Comparison between MRI and 3D-SSP in olivopontocerebellar atrophy and cortical cerebellar atrophy]

We compared images of three-dimensional stereotactic surface projections (3D-SSP) of SPECT with MRI images in spinocerebellar degeneration patients (13 olivopontocerebellar atrophy (OPCA) and 7 cortical cerebellar atrophy (CCA)). We analyzed a brain blood flow pattern with an image of statistics by 123I-IMP SPECT. In OPCA patients, a blood flow reduction was more remarkable in 3D-SSP than a degree of cerebellar atrophy in MRI. In patients with CCA, the cerebellum showed little blood flow reduction in 3D-SSP despite of apparent atrophy in MRI. Simultaneous examination both MRI and 3D-SSP might be useful for differential diagnosis of spinocerebellar degenerations.     

橄榄脑桥小脑萎缩20例临床分析

目的探讨橄榄脑桥小脑萎缩的临床表现和影像学检查特点,以便早期诊断并改善患者预后。方法回顾性分析经临床诊断的20例橄榄脑桥小脑萎缩患者的相关资料。结果橄榄脑桥小脑萎缩患者临床以小脑性共济失调、言语不清、排尿功能障碍、帕金森症状等最常见。16例患者头颅磁共振检查结果示脑萎缩,主要为小脑和脑干萎缩。结论橄榄脑桥小脑萎缩临床以小脑性共济失调为主要表现,言语障碍较继往报道发生率高,头颅磁共振可表现为小脑、脑干萎缩,并可一定程度上反映病程。     

Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients

We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.     

Transcranial magnetic stimulation in multiple system and late onset cerebellar atrophies

Central motor conduction time (CMCT) after transcranial magnetic stimulation (TMS) of the cortex, electromyography and nerve conduction velocity were performed in 24 patients with multiple system (MSA) and late onset cerebellar atrophy (LOCA) (often olivopontocerebellar atrophy –OPCA –). CMCT was abnormal in 7 patients with OPCA and one with LOCA. CMCT abnormalities (43% of cases) and increased threshold (68%) were more often found within OPCA group than in another multisystem atrophy and LOCA. Reduction in amplitude of the response after TMS was significantly correlated with cerebral hemispheres's atrophy. Increased threshold was correlated with upper vermal hemisphere atrophy and enlargement of the fourth ventricle. Electrophysiologic signs of mixed peripheral neuropathy were found in 8 patients. TMS abnormalities were not related to peripheral nerve involvement. Marked variation in CMCT suggests heterogeneity in these diseases. However, the percentage of CMCT abnormalities in OPCA group suggests that TMS seems to play a role in the neurophysiological diagnosis of these heterogeneous disorders.     

Correlation of clinical course with MRI findings in olivo-pontocerebellar atrophy and late-cortical cerebellar atrophy

We quantitatively analyzed 1.5 T MRI in 36 cases of sporadic spinocerebellar degeneration (SCD) and 30 control cases without intracranial lesions, using graphic analyzer. SCD consisted of 21 olivo-ponto-cerebellar atrophy (OPCA) and 15 late cortical cerebellar atrophy (LCCA). There was negative correlation between vermian size and the duration of illness both in OPCA (r = 0.8960, p less than 0.001) and LCCA (r = 0.7756, p less than 0.01), but the progression rate in OPCA was three times greater than that in LCCA. LCCA was suggested the preclinical vermian atrophy by the statistical regression study. In OPCA, the duration of illness also revealed significant correlations with atrophy of ventral pons (r = 0.8308, p less than 0.001) and also cerebellar hemisphere (medial hemisphere; r = 0.7278, p less than 0.001. lateral hemisphere; r = 0.6039, p less than 0.01). OPCA showed diffuse atrophy of cerebellar hemisphere, whereas LCCA showed medial dominant atrophy. OPCA demonstrated significant correlation between the fourth ventricle dilatation and the duration of illness (r = 0.6005, p less than 0.01). A discriminant study significantly separated OPCA, LCCA and control each other by sizes of ventral pons and cerebellar vermis (p less than 0.001). In T2 weighted MRI, 10 cases out of 14 LCCA did not show hypointensity in dentate nucleus in spite of normal appearance in the other portions usually decreased intensity. The dentate nucleus of OPCA showed a significant atrophy. The incidence of putaminal hypointensity in OPCA was significantly greater than that of control group (chi-square = 6.476, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative MRI study of progressive cerebral atrophy in multiple system atrophy]

We investigated cerebral atrophy in multiple system atrophy (MSA) by quantitative analysis of MRI. The subjects were 28 patients with MSA (14 striato-nigral degeneration; SND, 14 olivo-ponto-cerebellar atrophy; OPCA. 106 MRI examinations were performed totally) and 85 normal persons for control. The ratios of the ventral pons to the infratentorial space in the sagittal section, the putamen, cerebrum, frontal lobe and parietal & occipital lobes to the intracranial space in the horizontal section, and the temporal lobe to the intracranial space in the coronal section were measured. In the early stage of the disease, OPCA showed significant atrophy of the ventral pons compared with SND, and conversely, SND demonstrated significantly smaller putamen than that in OPCA. According to the progression of the disease, the atrophy of these neural tissues progressed, which resulted in no significant differences between SND and OPCA. The cerebral atrophy was observed in 17 MSA patients. The atrophy of the frontal lobe was much frequent and prominent to that in the temporal lobe and parietal & occipital lobes. SND showed higher incidence of the cerebral atrophy than OPCA in the early stage of the disease. In long period follow-up cases, one case showed cerebral atrophy in earlier stage, and another case in late stage. We indicated the involvement of the cerebral hemispheres in MSA, especially the frontal lobe.     

Cerebellar and brainstem hypometabolism in olivopontocerebellar atrophy detected with positron emission tomography

We studied local cerebral metabolic rates for glucose (1CMRglc) with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 30 patients with olivopontocerebellar atrophy (OPCA) and 30 age-matched control subjects without neurological disease. The diagnosis of OPCA was based on the history and physical findings and on the exclusion of other causes of cerebellar ataxia by means of laboratory investigations. Computed tomographic scans revealed some degree of atrophy of the cerebellum in most patients with OPCA, and many also had atrophy of the brainstem. PET studies in these patients revealed significant hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem in comparison with the normal control subjects. A significant relationship was found between the degree of atrophy and the level of 1CMRglc in the cerebellum and brainstem. Nevertheless, several patients had minimal atrophy and substantially reduced 1CMRglc, suggesting that atrophy does not fully account for the finding of hypometabolism. 1CMRglc was within normal limits for the thalamus and cerebral cortex. The data suggest that PET/1CMRglc may be useful as a diagnostic test in patients with the adult onset of cerebellar ataxia.     

Motor dysfunction in olivopontocerebellar atrophy is related to cerebral metabolic rate studied with positron emission tomography

We compared the severity of motor dysfunction with local cerebral metabolic rates for glucose (lCMRGlc) and the; degree of tissue atrophy in 30 patients with olivopontocerebellar atrophy (OPCA). We devised a scale to quantitate the degree of ataxia in the neurological examinations. lCMRGlc was measured with¹⁸F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). Tissue atrophy was assessed by visual rating of computed tomographic scans. PET studies revealed Marchked hypometabolism in the cerebellar vermis, cerebellar hemispheres, and brainstem of OPCA patients compared with 30 control subjects. A significant correlation was found between severity of motor impairment and lCMRGlc within the cerebellar vermis, both cerebellar hemispheres, and the brainstem. A significant but weaker relationship was noted between the degree of tissue atrophy in these regions and clinical severity. Partial correlation analysis revealed that motor dysfunction in OPCA correlated more strongly with lCMRGlc than with the amount of tissue atrophy. These results suggest that the clinical manifestations of OPCA are more closely related to the metabolic state of the tissue than to the structural changes in the cerebellum.     

Man aged 49 years suffering from progressive clinical picture with palatal tremor,segmental myoclonus,ataxia, parkinsonism,amyotrophy, pyramidal signs,supranuclear ophthalmoplegia and cognitive decline

In this clinicopathological conference we discuss the case of a patient aged 49 years, who developed progressive clinical picture characterized by palatal tremor (PT), segmental myoclonus, cerebellar ataxia, parkinsonism, amyotrophy, pyramidal signs, supranuclear ophthalmoplegia, parkinsonism and cognitive decline. He died 10 years after onset. There was no family history of ataxia. Initially a diagnosis of cerebral Whipple's disease was given, but prolonged treatment with ampicilin and cloramfenicol did not modify the clinical course. Magnetic resonance imaging study showed cerebellar and brainstem atrophy. Electrophysiological examination revealed neurogenic electromyographic pattern and abnormal somatosensory and brainstem evoked potentials. Starting from symptomatic PT, as the guide sign, a presumptive pathological diagnosis of sporadic olivopontocerebellar atrophy (OPCA) was established, probably of multiple system atrophy (MSA) type. Neuropathological study demonstrated OPCA with preferential involvement of cerebellum but without glial inclusions. This case illustrates the great clinicopathological complexity of OPCA and that not all forms of sporadic OPCA may be included within MSA.     

The distribution and dynamic density of oligodendroglial cytoplasmic inclusions (GCIs) in multiple system atrophy: a correlation between the density of GCIs and the degree of involvement of striatonigral and olivopontocerebellar systems

The distribution and dynamic density of oligodendroglial cytoplasmic inclusions (GCIs) were studied based on 30 cases of multiple system atrophy (MSA), including striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) and Shy-Drager syndrome. GCIs were widely spread throughout the central nervous system, including the striatonigral and olivopontocerebellar systems. Inclusion-bearing cells appeared to be oligodendrocytes which usually had larger and lighter nuclei than those of normal-looking oligodendrocytes. The distribution of GCIs was similar in all cases, irrespective of the degrees of OPCA and SND, but the frequency of GCIs varied from case to case. We classified all the cases into two categories based on the degree of neuropathological changes of SND (mild and severe) and, independently, into three groups based on that of OPCA (minimal, moderate, and severe), i.e., a total of six groups. An association between the frequency of GCIs and the severity of the lesions was obtained. For example, many GCIs exist in the cerebellar white matter in the cases in which OPCA was not histologically confirmed. More GCIs were seen in the cases with moderate OPCA. In the cases with severe OPCA, GCIs were rarer and smaller, in proportion to the devastation of fibers; no GCIs were seen in the cases with more severe OPCA. The incidence of GCIs showed a positive correlation to the severity of OPCA but not that of SND in the corticopontine tracts, of both OPCA and SND in the pyramidal tracts, and of SND but not of OPCA in the pencil fibers of the putamen. It is suggested that GCIs may represent either a change synchronous with neuronal degeneration or a phenomenon preceding neuronal changes, especially in the cerebellar white matter. Thus, they may represent the early changes in MSA and may be a useful neuropathological hallmark for diagnosis of MSA, even in cases with minimal OPCA and SND. Received: 11 September 1996 / Revised: 6 November 1996 / Accepted: 6 December 1996     

Multiple system atrophy. Clinical and MR observations on 42 cases

Probable or possible multiple system atrophy (MSA) was diagnosed on strict clinical criteria in 42 patients: 20 with combined parkinsonism and cerebellar ataxia, 9 with striatonigral degeneration (SND) and 13 with olivopontocerebellar atrophy (OPCA). All patients were then studied with 0.5 and/or 1.5 Tesla magnetic resonance (MR) units. MR imaged putaminal abnormalities in all 9 patients with SND and posterior fossa obnormalities consistent with OPCA in all 13 patients with this diagnosis. Of the 20 patients with parkinsonism and cerebellar involvement, classified as probable MSA, 7 presented putaminal abnormalities only, 3 abnormalities consistent with OPCA only and 10 a combination of both. These findings show strong MRI support for the clinical diagnosis of MSA.

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Sommario In base a precisi criteri clinici 42 pazienti furono riconosciuti affetti da atrofia multisistemica (MSA) probabile o possibile. Venti pazienti presentavano parkinsonismo e atassia cerebellare; in 9 fu fatta diagnosi di degenerazione strio-nigrica (SND) e in altri 13 di atrofia olivopontocerebellare (OPCA). Tutti i pazienti furono sottoposti a risonanza magnetica 0.5 e/o 1.5 T. La RM mostrava alterazioni nei putamen nei 9 pazienti con SND e alterazioni in fossa posteriore come attese nell'OPCA nei 13 casi diagnosticati affetti da OPCA. In 10 dei 20 pazienti con parkinsonismo e atassia cerebellare le alterazioni nei putamen e in fossa posteriore erano associate. I nostri dati confermano che la RM è un supporto diagnostico fondamentale nella diagnosi di MSA.

     

A clinical study of a family affected with HLA-linked hereditary spinocerebellar ataxia

The gene locus of hereditary olivopontocerebellar atrophy (OPCA) has been mapped to the short arm of chromosome 6. This locus has been termed as SCA 1 and it is linked to HLA locus. Linkage for OPCA locus to HLA was first been reported by Yakura et al. We had a chance to re-investigate the original family reported by them. Among the members affected, 6 cases were autopsied and their clinical and pathological features were reported by Fujimoto et al. Kudoh et al, and Ikeda. We clinically studied 2 additional patients in this pedigree. The clinical features of these patients, including 6 previously reported cases, were characterized by 1) cerebellar ataxia predominating throughout clinical course; 2) pyramidal tract involvement, characterized by pathological reflexes, with hyper-reflexia or terminal hyporeflexia; 3) generalized muscle atrophy; 4) slow eye movement; 5) facial and tongue atrophy; 6) optic disc pallor; 7) terminal external ophthalmoparesis; 8) mydriasis and sluggish light reflex; 9) mild peripheral neuropathy; 10) mild reduction of deep sense; 11) bulbar symptom; 12) emotional lability, irritation, or euphoria dominating terminally. Clinically, there are certain similarities between this pedigree and other reported pedigrees of which linkage for OPCA locus to HLA have been proved. Furthermore, clinico-pathological reports of hereditary OPCA showing slow eye movement share numbers of clinical characteristics observed in the patients of this pedigree. Accumulating linkage data suggest that hereditary OPCA might be heterogenous disorder genetically. Whether there are any correlation between linkage data and clinico-pathological findings is essential to establish disease entities, and to re-classify hereditary OPCA and its related disorders.     

多系统萎缩的临床与影像学分析

目的 探讨多系统萎缩(MSA)的临床特点、影像学特征与临床表现的相关性，为临床诊断提供依据。方法 按Gilman诊断标准，回顾性分析26例MSA病人临床资料、一般辅助检查结果及脑CT、MRI资料。结果 拟诊MSA2l例，可能MSA5例，其中橄榄桥脑小脑萎缩(OPCA)14例，Slay-Drager综合征(SDS)8例，纹状体黑质变性(SND）4例。MRI显示OPCA的主要病变部位在小脑、桥脑、延髓；SDS仅部分有小脑病变，大部分正常；SND主要病变在壳核。而小脑、桥脑、延髓病变不明显。脑CT改变均不明显。结论 临床表现与MRI结合可提高MSA中OPCA、SND的诊断率。在SDS病人MRI改变不明显。一般辅助检查、脑CT对MSA诊断意义不大。     

橄榄桥脑小脑萎缩51例临床分析

目的：分析橄榄桥脑小脑萎缩（OPCA）的临床表现、CT及MRI特征,以利早期诊断。方法：对51例OPCA病人的临床表现及其18头颅CT和33例头颅MRI特征进行回顾性分析。结果：OPCA男性多于女性,平均年龄45．5岁,平均病程12年,其临床表现多种多样,以小脑症状,植物神经症状及锥体外系症状多见,头颅MRI比头颅CT效果好,以小脑和干萎缩为主,大脑皮质萎缩轻,结论,成年人出现小脑性共济失调,植物神经功能紊乱和锥体外系症状,应高度怀疑OPCA,且MRI有助于早期诊断。     

A syndrome of olivopontocerebellar atrophy and deafness with onset in infancy

Olivopontocerebellar atrophy (OPCA) is rare in childhood and onset in infancy is uncommon. We encountered 11 consecutive children with clinical and radiological features of OPCA which started in infancy. In addition to cerebellar ataxia, these children also had sensorineural deafness and speech impairment. Of the present cases, 8 were sporadic and the pedigree patterns in 3 (with a sibling also involved) point to an AR inheritance. The CT scan showed varying degrees of cerebellar and ppntine atrophy. The underlying genetic and neurochemical substrates of this syndrome await further study.     

橄榄脑桥小脑萎缩与“十字征”

目的:探讨橄榄脑桥小脑萎缩(OPCA)的临床和影像学特点。方法:对1例橄榄脑桥小脑萎缩患者的临床资料进行回顾性分析并文献复习。结果:本病以小脑共济失调为首发表现,部分出现植物神经系统受损、锥体束或锥体外系症状。影像学除脑干变细、小脑体积变小外,可出现特征性的十字征表现。结论:因该病和某些小脑变性疾病表现相重叠,且无有意义的生化标记物,故其影像学十字征的发现对此病的诊断和鉴别诊断意义重大。     

Reflex myoclonus in olivopontocerebellar atrophy.

The presence of reflex myoclonus in response to touching and pin-pricking the wrist or stretching the fingers and to photic stimulation was assessed in 24 patients with a presumed diagnosis of olivopontocerebellar atrophy (OPCA) and in 30 age matched control subjects. Reflex myoclonus to soma-esthetic stimulation was found in 23 patients and in none of the controls. Photic myoclonus was present in 12 patients and in none of the controls. Electrophysiological study of the reflex myoclonus showed enhanced (> 10 microV) somatosensory evoked potentials and an associated reflex electromyographic discharge (C-wave) in 15 patients. These findings indicate that reflex myoclonus is common in OPCA and probably of cortical origin.     

Argentophilic intracytoplasmic inclusions in multiple system atrophy

Summary Argentophilic intracytoplasmic glial inclusions were recently reported in olivo-ponto-cerebellar atrophy (OPCA). We examined the brains of 3 cases of OPCA [2 with striato-nigral degeneration (SND) and 1 without SND], 1 case of pure autonomic failure (PAF) without pathology of OPCA or SND, as well as 36 controls including 2 cases of Holmes' type cerebellar cortical atrophy and 2 cases of Joseph's disease. Although the inclusions were tubulin-positive, the immunoreactivity was different from that of the dendrites. Electron microscopically, the microtubular structures composing the inclusion were fuzzy with granular material. These findings may indicate that the microtubules composing the inclusions are modified. Inclusion-bearing cells appeared to be oligodendrocytes while many of them had larger and lighter nuclei than those of normal-looking oligodendrocytes without the inclusions. The inclusions were widely distributed in a characteristic fashion beyond the typical lesions of OPCA, SND and PAF. The distribution pattern was essentially the same in the case of PAF and 3 cases of OPCA irrespective of the presence or absence of OPCA or SND lesions. In contrast, argentophilic inclusions were not observed in other types of spinocerebellar degeneration, in Holmes' type cerebellar cortical atrophy or in Joseph's disease. It is suggested, in line with other studies, that the inclusion may be specific to OPCA and related disorders which include PAF and a useful marker to distinguish OPCA from other neurodegenerative diseases.     

Magnetic resonance imaging in spinocerebellar degeneration

Magnetic resonance imaging (MRI) was evaluated in 11 patients with non-familial spinocerebellar degeneration (6 olivo-ponto-cerebellar atrophy (OPCA) and 5 late cortical cerebellar atrophy (LCCA]. MRI was carried out using a superconducting magnet of 0.256 tesla (VISTA-MR) and an inversion recovery pulse sequence of repetition time 2.08 sec and inversion time 0.5 sec. The degree of atrophy was assessed with regard to ponto-cerebellar system (basis pontis and middle cerebellar peduncle) and cerebellum in the sagittal and coronal images. In the mid-sagittal images, the width of ventral pons, dorsal pons, tegmentum and tectum of midbrain, and the height of fourth ventricle were measured. Especially, the degrees of atrophy of basis pontis in the mid-sagittal image and middle cerebellar peduncle in the coronal image were divided into 4 grades and evaluated respectively. On the other hand, atrophy of cerebellum was judged from enlargement of cerebellar fissures and reduction of cerebellar volume in the sagittal and coronal images. Atrophy of ponto-cerebellar system was found in OPCA, but not in LCCA. In OPCA, atrophy of middle cerebellar peduncle in the coronal image, which was likely to begin in an inferior part of pons, was more marked than, or equal to, atrophy of basis pontis in the mid-sagittal image. With regard to cerebellar vermis, the superior faces were more atrophic than the inferior faces in both OPCA and LCCA, but in OPCA, atrophy on the superior faces was dominant in the posterior lobe including declive and folium as against dominance in the anterior lobe in LCCA.(ABSTRACT TRUNCATED AT 250 WORDS)