Medical Care

Care of olivopontocerebellar atrophy (OPCA) is directed to the treatment of symptoms.

Dopaminergic agents, such as levodopa, bromocriptine, or amantadine, have shown minimal benefit.
Propranolol has been used for tremor, but the clinical response is generally minimal.
Related to the fact that serotonin 5-hydroxytryptophan (5HT) 1-A receptor agonists modulate the serotonergic motor output from the cerebellum, a few small studies have focused on 5HT 1-A receptor agonists, such as tandospirone or buspirone, as a treatment for ataxia. Several such studies have indicated that such medications may produce modest improvement in ataxia caused by various neurodegenerative conditions, including OPCA.^{[121, 122]}
Another small trial concluded that buspirone is ineffective.^[123]
It had also been hypothesized that estrogen might potentiate the 5-HT1A effect because it is neuroprotective of the nigrostriatal system in some animal models.^{[124, 125, 126]}It also appears to have a beneficial effect on the dopamine transporter.^[127]Therefore, investigators undertook a trial of 18 patients to study the effect of combined estrogen and buspirone therapy for OPCA. Both groups showed significant improvements in finger-to-nose and rapid alternating movements at 1 month; however, at 12 months (which was the end of the study), there was no statistically significant improvement in any test of cerebellar function. Indeed, there was no evidence that the benefits lasted longer than 3 months. There were trends toward improvement in dysarthria, heel-to-shin testing, and gait speed. No benefit was seen by adding estrogen.^[128]
A small, brief randomized, double-blind pilot study of patients with cerebellar ataxia of different etiologies assessed the responses of 20 patients given riluzole versus 20 patients given a placebo. Assessment at 4 and 8 weeks showed Class I evidence that riluzole reduced the International Cooperative Ataxia Rating Scale (ICARS) score by at least 5 points.^[129]The authors stated their belief that riluzole should now be tested in larger and longer studies. Also needed are studies that use more homogenous patient groups.
Supportive care with gait-assisting devices is especially important to minimize falls.

Surgical Care

At times, olivopontocerebellar atrophy (OPCA) patients may require enteral feeding to decrease the risk of aspiration.

Percutaneous endoscopic gastrostomy and jejunostomy tube (J-tube) placement may be necessary.

Consultations

Consultations with physical and occupational therapists are helpful to increase mobility of patients with olivopontocerebellar atrophy (OPCA); the use of assistive devices can significantly increase functional ability. A case study using progressively more challenging static and dynamic balance tasks over a 12-week period produced significant improvement in balance in a patient with proven OPCA.^[130]A swallowing evaluation can be a very important part of the early consultation.

Now that genetic testing is available, it can be performed to confirm the diagnosis of autosomal dominant OPCAs. These patients may not develop symptoms until after the onset of their reproductive years; therefore, family members must be evaluated early if a diagnosis of autosomal dominant OPCA is made. Referral for genetic counseling is advisable in these individuals. Not all patients wish to learn of their risks in the absence of an available treatment, while some individuals may use the information for family planning and other types of planning for the future.

Diet

As dysphagia progresses with olivopontocerebellar atrophy (OPCA), a pureed diet or enteral feeding may be required.

Activity

Activity in patients with olivopontocerebellar atrophy (OPCA) should be allowed ad libitum; however, appropriate measures should be used to minimize falls.

Medication

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Axial T2 brain shows hyperintensity signals within pons ("hot cross bun" sign).
Axial T2 weighed shows putaminal hyposignal intensity with hypersinal intensity rim.

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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^[20]
#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^[21]
%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^{[10, 22, 23]}
#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^[21]
^ 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^[24]
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^{[25, 9]}
%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^{[26, 27]}

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^{[28, 29]}
%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^[30]
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^{[31, 32]}
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^[32]
#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^{[33, 34, 35]}
#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^{[36, 37]}

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^[38]; Waggoner et al, 1938^[39]; Schut, 1950^[40]; Schut and Haymaker, 1951^[24]; Orr et al, 1993^[41] Donato et al. 2012^[42]
#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^[43]; Wadia and Swami, 1971^[44]; Ueyama et al, 1998^[45]
#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^[46]; Kawaguchi et al, 1994^[47]
%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^[48]; Hellenbroich et al, 2003^[49]
#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^[50]
#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^[51]
#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^[52]; Zhuchenko et al, 1997^[53]
#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^[54]; Harding, 1982^[8]
#608768	SCA-8, ADCA-2	KLHL1AS, 13q21	Genetic test available	Onset 20s to 70s; ataxia, dysarthria, nystagmus, impaired smooth pursuit	Koob et al, 1999^[55]; Ikeda et al, 2000^[56]; Factor et al, 2005^[57](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^[58]; Zu et al, 1999^[59]; Grewal et al, 2002^[60]
%604432	SCA-11	SCA11, 15q14-q21.3	Tau-tubulin kinase 2	Onset at 20-40 years; ataxia, dysarthria, nystagmus	Worth et al, 1999^[61]
#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^[62]; Fujigasaki et al, 2001^[63]
#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^[64]
#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^[65]; Brkanac, Bylenok et al 2002^[66]; Chen, Brkanac et al 2003^[67]; Yabe et al 2003^[68]
%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^[69]; Knight et al, 2003^[70]; Hara et al, 2004^[71]
%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^[72]
#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^[73]; Rolfs et al, 2003^[74]; Maltecca et al, 2003^[75]
%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^[76]
%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^[77]; Verbeek et al, 2002^[78]; Chung et al, 2003^[79]; Schelhaas et al, 2004^[80]
%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^[81]
%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^[82]; Vuillaume et al, 2002^[83]
%607346	SCA-22	1p21-q21		Now believed to be identical to SCA-19 (Schelhaas et al, 2004^[80]) though Chung et al (2004)^[79]dispute this	Schelhaas et al, 2001^[77]; Verbeek et al, 2002^[78]; Chung et al, 2004^[79]; Schelhaas et al, 2004^[80]
%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^[84]
%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^[85]
%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^[86]
#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^[87]
%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^[88]
#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^[89]; Koide et al, 1994^[90]
#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^[91]; Hanson et al, 1977^[92]; Gancher and Nutt, 1986^[93]; Browne et al, 1994^[94]; Brandt and Strupp, 1997^[95]; Eunson et al, 2000^[96]
#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^[97]; White, 1969^[98]; Subramony et al, 2003^[99]; Spacey et al, 2005^[100]; Imbrici et al, 2005^[101]
%606554	Episodic ataxia type 3, EA-3	1q42	Unknown	Onset at 1-42 years; vestibular ataxia, vertigo, tinnitus, interictal myokymia	Steckley et al, 2001^[102]; Cader et al, 2005^[103]
%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^[104]; Vance et al, 1984^[105]; Damji et al, 1996^[106]
+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^[107]; Escayg et al, 2000^[108]; Herrmann et al, 2005^[109]
%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^[110]; Müller et al, 1998^[111]
%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^[112]; Gayle and Williams, 1933^[113]; Mahloudji, 1963^[114]; Meijer et al, 2002^[115]; Grewal et al, 2004^[116]

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 ataxia^ll, 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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Author

Sombat Muengtaweepongsa, MD, MSc Professor, Center of Excellence in Stroke, Associate Dean for Research and Innovations, Department of Neurology, Faculty of Medicine, Thammasat University, Thailand

Sombat Muengtaweepongsa, MD, MSc is a member of the following medical societies: American Academy of Neurology, Royal College of Physicians of Thailand

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Boehringer Ingelheim; Astra Zeneca; Novo Nordisk; Daiichi Sankyo; Bayer<br/>Received research grant from: Faculty of Medicine, Thammasat University.

Coauthor(s)

Praween Lolekha, MD, MSc Assistant Professor of Medicine, Division of Neurology, Department of Medicine, Faculty of Medicine, Thammasat University, Thailand

Praween Lolekha, MD, MSc is a member of the following medical societies: International Parkinson and Movement Disorder Society, Medical Association of Thailand, Medical Council of Thailand, Movement Disorder Society, Neurological Society of Thailand, Royal College of Physicians of Thailand, Thai Parkinson Disease - Movement Disorders Society

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 Morsani College of Medicine

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

Additional Contributors

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.

Christina J Azevedo, MD Assistant Professor of Clinical Neurology, Department of Neurology, Keck School of Medicine of the University of Southern California

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

Disclosure: Nothing to disclose.

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.