Olivopontocerebellar Atrophy
Clinical Aspects
The term 'olivopontocerebellar atrophy' was introduced by Dejerine and
Thomas in 1900 to describe a group of heterngeneous disorders characterized
clinically by the combination of progressive parkinsonism and cerebellar
ataxia and pathologically by neuronal loss in the ventral pons, inferior
olives, and cerebellar cortex.{4} OPCA may be inherited, usually in an
autosomal dominant pattern, but only sporadic OPCA is classified as a form
of MSA, along with SDS and SND.{4,94} Berciano{4} recently reviewed 133, 68
familial and 65 sporadic, pathologically proved cases of OPCA. Although
there was nearly 2 to 1 male preponderance in the familial OPCA, no gender
difference was found in the sporadic form. Age at onset is more variable
in this disorder than in the other parkinsonism plus syndromes, ranging
from infancy to 66 years. Cerebellar ataxia is the presenting symptom in
73% of all patients; 8.2% begin with parkinsonian symptoms, and the
remainder present with nonspecific symptoms. Dementia, gaze impairment,
dysarthria, dysphagia, incontinence, and upper and lower motor neuron
signs usually become apparent within a few years after onset. In one large
Japanese family with OPCA, the oculomotor abnormalities consisted of
limitation of up-gaze and convergence, horizontal gaze nystagmus relative
sparing of pupil reactivity, and loss of vestibulo-ocular responses.{102}
Autopsy of one patient in this series revealed degeneration of the
oculumolor nucleus with sparing of the Edinger-Westphal nucleus.
Neuropsychologic evaluation in patients with clinically diagnosed OPCA
revealed emotionality anxiety and a tendency toward depression without
cognitive decline.{14} Other studies. however, noted some degree of
dementia in up to 80% of patients.{4}
Neurodiagnostic Studies
CT and MRI scans in patients with OPCA typically show
pancerebellar and brain stem atrophy, enlarged 4th ventricle and
cerebellopontine angle cisterns, and demyelination of transverse
pontine fibers on T2-weighted MRl images.{4} PET scans show reduced
metabolic rate in the brain stem and cerebellum.{36} In one study,
73% of brain stem auditory evoked responses were abnormal.{104}
Neuropathology and Neurochemistry
Pathologic studies show a wide variation of neuronal damage. The
fundamental pathologic change in OPCA is loss of Purkinje cells in the
cerebellar cortex, particularly in the vermis.{56} In addition to cerebellar
atrophy, substantia nigra degeneration and depigmentation, neuronal loss
in other brain stem nuclei, and demyelination of corticospinal tracts and
posterior columns are seen.{62} Recently clear, argyrophilic,
introcytoplasmic structures that react with antitubulin antibodies were
demonstrated in nearly all patients with OPCA.{58,82,87} These glial
cytoplasmic inclusions are located prominently in the white matter of the
putamen, internal capsule, cerebral peduncles, and substantia nigra. They
were found in the brains of all 11 patients diagnosed with MSA but not in
any of the other 284 brains from patients with different neurologic
diseases.{87} All of Nakazato et al's {82} six patients with sporadic
OPCA were found to have 'oligodendroglial cytoplasmic inclusions',
whereas one of two brains with the hereditary forms showed similar
lesions. The concurrent cellular and myelin destruction was suggested
to be caused by generation of oligodendroglial cytoplasmic inclusions
in affected cells triggering a complement activated secondary
demyelinating response.{4} The observation of oligodendroglial
cytoplasmic inclusions in nearly all cases of MSA suggest the
possibility that the three forms of MSA are related and that the
disease process originates in the myelin or axons.
Detailed morphometric and biochemical studies correlated reductions in
aspartic and glutamic acid with Purkinje cell loss in the cerebellar
cortex and with neuronal cell loss in the inferior olives (aspartic
acid).{1} In addition, quisqualate receptors appear to be decreased,
whereas quinolinic acid metabolism is increased.{61,73} The
increased quinolinic acid phosphoribosyl-transferase activity in
OPCA was interpreted as a compensatory mechanism designed to protect
quinolinic acid-sensitive granule cells.{61} In addition, low
glutamate dehydrogenase activity was found in most but not all
studies; however, this defect probably is not disease-specific.{4,65}
Recently mitochondrial DNA abnormalities were postulated to be
important in the pathogenesis of OPCA in some patients.{112}
Ronald Vetter 1936, dz PD 1984, carbidopa/levodopa, Mirapex, selegiline
[log in to unmask] Ridgecrest, California
http://www.ridgecrest.ca.us/~rfvetter
