G Nagels

Multidisciplinary fatigue management programme in multiple sclerosis : a randomized clinical trial

Objective To establish the efficacy of a multidisciplinary fatigue management programme (MFMP) in MS. Method Fifty-one subjects with MS were randomly allocated to group A, who only received the four weeks MFMP, or group B receiving a placebo intervention programme first and the MFMP after 6 months. In both groups, assessment was performed at baseline, 3 weeks and 6 months after the programmes and included Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), MS Self-Efficacy scale (MSSE), Mental Health Inventory (MHI) and Impact on Participation and Autonomy (IPA). Results The MFIS showed a significant change over time (F(4,152) = 3.346, P = 0.012), which was similar in both groups (time*group interaction: F(4,152) = 1.094, P = 0.361). A clinically relevant reduction of MFIS score of 10 points or more was found in 17% of individuals following the MFMP, compared to 44% after the placebo intervention programme (P = 0.06). Compared to no intervention, a significant effect of the MFMP after 6 months (P = 0.003) was found in five participants (31%). No significant changes in FSS, MSSE, MHI and IPA, in both groups, were found. Conclusion Although an additional effect was found, the multidisciplinary fatigue management programme showed no efficacy in reducing the impact of fatigue compared to a placebo intervention programme. Multiple Sclerosis 2007; 13: 996—1003. http://msj.sagepub.com

Partial cure of established disease in an animal model of metachromatic leukodystrophy after intracerebral adeno-associated virus-mediated gene transfer

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by genetic deficiency of arylsulfatase A (ARSA) enzyme. Failure in catalyzing the degradation of its major substrate, sulfatide (Sulf), in oligodendrocytes and Schwann cells leads to severe demyelination in the peripheral (PNS) and central nervous system (CNS), and early death of MLD patients. The ARSA knockout mice develop a disease that resembles MLD but is milder, without significant demyelination in the PNS and CNS. We showed that adeno-associated virus serotype 5-mediated gene transfer in the brain of ARSA knockout mice reverses Sulf storage and prevents neuropathological abnormalities and neuromotor disabilities when vector injections are performed at a pre-symptomatic stage of disease. Direct injection of viral particles into the brain of ARSA knockout mice at a symptomatic stage results in sustained expression of ARSA, prevention of Sulf storage and neuropathological abnormalities. Despite these significant corrections, the treated mice continue to develop neuromotor disability. We show that more subtle biochemical abnormalities involving gangliosides and galactocerebroside are in fact not corrected.

Actigraphic Measurement of Motor Deficits in Acute Ischemic Stroke

Background: This study aimed to investigate the use of actigraphy (accelerometry) to measure disuse of the impaired arm in acute stroke patients. We correlated the National Institute of Health Stroke Scale (NIHSS) and the Fugl-Meyer Assessment arm section (FMA) findings with actigraphic data as a measure of validity. Methods: Thirty-nine acute ischemic stroke patients were included within 1 week after stroke onset. At inclusion, motor deficits were assessed by the NIHSS, FMA and 48-hour actigraphic recordings of both wrists were performed. Results: Moderate but highly significant correlations (Spearman’s rho) between actigraphic recordings and total NIHSS (ratio r = –0.59 and activity of impaired arm r = –0.75; p < 0.001) and FMA (ratio r = 0.54 and activity of impaired arm r = 0.69; p < 0.001) scores were found. Based on actigraphic motor activity scores, ROC curves were calculated following dichotomization of the population based on NIHSS = 7 and FMA = 45, showing good sensitivity and specificity, with negative predictive value of 100% and positive predictive value of 91% for the ratio variable. Conclusions: Moderate but highly significant correlations were found between actigraphy and the stroke scales NIHSS and FMA. Actigraphy was able to reliably discriminate less impaired from more impaired stroke patients with excellent sensitivity and specificity values. Actigraphy is a simple, valid, objective and reliable clinical research tool that can be used to determine motor impairment of the upper limb in stroke patients.

Genetic association study of the P300 endophenotype in schizophrenia

OBJECTIVE Although reduced amplitude of the P300 event-related potential is a well-documented intermediate phenotype of schizophrenia, little is known about its genetic underpinnings in patients with schizophrenia. This study aims to examine associations between P300 and a range of candidate genetic variants, selected from either candidate gene studies or genome-wide association studies, in a large sample of patients with schizophrenia. METHODS P300 amplitude at the midline parietal electrode and 193 single nucleotide polymorphisms (SNPs) in 67 genes were assessed in 336 patients with schizophrenia. The association between each SNP and P300 amplitude, controlled for illness duration and gender, was evaluated. Associations at p<.01 were considered of potential relevance, while Bonferroni correction was applied to determine formal statistical significance (Bonferroni-corrected threshold of significance p=.0003). RESULTS Of the 193 selected SNPs, 4 SNPs showed potentially relevant association with P300 amplitude at a significance level of p<.01. One of these SNPs, rs1045642 in ABCB1, was most convincingly associated with P300 amplitude, reaching formal (Bonferroni-corrected) significance, while there was evidence for possible association with rs1572899 in DISC-1, rs6265 in BDNF and rs1625579 in MIR137. CONCLUSION Genetic variation in ABCB1 may be associated with P300 amplitude in patients with schizophrenia. This result may encourage further efforts to elucidate the genetic underpinnings of P300 generation.

The squares test as a measure of hand function in multiple sclerosis

Deterioration of hand function can be important in multiple sclerosis (MS). The standard way of assessing hand function in MS is the 9-hole peg test (9HPT), one of the three components of the MS functional composite measure. In this study we examine the squares test (ST), a test of hand function that is used extensively in handedness research. We evaluated reproducibility of the ST in 49 healthy controls, and both discriminatory power and concurrent validity of the ST in 38 MS patients and 18 age and gender matched controls. The ST proved to be a reliable and easy to administrate paper-and-pencil test of hand function. The ST showed a high and highly significant correlation with the standard 9HPT over a broad range of Expanded Disability Status Scale (EDSS) scores, and had high discriminatory power, also comparable to the 9HPT. Therefore, the ST is a candidate test for use in composite measures of MS related functional deficits for clinical practice and in clinical trials.