Stiff-person syndrome associated with cerebellar ataxia and high glutamic acid decarboxylase antibody titer. (41/449)

Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in patients with insulin-dependent diabetes mellitus (IDDM) and stiff-person syndrome. We reviewed the case of a 46-year-old woman who had cerebellar ataxia before getting stiff-person syndrome and IDDM with high anti-GAD autoantibody titers. This was a rare case in which there were both the clinical symptoms of stiff-person syndrome and cerebellar ataxia. In western blot analysis her serum reacted with 65-kDa proteins from rat cerebellum, cerebral cortex, and spinal cord. Autoantibodies to GAD may cause functional impairment of gamma-aminobutyric acid (GABA) neurons in the spinal cord as well as in the cerebellum.  (+info)

Otolith function in cerebellar ataxia due to mutations in the calcium channel gene CACNA1A. (42/449)

The vestibulo-ocular reflexes stabilize retinal images during head movements. While there is a wealth of information about the interaction between the cerebellum and vestibulo-ocular reflexes mediated by the semicircular canals, little is known about the role of the cerebellum in the generation of the otolith-mediated linear vestibulo-ocular reflex (LVOR). By means of transient linear acceleration of the whole body along the interaural axis, we examined the LVOR in six patients with hereditary cerebellar ataxia due to mutations of the calcium channel gene CACNA1A, five with spinocerebellar ataxia type 6 (SCA6) and one with episodic ataxia type 2 (EA-2). Six age-matched normal subjects served as controls. Using a peak acceleration of 0.5 g in combination with recording by the binocular scleral magnetic search coil method, it was possible to study the latency and sensitivity of the LVOR in the first 150 ms after motion onset. The normal LVOR showed a significant dependence on viewing distance and covaried with vergence angle, and could be enhanced by the presence of a visible target. In contrast, the LVOR of ataxic patients had normal latency but significantly decreased sensitivity that was not enhanced with visible or nearer targets despite normal vergence. Substituting for the normal smooth LVOR slow phase, ataxic patients employed catch-up saccades 150-250 ms after motion onset. These findings suggest a critical role of the cerebellum in the modulation of otolith-ocular signals that is independent of motor vergence.  (+info)

Increased variability in finger position occurs throughout overarm throws made by cerebellar and unskilled subjects. (43/449)

We investigated the ability of cerebellar patients and unskilled subjects to control finger grip position and the amplitude of finger opening during a multijoint overarm throw. This situation is of interest because the appropriate finger control requires predicting the magnitude of back forces from the ball on the finger throughout the throw and generating the appropriate level and rate of change of finger flexor torque to oppose the back force. Cerebellar patients, matched controls, and unskilled subjects threw tennis balls and tennis-sized balls of different weights. In all cases angular positions of five arm segments in three dimension were recorded at 1,000 Hz with the search-coil technique as subjects threw from a seated position. When the hand was stationary, cerebellar patients showed a normal ability to grip the ball and open the fingers and drop the ball. In contrast, in overarm throws where a back force occurred on the fingers, cerebellar patients showed an abnormally large variability in amplitude of the change in finger position when gripping, in amplitude of finger opening, and in amplitude of the change in finger position 10 ms after ball release. This was not due to more trial-to-trial variation in throwing speed. When throwing balls of increasing weights, both controls and cerebellar patients had increasing finger flexions after ball release that indicated that, on average, both scaled finger force in proportion to ball weight during the throw. Unlike skilled controls, cerebellar patients showed a small (<20 degrees ) increase in the amplitude of finger opening with balls of increasing weight. However, neither the increase in variability of finger position nor the increase in finger amplitude with balls of increasing weight were unique cerebellar signs because both were observed to various degrees in unskilled throwers. It is concluded that in the absence of either normal cerebellar function or skill, the central neural activity that controls finger opening in throwing can increase finger flexor force to oppose an increase in back force from heavier balls and can open the fingers but cannot control finger force or finger opening precisely and consistently from throw to throw. These results fit with the idea that cerebellar disorders are greater in multijoint than single-joint movements because control of force is more complicated. They are also consistent with the hypothesis that the cerebellum produces skill in movement by reducing variability in the timing and force of muscle contractions.  (+info)

Creutzfeldt-Jakob disease : report of 10 cases from North India. (44/449)

Creutzfeldt-Jakob disease (CJD) is increasingly being reported over the last three decades as a result of heightened awareness of the disease. Various studies have reported annual incidence of 0.5-1.5 cases of CJD per million of general population. In India, the disease is still under reported. Over the period spanning from 1968-1997, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore recorded 69 cases of CJD from different parts of India in the CJD registry. This paper describes the clinical experience with cases of CJD managed at the Department of Neurology, G.B. Pant Hospital, New Delhi from 1990-1998. In this series, the mean age of the patients was 53.80 (+/- 7.32) years and there were 5 females and 5 males. Myoclonus was present in all the cases and abnormal behaviour with or without other features was the presenting complaint in 7 of the 10 patients, while one patient of CJD had cerebellar ataxia as the presenting feature. One patient with occipital variant of CJD presented with acute onset cortical blindness and myoclonic jerks. One of the patients had acute psychosis precipitated by emotional stress at the onset. Extrapyramidal features were noted in 7 of the 10 patients before death. The mean duration of symptoms from the onset of disease to death was 6.6 (+/- 6.11) months. Classical EEG changes were observed in all the patients, except in one possible case of occipital variant of CJD, where we did not have access to EEG record. Brain biopsy could be undertaken in 3 patients, and in 2 patients the features of subacute spongiform encephalopathy (SSE) were noted.  (+info)

Acute ataxia complicating Langherans cell histiocytosis. (45/449)

A case is reported of a 3 year old boy with an acute history of cerebellar impairment and x ray evidence of apparent chest infection. At postmortem examination, his lungs but not the nervous system were found to be massively infiltrated by Langherans histiocytes. In retrospect, the acute ataxia was diagnosed as a paraneoplastic phenomenon secondary to Langherans cell histiocytosis (LCH). This represents a unique occurrence complicating LCH in childhood.  (+info)

Phase I clinical and pharmacokinetic study of oral penclomedine (NSC 338720) in adults with advanced solid malignancy. (46/449)

Penclomedine is a synthetic alpha-picoline derivative that has shown antitumor activity both in preclinical development and in Phase I work using an i.v. preparation. The main toxicities seen in those studies were dose dependent and mainly neurocerebellar, with hematological toxicity being far less severe. This Phase I trial of p.o. penclomedine was conducted to potentially alter the toxicity profile and to avoid the neurological side effects seen with i.v. penclomedine. Eligibility criteria included microscopic confirmation of a solid malignancy or lymphoma with a lack of effective anticancer therapy. Twenty patients were enrolled. The median age was 60.5 years, and the median performance status was one. All but one patient had received prior systemic therapy. The starting dose of penclomedine was 200 mg/m(2) p.o. for 5 days, and was escalated according to a traditional Fibonacci sequence until the maximum tolerated dose (MTD) was observed. No treatment-related deaths were observed during the study. The MTD was determined to be 800 mg/m(2) p.o. for 5 days. Dose-limiting toxicities included mainly neurocerebellar symptoms such as ataxia and dysmetria, but neurocortical symptoms, such as confusion, were seen as well. Myelosuppression was less common and resulted in the discontinuation of therapy in only two patients. Pharmacokinetics show that the observed MTD is consistent with the i.v. preparations, and that the bioavailability of p.o. penclomedine is 49 +/- 18%. This regimen can be considered for additional studies in patients with intracranial neoplasms, because good central nervous system penetration is evident. Further development of penclomedine metabolites, such as 4-O-demethylpenclomedine, should be considered to minimize dose-limiting neurotoxicity.  (+info)

Presigmoid transpetrosal approach for the treatment of a large trochlear nerve schwannoma--case report. (47/449)

A 61-year-old man presented with a rare, large trochlear nerve schwannoma manifesting as left-sided weakness and hypesthesia, bilateral bulbar pareses, and trochlear nerve paresis persisting for 3 months. T1-weighted magnetic resonance imaging with gadolinium revealed an intensely enhanced, well-circumscribed lesion with multicystic formation occupying the prepontine and interpeduncular cisterns and compressing the pons and midbrain with greater extension to the right. The mass was completely removed through the presigmoid transpetrosal approach with preservation of the posterior cerebral, superior cerebellar, and basilar arteries and their branches. Neuroradiological examination after 3 years demonstrated no recurrence. Enlargement of a tumor in the cisternal portion is inclined to involve and/or encase the adjacent major arteries and their branches. The presigmoid transpetrosal approach is one of the best surgical routes to remove a large trochlear nerve schwannoma safely and completely.  (+info)

Unusual arachnoid cyst of the quadrigeminal cistern in an adult presenting with apneic spells and normal pressure hydrocephalus--case report. (48/449)

A 67-year-old woman was admitted to our clinic with symptoms of normal pressure hydrocephalus, lower cranial nerve pareses, and pyramidal and cerebellar signs associated with respiratory disturbances. Computed tomography (CT) and magnetic resonance imaging revealed a 4.7 x 5.4 cm quadrigeminal arachnoid cyst causing severe compression of the tectum and entire brain stem, aqueduct, and cerebellum, associated with moderate dilation of the third and lateral ventricles. Emergency surgery was undertaken due to sudden loss of consciousness and impaired breathing. The cyst was totally removed by midline suboccipital craniotomy in the prone position. Postoperatively, her symptoms improved except for the ataxia and impaired breathing. She was monitored cautiously for over 15 days. CT at discharge on the 18th postoperative day revealed decreased cyst size to 3.9 x 4.1 cm. Histological examination confirmed the diagnosis of the arachnoid cyst of the quadrigeminal cistern. The patient died of respiratory problems on the 5th day after discharge. Quadrigeminal arachnoid cysts may compress the brain stem and cause severe respiratory disturbances, which can be fatal due to apneic spells. Patients should be monitored continuously in the preoperative and postoperative period until the restoration of autonomous ventilation is achieved.  (+info)