The relationship between relapse, impairment and disability in multiple sclerosis.

OBJECTIVE: To describe the spatial relationship between relapse and disability in multiple sclerosis (MS). METHODS: 141 relapse onset MS patients were studied. For each patient an examination was performed and a relapse history obtained. Multivariate logistic regression examined whether there was an association between localizing clinical signs and a history of relevant relapse in order to explore the spatial relationship between relapse and subsequent disability. RESULTS: The presence of impaired vision or sensation was independently associated with a history of one or more anatomically related relapses. The presence of weakness or cerebellar ataxia in a limb was not associated with a single relevant relapse but was associated with multiple relevant relapses. A history of multiple episodes of weakness or ataxia in the same limb was uncommon. CONCLUSIONS: Our data suggest that motor pathways are relatively resistant to chronic impairment from acute relapse, whereas afferent pathways are more susceptible. This, in combination with prominent usage of the Expanded Disability Status Scale, which is dependent on mobility and motor function at higher scores, may explain the paradox between natural history studies that suggest relapses are irrelevant to long-term disability and shorter studies at lower disability levels suggesting relapses are responsible for disability accumulation.

Profile of cognitive functioning in women with the fragile X mutation.

Two studies tested the specificity of the neurocognitive profile of women with fragile X syndrome (FXS). First, women with an FXS full mutation were compared with women with a premutation and women without FXS who grew up in FXS families. Women with FXS had a significantly lower IQ than the other groups, and analyses of subtest profiles showed they had a relative weakness on Arithmetic and strength on Picture Completion. Women with FXS performed worse than the other groups on executive function, spatial ability, and visual memory. Next, women with FXS were compared with women without FXS matched on age and IQ. A similar IQ profile was found, but women with FXS were worse than controls only on executive function. The authors also examined which neurocognitive indices were related to the underlying biology of the disorder. Overall, the results indicated that executive rather than visuospatial deficits were primary in the neurocognitive profile of FXS.

Ki-67 immunolabelling index is a prognostic indicator in childhood posterior fossa ependymomas.

Conventional histological evaluation and subclassification of childhood ependymomas poorly predict their biological behaviour. The Ki-67 labelling index (Ki-67 LI), a measure of growth fraction, correlates with the biological behaviour of several neoplasms, and this retrospective study tested the hypothesis that Ki-67 LI is a prognostic indicator in childhood posterior fossa ependymomas. Immunocytochemistry using an antibody to Ki-67 was undertaken on 5 microns sections of formalin-fixed, paraffin-embedded tissue from 74 cases of childhood (age < 16 years.) posterior fossa ependymoma. A Ki-67 LI was established by counting the proportion of labelled nuclei in more than 1000 cells from several histological fields. Several clinical and histological variables (including Ki-67 LI) potentially associated with survival were entered into univariate and multivariate analyses using a Cox proportional hazards model. Variables that showed a significant and independent association with survival were Ki-67 LI (P < 0.002), whether total surgical resection had been achieved according to operation records (P < 0.03), and whether no adjuvant therapy had been given (P < 0.01). Age, sex, and the presence of necrosis or microvascular proliferation did not correlate with survival. In our defined population of patients with ependymomas, Ki-67 LI is a strong prognostic indicator. We recommend that Ki-67 LI is used in the histological evaluation of childhood posterior fossa ependymomas during trials of novel adjunctive therapies.

Imitation and pantomime in high-functioning adolescents with autism spectrum disorders.

A study was designed to test 2 alternative hypotheses--a symbolic hypothesis and an executive function hypotheses--for the imitation and pantomime deficits found in previous studies of autism. The subjects were 17 adolescent high-functioning subjects with autism spectrum disorders and 15 clinical comparison subjects who were matched on chronological age and verbal IQ. Meaning and sequence were manipulated in facial and manual imitation tasks. Sequence was manipulated in the pantomime and control tasks. Recognition memory and motor control tasks were matched to the experimental tasks. The results provided no support for the symbolic deficit hypothesis; meaning aided rather than hindered the performance of the group with autism. Partial support for the executive deficit hypothesis was found. There were no group differences on motor control tasks, and few on the memory control tasks, arguing against deficits in motor initiation, basic motor coordination, or visual recognition memory.

Molecular/clinical correlations in females with fragile X.

Females who are affected by fragile X syndrome (FXS) can have significant physical, neuropsychological and emotional involvement. This study was designed to explore the relationships between these three domains and to learn how the degree of involvement in each of these phenotypic areas relates to molecular parameters including CGG repeat length and activation ratio (the proportion of normal FMR1 alleles on the active X chromosome). Three groups of females were studied: 35 women who grew up in a fragile X family but do not carry an FMR1 mutation, 92 women with a premutation, and 29 women with a full mutation. Correlations between neurocognitive, physical and emotional traits were calculated for each of the three groups. Within the full mutation group significant correlations were seen between schizotypal traits and full scale IQ. The Lie scale was significantly correlated with the physical findings index. The activation ratio correlated significantly with the measure of executive function (r = .50, P = .01). There was a trend toward correlations of activation ratio with the physical index score, outer ear prominence and IQ. CGG repeat number significantly correlated only with the physical index (r = .44, P = .01). Thus, activation ratio may be the more pertinent molecular parameter in full mutation women in determining the degree of cognitive and physical phenotypic involvement.

Intact and impaired memory functions in autism.

This study examined memory functions in individuals with autism. Based on previous evidence of executive function (EF) deficits, we hypothesized that subjects with autism would demonstrate a pattern of intact and impaired memory functions similar to that found in other groups with EF deficits, such as patients with frontal lobe pathology. We compared the performance of high-functioning children and adolescents with autism (n = 19) and clinical comparison subjects (n = 19) matched on sex, CA, and VIQ on measures of memory and EF. The group with autism performed significantly worse than comparison subjects on measures of temporal order memory, source memory, supraspan free recall, working memory, and EF, but not on short- and long-term recognition, cued recall, or new learning ability, consistent with the predictions of the EF theory. The cognitive measures were significantly more intercorrelated in the autism group than the comparison group, consistent with a limit in central cognition.