Early onset cerebellar ataxia with retained tendon reflexes (EOCA) and olivopontocerebellar atrophy (OPCA) : a computed tomographic study.
Computed tomographic (CT) studies in olivopontocerebellar atrophies (OPCA) and 'early onset cerebellar ataxia with retained tendon reflexes (EOCA)' are few and vary widely in methodology and criteria for cerebellar and brainstem atrophy. In this prospective study, CT scan observations on 26 patients (EOCA-11, OPCA-15) were compared with 31 controls using qualitative and quantitative assessment of cisterns, ventricles and atrophy of brain. Vermian and/or cerebellar hemispheric (predominantly anterior) atrophy was present in 80.8% and both were equally common. Cerebral cortical atrophy (26.9%) and leukoariosis (15.4%) were less frequently seen. Statistically significant atrophy of pons, brachium pontis, cerebellum and midbrain was noted in patient group. No significant differences were observed between EOCA and OPCA groups. Evidence of atrophy did not correlate with either the duration of illness or the severity of cerebellar ataxia in both the groups. The severity of brainstem atrophy in 14 patients with and 12 patients without abnormal brainstem auditory evoked response did not differ significantly. This study highlights the methodology of CT evaluation for brainstem and cerebellar atrophy, draws attention to cerebral atrophy and emphasizes the lack of significant differences in CT morphology between OPCA and EOCA patients.
Spinocerebellar degeneration (SCD) comprise a heterogeneous group of disorders whose nomenclature is controversial. Neuroimaging techniques are important investigations, short of autopsy, for determining structural changes in SCD. Currently, the procedures include computerized tomography (CT scan) and magnetic resonance imaging. The latter, however, is still not easily accessible to most of the patients in developing and underdeveloped countries. The limited CT studies available vary widely in methodology and morphometric criteria of cerebellar and brainstem atrophy. While there are several studies,,, involving spinocerebellar degeneration from our country, none of them focus exclusively on CT scan. We prospectively evaluated 26 patients of SCDs with CT scan to determine the pattern of atrophy and to identify differences, if any, between patients with early onset cerebellar ataxia with retained tendon reflexes (EOCA) and those with olivopontocerebellar atrophy (OPCA). An attempt has been made to correlate the duration of disease, degree of disability, abnormality of brainstem auditory evoked responses (BAER) and the CT scan evidence of cerebellar and brainstem atrophy.
Patients : Twenty six patients of progressive cerebellar ataxia seen over a period of 2 years at National Institute of Mental Health and Neurosciences, Bangalore, form the basis of this study. Patients with ataxia due to known causes, static encephalopathies and Friedreich's ataxia were excluded by appropriate investigations. Eleven patients had EOCA as per Harding's criteria and 15 had OPCA. After a detailed history and clinical examination, the severity of disability was assessed by a cerebellar ataxia score (CAS) based on impairment of finger-nose test, heel-knee test, disdiadochokinesia and impaired tandem walking. The maximum score was 22 for the most severe disability. All patients had BAER, which was considered abnormal when I-III or III-V interpeak latencies (IPL) were +3 SD beyond the mean value established in the laboratory controls or when there were poor or absent waves.
Methodology of CT evaluation : CT scans were done on CE-9000 scanner. Contiguous 10 mm sections were taken parallel to the orbitomeatal line from the base to the vertex. All the sections were magnified on a magnifier and measurements were made on them with the use of a vernier calipers (accuracy of 0.02 mm). Two types of assessments were done :
1. Qualitative assessments : These included : (i) vermian sulci, (ii) cerebellar hemispheric sulci, (iii) presence and size of cisterna magna, (iv) superior cerebellar cistern (SCC), (v) lateral cerebellar cistern (LCC), and (vi) cerebral cortical atrophy (CCA).
2. Quantitative assessment [Figure. 1] : The following measurements were made : (i) anteroposterior diameter (APD) and transverse diameter (TD) of pons, midbrain and 4th ventricle; (ii) mean width of brachium pontis, prepontine cistern, cerebellopontine angle cistern, quadrigeminal cistern and cisterna ambiens (iii) maximum width of 3rd ventricle; (iv) minimum transverse width of lateral ventricles at the level of cella media; (v) APD and TD of skull at the level of midbrain; (vi) interparietal diameter of skull at the level of lateral ventricles; and (vii) bimastoid diameter. Based on these measurements, 11 brainstem, cisternal and ventricular ratios were determined [Table I]. Comparisons were made between patients having : (i) EOCA and OPCA; (ii) duration of illness of <5 years and >5 years; (iii) CAS<11 and >11; and (iv) normal and abnormal BAER. CT scans of age and sex matched subjects (M:F - 23:8; age : 28.2+14.3 years) who underwent scans for headache, were taken as control. Student's test was used for the statistical method.
There were 19 men and 7 women. Their mean age was 30.4+14.9 years (range 6-66 years) and the mean duration of illness was 7.7+5.3 years (range 5-20 years). The age at presentation and the duration of illness of the 11 EOCA patients (M-7, F-4) was 18.9˝8.1 years (mean+SD) and 8.0˝5.2 years respectively. The corresponding Figures for the 15 OPCA patients (M-12, F-3) were 38.9˝13.0 years and 7.5˝5.6 years respectively. Positive family history was present in 13 patients (autosomal recessive type : EOCA-7, OPCA-3; autosomal dominant type : OPCA-3). The CAS was 12.9˝5.9 for the EOCA group and 12.5˝4.4 for the OPCA group. Fourteen patients each had duration of illness >5 years, CAS>11, and an abnormal BAER (absent waves-4, poor waveform-4, prolonged I-III IPL-2, and a combination of the latter two abnormalities-4).
Qualitative evaluation [Table I]
None of the `control' CT scans showed any cerebellar hemispheric sulcus, >2 vermian sulci, visible SCC or CCA. LCC was seen in 2 and cisterna magna was large in one subject. Based on these observations, cerebellar atrophy was indicated if : (i) >2 vermian sulci were visible (vermian atrophy-VA), (ii) visualization of any cerebellar hemispheric sulcus > 1mm, except the primary fissure (cerebellar hemispheric atrophy-CHA), or (iii) SCC was visible.
Though the incidence of CA was similar in EOCA and OPCA, the pattern of atrophy was slightly different. While the former group showed combined VA and CHA (45.4%) more frequently than isolated VA (18.2%) or isolated CHA (18.2%), the OPCA group showed an equal incidence (26.7%) of all the 3 patterns of atrophy. CHA was limited to the anterior part of cerebellum in 4 EOCA and 3 OPCA patients, and involved diffusely in the rest. Apart from CA, frontal CCA with variable involvement of parietotemporal cortices and leukoariosis were present in 7 (26.9%) (EOCA-3, OPCA-4) and 4 (15.4%) (EOCA-1, OPCA-3) patients respectively. Neuropsychological tests were impaired in all except one patient with leukoariosis.
Five patients (EOCA-2, OPCA-3) who did not have CA on qualitative evaluation of CT scans had variable duration of symptoms ranging from 5 months to 17 years. CT scans of more than one member were studied in 3 families. In 2 families, the sibs showed similar changes. In one family, 2 sibs (OPCA) showed severe VA and in the other family 3 sibs (EOCA) showed predominant VA with large cisterna magna. The third family had 3 affected sibs (EOCA); Two of these were studied. The elder sib (11 years) had pancerebellar atrophy with mild CCA, while the younger sib (6 years) had predominant CCA and large 4th ventricle, CP angle cisterns and cisterna magna.
Quantitative Evaluation [Table II]
Ten of the 11 parameters showed significant differences between patients and controls [Table I]. The only exception was the ratio of the transverse diameter of midbrain to that of skull at the level of midbrain. Noteworthy are the most severe changes concerning the ratios of pons, brachium pontis, 4th ventricle, quadrigeminal, ambiens and cerebellopontine angle cisterns and 3rd ventricle, all of which suggest severe degree of atrophy of brainstem. Less significant was the change of cella media index (CMI) suggesting lesser involvement of the supratentorial structures.
Patients having EOCA did not show any significant difference when compared to those with OPCA group. Fourteen patients with duration of illness >5 years showed statistically significant (p<0.05) lower ratio of antero posterior diameter of midbrain to the mean width of quadrigeminal cistern compared to those (n=12) with shorter duration, suggesting greater mid brain atrophy. No other parameters showed any significant difference. On the other hand 14 patients with greater disability (CAS>11) did not reveal any statistically significant difference in CT values from the remaining lesser disabled patients (CAS<11). On qualitative examination, patients having 15 and 17 years of symptoms and CAS of 22 had no CHA or VA. The width of the 3rd ventricle and cella media index were significantly increased (p<0.05) in the 14 patients with abnormal BAER compared to the 12 patients with normal BAER. However, the brainstem parameters did not show any significant changes. [Figure - 2] and [Figure - 3] show the spectrum of cerebellar, brainstem and cerebral cortical atrophy in patients with SCD.
The methodologies for CT study vary widely, especially for structures of posterior fossa which are difficult to evaluate due to artifacts. The results of our study are difficult to compare with previous ones as these studies differ in methodology and patient sample. Nevertheless, there was a higher incidence of cerebellar and brain stem atrophy in our patients. The prevalence of CA in EOCA has been reported to be 50% to 75% in previous studies,, which is less than that (81.8%) in our study. Our criteria of CA on qualitative analysis were similar to the modified criteria of Allen et al, but unlike those of Koller et al and Ramaos et al who had taken visualisation of even 2 vermian sulci to be abnormal. However, in contrast to Allen et al, we have not taken absolute measurements of the cerebellopontine angle cisterns and 4th ventricle into consideration in order to avoid the adverse influence of normal anatomical variations. Enlarged SCC was also considered as an indicator of CA, as it was not seen in the controls. In our opinion the individual variations of the qualitative observations are largely unreliable to serve as indicators of cerebellar and brainstem atrophy. The earlier observations of equal affections of cerebellar hemispheres and vermis and predominant atrophy of anterior part of hemispheres were confirmed in the present study. The significance of isolated VA or CHA, which were more frequent in OPCA, remains uncertain. Clinically, there was no appreciable difference between the patients with different varieties of cerebellar atrophy.
Quantitative measurements on the other hand are more reliable and our results are similar to the ones previously reported., In contrast to the study reported by Koller et al10 where only 3 parameters were measured, we included additional mensurations at different levels of brain for a more comprehensive evaluation of the morphological nature of atrophy. Diffuse atrophy of the pons, brachium pontis and cerebellar hemispheres were reflected by the significant differences from the controls in the mensurations in both coronal and sagittal axes. Increase in size of the 4th ventricle in the coronal axis suggests atrophy of the paraventricular areas of cerebellar hemispheres which includes the dentate nuclei. However, in the sagittal diameter it suggests atrophy of pontine tegmentum and basis pontis anteriorly, and inferior vermis posteriorly. Comparison of the relationship of the size of the midbrain in the sagittal axis to the skull and the quadrigeminal cistern showed the latter to be more significant than the former, indicating that though the midbrain is atrophied anteroposteriorly, the largeness of the quadrigeminal cistern is mainly due to the atrophy of the superior vermis which forms the posterior boundary of the cistern. Similarly, the atrophy of the midbrain in the coronal axis, reflected by the enlarged cisterna ambiens, is probably due to atrophy of the lateral part of the midbrain formed mainly by the brachium conjunctivum.
Information on cortical and subcortical changes in SCDs is limited. Dementia on clinical examination and degeneration of prefrontal and temporal regions of brain on autopsy have been reported in some patients with OPCA.13 In the present study, all except 2 patients with CCA and leukoariosis had impaired neuropsychological tests. To our knowledge, reports of leukoariosis in SCDs have not been reported. There was also evidence of subcortical atrophy, though the CMI did not reach the same degree of statistical significance as in the infratentorial compartment. This could be due to the involvement, albeit to a lesser extent, of the subcortical structures in a progressive disease involving the cerebellum and its connections. Similar patterns of CA observed in sibs of 2 families suggest that the patterns of VA and CHA may, to some extent, breed true within a given family. No previous reports are available on this aspect.
Lack of correlation of CA on CT scan with the duration of illness and the severity of ataxia is not surprising, since even the correlation between the symptomatology and anatomic pathology is disappointing. Previous findings of correlations of gait and truncal ataxia, and nystagmus with CHA and enlargement of quadrigeminal and lateral cisterns were not substantiated in our study. Abnormalities of saccades and optokinetic nystagmus were almost a constant feature in our patients and correlated well with the severe degree of atrophy of pons, the part of brain where horizontal saccadic eye movements are generated.
This study did not reveal significant differences between EOCA and OPCA on CT except for more frequent combined VA and CHA in EOCA. Klockgether et al also reported equally severe changes in the vermis and cerebellar hemispheres on MRI in 14 patients with EOCA and 2 patients in addition had severe brainstem atrophy suggesting OPCA.