Oculomotor abnormalities and MRI findings in idiopathic cerebellar ataxia

Extensive oculomotor testing and quantitative MRI evaluation was performed in seven patients with idiopathic cerebellar ataxia without extracerebellar symptoms (IDCA-C) and in ten patients with additional extracerebellar symptoms (IDCA-P). The most severe oculomotor deficits were disturbed smooth pursuit, optokinetic nystagmus and suppression of the vestibulo-ocular reflex (VOR). The symptoms correlated well and consistently with the amount of atrophy of the flocculus and the dorsal vermis. These correlations, however, were not specific, and deficits also correlated with the amount of atrophy of other cerebellar structures. No correlation was found between saccade velocity and brain-stem atrophy or between saccade metrics and atrophy of the dorsal vermis. Although patients with IDCA-P had more severe oculomotor deficits than patients with IDCA-C, the pattern of the oculomotor disturbances was the same for both groups. Thus, eye movement analysis alone is not sufficient to distinguish between patients with pure cerebellar ataxia and those with additional extracerebellar symptoms.     

Visuomotor Cerebellum in Human and Nonhuman Primates

In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula?Cnodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.     

Roles of the cerebellum in pursuit-vestibular interactions

This mini-review focuses on cerebellar roles in on-line control of smooth-pursuit eye movements during vestibular stimulation in primates. The smooth-pursuit system is necessary to track smoothly moving targets and must interact with the vestibular system during movement of the head and/or whole body to maintain the precision of eye movements in space (i.e. gaze movements). This interaction requires calculation of gaze velocity commands that match the eye velocity in space to the actual target velocity. Two cerebellar regions, the floccular lobe that consists of the flocculus and ventral paraflocculus, and the dorsal vermis, are known to be involved in smooth-pursuit. However, potential differences in their involvement are incompletely understood. To understand their roles, in particular whether the output of these regions codes gaze velocity or eye velocity, simple-spike activity of Purkinje (P-) cells was examined during smooth-pursuit and pursuit-vestibular interaction tasks in various directions in head-restrained monkeys. The results showed differences in discharge characteristics of vertical and horizontal P-cells within the floccular lobe and between the floccular lobe and dorsal vermis. These differences and other available evidence suggest that the dorsal vermis is involved more in the control of gaze movement whereas the floccular lobe primarily controls eye movement (in the orbit) as a component of the oculomotor neural integrator. Smooth-pursuit without vestibular stimulation cannot dissociate eye movement from gaze movement. To understand the cerebellar role in various aspects of smooth tracking of targets moving in the three dimensional space, more information is needed particularly on how the above mentioned two regions along with the dorsal paraflocclus and underlying deep cerebellar nuclei are involved in vergence tracking, how the cerebellum is involved in prediction and perception of target motion, and whether complex-spike discharge is involved in a fast adaptive process that may be used for prediction in smooth ocular tracking.     

Atrophy of the Cerebellar Vermis in Essential Tremor: Segmental Volumetric MRI Analysis

Postmortem studies of essential tremor (ET) have demonstrated the presence of degenerative changes in the cerebellum, and imaging studies have examined related structural changes in the brain. However, their results have not been completely consistent and the number of imaging studies has been limited. We aimed to study cerebellar involvement in ET using MRI segmental volumetric analysis. In addition, a unique feature of this study was that we stratified ET patients into subtypes based on the clinical presence of cerebellar signs and compared their MRI findings. Thirty-nine ET patients and 36 normal healthy controls, matched for age and sex, were enrolled. Cerebellar signs in ET patients were assessed using the clinical tremor rating scale and International Cooperative Ataxia Rating Scale. ET patients were divided into two groups: patients with cerebellar signs (cerebellar-ET) and those without (classic-ET). MRI volumetry was performed using CIVET pipeline software. Data on whole and segmented cerebellar volumes were analyzed using SPSS. While there was a trend for whole cerebellar volume to decrease from controls to classic-ET to cerebellar-ET, this trend was not significant. The volume of several contiguous segments of the cerebellar vermis was reduced in ET patients versus controls. Furthermore, these vermis volumes were reduced in the cerebellar-ET group versus the classic-ET group. The volume of several adjacent segments of the cerebellar vermis was reduced in ET. This effect was more evident in ET patients with clinical signs of cerebellar dysfunction. The presence of tissue atrophy suggests that ET might be a neurodegenerative disease.     

Spinocerebellar syndrome in patients infected with human T-lymphotropic virus types I and II (HTLV-I/HTLV-II): report of 3 cases from Panama

Cerebellar symptoms at onset are unusual in HTLV-I/II-associated tropical spastic paraparesis (TSP). A prospective study of neurological disorders in Panama (1985-1990) revealed 13 patients with TSP and 3 with HTLV-I/II-associated spinocerebellar syndrome (HSCS) presenting at onset loss of balance, wide-based stance and gait, truncal instability, and mild leg ataxia (vermian cerebellar syndrome), with absent upper limb dysmetria but with postural tremor, downbeat nystagmus, and dysarthria. In 4-5 years, spinal cord manifestations of TSP developed, including spastic paraparesis, pyramidal signs, bladder and sphincter disturbances. Two patients were infected with HTLV-I and another one, a Guaymi Amerindian woman, with HTLV-II. Magnetic resonance imaging (MRI) demonstrated cerebellar atrophy involving predominantly the superior vermis. Mild axonal peripheral neuropathy in the lower limbs, dorsal column involvement and inflammatory myopathy were found by neurophysiology studies. There are 14 similar cases reported in Japan and Canada, but to our knowledge these are the first documented cases of HSCS in the tropics. A cerebellar syndrome constitutes another form of presentation of HTLV-I/II infection of the nervous system.     

Cerebellum and neuropsychiatric disorders: insights from ARSACS

Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by ataxia, spastic paraparesis, polyneuropathy, and evidence of superior cerebellar vermis atrophy at magnetic resonance imaging (MRI). Reports of atypical presentations and additional clinical or MRI findings have been recently published, but psychiatric disturbances have never been associated with ARSACS. We describe four ARSACS patients manifesting severe psychiatric symptoms including psychosis, panic disorder, and depression during the course of the disease. Our case reports further expand the ARSACS phenotype and add clinical data in favor of the hypothesized relationship between cerebellar dysfunction and psychiatric disorders.     

Spinocerebellar Ataxia Types 1, 2, 3 and 6: the Clinical Spectrum of Ataxia and Morphometric Brainstem and Cerebellar Findings

To assess the clinical spectrum of ataxia and cerebellar oculomotor deficits in the most common spinocerebellar ataxias (SCAs), we analysed the baseline data of the EUROSCA natural history study, a multicentric cohort study of 526 patients with either spinocerebellar ataxia type 1, 2, 3 or 6. To quantify ataxia symptoms, we used the Scale for the Assessment and Rating of Ataxia (SARA). The presence of cerebellar oculomotor signs was assessed using the Inventory of Non-Ataxia Symptoms (INAS). In a subgroup of patients, in which magnetic resonance images (MRIs) were available, we correlated MRI morphometric measures with clinical signs on an exploratory basis. The SARA subscores posture and gait (items 1-3), speech (item 4) and the limb kinetic subscore (items 5-8) did not differ between the genotypes. The scores of SARA item 3 (sitting), 5 (finger chase) and 6 (nose-finger test) differed between the subtypes whereas the scores of the remaining items were not different. In SCA1, ataxia symptoms were correlated with brainstem atrophy and in SCA3 with both brainstem and cerebellar atrophy. Cerebellar oculomotor deficits were most frequent in SCA6 followed by SCA3, whereas these abnormalities were less frequent in SCA1 and SCA2. Our data suggest that vestibulocerebellar, spinocerebellar and pontocerebellar circuits in SCA1, SCA2, SCA3 and SCA6 are functionally impaired to almost the same degree, but at different anatomical levels. The seemingly low prevalence of cerebellar oculomotor deficits in SCA1 and SCA2 is most probably related to the defective saccadic system in these disorders.     

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)     

Magnetic resonance imaging in degenerative ataxic disorders.

MRI of the brain was performed in 53 patients with a variety of degenerative ataxias and related disorders and 96 control subjects. Atrophy of intracranial structures was not seen in patients with the pure type of hereditary spastic paraplegia, or in early cases of Friedreich's ataxia. In advanced Friedreich's ataxia there was atrophy of the vermis and medulla. The MRI features of early onset cerebellar ataxia with retained reflexes were variable, and suggest heterogeneity. In autosomal dominant cerebellar ataxias, most patients had cerebellar and brainstem atrophy, probably reflecting the pathological process of olivopontocerebellar atrophy; there was no clearly defined group with both clinical and imaging features of isolated cerebellar involvement. The MRI abnormalities in idiopathic late onset cerebellar ataxia were predominantly those of cerebellar and brainstem atrophy or pure cerebellar atrophy. The clinical and imaging features of brainstem abnormalities were discordant in several patients. Pure cerebellar atrophy was associated with slower progression of disability. Cerebral atrophy was common in the late onset ataxias. Cerebral white matter lesions, although usually few in number, were observed in significantly more patients than controls, particularly those aged over 50 years.     

Correlation of clinical signs with CT findings in patients with cerebellar disease

Summary The severity of cerebellar signs and the degree of cerebellar atrophy depicted by computed tomography (CT) were independently graded in 108 patients with cerebellar disorders. The overall agreement between these independently scaled measures was only 28%. In patients with involvement of the cerebellar hemispheres and anterior lobe, clinical signs tended to be more pronounced than the cerebellar atrophy revealed by CT. The opposite was true for patients with lesions of the caudal vermis. Patients with Friedreich's ataxia had no or only minor CT abnormalities. Close correlation between the degree of infra- and supratentorial atrophy was found only in chronic alcoholics. The poor correlation between changes in cerebellar structure detected by CT and clinical disability suggests the need for caution in CT interpretation.     

Contribution of MRI to the topography of oculomotor disorders in multiple sclerosis

Magnetic resonance imaging (MRI) was performed in 20 patients with multiple sclerosis and abnormal electro-oculographic examination. All but 2 patients showed MRI abnormalities in the infratentorial region: hypersignal on T2-weighted sequences and/or images of atrophy. Usually, each patient had multiple abnormalities, which could prevent anatomico-oculographic correlations. With oculomotor disorders of cerebellar origin, correlations between clinical findings and MRI images were satisfactory, but with disorders due to brainstem lesions correlations were not so good, as shown by the results in 9 patients with internuclear ophthalmoplegia.     

Atrophy pattern in SCA2 determined by voxel-based morphometry

We applied voxel-based morphometry, an indirect volumetric technique, to MRI volumes of patients carrying the spinocerebellar ataxia type 2 mutation to determine patterns of brain atrophy. Nine patients were compared to 27 controls matched for age, sex and handedness. An optimised voxel-based morphometry protocol was used for pre-processing to minimize systematic bias. We observed significant volume loss in the cerebellar hemispheres, vermis, pons, mesencephalon and thalamus. Also affected were several supratentorial areas such as the right orbito-frontal cortex, right temporo-mesial cortex and the primary sensorimotor cortex bilaterally. The volumetric changes of cerebellar hemispheres were inversely correlated to cerebellar symptoms rated by a cerebellar ataxia scale. Two mechanisms could contribute to the observed cortical atrophy. It could be either the result of primary supratentorial degeneration as part of the disease process and/or secondary atrophy due to cerebellar deafferentation.     

Alzheimer's disease and the cerebellum: a morphologic study on neuronal and glial changes

Structural manifestations of Alzheimer's disease (AD) including neuronal loss were investigated in 12 cases of AD and in 10 healthy age-matched controls, with focus on the cerebellum. Linear Purkinje cell (PC) density was measured in the vermis and cerebellar hemispheres. Neurons were also counted in the inferior olivary nucleus. In vermis of the AD cases, the mean PC number was significantly lower (p = 0.019) than in the controls. The neurons in the inferior olive were similarly fewer, though not significantly (p = 0.13). Molecular layer gliosis and atrophy in the vermis was clearly severer in AD than in the controls. Features typical of cerebral Alzheimer encephalopathy (plaques, tangles and microvacuolization) were inconspicious. The structural cerebellar changes in the AD cases were thus neuronal loss, atrophy and gliosis, judged to represent the disease process, and with a main involvement in the vermis. This may be reflected in some of the symptoms and signs seen in AD, signs that are generally overlooked or judged to be of noncerebellar origin.     

Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography

Local cerebral metabolic rate for glucose was studied utilizing 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 14 chronically alcohol-dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects. Group B did not show decreased rates in the cerebellum. Both Groups A and B showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects. The severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex. The degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex, but not in the cerebellum. The data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration, and does not occur in alcohol-dependent patients without clinical evidence of cerebellar dysfunction. Hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol-dependent patients with or without alcoholic cerebellar degeneration.     

Cerebellar agenesis: a case report with clinical and MR imaging findings and a review of the literature

We describe the clinical and MRI findings in a 22-year-old male patient with absence of the cerebellum, an extremely rare anomaly. Clinical features included ataxia of limbs, gait and stance, cerebellar oculomotor signs. MRI evaluation showed minute remnants of cerebellar tissue corresponding to the anterior quadrangular lobules. Nine previous cases of total or subtotal cerebellar agenesis have been reported, including Combettes's first report in 1831. We report an additional case and provide MRI of this unusual anomaly detected during life. Diagnosis in this case was made on the basis of MR findings. To our knowledge, this is the fifth report of this disorder being diagnosed in a living patient.     

Reduced cerebellar blood flow and oxygen metabolism in spinocerebellar degeneration: a combined PET and MRI study

Fourteen patients with spinocerebellar degeneration (SCD) were subjected to MRI and PET studies. The quantitative MRI data revealed significant cerebellar and pontine atrophy in the patients with olivopontocerebellar atrophy (OPCA), and cerebellar atrophy in the patients with late cerebellar cortical atrophy (LCCA). We failed to demonstrate significant differences in the pons between LCCA patients and normal controls. PET measurements revealed decreases in cerebral oxygen metabolic rate (CMRO₂) in the cerebellar hemisphere and vermis in both groups of patients. The markedly decreased cerebral blood flow (CBF) and CMRO₂ in the pons were found only in the patients with OPCA. PET data corrected for the tissue shrinkage on the basis of MRI morphometry indicated a net reduction in cerebellar CMRO₂ and CBE The present study has demonstrated that a combination of functional and anatomical data offers further evidence in favour of the current acceptable classification of SCD based on clinicopathological grounds. Our data further suggest that the amount of atrophy in the cerebellum could not fully account for the decreased metabolic rates observed in PET studies.     

Visualization and quantification of disease progression in multiple system atrophy.

To visualize and quantify disease progression in multiple system atrophy (MSA) from cerebellar type (MSA-C), we combined two magnetic resonance imaging (MRI) techniques, voxel-based morphometry (VBM) and 3D-based volumetry. Patients suffering from MSA-C (n = 14) were imaged twice with an interval of 2.0 +/- 0.2 years. We first applied VBM to map brain morphology changes between MSA patients and controls and to identify brain areas that showed a significant amount of atrophy. Using 3D-based volumetry, we confirmed that in MSA-C patients, the brainstem including medulla and pons, vermis and cerebellar hemispheres, caudate nucleus and putamen showed significant atrophy compared with controls. Next, we used 3D-based volumetry to analyze the atrophy rates. Atrophy rates in patients with MSA were significantly different from controls for putamen (-11.4% +/- 2.6%/year), vermis (-12.3% +/- 2.9%/year), and cerebellar hemispheres (-6.6% +/- 1.1%/year). The results show that 3D-based MRI volumetry is a tool that allows the disease progression of MSA to be followed over a time period of 2 years and suggest that it may serve as a surrogate marker in clinical trials to measure disease progression.     

Paroxysmal cerebellar ataxia--an evaluation using the findings from magnetic resonance imaging, positron emission tomography, and acetazolamide treatment

Paroxysmal cerebellar ataxia (PCA) is a specific disease which exhibits spasmodic cerebellar ataxia but rarely shows abnormal neurological findings in the intermission. Verger first described an isolated case. Subsequent reports of the disease included mostly cases with autosomal dominant inheritance, but the reports have been limited to about 20 families. Although both the lesion and the cause have not been clearly identified, since Vighetto et al. demonstrated the atrophy of the anterosuperior region of the cerebellar vermis using magnetic resonance imaging (MRI), the lesion of PCA captured the attention of researchers. The patient was a 40-year-old male, who exhibited spasmodic inarticulation and dizziness during walking when he was 10 years old. The symptoms gradually became aggravated in both frequency and duration. Abnormal findings were observed by electroencephalography and Hydantol F was given with no successful effect. The results of a CT scan of the head revealed no abnormality, whereas those of MRI revealed the atrophy in the folia of anterosuperior region of the cerebellar vermis by MRI as in the case of Vighetto et al., and PCA was suspected. Findings from positron emission tomography (PET) for the first time disclosed the abnormality in the cerebellar vermis and brainstem, and suggested an organic disorder in the cerebellar vermis and a functional abnormality in the cerebellum and brainstem. Since the report by Griggs et al., it has been known that acetazolamide is effective for PCA although the pharmacological mechanism is not yet clear. In our present case, the attack was improved in both frequency and duration by the administration of acetazolamide, and the effectiveness of acetazolamide in the patient was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)     

An MRI study of hereditary spinocerebellar degenerations

We evaluated magnetic resonance image (MRI) in 21 cases of hereditary spinocerebellar degenerations (SCD) of autosomal dominant trait. By the discriminant formula based on size of the cerebellar vermis and ventral pons, which was reported in our previous study, the patients were classified into three types. Group 1 included the cases with atrophies in the vermis and pons; OPCA type. Group 2 showed vermian atrophy and less significant atrophy in pons; LCCA type. And Group 3 was no significant atrophies both in vermis and pons. Cases in Group 1 were furthermore divided into two groups according to width of the midbrain tegmentum. Group 1A, with normal midbrain tegmentum, was consisted of five cases. Four cases were diagnosed as Menzel type OPCA. Another case showed various clinical symptoms and relatively mild atrophies for his duration of illness. His family members were classified to Group 3. Seven cases in Group 1B showed reduced midbrain tegmentum. Four cases showed ataxia, spasticity, ocular symptoms, bladder dysfunction and amyotrophy with or without fasciculation, and they seemed to be a special type of SCD mimicking Joseph disease. One case showed bulging eyes, ocular movement palsy and dystonia. However, his sister manifested only ataxia with very mild ocular movement disorder. Their MRI demonstrated severe atrophies in the cerebellum, pons and afferent cerebellar peduncli, and this pedigree was thought to be Menzel type OPCA with various associated disorders. Another case was clinically diagnosed as dentate-rubro-pallido-luysian atrophy. Group 2 was consisted of 6 cases who were clinically diagnosed as Holmes type LCCA. MRI demonstrated medial dominant cerebellar atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proton magnetic resonance spectroscopy (1H MRS) in patients with sporadic cerebellar degeneration.

The authors studied 23 patients with cerebellar degeneration including multiple systemic atrophy (MSA) and cerebellar cortical atrophy (CCA) by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS allowed noninvasive measurement of the signal intensities derived from N-acetylaspartate (NAA), creatine + phosphocreatine (CRE), and choline-containing compounds (CHO). There was significant reduction of the NAA/CRE level in the frontal cortex, putamen, cerebellar hemisphere and cerebellar vermis of patients with MSA, and in the frontal cortex, cerebellar hemisphere and cerebellar vermis of patients with CCA as compared with those of normal controls. There was significant reduction of the NAA/CRE level also in the putamen of patients with MSA as compared with that of patients with CCA. These results indicated the presence of a degenerative process and/or functional impairment in the frontal cortex and putamen of patients with MSA and in the frontal cortex of patients with CCA, in addition to a degenerative process in the cerebellum. There was a significant correlation between the NAA/CRE level and the severity of clinical signs. 1H-MRS is valuable in providing information regarding the pathophysiology and the progress of cerebellar degenerative diseases.