Olivopontocerebellar Atrophy Clinical Presentation

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

  • Dysphagia and dysarthria (and occasionally anarthria) are common manifestations of OPCA.
  • Respiratory stridor from vocal cord paralysis has been reported.
  • Dementia can appear at any age; it is especially common later in the disease.
  • Urinary incontinence occurs late in the course of the disease.
  • Sleep disturbances are common in persons with OPCA. [160]


Generally, cerebellar signs and extrapyramidal signs are the predominant signs of OPCA. In addition, peripheral neuropathy is common. Ophthalmoplegia, retinopathy, and parkinsonism may be present.

Typically, the clinical manifestations of OPCA consist of a slowly progressive pancerebellar syndrome that usually begins in the lower extremities and then progresses to the upper extremities and the bulbar musculature. Usually, the initial sign in OPCA is a broad-based cerebellar ataxic gait. A parkinsonian gait is a less common but recognized variant.

Cerebellar dysarthria is also common. The patient's speech has a poorly modulated and slurred quality, similar to that of a person intoxicated with alcohol. Other cerebellar findings include nystagmus, dysmetria on finger-to-nose testing, and ataxia on heel-to-shin testing.

The entire spectrum of cerebellar ocular motility disorders can occur in persons with OPCA. Nystagmus, slow saccades, and abnormal fundoscopic examination findings are present in varying degrees. Hyperactive vestibulo-ocular reflex also has been reported. In some cases, limitation of extraocular movements, particularly of upward gaze, is also present. This nuclear or supranuclear ophthalmoplegia occurs more frequently in familial OPCA than in sporadic OPCA. Retinal degeneration may be present.

Parkinsonian symptoms with cogwheel rigidity, bradykinesia, and tremor may be the predominant picture in some cases of OPCA. In these cases, distinguishing OPCA from Parkinson disease may be difficult.

The pyramidal finding that is most uniformly present is a bilateral extensor plantar response. Hyperactive deep tendon reflexes and spasticity due to pyramidal tract dysfunction are present early in the course of the disease. These are often lost later, especially the ankle jerks, as part of a concomitant peripheral neuropathy.

Position sense and vibratory function are reduced secondary to neuropathy.

The clinical presentation may vary among the subtypes of OPCA. It includes the following:

  • Abnormal movements are more frequent in familial OPCA. Abnormal movements may include myoclonus, spasmodic torticollis, chorea, and athetosis.
  • Nonpyramidal signs, such as amyotrophy, fasciculations, peripheral neuropathy, lightning pains, and pes cavus, are more common in sporadic OPCA than familial OPCA.
  • Autonomic failure is often seen, especially if sensitive methods of detection such as heart rate variability analysis are used. Severe autonomic impairment is more common in sporadic OPCA, which frequently evolves to a full-blown MSA.

Postural hypotension may predominate among the clinical features.



A unifying etiology of OPCA has not been established. [159] In the sporadic cases, abnormalities of alpha-synuclein (which is found as inclusion bodies in degenerating neurons) appear to play a significant role. In any of the inherited cases, specific genes have been identified, although in most cases the precise way in which the genes exert a pathological influence is not known. Many of the abnormal genes are of the expansion repeat variety. For example, in OPCA-I (or SCA-1), the SCA1 gene is on chromosome 6. It is a triple nucleotide repeat, with age of onset correlating with the length of repeat. The SCA2 gene is on chromosome 12.

To clarify the subtypes of the genetically determined OPCAs, the authors have placed them in tables. Table 1 below contains the most common types. Although the table is largely self-explanatory, a few points should be emphasized. The genetic OPCAs are now, at best, a subordinate category. Many neurogeneticists would say they are an obsolete category.

Where an OPCA represents a known mutation, it does do so because it is identified with a specific SCA (in the case of dominant mutations) or another specific genetically defined disease. For example, OPCA-IV was not previously genetically defined. However, OPCA-IV is now believed to be genetically the same as SCA-1. OPCA-I has also been found to be the same as SCA-1. Thus, no real distinction can now be made between OPCA-I, OPCA-IV, and SCA-1, except perhaps that in the historical cases of these syndromes, some differences existed in the phenotypic presentations of the same underlying disease.

Note also in the table that OPCA-2 and OPCA-II are not the same. This is unusual because for the other numbered OPCAs, the Arabic and Roman numbers can be used interchangeably. OPCA-2 is identical to SCA-2 and is autosomal dominant. OPCA-II, sometimes called Fickler-Winkler syndrome, is autosomal recessive and its gene is unknown. Separating the 2 types by using an Arabic 2 and a Roman II is not fully standard, and some books speak of the dominant versus recessive OPCA-2 (OPCA-II). Despite their similar names, the phenotypes are not very similar. In this text, Roman numerals are used for the OPCA types, with the exception of OPCA-X, which means X-linked OPCA, not OPCA type 10.

In the organization of the table, the first column contains the Online Mendelian Inheritance in Man number (OMIM#). The OMIM catalog was developed by Dr Victor McKusick and his colleagues at Johns Hopkins University, and the OMIM Web site is hosted by the US National Center for Biotechnology Information (NCBI) on what is essentially the same Web site as PubMed.

In the table, both the OPCA specific names and other names for each condition are listed; also listed is the genetic pattern, including the mode of Inheritance, the locus (including the chromosomal region and the names of the gene and protein if available), and a concise description of the condition.

Table 1. Most Common OPCAs With Alternative Names (Open Table in a new window)

OMIM # OPCA Names Other Names Genetic Pattern Description
#164400 OPCA-1,


Menzel type OPCA





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]

In addition to what are considered the standard types of OPCA, some types are even rarer and more obscure. These are pediatric disease in which involvement of the cerebellum, pons, and the region of the inferior oliva is noted. They are not what most neurologists think of when they use the term OPCA. The only reason they are listed here is because the reader may encounter these and see them referred to as infantile OPCA or some variant thereof.

Table 2. Extremely Rare Types of OPCAs (Open Table in a new window)

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]

Although Table 1 gives the SCA equivalent for the OPCAs, many neurology residents have asked to see a table showing how the OPCAs fit into the larger SCA category. Table 3 gives that framework and the OPCAs are identified in the larger context.

Table 3. Dominant SCAs with OPCAs Identified (Open Table in a new window)

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]

Finally, the question of how the OPCAs and SCAs fit with the 2 other systems of terminology is addressed: (1) the ADCAs and (2) the individual eponyms that honor the various physicians from the past who described the conditions that are now better (though still imperfectly) understood today.

Table 4 shows these correspondences. The first row consists of the SCAs because these represent the most accurate and finely divided category. The reader can then go down each column and find the ADCA number, the OPCAs, and the individual eponyms that are essentially equivalent.

In using this table, realize that all of these terms have been used inconsistently through the years. The SCAs are most closely linked to the actual genes involved. Although the ADCAs, with only 3 categories, represent a rather coarse division of these conditions, their phenotypic descriptions are rather simple and they have generally been used consistently in those cases in which they have been used. The use of the OPCA terms for diagnosis has been less consistent and it has been common to use the designation OPCA somewhat loosely. Finally, the eponyms have not been used very consistently, with the exception of Machado-Joseph disease (SCA-3) (which is not an OPCA). Thus, as one moves down the columns in the table, the names become less reliable.

The authors recommend against using the eponyms for fresh diagnoses. The ADCA and OPCA categories may be helpful for formulating ideas about the diagnosis, but one should try to think in terms of the SCA system in order to more readily connect the patient to a proper genetic diagnosis.

Table 4. Dominant Ataxia Nomenclature (Open Table in a new window)

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
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.