Has anyone heard of olivopontocerebellar degeneration?

Question

My grandfather was just recently diagnosed with olivopontocerebellar degeneration. Does anyone out there know a friend or family member who has this disease?

Answer 1

Olivopontocerebellar atrophy is a neurodegenerative illness that causes certain brain areas (which may include the olivary nucleus, the pons, and the cerebellum) to shrink.

Answer 2

Olivopontocerebellar Degeneration

Answer 3

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Answer 4

1

Answer 5

basic info. on OPCD:
http://www.thedoctorslounge.net/neurology/diseases/opcd.htm

A more in-depth article from eMedicine.com:
http://www.emedicine.com/NEURO/topic282.htm

Answer 6

I do not have anyone that has olivopontocerebellar degeneration
but found this information I hope it helps and my prayers are with your grandfather.




Olivopontocerebellar Atrophy
Last Updated: October 18, 2006

Synonyms and related keywords: spinocerebellar ataxia, SCA, OPCA, ataxia, multiple system atrophy, MSA, autosomal dominant cerebellar atrophy, ADCA, Menzel OPCA, Menzel ataxia, Schut-Haymaker OPCA, Schut-Haymaker ataxia, Dejerine-Thomas ataxia, Holguin ataxia, Wadia-Swami syndrome, Sanger-Brown ataxia, Holmes ataxia, Marie ataxia, Nonne syndrome, ataxia of Holmes



Author: Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center

Coauthor(s): Syed Arshad, MD; Kalpana Kari, MD, Staff Physician, Department of Neurology, Veterans Affairs Medical Center, Georgetown University; Yash Mehndiratta, MD, Assistant Professor, Department of Neurology, Howard University Hospital

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

Editor(s): Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Nestor Galvez-Jimenez, MD, Program Director of Movement Disorders, Director of Neurology Residency Training Program, Department of Neurology, Division of Medicine, Cleveland Clinic Florida; Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida College of Medicine; and Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants

Disclosure




Background: Doctors who study olivopontocerebellar atrophy (OPCA) quickly learn that it is not a single entity. Its nosology is confusing. The OPCA classification system overlaps with those for the autosomal dominant spinocerebellar atrophies (SCAs) and the autosomal dominant cerebellar atrophies (ADCAs), which, in turn, overlap with each other. Nondominant hereditary cases, including recessive and X-linked types, are also described. Finally, sporadic cases of OPCA have been reported, at least some of which are a subset of multiple system atrophy (MSA). No wonder the subject is confusing.

Good reasoning, however, is behind the complexity. The study of the neurodegenerative ataxias, of which the OPCAs are a part, has continually drawn from the exciting interplay between clinical observations, neuropathological analysis, and, more recently, biochemistry and molecular genetics. Initially, clinical observation combined with pathology were the dominant methods of carving out disease entities from the welter of clinical observations. The first ataxia to emerge was not an OPCA, but Friedreich ataxia (Friedreich, 1863), which Nicolaus Friedreich (1825-1882) managed to separate from numerous other conditions, including especially multiple sclerosis (then called disseminated sclerosis) and neurosyphillis.

Thirty years later, Pierre Marie described another grouping of hereditary cerebellar ataxias (Marie, 1893). In essence, he proposed a classification to include all the non-Friedreich ataxia cases and suggested the name "heredoataxia cerebelleuse.” This included what is now termed the OPCAs and several other varieties. In some families, the ataxia was either totally or almost totally cerebellar. These would currently not be considered OPCA cases. Other families had different features, including brainstem and/or spinal cord involvement, peripheral neuropathies, or retinal problems. Some of these would be termed OPCAs based on later standards.

In 1907, Holmes described a family with a pure cerebellar form of ataxia and the term Holmes ataxia or ataxia of Holmes was born and stuck to this category for decades. Later (1922), Marie, Foix, and Alajouanine reported a similar family that probably had the same disease. Thus, both Holmes ataxia and the ataxia of Marie, Foix, and Alajouanine are pure cerebellar ataxias. Neither would be considered a type of OPCA. Sometimes, the term Marie ataxia is also used interchangeably with ataxia of Marie, Foix, and Alajouanine to designate a pure cerebellar ataxia. In other cases, Marie ataxia may refer to a member of the larger group from the 1893 paper, and, in this case, it may refer to an OPCA. As used in practice, the term has generally been ambiguous.

In 1900, Dejerine and Thomas identified cases that combined purely cerebellar problems with evidence of brainstem pathology. They coined the term OPCA. The name was accepted by the neurological community, and many cases were collected under this rubric. Gradually, researchers realized that both sporadic and hereditary (mostly autosomal dominant) cases comprised this group, and, broadly speaking, the neuropathology typically showed degeneration of the cerebellum with extensive cerebellar white matter degeneration. Major neuronal loss occurs in the inferior olivary nuclei and the pontine and arcuate nuclei. Actual Purkinje cell loss in the cerebellum is also common but is more variable. The white matter loss is probably due to dying back of axons from the degenerating neurons rather than a primary attack on myelinated tracts.

Menzel (1890) also had described a similar case. Through the years, both Dejerine-Thomas ataxia and Menzel ataxia have been used as terms for certain cases of either hereditary or sporadic OPCA.

Disputes in the clinic, on paper, and in conferences have occurred about the usage of these terms, such as fine distinctions between Menzel ataxia and ataxia of Dejerine-Thomas, but they are mainly now of historical interest only. OPCA type 1 (OPCA-I), to be described below, is synonymous with SCA type 1 (SCA-1) and is sometimes referred to as Menzel type ataxia. Dejerine-Thomas ataxia might be used for any of the 6 major phenotypic OPCAs, which are better defined below. However, the authors recommend against applying either of these terms to any new cases of ataxia. These terms are mentioned here only so that the reader may understand where they came from if they are encountered in other (hopefully much older) literature.

Over time, other genetic syndromes were also elucidated, such as ataxia-telangiectasia, originally described by Syllaba and Henner in 1926, who reported 3 adolescent siblings with progressive ataxia, choreoathetosis, and ocular telangiectasia. This syndrome was examined clinicopathologically by Boder and Sedgwick in 1957, who named it ataxia-telangiectasia. This is not an OPCA.

In 1954, Greenfield proposed a new clinicopathological classification, as follows:

* Type 1 - Predominantly spinal and includes Friedreich ataxia, abetalipoproteinemia, and hereditary spastic paraparesis

* Type 2 - Predominantly cerebellar and includes ataxia-telangiectasia, late-onset cerebellar atrophy (Holmes type), and Marinesco-Sjögren-Garland disease (Mendelian Inheritance in Man [MIM] #248800; cerebellar dysfunction, congenital cataracts, and mental retardation)

* Type 3 - Combined spinocerebellar plus other parts of the neuroaxis such as the brainstem; includes the OPCAs, hereditary spastic ataxia, Ramsay Hunt syndrome, and hereditary periodic ataxia

This classification embraced a mixture of genetic modes of transmission. The Greenfield categorization was elaborated in 1982 by Harding, who used a combination of anatomical, pathological, and biochemical approaches; at the time, it was considered very advanced and up-to-date. As applied to the purely dominant ataxias, this produced the ADCA classification, as follows:

* Type 1 ADCA (ADCA-1) - Ataxia and noncerebellar findings (eg, pyramidal or extrapyramidal dysfunction and ophthalmoplegia)

* Type 2 ADCA (ADCA-2) - Similar to ADCA-1 but includes retinal degeneration

* Type 3 ADCA (ADCA-3) - Includes relatively pure cerebellar dysfunction

In the ADCA grouping, the OPCAs are found in ADCA-1 and ADCA-2.

Harding was well aware that this was essentially a phenotypic grouping that lumped a number of different genetic diseases into 3 classes. However, the system was very valuable for further genetic and other scientific work, in which Harding herself has been a significant contributor.

Working on a somewhat separate but related track, in 1970, Konigsmark and Weiner attempted to bring some order to the heterogeneity found among the OPCAs. The proposed classification was based on clinical, genetic, and anatomic factors, as follows:

* OPCA-I (Menzel-type OPCA) - Autosomal dominant

* OPCA type 2 (OPCA-II or Fickler-Winkler type OPCA) - Autosomal dominant

* OPCA type 3 (OPCA-III or OPCA with retinal degeneration) - Autosomal recessive

* OPCA type 4 (OPCA-IV or Schut-Haymaker type OPCA) - Autosomal dominant

* OPCA type 5 (OPCA-V or OPCA with dementia and extrapyramidal signs - Likely autosomal dominant

* OPCA type X (OPCA-X) - X-linked OPCAs (added to classification at later date)

These are detailed in Table 1.

In 1974, Skre studied the hereditary ataxia diseases in western Norway and chose to consider all these disorders as members of a comprehensive group of diseases termed spinocerebellar ataxias. This classification then evolved in the classification of SCAs. According to Paulson and Ammache from 2001, it includes all well-understood types of dominant OPCA and many other dominant ataxias. Geneticists sometimes state that the OPCA classification has been replaced by the SCA classification. This does not mean that every currently defined SCA is also an OPCA. The SCAs that could typically be considered to be an OPCA are SCA types 1, 2, 3, 7, and possibly 17.

In addition to these major forms, which might be called the traditional or classic OPCAs, some extremely rare diseases also involve degeneration of the same, or very similar, anatomical regions. These are mainly infantile or childhood diseases. They are not what neurologists (even pediatric neurologists) usually call OPCAs. However, occasionally in the literature, they are called infantile OPCAs and thus they are included in Table 2.

Table 3 lists a large number of the known SCAs (no table of such diseases is ever totally up-to-date for long), and those that can be reasonably identified as OPCAs are noted.

Finally, the sporadic OPCAs are considered. According to current knowledge, sporadic cases can be classified into the 3 following categories, which may be modified later based on further research findings:

* Type 1 - A subtype; essentially the presentation of MSA

* Type 2 - Sporadic cases that are not part of an MSA, as presently understood

* Type 3 - De novo mutations that are actually genetic cases (but authorities do not realize they are genetic)

In addition, a separate, but related, question is whether the sporadic diseases are simply multigenetic, with the genetics being presently too complex to recognize as such.

A large percentage of the sporadic OPCAs are a subset of MSA. Some authorities have claimed that all sporadic OPCAs will progress to include significant autonomic and parkinsonian features and thus evolve into full-blown MSA if the patient lives long enough. According to this view, MSA typically starts as an ataxic OPCA form, an autonomic form (Shy-Drager syndrome), or a parkinsonian form (striatonigral degeneration). Motor neuron degeneration and dementia also eventually occur.

However, a large and careful study by Gilman et al published in 2000 showed that of the cases they selected for analysis, only 25% of the sporadic OPCAs converted to full-blown MSA within 5 years. Nevertheless, all the sporadic OPCAs, Shy-Drager syndrome, striatonigral degeneration, and full-blown MSAs appear on the molecular level to be alpha-synucleinopathies; that is, they involve abnormalities of the protein alpha-synuclein. In addition, Jellinger reports in 2003 that the molecular pathology involves alpha-synuclein–positive glial (and less abundant neuronal) cytoplasmic inclusions in MSA and in all the purported subtypes. These inclusions are also different from the alpha-synucelinopathic inclusions (eg, Lewey bodies), which are seen in other diseases.

The genetic OPCAs are all more pure in the sense that they do not evolve to an MSA picture. Many of the genetic forms are considered SCAs. Some genetic forms have additional characteristics such as retinal involvement, extrapyramidal degeneration, spinal cord degeneration, dystonia, dementia, and other neurological abnormalities dependent mainly on the genetic subtype but even showing variability within the same subtype. For the genetic OPCAs, the primary molecular lesion is related to the gene that defines the genetics, rather than alpha-synuclein.

Clinical distinction of these entities is based on the dominant feature, which may be cerebellar ataxia (observed in OPCAs, SCAs, and MSA), parkinsonism (observed in MSA, striatonigral degeneration, and Shy-Drager syndrome), or autonomic failure (observed in MSA and Shy-Drager syndrome). Whatever the subtype, the term OPCA indicates a form of progressive ataxia distinguished by pontine flattening and cerebellar atrophy on brain imaging studies and at autopsy.

When faced with an adult having progressive ataxia suggestive of OPCA, the role of the clinician includes (1) excluding readily treatable alternative diagnoses, (2) discussing the value of genetic testing with patients in whom such testing is informative, (3) managing symptoms, and (4) advising the patient and family regarding the natural history and the need to plan for the future. No definitive therapy exists for OPCA.

Pathophysiology: The OPCAs are progressive neurodegenerative conditions. Sporadic forms involve abnormalities of alpha-synuclein, but that does not fully explain the abnormality that must involve many other yet unknown details. Many specific genes have been identified for the genetic forms, although how the genetic abnormalities cause the clinical findings remains uncertain.

On the gross level, brains show some common characteristics in all cases of OPCA. The pons is diminutive, especially in the area of the basis pontis. The cerebellum is small with loss of Purkinje cells, but the dentate nuclei are well preserved. The middle cerebellar peduncles also are atrophic, possibly secondary to degeneration of the basal pontine gray matter. The substantia nigra of the midbrain shows evidence of tissue loss. Cellularly, one sees neuronal degeneration in the arcuate, pontine, inferior olivary, pontobulbar nuclei, and the cerebellar cortex.

Additional areas of degeneration probably account for the difference in subtypes. In sporadic OPCA, oligodendroglial and neuronal intracytoplasmic and intranuclear inclusions characteristic of MSA frequently are seen. Many of these are accumulations of alpha-synuclein. In autosomal dominant OPCA, spinal cord lesions, especially in the posterior columns, spinocerebellar tracts, and anterior gray horn cells, are more common. The cerebellar features may be less prominent. However, so many variations of both the sporadic and genetic forms are described that one can find cases that appear to be exceptions to these generalizations.

Frequency:

* In the US: The prevalence of OPCA is 3-5 cases per 100,000 individuals; this may represent approximately 5-6% of patients diagnosed with atypical Parkinson disease.

Mortality/Morbidity: The OPCAs are progressive neurodegenerative disorders that have no definitive treatment. Eventually, many patients become wheelchair bound. Severe dysarthria, anarthria, and dysphagia are not uncommon as the disease progresses.

* Morbidity increases significantly, including falls and aspiration pneumonia.

* Enteral feeding becomes necessary for many patients.

* Death commonly results from aspiration pneumonia.

* The duration of familial OPCA is approximately 15 years. The duration of sporadic OPCA is approximately 6 years.

Race: No apparent racial preference is observed in OPCA. This is unlike Machado-Joseph disease, which has a predominance in certain Azorean, Indian, and Italian families.

Sex: A male preponderance is observed in familial cases of OPCA, with a male-to-female ratio of 2:1. However, no such distinction is seen in sporadic cases.

Age: The mean age of onset of sporadic OPCA is 53 years. The mean age of onset of familial OPCA is 28 years (excluding the infantile forms in Table 2).

CLINICAL Section 3 of 10 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History:

* 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.

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

* Usually, the initial sign in OPCA is a broad-based cerebellar ataxic gait. A parkinsonian gait is a less common but recognized variant.

* One of the other prominent features is dysarthria that is distinctly cerebellar in nature. 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 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 often masked by a concomitant peripheral neuropathy.

* Nystagmus, slow saccades, and abnormal funduscopic examination findings are present in varying degrees.

* Hyperactive vestibuloocular reflex also has been reported.

* In some cases, limitation of extraocular movements, particularly of the upward gaze, also is present.

* Reflexes generally are hyperactive early in the course of the disease but are lost later, especially reflexes of the Achilles tendon.

* Position sense and vibratory function are reduced secondary to neuropathy.

* Cogwheel rigidity, bradykinesia, and, occasionally, tremor may be the dominant physical manifestations.

* The clinical manifestations of OPCA typically 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. However, during the course of the disease, serial examinations may reveal noncerebellar signs.

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

* The entire spectrum of cerebellar ocular motility disorders can occur in persons with OPCA. Retinal degeneration may be present. Nuclear or supranuclear ophthalmoplegia occurs more frequently in familial OPCA than sporadic OPCA.

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

o Abnormal movements are more frequent in familial OPCA. Abnormal movements may include myoclonus, spasmodic torticollis, chorea, and athetosis.

o Nonpyramidal signs, such as amyotrophy, fasciculations, peripheral neuropathy, lightning pains, and pes cavus, are more common in sporadic OPCA than familial OPCA.

o 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.

Causes: A unifying etiology of OPCA has not been established. 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.

In order to clarify the subtypes of the genetically determined OPCAs, the authors have placed them in tables. Table 1 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. In fact, the historical cases may have been somewhat heterogeneous (which is not unusual in retrospective analyses of genetic syndromes). 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 and OPCA-IV except perhaps that in the historical cases of these syndromes, some differences existed in the phenotypic presentations of the same underlying disease. (The main difference is that in the Schut-Haymaker OPCA-IV, involvement of cranial nerves IX, X, and XII was noted.)

Note also in the table that OPCA-2 and OPCA-II are not the same. OPCA-2 is identical to SCA-2 and a particular gene is specifically associated with it. It is autosomal dominant. OPCA-II is autosomal recessive and its gene is unknown. It is sometimes called Fickler-Winkler syndrome after the 2 early discoverers. Little is known of the underlying biochemistry or genetic locus of OPCA-II. Interestingly, some confusion exists in the older literature and some confusion exists between the clinical descriptions of OPCA-2 and OPCA-II. 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). The phenotypes are not very similar. Actually, OPCA-II is closer to OPCA-I in phenotype. For the other numbered OPCAs, either Arabic or Roman numbers can be used interchangeably. 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 MIM 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
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 (Banfi et al, 1994)
#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 (Bürk et al, 1996)
%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 (Skre and Berg, 1974; Fickler, 1911; Winkler, 1923)
#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 (Bürk et al, 1996)
^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 (Schut and Haymaker, 1951)
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 (Carter and Sukavajana, 1956; Konigsmark and Weiner, 1970)
%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 (Illarioshkin et al, 1996; Bertini et al, 2000)

* 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
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 (Chou et al, 1990; Barth, 1993)
%277470 Pontocerebellar hypoplasia type 2, PCH-2 Pontocerebellar hypoplasia with progressive cerebral atrophy, Volendam neurogenerative 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-q21 Gene 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 (Rajab et al, 2003)
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 (Albrecht et al, 1993; Patel et al, 2006)
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 (Patel et al, 2006)
#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 (Colella et al, 2000; Kanda et al, 1990; De Sanctis and Cacchione, 1932)
#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 (Agamanolis et al, 1986; Harding et al, 1988)

* 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
Disease OMIM # Disease Names Locus Gene Product (OMIM #) Description References
#164400 SCA-1, OPCA-I, OPCA-IV (OPCA-IV same as OPCA-I), ADCA-1 ATXN1, 6p23 Ataxin-1 (*601556); 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 Menzel, 1890; Waggoner et al, 1938; Schut, 1950; Schut and Haymaker, 1951; Orr et al, 1993
#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; Wadia and Swami, 1971; Ueyama et al, 1998
#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; Kawaguchi et al, 1994
%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; Hellenbroich et al, 2003
#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
#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
#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; Zhuchenko et al, 1997
#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; Harding, 1982
#608768 SCA-8, ADCA-2 KLHL1AS, 13q21 Genetic test available Onset 20s to 70s; ataxia, dysarthria, nystagmus, impaired smooth pursuit Koob et al, 1999; Ikeda et al, 2000; Factor et al, 2005 (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; Zu et al, 1999; Grewal et al, 2002
%604432 SCA-11 SCA11, 15q14-q21.3
Onset at 20-40 years; ataxia, dysarthria, nystagmus Worth et al, 1999
#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; Fujigasaki et al, 2001
#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
#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; Brkanac, Bylenok et al 2002; Chen, Brkanac et al 2003; Yabe et al 2003
%606658 SCA-15 Gene unknown, 3p26.1-p25.3 Unknown 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; Knight et al, 2003; Hara et al, 2004
%606364 SCA-16 SCA16, 8q22.1-q24.1
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
#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; Rolfs et al, 2003; Maltecca et al, 2003
%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
%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; Verbeek et al, 2002; Chung et al, 2004; Schelhaas et al, 2004
%608687 SCA-20 SCA20, 11cen
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
%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; Vuillaume et al, 2002
%607346 SCA-22 1p21-q21
Now believed to be identical to SCA-19 (Schelhaas et al, 2004) though Chung et al (2004) dispute this Schelhaas et al, 2001; Verbeek et al, 2002; Chung et al, 2004; Schelhaas et al, 2004
%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
%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
%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
#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
%610246 SCA-28 18p11.22-q11.2
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
#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; Koide et al, 1994
#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; Hanson et al, 1977; Gancher and Nutt, 1986; Browne et al, 1994; Brandt and Strupp, 1997; Eunson et al, 2000
#108500 Episodic ataxia type 2, EA-2 CACNA1A, 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; White, 1969; Subramony et al, 2003; Spacey et al, 2005; Imbrici et al, 2005
%606554 Episodic ataxia type 3, EA-3 1q42 Unknown Onset at 1-42 years; vestibular ataxia, vertigo, tinnitus, interictal myokymia Steckley et al, 2001; Cader et al, 2005
%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; Vance et al, 1984; Damji et al, 1996
+601949 Episodic ataxia type 5, EA-5 CACNB4, 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; Escayg et al, 2000; Herrmann et al, 2005
%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; Müller et al, 1998
%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; Gayle and Williams, 1933; Mahloudji, 1963; Meijer et al, 2002; Grewal et al, 2004

* Finally, the question of how the OPCAs and SCAs fit with the 2 other systems of terminology is addressed The 2 systems of terminology in question are (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 rows 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
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.
llHolmes 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.

DIFFERENTIALS Section 4 of 10 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic
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Cortical Basal Ganglionic Degeneration
Friedreich Ataxia
Hallervorden-Spatz Disease
Inherited Metabolic Disorders
Multiple Sclerosis
Multiple System Atrophy
Paraneoplastic Cerebellar Degeneration
Parkinson Disease
Parkinson Disease in Young Adults
Parkinson-Plus Syndromes
Prion-Related Diseases
Progressive Supranuclear Palsy
Striatonigral Degeneration
Wilson Disease


Other Problems to be Considered:

Shy-Drager syndrome
Refsum disease
Machado-Joseph disease
Vitamin E deficiency


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Cortical Basal Ganglionic Degeneration

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Inherited Metabolic Disorders

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Paraneoplastic Cerebellar Degeneration

Parkinson Disease

Parkinson Disease in Young Adults

Parkinson-Plus Syndromes

Prion-Related Diseases

Progressive Supranuclear Palsy

Striatonigral Degeneration

Wilson Disease


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WORKUP Section 5 of 10 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic
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Lab 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.

Imaging Studies:

* MRI

o MRI is the imaging study of choice in patients with 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.

o 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.

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

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

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

Other Tests:

* Table 3 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.

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.

Staging: A staging system specific to OPCA is not available.
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Medical Care: Care 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.

* Supportive care with gait-assisting devices is especially important to minimize falls.

Surgical Care:

* At times, 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; the use of assistive devices can significantly increase functional ability.

* 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 the disease, a pureed diet or enteral feeding may be required.

Activity: Activity should be allowed ad libitum; however, appropriate measures should be used to minimize falls.
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As previously stated, to date, medical therapy has provided only minimal benefits.

Drug Category: Dopaminergic agents -- Used to improve parkinsonian and tremor-related symptoms.
Drug Name
Levodopa/carbidopa (Sinemet) -- Direct dopaminergic agent. Carbidopa prevents peripheral decarboxylation of levodopa, thus facilitating entry into CNS. Comes in different strengths of 25/100 mg, 25/250 mg, and 10/100 mg.
Adult DoseInitial dose: 25/100 mg PO tid; can titrate upwards depending on adverse effect profile
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; malignant melanoma or undiagnosed skin lesions
InteractionsHydantoins, pyridoxine, phenothiazine, and hypotensive agents may decrease effects; antacids and MAOIs increase toxicity
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsCertain adverse CNS effects (eg, dyskinesias) may occur at lower dosages and earlier in therapy with SR form; caution in patients with history of myocardial infarction, arrhythmias, asthma, or peptic ulcer disease; sudden discontinuation may cause worsening of Parkinson disease; high-protein diets should be distributed throughout day to avoid fluctuations in levodopa absorption
Drug Name
Amantadine (Symmetrel) -- Unknown mechanism of action; may release dopamine from remaining dopaminergic terminals in Parkinson patients or from other central sites. Less effective than levodopa in treating Parkinson disease; slightly more effective than anticholinergic agents.
Adult Dose100 mg PO bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsDrugs with anticholinergic or CNS stimulant activity increase toxicity; hydrochlorothiazide plus triamterene may increase plasma concentrations
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsCaution in liver disease, uncontrolled psychosis, eczematoid dermatitis, seizures, and those receiving CNS stimulant drugs; reduce dose in renal disease when treating Parkinson disease; do not abruptly discontinue this medication
Drug Category: Antihypertensive agents -- Pharmacologic therapy should be individualized based on a patient's age, race, known pathophysiologic variables, and concurrent conditions. Treatment should be designed to lower blood pressure safely and effectively and to avoid or reverse hyperlipidemia, glucose intolerance, and left ventricular hypertrophy.
Drug Name
Propranolol (Inderal, Betachron E-R) -- Nonselective beta-adrenergic agonist; mechanism of action for tremor suppression not fully known.
Adult DoseInitial dose: 40 mg PO bid; can be increased to 120-240 mg/d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities
InteractionsAluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; may increase toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsBeta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely
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Complications:

* Falls are the primary complications in the early stages of OPCA.

* Aspiration pneumonia is more common in later stages of OPCA.

Prognosis:

* Currently, no effective therapy is available for the neurodegenerative processes that constitute OPCA. Clinically, only supportive care can be given to patients with this progressive disease.

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Medical/Legal Pitfalls:

* Mental status and expressive abilities generally are preserved early in the disease. In cases that appear to be progressing to severe disability relatively rapidly, clarifying resuscitation status and advanced directives regarding feeding tube, tracheostomy, and aggressive care is advisable while the patient is able to express his or her wishes.

BIBLIOGRAPHY Section 10 of 10 Click here to go to the previous section in this topic Click here to go to the top of this page
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