Autoantibodies in postinfectious acute cerebellar ataxia

The authors found serum immunoglobulin M (IgM) autoantibody in a patient with typical acute cerebellar ataxia (ACA) and identified the antigen molecule as triosephosphate isomerase (TPI). TPI antigenicity to the patient's antibody was the highest in the cerebellar tissue. Eight of 23 patients with ACA had increased IgM anti-TPI antibody titers vs those of healthy controls. Preceding Epstein-Barr virus infection was confirmed serologically in all 8 patients. Anti-TPI antibody decreased with clinical improvement.     

Decreased cerebellar blood flow in postinfectious acute cerebellar ataxia

OBJECTIVE: The aim of the present study was to evaluate the regional cerebral blood flow (rCBF) in patients with postinfectious acute cerebellar ataxia using single photon emission computed tomography (SPECT). METHODS: Five children with postinfectious acute cerebellar ataxia and five control subjects were examined. The distribution of rCBF was measured by SPECT imaging after intravenous administration of 123I-IMP (111 MBq). The rCBF ratio-defined as the ratio of rCBF in the region of interest (ROI) to that in the occipital cortex-was calculated for each cortical and subcortical ROI. The mean rCBF ratio of each region was then compared between the ataxic and control subjects. These patients and all control subjects were also evaluated using MRI. RESULTS: The rCBF ratio was significantly lower in the cerebellum of the ataxic patients than in the cerebellum of the control subjects (p<0.05). No abnormal cerebellar morphology and no abnormal signal intensities were found on MRI. CONCLUSION: 123I-IMP SPECT clearly demonstrated the decreased rCBF in the cerebellum of all patients with postinfectious acute cerebellar ataxia.     

Cerebellar stimulation in acute cerebellar ataxia.

OBJECTIVES: To report follow-up studies of cerebellar stimulation in patients with acute cerebellar ataxia (ACA). METHODS: We studied two patients with ACA. One patient also had decreased deep sensations in the feet due to combined diseases such as diabetic polyneuropathy and lumbosacral radiculopathies. We applied the technique of electrical stimulation over the cerebellum which was reported previously (Ugawa et al., J Physiol 441 (1991a) 57). RESULTS: Conditioning stimulation over the cerebellum did not reduce the size of motor-evoked potentials to test magnetic stimulation of the motor cortex at conditioning-test intervals of 5, 6, and 7 ms in the acute stage in both patients. However, normal suppression was recognized in the recovery stage in both patients. CONCLUSIONS: This technique was useful for follow-up evaluation of cerebellar function in patients with ACA and was also useful for distinguishing cerebellar ataxia from sensory ataxia in a patient with combined diseases.     

Neuropsychological recovery following acute cerebellar ataxia

Abstract

Acute Cerebellar Ataxia (ACA) is a not infrequent disorder in childhood characterized by sudden onset of such cerebellar signs as truncal ataxia, dysmetria, tremors, nystagmus, and hypotonicity. Despite the suggestion in the literature that children who have suffered from ACA may continue to have neurological deficits, there have not been any attempts to address systematically and quantitatively the nature and frequency of dysfunction in the cognitive and motor domains. To this end, 15 patients with a discharge diagnosis of ACA at Children's Hospital of Michigan were administered a Wechsler Intelligence Scale, visual-spatial tests, achievement tests, and a test of motor speed, targeting, and finger dexterity (the Purdue Pegboard). Results indicated that higher level cognitive functions, ncluding those in the linguistic and visual-perceptual domain, remained intact. In addition, the distribution of academic achievement scores was not markedly atypical. However, Purdue Pegboard performances in the majority of patients were notably impaired. Correlations among cognitive variables and such variables as age at onset and length of hospitalization were nonsignificant: no adequate prognostic indicators were ascertained. The implications of the results for theories of cerebellar plasticity or lack thereof are commented upon.     

Autoantibodies in childhood post-varicella acute cerebellar ataxia

BACKGROUND: Anti-Purkinje cell antibodies have been reported in cerebellar ataxia following Epstein-Barr virus (EBV) infection. We investigated autoantibody responses, including anti-Purkinje cell antibodies, and the clinical course in eight children who developed post-varicella ataxia, five of their siblings with uncomplicated varicella, one child with post-EBV ataxia, two children with acute disseminated encephalomyelitis (ADEM) and one with neuroblastoma associated ataxia, and in age and gender matched controls. METHODS: Autoantibodies were tested by indirect immunofluorescence (IIF) on cryopreserved cerebrum and cerebellum sections. Other autoantibodies were measured by conventional IIF protocols using HEp-2 cells as a substrate. Antibodies to myelin associated glycoprotein (MAG), asialo-GM1, beta2 glycoprotein 1, cardiolipin and myelin basic protein (MBP) were measured by ELISA. RESULTS: Three of eight children with acute post-varicella ataxia, one child with post-EBV ataxia, one child with ADEM and one child with uncomplicated varicella, had high titer autoantibodies (>1/160) that reacted with cerebrum and cerebellar tissue. This reactivity was not seen in one child with ADEM, in one with neuroblastoma and ataxia, in the remainder of the children with uncomplicated varicella or age and gender matched controls. Autoantibodies were not seen in CSF from two children with post-varicella ataxia. The punctate staining seen on cerebrum and cerebellum sections co-localized with rabbit antibodies to the centrosome protein pericentrin. All patients with strong reactivity with cerebrum and cerebellar tissue by IIF had elevated levels of anti-MAG that was not confirmed by absorption assay. No reactivity was seen with asialo-GM1, MBP, beta2 glycoprotein 1 or cardiolipin. None of the sera had autoantibodies directed against endosomes, the Golgi complex, or the paraneoplastic autoantigens Hu and Yo. CONCLUSION: Some children with post-viral ataxia develop antibodies that have strong reactivity with cerebral and cerebellar tissue. Some of the antigenic reactivity co-localized with the centrosome protein pericentrin.     

Varicella and acute cerebellar ataxia.

In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism.     

Risk factors for the occurrence and recurrence of acute cerebellar ataxia: a retrospective observational study

Neurological Sciences - There is little evidence to support a correlation between abdominal surgery and acute cerebellar ataxia (ACA). We reviewed the records of children with ACA treated at our...     

Neoplastic meningitis presenting with acute cerebellar ataxia

Acute cerebellar ataxia is a rare initial presenting feature of neoplastic meningitis (NM), particularly in gastric cancer. The authors report a 61-year-old woman with acute cerebellar ataxia secondary to NM from gastric cancer, which was not accompanied by other symptoms commonly associated with NM at initial presentation. It is suggested that NM should be considered in the differential diagnosis of cancer patients with acute cerebellar ataxia.     

Course and outcome of acute cerebellar ataxia

We report a study of 73 consecutive children with acute cerebellar ataxia, representing all of the children evaluated at St. Louis Children's Hospital during a 23-year-period to whom this diagnosis could appropriately be assigned. Twenty-six percent had chickenpox, 52% had other illnesses that were presumed to be viral, and in 3% the ataxia was related to immunization. Nineteen percent had no definite prodrome. Sixty children were followed for 4 months or longer after onset of their ataxia (mean, 7.4 ± 6.0 years). Ninety-one percent (55/60) of these, including all children with chickenpox, recovered completely from ataxia. Eighty-nine percent (39/44) of the children with non-varicella-related ataxia recovered completely from the ataxia, a much better rate of recovery than what was found in prior large studies. One fifth of the children followed for more than 4 months experienced transient behavioral or intellectual difficulties, but only 5 of the 60 children demonstrated sustained learning problems. This study represents the largest reported series of acute cerebellar ataxia and the most complete characterization of the clinical features and outcome of this illness.     

Recurrent and pre-eruptive acute cerebellar ataxia: a rare case of varicella

This is a report of an unusual case of acute cerebellar ataxia in which the ataxia recurred after a 6 week interval and the second episode of ataxia antedated the varicella exanthem by 19 days, suggesting the direct invasion of the central nervous system by the varicella virus.     

Residual cerebellar ataxia following acute phenytoin intoxication]

A 30-year-old man was given high doses of phenytoin together with 4 antituberculous drugs for a seizure associated with a probable brain tuberculoma. He developed hepatic toxicity and his serum phenytoin reached the high level of 298 mumol/l (therapeutic range 40-79 mumol/l). All drugs were stopped and the biological parameters returned progressively to normal over the next 15 days. However, he remained with a cerebellar axial syndrome and was still severely ataxic 2 months later. Brain CT and MRI showed mild cerebellar atrophy. This case and the few other published ones, together with some recent experimental data, show that high doses of phenytoin can be toxic to the cerebellar cortical cells. The rarity of similar cases, while millions of epileptics are under phenytoin treatment, would however suggest that individual susceptibility may play a role in this toxicity.     

Recurrent acute cerebellar ataxia associated with anti-cardiolipin antibodies

Various autoantibodies are detected in patients with acute cerebellar ataxia (ACA). Although an autoimmune process may contribute to the mechanism of ACA, its pathophysiology is not completely understood. We report a girl with recurrent ACA and anti-cardiolipin antibodies. Her cerebral blood flow imaging showed hypoperfusion in the cerebellum, which improved when the anti-cardiolipin antibodies disappeared. Our case suggests that vasculopathy or non-vascular neurotoxicity in the cerebellum caused by antiphospholipid antibodies leads to acute cerebellar ataxia.     

Acute cerebellar ataxia with abnormal MRI lesions after varicella vaccination

A 2-year-old boy, with the primary difficulties of nausea and vomiting, developed a staggering gait and dysarthria 10 days after varicella vaccination. Magnetic resonance imaging demonstrated multiple areas of high signal intensity in the white matter of the cerebellum, predominantly in the parieto-occipital white matter and both globus pallidi. He did not present any signs of myelitis or encephalitis and thus his cerebellar dysfunction was diagnosed as acute cerebellar ataxia, which is, generally speaking, not an etiologic entity but a clinical syndrome. Magnetic resonance imaging may reveal a variety of abnormalities of the central nervous system in acutecerebellar ataxia.     

16q-linked autosomal dominant cerebellar ataxia: a clinical and genetic study

The autosomal dominant cerebellar ataxias (ADCAs) comprise a genetically and clinically heterogenous group of neurodegenerative disorders. Very recently, a C-to-T single nucleotide substitution in the puratrophin-1 gene was found to be strongly associated with a form of ADCA linked to chromosome 16q22.1 (16q-linked ADCA; OMIM 600223). We found the C-to-T substitution in the puratrophin-1 gene in 20 patients with ataxia (16 heterozygotes and four homozygotes) and four asymptomatic carriers in 9 of 24 families with an unknown type of ADCA. We also found two cases with 16q-linked ADCA among 43 sporadic patients with late-onset cortical cerebellar atrophy (LCCA). The mean age at onset in the 22 patients was 61.8 years, and that of homozygous patients was lower than that of heterozygous ones in one family. Neurological examination revealed that the majority of our patients showed exaggerated deep tendon reflexes in addition to the cardinal symptom of cerebellar ataxia (100%), and 37.5% of them had sensorineural hearing impairment, whereas sensory axonal neuropathy was absent. The frequency of 16q-linked ADCA was about 1/10 of our series of 110 ADCA families, making it the third most frequent ADCA in Japan.     

Acute cerebellar ataxia in a child with transient pontine lesions demonstrated by MRI.

A case of acute cerebellar ataxia with discrete signs of pyramidal and tegmental involvement is reported, several days after recovery from an upper respiratory infection of unknown etiology. Magnetic resonance imaging showed transient pontine lesions, disappearing in the convalescence phase. Laboratory tests established the etiologic diagnosis of post-infectious encephalitis. An allergic autoimmune response with subsequent demyelinisation is assumed. The important role of MR-imaging in similar acute syndromes is emphasized.     

Speech changes after coordinative training in patients with cerebellar ataxia: a pilot study

Although rehabilitative training is a necessary adjunct in the management of gait ataxia, it remains unknown whether the possible beneficial effect of intensive coordinative training may translate to activities of daily living, which are closely connected with postural alignment. The aim of the present study was to examine the effectiveness of a 2-week intensive coordinative motor training on speech production. Speech and motor performances in a cohort of ten individuals with cerebellar degeneration were examined three times; before the introduction of training, directly and 4 weeks after the last training session. Each patient was instructed to perform a speaking task of fast syllable repetition and monologue. Objective acoustic analyses were used to investigate six key aspects of speech production disturbed in ataxic dysarthria including accuracy of consonant articulation, accuracy of vowel articulation, irregular alternating motion rates, prolonged phonemes, slow alternating motion rates and inappropriate segmentation. We found that coordinative training had a mild beneficial effect on speech in cerebellar patients. Immediately after the last training session, slight speech improvements were evident in all ten patients. Furthermore, follow-up assessment performed 4 weeks later revealed that 90 % of the patients showed better speech performance than before initiation of the therapy. The present study supports evidence that the intensive rehabilitative training may positively affect fine-motor movements such as speech in patients with cerebellar ataxia.