[Lashing out in the A&E department]. / Slaande bewegingen op de SEH.

BACKGROUND: Subacute hemichorea-hemiballismus in an older patient can be induced by non-ketotic hyperglycaemia. The triad of onset of subacute hemichorea-hemiballismus, hyperglycaemia and hyperdensity in the contralateral putamen on a CT scan or hyperintensity on a T1-weighted MRI scan is pathognomic for this diagnosis. Close observation of the motor restlessness and knowledge of this triad are important for making this diagnosis. CASE DESCRIPTION: A 92-year-old female patient was admitted to the accident and emergency department with a history of motor restlessness for the past few days, confused speech and a glucose level of 20.5 mmol/l. Delirium was initially suspected. Abnormalities on the CT scan were indicative of hemichorea-hemiballismus caused by hyperglycaemia. The patient recovered fully once euglycaemic levels were restored. CONCLUSION: Hemichorea-hemiballismus is a rare motor disorder, often due to an infarct in the contralateral basal ganglia. It can, however, be an expression of non-ketotic hyperglycaemia. The condition is sometimes confused with the motor restlessness of delirium.

Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression.

BACKGROUND: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. OBJECTIVE: To study whether plasma isoprostane levels were related to disease progression in MS. METHODS: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing-remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. RESULTS: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7-77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9-82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1-49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). CONCLUSION: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.

Glucocorticoid receptor gene polymorphisms associated with more aggressive disease phenotype in MS.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system, in which unknown environmental factors are thought to trigger disease in genetically susceptible persons. Glucocorticoids (GCs) play an important role in controlling chronic inflammatory diseases, like MS. Three polymorphisms in the glucocorticoid receptor (GR) gene (N363S, ER22/23EK and the Bcl I C/G) have been shown to alter glucocorticoid sensitivity, and therefore may influence disease course. We investigated the influence of these polymorphisms on clinical and MRI parameters. The ER22/23EK polymorphism was associated with a more aggressive MS phenotype, measured both clinically and on MRI.

No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis.

BACKGROUND: Whereas a number of studies suggest that the ApoE polymorphism is not associated with disease susceptibility in multiple sclerosis (MS), results with regard to disease severity, however, are conflicting. Some studies suggest an unfavourable role of the epsilon4 allele. This study was performed to assess the association of the ApoE polymorphism with both disease susceptibility and disease course in a large group of MS patients using clinical and MRI measures. In addition the data were combined with available data from the literature. METHODS: In a group of 408 patients with clinically definite MS, genotype distribution was compared with that of 144 healthy controls. Combined analysis of published data on the association of ApoE polymorphism with MS was performed. Demographic and clinical findings were recorded and related to the ApoE genotype. In a subgroup, longitudinal MRI findings were available and related to the ApoE genotype. RESULTS: No significant differences were found in the distribution of genotypes between MS patients and controls. Combined analysis of published data showed a slightly increased susceptibility for MS in epsilon2-carriers. Disease characteristics (including age at onset and onset type), disease severity (progression index, time to reach EDSS 6) and MRI findings (lesion volumes and atrophy measures) were not associated with carriership o epsilon2 or epsilon4. CONCLUSIONS: In this cohort no association of the ApoE genotype with disease susceptibility nor clinical and MRI measures could be identified. However, combined analysis of published data could not definitely exclude the possibility of a minor role for epsilon2-carriership in MS.

[Alpha]B-crystallin genotype has impact on the multiple sclerosis phenotype.

BACKGROUND: Both multiple sclerosis (MS) susceptibility and MS clinical phenotype are in part genetically determined. [Alpha]B-crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene (CRYAB): at positions -C249G, -C650G, and -A652G. METHODS: These polymorphisms were studied in sporadic cases of MS, assessing disease susceptibility, clinical phenotype, and MRI appearance. RESULTS: The CRYAB polymorphisms influenced susceptibility as well as disease expression in MS. CONCLUSION: Carriers of the rare allele CRYAB-650*C had an increased likelihood of a noninflammatory, neurodegenerative phenotype characterized by a relatively rapid, primary progressive clinical disease course.

The FAS-670 polymorphism influences susceptibility to multiple sclerosis.

Several studies have reported a defective Fas function in patients with multiple sclerosis (MS). We were interested whether this could result from a genetically altered Fas regulation. We examined the FAS-670 polymorphism in 382 patients with MS and 206 controls, and found that the carriership of allele FAS-670*G was significantly less frequent in patients than in controls. We found no association between the carriership of FAS-670*G and clinical features. For a subgroup of patients, longitudinal MRI data were available. We observed similar brain and lesion volumes in carriers and noncarriers of FAS-670*G. These data suggest that FAS-670*G decreases the risk of developing MS, but does not affect the course of disease.

Comparisons of patient self-report, neurologic examination, and functional impairment in MS.

OBJECTIVE: To compare the recently developed Guy's Neurologic Disability Scale (GNDS), based on patient self-report, with both neurologist rating of neurologic examination abnormalities using the Expanded Disability Status Scale (EDSS) and observations of functional impairment on the Multiple Sclerosis Functional Composite (MSFC) in the assessment of disease impact in MS. METHODS: Two hundred ninety MS patients were recruited at an outpatient clinic. Impairment and disability were assessed using GNDS, EDSS, and MSFC. Correlations between GNDS, EDSS, MSFC, and their corresponding components were studied for the total population, MS phenotypes, and three disability strata. RESULTS: Mean scores were 4.6 (SD, 2.0) for EDSS, 0.0 (SD, 0.8) for MSFC, and 14.6 (SD, 7.9) for GNDS. Good correlations were found between GNDS and EDSS (r = 0.73), between GNDS and MSFC (r = -0.68), and between different subcategories of the GNDS and EDSS, MSFC, and their corresponding components. Remarkably good correlations were found between lower limb function and all three scales. Poor correlations were also found, especially between different measurements focusing on cognitive function. CONCLUSION: The good correlations between GNDS and both EDSS and MSFC were mainly due to the importance of spinal-cord-related neurologic functions in all three scoring systems. A marked discrepancy was found for the assessment of cognition between objective measurements and subjective complaints. Because patients' self-reporting correlates well with results of physical examination, GNDS can offer a valuable way to measure disease impact in MS. However, GNDS is not an adequate screen of cognitive dysfunction.

Influence of delivery on numbers of leukocytes, leukocyte subpopulations, and hematopoietic progenitor cells in human umbilical cord blood.

Human umbilical cord blood (UCB) may be used as an alternative source of bone marrow repopulating cells in allogeneic bone marrow transplantation. The quality and quantity of UCB harvests for transplantation is affected by several factors. In this study we analyzed the influence of delivery, in particular stress during delivery, on the numbers of leukocytes and leukocyte subsets in UCB. Four groups of women with different types of deliveries were included in the study, and from each group samples of UCB were analyzed. Blood samples from healthy adults were used as control. In UCB there was a higher absolute number of leukocytes than in peripheral blood (PB). UCB leukocytes were highest after deliveries with a prolonged second stage of labor, which was mainly due to granulocytosis. The percentage of T cells in UCB was lower than in PB, in particular when stress during delivery was higher. In all groups, however, the absolute concentration of T cells per milliliter of UCB was higher than in adult PB. The differences in T cells in stressful deliveries were mainly due to a relative decrease in CD3+/CD4+ cells in UCB. The relative frequency and absolute concentration of the CD56+ cell population in UCB was higher than in PB, which was mostly due to an increase of CD2-/CD56+ cells, in particular in stressful deliveries. The absolute number of CD34+ cells as well as hematopoietic progenitor cells as determined in semisolid medium cultures was high in UCB and was increased in cases of prolonged secondary stage of labor. This study demonstrates that the quality of UCB transplants is influenced by the course of delivery, in particular by stress during delivery.