus, decreased visual acuity, facial tics, extensor plantar responses, urinary urgency, and gastrointestinal symptoms Stevanin et al, 2004[80]
%609306 SCA-26 19p13.3   Onset t 25-60 years; pure cerebellar signs, including ataxia of the trunk and limbs, dysarthria, and irregular visual pursuit movements; intelligence normal; MRI shows atrophy of cerebellum, sparing pons and medulla Yu et al, 2005[81]
#609307 SCA-27 FGF14, 13q34 Fibroblast growth factor 14 (601515) Onset in childhood; cerebellar ataxia, tremor, low IQ, aggressive behavior, eye movement abnormalities are nystagmus, cerebellar dysarthria, head tremor, orofacial dyskinesias, cerebellar atrophy, pes cavus, axonal sensory neuropathy, neuronal loss in cerebral cortex, amygdala, and basal ganglia van Swieten et al, 2003[82]
%610246 SCA-28 18p11.22-q11.2 AFG3-like protein 2 Onset at 19.5 years (range, 12-36 y); imbalance and mild gait incoordination; gaze-evoked nystagmus, slow saccades, ophthalmoparesis, and, often, ptosis; frequently lower limb hyporeflexia Cagnoli et al, 2006[83]
#125370 Dentatorubral-pallidoluysian atrophy (DRPLA) DRPLA, 12p13.31 Atropin-1–related protein (607462); genetic test available Onset in 20s to 30s; myoclonic epilepsy, dementia, ataxia, choreoathetosis, degeneration of dentatorubral and pallidoluysian systems Naito and Oyanagi, 1982[84] ; Koide et al, 1994[85]
#160120 Episodic ataxia type 1, EA-1 KCNA1, 12p13 K+1 voltage-gated channel (A1) (600111); genetic test available on research basis Onset usually in childhood; continuous muscle movement (myokymia) and periodic ataxia Van Dyke et al, 1975[86] ; Hanson et al, 1977[87] ; Gancher and Nutt, 1986[88] ; Browne et al, 1994[89] ; Brandt and Strupp, 1997[90] ; Eunson et al, 2000[91]
#108500 Episodic ataxia type 2, EA-2 CACNA 1A, 19p13 Voltage-dependent P/Q-type Ca+2 channel alpha-1A subunit (601011); genetic test available on research basis Onset in childhood; ataxia, downbeating nystagmus dizziness treated with acetazolamide; no progression after childhood; cerebellar atrophy Parker, 1946[92] ; White, 1969[93] ; Subramony et al, 2003[94] ; Spacey et al, 2005[95] ; Imbrici et al, 2005[96]
%606554 Episodic ataxia type 3, EA-3 1q42 Unknown Onset at 1-42 years; vestibular ataxia, vertigo, tinnitus, interictal myokymia Steckley et al, 2001[97] ; Cader et al, 2005[98]
%606552 Episodic ataxia type 4, EA-4 Unknown Unknown Onset in third to sixth decade; recurrent attacks of vertigo, diplopia, and ataxia; slowly progressive cerebellar ataxia in some; periodic vestibulocerebellar ataxia in an autosomal dominant pedigree pattern, defective smooth pursuit, gaze-evoked nystagmus, ataxia, vertigo Farmer and Mustian, 1963[99] ; Vance et al, 1984[100] ; Damji et al, 1996[101]
+601949 Episodic ataxia type 5, EA-5 CACNB 4, 2q22-q23 Voltage-dependent L-type calcium beta-4 subunit (+601949) Onset in third or fourth decade; mutation at C104F in French-Canadian family; ataxia similar to EA-2; severe episodic lasting hours to weeks; treatment with acetazolamide; interictal ataxia includes gait and truncal, mild dysarthria; nystagmus (downbeat, spontaneous, gaze evoked); seizures Escayg et al, 1998[102] ; Escayg et al, 2000[103] ; Herrmann et al, 2005[104]
%601042 Choreoathetosis spasticity, episodic, CSE 12p13 (close to potassium channel gene KCNA1 but not the same) Unknown Onset at 2-15 years; paroxysmal choreoathetosis with episodic ataxia and spasticity Auburger et al, 1996[105] ; Müller et al, 1998[106]
%108600 Hereditary (autosomal dominant) spastic ataxia SAX1, 12p13 Unknown Onset at 10-20 years; lower limb spasticity, generalized ataxia with dysarthria, dysphagia, impaired ocular movements, gait abnormalities; brain and cord MRIs normal; neuropathology shows midbrain neuronal loss Ferguson and Critchley, 1929[107] ; Gayle and Williams, 1933[108] ; Mahloudji, 1963[109] ; Meijer et al, 2002[110] ; Grewal et al, 2004[111]
Table 4. Dominant Ataxia Nomenclature
SCAs SCA-1 SCA-2 SCA-3 SCA types 8, 12, 17, 25, 27, 28, (13) SCA-7 SCAs 4, 5, 6, 10, 11, 14, 15, 22, 26, (13)
OPCAs OPCA-1, OPCA-IV OPCA-2 No OPCA matching SCA-3 No OPCA matching above SCAs OPCA-III No OPCA matching above SCAs
ADCAs ADCA-1 ADCA-1 ADCA-1 ADCA-1 ADCA-2 ADCA-3
Eponyms Menzel type OPCA (or Menzel ataxia), Schut- Haymaker type OPCA, Dejerine-Thomas ataxia Holguin type ataxia, Wadia-Swami syndrome, Dejerine-Thomas ataxia Machado-Joseph disease, Dejerine-Thomas ataxia Dejerine-Thomas ataxia Sanger-Brown ataxia§, Dejerine-Thomas ataxia Holmes ataxiall, ataxia of Marie, Foix, and Alajouanine, Marie ataxia, Nonne syndrome#
*SCA-13 is often said to not be part of ADCA classification. It is mainly a childhood mental retardation/ataxia syndrome. The ataxia is not accompanied by significant brainstem pathology, similar to ADCA-3. The mental retardation can be interpreted as a dementia, putting it in ADCA-1.



OPCA-IV (Schut-Haymaker OPCA) is now thought to be an SCA-1, which makes it OPCA-I (ie, strictly speaking, OPCA-IV no longer exists).



Menzel OPCA is sometimes taken much more broadly as virtually any OPCA except perhaps OPCA-III. Alternatively, it is taken as essentially the same as ADCA-1. In addition, it is sometimes applied to sporadic OPCAs that have similar presentations to any of the syndromes under ADCA-1.



§ Sanger-Brown ataxia is sometimes taken more broadly. As expansively defined, the term could be used for virtually any of these.



ll Holmes ataxia is sometimes applied to pure sporadic cerebellar ataxia of late onset.



This is sometimes used for most any of these syndromes, which seems to be the sense in which it was used in the original 1893 paper by Marie.



# This is a very obscure term. It is most commonly used for conditions fitting ADCA-3.



**The authors found no papers calling SCA-3 Dejerine-Thomas ataxia, but Dejerine-Thomas ataxia is so broadly defined, the term could possibly be applied to SCA-3.



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