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Show ,. eli,l. NCllr(l-(ll'hlllilllllll/. 5: 144-147, IlJH5 Il' ILJH5 R,l\'l'11 l)rl'~~, Nl'W Vor" Neuroradiological Clinical Pathological Correlations Optokinetic Dissociation, Saccadic Hypomotility, and Sakkidierung BRIAN J. MURPHY, M.D. ROBERT M. QUENCER, M.D. Case History A 32-year-old man was seen in ophthalmologic consultation for abnormal ocular motility. At 27 years of age, he had begun to develop progressive cerebellar dysfunction manifested by gait ataxia, dysarthria, and difficulty in handwriting. There was a remarkable family history of cerebellar dysfunction in his mother, who developed progressive cerebellar ataxia and dysarthria at the age of 28, and in his younger brother, who at age 28 was developing a similar clinical course. There was no history of alcoholism, long-term Dilantin use, head trauma, or carcinoma. On physical examination, the patient was alert and mentation was normal. He had a scanning type dysarthria, marked titubation of the head, facial hypomimia, and intention tremor. Cranial nerves were intact without evidence of nystagmus. On sensory testing there was impaired vibratory, pin-prick, and light touch sensation. Proprioception was intact. Cerebellar testing revealed truncal and appendicular ataxia with significant past pointing found bilaterally. Deep tendon reflexes were 0/4 to 1/4 in all extremities. There was no occulopalatal myoclonus. Ophthalmologic examination revealed normal acuity, normal visual fields, and intact pupils. Optokinetic responses were abnormal, with horizontal-vertical dissociation manifested as foreshortened horizontal responses and essentially absent vertical responses. Sak- From the Department of Radiology, Uniwrsity of Mi,lmi School of Medicine, University of Miami/Jackson M.'morial Medical Center, Miami, Florida. Writc for rCl'rillts to: B. J. Murphy, M.D., Department of Radiology (R130), University of Miami School of Mt'dicine, P.O. Box 016960, Miami, FL 33101, U.S.A. 144 kidierung (cogwheel eye movements vertically and horizontally) was present bilaterally, Blood chemistries, thyroid function tests, and Bl2 and folate levels were normal. Cerebrospinal fluid (CSF) was microscopically and culture negative but exhibited a slightly elevated protein concentration of 36 mg/dl. Oligoclonal banding was negative. The radiologic evaluation included computed tomography (CT) and magnetic resonance imaging. Discussion The initial CT scan (Fig. 1, left) illustrates a generalized enlargement of the CSF spaces surrounding the cerebellum and the pons. A more craniad section (Fig. 1, right) demonstrates that the sulci of the cerebral hemispheres as well as the lateral ventricles are normal in size and contour. This implies that a local rather than general atrophic process is occurring. Radiologically, the cerebellum and the pons are affected grossly, but it is difficult to determine which, if any, specific nuclei are atrophic. The magnetic resonance image (Fig. 2) is at a higher anatomic level than the CT scan in Fig. 1 (left). The pulse sequence used (spin echo, TR = 1.5 s, TE = 35 ms) is somewhat T1 weighted and thus is useful for anatomic detail. It also demonstrates atrophy of the cerebellum and confirms the results shown by CT. Of importance, however, is that various other T1 and T2 weighted pulse sequences failed to reveal any focal areas of abnormal signal within the atrophic areas. The cerebellum and pons have essentially the same relaxation times as the surrounding normal parenchyma and thus are interpreted as being atrophic neuronal tissue without coexistent inflammation, ischemia, edema, or malignancy. In patients presenting with the progressive onset of cerebellar dysfunction as the dominant Murphy, Quencer Figure 1. "t>nc"ntr.I~t-t.'nhilnct'd lllmputed t"n1(lgraphy in tht' .Ixial plant' (left) sh"ws enlargt'ment uf the prepuntine cistern I"'hite arm",) and thl' ambit'nt ci~tt'rns (black arrow~), Tht' fuurth wntride (curved arww) is markedh' enlarged and the cerebellar ~ukl (arrll\d1t'ads) are pwminent, Tht' higher sectiun (right) is lwll abuve the tt'nturium and shtlws nnrmallateral "entrides and suki. feature of the clinical picture, CT, with emphasis on the posterior fossa, has the highest diagnostic ~'ield in the imaging evaluation, A clinical distinction must be made between a degenerative process involving the cerebellum, such as the presence of a mass lesion in the posterior fossa, or a noncerebellar cause for ataxia, such as proprioceptive sensory loss ("sensory ataxia") in labyrinthine pathology. Often, demyelinating processes will present with signs of abnormal cerebellar function, as wiII vascular insufficiency syndromes. In this case, degeneration of the cerebellum and pons was demonstrated but a precise diagnosis can only be suggested from the radiologic findings. In addition, once the finding of cerebellar atrophy is made, historical information, laboratory results, and physical examination must be integrated to arrive at a final diagnosis. This is because a multitude of acquired and inherited disorders exist in which cerebellar atrophy is present to various degrees. Atrophy of other central nervous system structures will aid in etiologic determination, as was the case here when pontine atrophy was found. Table 1 lists the more common causes of cerebellar atrophy, Radiologic evidence of cerebellar atrophy with thinning of the middle cerebellar peduncles and a small wedge-shaped pons is quite characteristic for olivopontocerebellar atrophy (OrCA). J A family history of the June 1985 disorder can be found in about SO'k of documented cases,~ and thus was contributof\' in this patient. There was no history of aic()hol abuse, Dilantin use, or carcinoma; thus, the ac- Figure 2. Magndic rt'SU'h1l1Ct' imaging (pulst' ~t'qut'no" i~ spin echu, TR ~ 1.5 s, TE = 35 ms, 0.35 T) St'ctitln in tht' .lxi.11 plane shows pwminent supt'ritlr ,'ermian ~uki (arrowIwads) and t'nlMgt'd ambient cistt'rns (arrows). 145 Ophlkilletic Disso(i,llioll figure 3. Noncontrast-enhanced computed tomography in patient on long-term Dilantin use. The fourth ventride is markedly enlarged and the cerebellar sulci are promin.. n!. Note the prepontine and ambient cisterns are normal as compared with those in Fig. 1 (left). qui red causes of cerebellar atrophy could be excluded. The presence of extrapyramidal signs (sakkidierung) and parkinsonian features (facial hypomimia) are quite variable in patients with OPCA.2.3 In 1891, Menzel4 described a disorder manifested clinically by cerebellar dysfunction and characterized pathologically by atrophy of the cerebellar cortex, inferior olives, gray matter of the pons, and middle cerebellar peduncles. Spinal cord changes were also noted, and an autosomal dominant mode of transmission was apparent. De'jerine and Andre-Thomas5 in 1900 described a similar disorder that was sporadic in nature. Both of these early descriptions would currently be classified as OPCA. OPCA is a well-defined entity distinct from cerebellar cortical atrophy (Holmes type), in which pontine nuclei are unaffected, and from Freidreich's ataxia, which predominantly affects the spinal cord. However, OPCA is essentially a term that encompasses a heterogeneous series of diseases whose only common feature is the loss of neurons in the ventral pons, inferior olives, and cerebellar cortex'" In general, the disease begins in late middle life, with steady progressive ataxia and dysarthria. Gait ataxia was the initial symptom in 67'1, 146 TABLE 1. Cerebellar Degeneration Acquired Alcoholic Phenytoin Carcinomatuus Myxedema Chronic malnutrition Common spinocerebellar atrophies and multisystem disorders Friedreich's ataxia Holmes cortical cerebellar atrophy Olivopontocerebellar atrophy Rdsum's disease of the 117 pathologically proven cases studied by Berciano. 2 Nystagmus is not a frequent finding and was present in only lOCk of cases of familial OPCA and 20 Ck of cases of sporadic OPCA.2 As the disease progresses, deep tendon reflexes tend to be lost, plantar responses are often extensor, and parkinsonian features develop. Dementia and autonomic dysfunction become apparent to variable degrees. Retmal degeneration and ophthalmoplegias are seen occasionallv. Palatal m\'oclonus is an uncommon associated sign, but when present it is almost pathognomonic for OPCA. Pathologically, the pons, middle cerebellar peduncles, cerebellar cortex, and olives are atrophic. The corticospinal tracts are preserved but the pontine tegmentum and cerebellar projections atrophy, giving the pons a wedgeshaped appearance. The cerebellar Purkinje cells are virtuall\' lost and there is cell loss in the pontine nudei and inferior olives. The dentate nuclei are frequently gliotic. The spinal cord shows variable degeneration of the posterior columns and the corticospinal tracts, with the cells of the dorsal nuclei and the interomediolateral cell columns being highly atrophic. In addition, gliosis and neuron loss is commonly found in the putamen and the substantia nigra, thus forming a basis for extrapvramidal find- . - - mgs.' Recentlv, a reduction of noradrenaline in the cerebellum of patients with familial OPCA has been described. s This most Iikelv reflects a degeneration of the locus ceruleus' noradrenergic system. An ill <'it'll biologic marker for OPCA has yet to be identified, although a reduction in leukocyte glutamate dehydrogenase activity was found in a handful of sporadic cases.9 A biochemical defect may be responsible for pathogenesis, but the basic etiologic mechanism in the development of OPCA remains unknown. The continuing development of magnetic res- Journal of Clinical Neuro-ophthalmology onance imaging modalitit:'s and the use of paramagnetic contrast agents such as gadoliniulll (Gd-DTPA) may permit visualization of fine anatomic detail allowing the nwasurenwnt of the cerebellum, the brainstem, and l'Vl'n individual nuclei. rather than ha\'ing tll defilw atwphv on the basis of eniargelllent \:If the surrounding cisterns. This ob\'iousl~' would pH",e useful in increasing the understanding of the cerebellar syndromes. References 1. SaH)i,irdl), 1\1.. Br,1(chi, 1\1.. rasserini, A., Vis( i,lI1i, A., DiDl1l1ato, S.. ,1I1d Cocchini, F.: Computed tl)nlll~r,lph\' l)j l)IiH)pllIltocerebellar de~ eneratilm. A I.\'/\. ~: 5lN-512, 1983, .., Bercial1l), J.: Oli"l)pl)nll)cl'rl'bellar atnlpl",: a re" iew l)j 117 c,lSt'S. I..\','/11',1/. 5..i. 53: 253-272, 1482. 3. "l)J1i~smar", B. \\' .. and Weiner, L. r.: The oli- June 1985 Murphy, Quencer \'opontocerebl'1liu atrophies. Medicilll' 49: 227241, 1')70. -t. Menzel. r.: l3eitril~ zur Kenntniss der hereditaren I\lilxil' und Kleinhirnalrophie. Arch. Psychiat. NCrl'C/lkr. 22: IhO-IYO, IS'JI. 5. De'il'rine, J., ilnd Andre-Thomas, M.: L'atrophie olivo-ponl\l cl'n:'belll'usl'. Nouv. I conogr. Sapia 13: 330-370, IYOO. h. Pdill), C. K., Hart, M. N., Porro, R. S., and Earll', K. M.: Ultrastructural studies of olivoponl\ Kerebellar atrophy. J. NClIro"l1thul. Ex!'. Nellrol. 27: 257 - 261. IY73. 7. Weller, Swash, McLellan, and Scholtz: Clil/icLlI N<'llw!,l1tllOluXY. Springer-Verlag, Berlin, 1'J83. II. Kish, S. J., Shannak, K. S., and Hornykiewicz, 0.: Reduction of noradrenaline in cerebellum of patients with oli\'opontocerebellar atrophy. ,. NClIwchcll/. 42: 1476- 1487, 1984. 9. Plaitkis, A., Nicklas, W., and Beal, S.: Further studies on glutamate dehydrogenase deficiency in spinocerebellar degeneration. NClIroluS-1f 30: 381. IY80. 147 |