Longitudinal changes in global structural brain connectivity and cognitive performance in former hospitalized COVID-19 survivors: an exploratory study.

BACKGROUND: Long-term sequelae of COVID-19 can result in reduced functionality of the central nervous system and substandard quality of life. Gaining insight into the recovery trajectory of admitted COVID-19 patients on their cognitive performance and global structural brain connectivity may allow a better understanding of the diseases' relevance. OBJECTIVES: To assess whole-brain structural connectivity in former non-intensive-care unit (ICU)- and ICU-admitted COVID-19 survivors over 2 months following hospital discharge and correlate structural connectivity measures to cognitive performance. METHODS: Participants underwent Magnetic Resonance Imaging brain scans and a cognitive test battery after hospital discharge to evaluate structural connectivity and cognitive performance. Multilevel models were constructed for each graph measure and cognitive test, assessing the groups' influence, time since discharge, and interactions. Linear regression models estimated whether the graph measurements affected cognitive measures and whether they differed between ICU and non-ICU patients. RESULTS: Six former ICU and six non-ICU patients completed the study. Across the various graph measures, the characteristic path length decreased over time (ß = 0.97, p = 0.006). We detected no group-level effects (ß = 1.07, p = 0.442) nor interaction effects (ß = 1.02, p = 0.220). Cognitive performance improved for both non-ICU and ICU COVID-19 survivors on four out of seven cognitive tests 2 months later (p < 0.05). CONCLUSION: Adverse effects of COVID-19 on brain functioning and structure abate over time. These results should be supported by future research including larger sample sizes, matched control groups of healthy non-infected individuals, and more extended follow-up periods.

Perceived neuropsychological impairment inversely related to self-reported health and employment in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) patients frequently report cognitive difficulties which impact daily functioning. The objective was to investigate the relationship between patient-reported cognitive impairment and depression, demographic and MS-related variables, and to clarify its impact on self-reported health measures and employment. METHOD: A large two-centre survey included the MS Neuropsychological Screening Questionnaire (MSNQ), the two-question screening tool for depression, vitality, health-related quality of life, the Health-Promoting Lifestyle Profile II and questions assessing social network satisfaction and employment status. RESULTS: Of the 751 respondents (median age 54 years, median Expanded Disability Status Scale 5, 66.2% female), two-thirds reported perceived neuropsychological impairment or depressive symptoms. Whilst depressive symptoms were related to higher MSNQ scores, the MSNQ poorly predicted depression. After correcting for confounders, higher MSNQ scores and depressive symptoms decreased vitality, health-related quality of life and health-promoting behaviours and increased the probability of being socially dissatisfied. In participants below retirement age, higher MSNQ and Expanded Disability Status Scale scores increased the probability of unemployment, whilst depression did not. CONCLUSION: The contribution of the MSNQ to self-reported health measures and its unique explanatory power regarding unemployment suggest that subjective cognitive complaints are connected to subtle, yet meaningful, neuropsychological dysfunction.

Electronic visual analogue scales for pain, fatigue, anxiety and quality of life in people with multiple sclerosis using smartphone and tablet: a reliability and feasibility study.

OBJECTIVE: To explore the reliability and feasibility of electronic visual analogue scales in people with multiple sclerosis (MS) and healthy individuals. DESIGN: Cross-sectional observational study Setting: Clinical setting Subjects: Convenience sample of 52 people with MS and 52 matched healthy controls Interventions: NA Main measures: Participants scored 15 statements assessing fatigue, pain, anxiety and quality of life on an electronic visual analogue scale (eVAS), either using a smartphone or a tablet (randomly allocated). To check for test-retest reliability, statements were administered in two separate randomly ordered groups. Subjects completed a feasibility questionnaire. RESULTS: Mean (SD) eVAS scores ranged from 35 (28.1) to 80 (22.1) in MS group, and from 57 (28.0) to 86 (13.2) in controls. Intra Class Correlations ranged from 0.73 to 0.95 in MS sample; 0.61 to 0.92 in controls. For most statements, Bland-Altman plots indicated no systematic error, but relatively large random error of the eVAS scores (exceeding 20mm). Considerable ceiling effects (i.e. better health) were found in healthy controls. Similar reliability was found among smartphone or tablet, different demographic groups and the experience-groups. CONCLUSION: Electronic visual analogue scales are reliable and useful for people with MS to register fatigue, pain, anxiety and quality of life.

Self-reported levels of education and disability progression in multiple sclerosis.

OBJECTIVES: The purpose of our study is to investigate whether socioeconomic indicators such as education, financial concerns, employment, and living status are associated with disease progression in relapsing-onset and progressive-onset Multiple Sclerosis (MS). MATERIALS AND METHODS: We performed a cross-sectional survey among individuals with MS, registered by the Flemish MS society and included socioeconomic indicators. A Cox proportional hazard regression was performed with the time from MS onset and from birth to reach an ambulatory disability milestone corresponding to Expanded Disability Status Scale (EDSS) 6 (requiring a cane) as outcome measure, adjusted for gender, age at MS onset, and immunomodulatory treatment. RESULTS: Among the participants with relapsing-onset MS, subjects reporting education for more than 12 years had a reduced risk of reaching EDSS 6 compared to subjects reporting education for less than 12 years [HR from onset 0.68 (95% CI 0.49-0.95); HR from birth 0.71 (95% CI 0.51-0.99)]. In progressive-onset MS, longer education was associated with an increased hazard to reach EDSS 6 [HR from onset 1.25 (95% CI 0.91-1.70); HR from birth 1.39 (95% CI 1.02-1.90)]. CONCLUSIONS: Our study shows an association of self-reported levels of education with disability progression in MS, with the highest level being protective in relapsing-onset MS.

The Symbol Digit Modalities Test as sentinel test for cognitive impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment (CI) is found in about half of the multiple sclerosis (MS) population and is an important contributor to employment status and social functioning. CI is encountered in all disease stages and correlates only moderately with disease duration or Expanded Disability Status Scale scores. Most present neuropsychological test batteries are time-demanding and expensive. The Symbol Digit Modalities Test (SDMT) has been suggested as a screening tool for CI in MS. In this paper, we aim to assess the performance of the SDMT in predicting the outcome of an extensive battery. METHODS: Neuropsychological test results from 359 patients were assessed in a multidisciplinary MS center (National MS Center Melsbroek, Belgium). Using receiver operating characteristic curves, the performance of the SDMT in predicting the general cognitive outcome of the extensive Neuropsychological Screening Battery for MS (NSBMS) could be assessed. The performance of the SDMT was assessed for different levels of CI and compared with other cognitive tests. Finally, useful covariates were included in a logistic regression model. RESULTS: At a specificity of 0.60 a high sensitivity (0.91) was obtained indicating the potential of the SDMT as a sentinel test for CI in MS. The SDMT outperformed the individual tests included in the NSBMS, used as benchmark. As the logistic regression model did not result in a relevant improvement, it is concluded that most clinical variables influence both the SDMT and the NSBMS in a similar way. Excluding patients with possible practice effects, an optimal cutoff of 40 was found for the SDMT. CONCLUSION: As the SDMT is an easy, low-cost and fast test, this result may help to detect CI in everyday clinical practice.

A corrected version of the Timed-25 Foot Walk Test with a dynamic start to capture the maximum ambulation speed in multiple sclerosis patients.

BACKGROUND: No clinical test is currently available and validated to measure the maximum walking speed (WS) of multiple sclerosis (MS) patients. Since the Timed 25-Foot Walk Test (T25FW) is performed with a static start, it takes a significant proportion of the distance for MS patients to reach their maximum pace. OBJECTIVES: In order to capture the maximum WS and to quantify the relative impact of the accelerating phase during the first meters, we compared the classical T25FW with a modified version (T25FW(+)allowing a dynamic start after a 3 meters run-up. METHODS: Sixty-four MS patients and 30 healthy subjects performed successively the T25FW and the T25FW(+). RESULTS: The T25FW(+)was performed faster than the T25FW for the vast majority of MS and healthy subjects. In the MS population, the mean relative gain of speed due to the dynamic start on T25FW(+) was independent from the EDSS and from the level of ambulation impairment. Compared to healthy subjects, the relative difference between dynamic versus static start was more important in the MS population even in patients devoid of apparent gait impairment according to the T25FW. CONCLUSION: The T25FW(+)allows a more accurate measurement of the maximum WS of MS patients, which is a prerequisite to reliably evaluate deceleration over longer distance tests. Indirect arguments suggest that the time to reach the maximum WS may be partially influenced by the cognitive impairment status. The maximum WS and the capacity of MS patients to accelerate on a specific distance may be independently regulated and assessed separately in clinical trials and rehabilitation programs.

Fractional-order time series models for extracting the haemodynamic response from functional magnetic resonance imaging data.

The postprocessing of functional magnetic resonance imaging (fMRI) data to study the brain functions deals mainly with two objectives: signal detection and extraction of the haemodynamic response. Signal detection consists of exploring and detecting those areas of the brain that are triggered due to an external stimulus. Extraction of the haemodynamic response deals with describing and measuring the physiological process of activated regions in the brain due to stimulus. The haemodynamic response represents the change in oxygen levels since the brain functions require more glucose and oxygen upon stimulus that implies a change in blood flow. In the literature, different approaches to estimate and model the haemodynamic response have been proposed. These approaches can be discriminated in model structures that either provide a proper representation of the obtained measurements but provide no or a limited amount of physiological information, or provide physiological insight but lacks a proper fit to the data. In this paper, a novel model structure is studied for describing the haemodynamics in fMRI measurements: fractional models. We show that these models are flexible enough to describe the gathered data with the additional merit of providing physiological information.

Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis.

BACKGROUND: Sunlight and vitamin D have been inversely associated with the risk of multiple sclerosis (MS). OBJECTIVE: We investigated sunlight exposure and sun sensitivity in relation to disability progression in MS. METHODS: We conducted a survey among persons with MS, registered by the Flemish MS society, Belgium, and stratified data according to relapsing-onset and progressive-onset MS. We used Kaplan-Meier survival and Cox proportional hazard regression analyses with time to Expanded Disability Status Scale (EDSS) 6 as outcome measure. Hazard ratios for the time from onset and from birth were calculated for the potentially predictive variables, adjusting for age at onset, gender and immunomodulatory treatment. RESULTS: 704 (51.3%) of the 1372 respondents had reached EDSS 6. In relapsing-onset MS, respondents reporting equal or higher levels of sun exposure than persons of the same age in the last 10 years had a decreased risk of reaching EDSS 6. In progressive-onset MS, increased sun sensitivity was associated with an increased hazard of reaching EDSS 6. CONCLUSION: The association of higher sun exposure with a better outcome in relapsing-onset MS may be explained by either a protective effect or reverse causality. Mechanisms underlying sun sensitivity might influence progression in progressive-onset MS.

Menarche, oral contraceptives, pregnancy and progression of disability in relapsing onset and progressive onset multiple sclerosis.

Female gender and hormones have been associated with disease activity in multiple sclerosis (MS). We investigated age at menarche, use of oral contraceptives and pregnancy in relation to progression of disability in relapsing onset and progressive onset MS. We conducted a cross-sectional survey among individuals with MS, registered by the Flemish MS Society in Belgium. A time-to-event analysis and Cox proportional hazard regression were performed with time to Expanded Disability Status Score (EDSS) of 6 (requires a cane) as outcome measure. Hazard ratios for the time from onset and the time from birth were adjusted for age at onset and immunomodulatory treatment. Data on 973 women with definite MS were collected. In the relapsing onset group, women with at least two pregnancies had a reduced risk to reach EDSS 6 compared with nulliparous women. In the progressive onset group, later age at menarche was associated with a reduced risk to reach EDSS 6, whereas oral contraceptive use was associated with a higher risk of reaching EDSS 6. Our study corroborates the association of pregnancies with a reduced progression of disability in relapsing onset MS. In progressive onset MS, a slower progression was found in women with a later onset of menarche and a more rapid progression occurred when women reported the use of oral contraceptives.

Alcohol, coffee, fish, smoking and disease progression in multiple sclerosis.

BACKGROUND: Certain lifestyle factors might influence disease activity in multiple sclerosis (MS). OBJECTIVES: To investigate the consumption of alcoholic beverages, caffeinated drinks, fish and cigarette smoking in relation to disability progression in relapsing onset and progressive onset MS. METHODS: We conducted a cross-sectional survey amongst individuals with MS, registered by the Flemish MS society in Belgium. A time-to-event analysis and Cox proportional-hazard regression were performed with time to Expanded Disability Status Scale (EDSS) 6 (requiring a cane or support to walk for a distance of 100 m) as outcome measure. Hazard ratios for the time from onset and from birth were adjusted for age at onset, gender and immunomodulatory treatment. RESULTS: Data of 1372 persons with definite MS were collected. In the relapsing onset group, a decreased risk for reaching EDSS 6 was found in regular consumers of alcohol, wine, coffee and fish compared with those who never consumed these substances. Cigarette smoking was associated with an enhanced risk for reaching EDSS 6. In the progressive onset group, no association with the risk of reaching EDSS 6 was found, except for the type of fish. Preference for fatty fish was associated with an increased risk to reach EDSS 6, when lean fish was taken as the reference category. CONCLUSION: Consumption of alcoholic beverages, coffee and fish were inversely associated with progression of disability in relapsing onset MS, but not in progressive onset MS. These findings allow to support the hypothesis that different mechanisms might underlie progression of disability in relapsing and progressive onset MS.

Modifiable factors influencing relapses and disability in multiple sclerosis.

A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and tetanus appear to be safe. Surgery, general and epidural anaesthesia, and physical trauma are not associated with an increased risk of relapses. Factors that have been associated with a reduced relapse rate are pregnancy, exclusive breastfeeding, sunlight exposure and higher vitamin D levels. A number of medications, including hormonal fertility treatment, seem to be able to trigger relapses. Factors that may worsen progression of disability include stressful life events, radiotherapy to the head, low levels of physical activity and low vitamin D levels. Strong evidence suggests that smoking promotes disease progression, both clinically and on brain magnetic resonance imaging. There is no evidence for an increased progression of disability following childbirth in women with multiple sclerosis. Moderate alcohol intake and exercise might have a neuroprotective effect, but this needs to be confirmed.

Long-term effects of childbirth in MS.

BACKGROUND: The uncertainty about long-term effects of childbirth presents MS patients with dilemmas. METHODS: Based on clinical data of 330 female MS patients, the long-term effects of childbirth were analysed, using a cross-sectional study design. Four groups of patients were distinguished: (1) without children (n = 80), (2) with children born before MS onset (n = 170), (3) with children born after MS onset (n = 61) and (4) with children born before and after MS onset (n = 19). A time-to-event analysis and Cox proportional hazard regression were performed with time from onset to EDSS 6 and age at EDSS 6 as outcome measure. RESULTS: After a mean disease duration of 18 years, 55% had reached EDSS 6. Survival curves show a distinct shift in the time to EDSS 6 between patients with no children after MS onset and patients with children after MS onset in favour of the latter. Cox regression analysis correcting for age at onset shows that patients with children only after MS onset had a reduced risk compared with patients without children (HR 0.61; 95% CI 0.37 to 0.99, p = 0.049). Also, patients who gave birth at any point in time had a reduced risk compared with patients without children (HR 0.66; 95% CI 0.47 to 0.95, p = 0.023). A similar pattern was seen for age at EDSS 6 (HR 0.57, p = 0.027 and HR 0.68, p = 0.032 respectively) CONCLUSION: Although a bias cannot fully be excluded, these results seem to support a possible favourable long-term effect of childbirth on the course of MS.

The effect of levetiracetam on tremor severity and functionality in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) intention tremor is a disabling symptom, which is difficult to treat. OBJECTIVES: To investigate the effects of levetiracetam, an antiepileptic drug, on tremor severity and related functionality in MS. METHODS: A randomized, double-blind, placebo-controlled, cross-over study examined the effects of 6 weeks of oral levetiracetam administration (starting dose=250 mg/day, maximal dose=2000 mg/day) in 18 MS patients with disabling intention tremor. Primary outcome was Fahn's Tremor Rating Scale (FTRS) A&B. Secondary outcome measures were the nine-hole peg test, patient's opinion rated with the visual analog scale, FTRS C, and an activities of daily life questionnaire and validated tremor indexes derived during the performance of a digitized spiral drawing task and a wrist step-tracking task. Repeated measures analysis of variance and Friedman tests were applied. RESULTS: In all, 14 patients completed the trial. Maximal dose intake ranged from 1000 to most commonly 2000 mg, depending on patients' tolerance level. No significant effects of levetiracetam were found for any outcome measure. Further analyses on subgroups with different tremor severity showed no differential effects. Eight patients reported adverse events such as fatigue and stomach ache. CONCLUSIONS: Levetiracetam intake of 2000 mg/day did not affect tremor severity or functionality in patients with MS.

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.

Proxy ratings from multiple sources: disagreement on the impact of multiple sclerosis on daily life.

BACKGROUND AND PURPOSE: The use of self-report measurements may be problematic in patients with limitations that interfere with reliable self-assessment like cognitive impairment, as may be the case in multiple sclerosis (MS). In these situations proxy respondents, such as close relatives or healthcare providers, may provide valuable information. To examine the accuracy and value of healthcare providers and close relatives to assess disease impact of MS. METHODS: MS patients, close relatives and healthcare providers completed the Multiple Sclerosis Impact Scale (MSIS-29) before and after a rehabilitation program. Agreement between outcomes was assessed by calculating mean absolute and directional differences and intraclass correlation coefficients. RESULTS: Comparison of ratings between patients and proxy respondents revealed low levels of agreement. Close relatives appeared to significantly overestimate the disease impact of MS whereas healthcare providers tended to underestimate the disease impact of MS. CONCLUSION: Caution is advised when incorporating close relatives and healthcare providers as proxy respondents in a rehabilitation setting. However, when close relatives are consulted, one should expect a certain level of overestimation of disease impact. When consulting healthcare providers, one should expect a certain level of underestimation of disease impact.

Origin of fatigue in multiple sclerosis: review of the literature.

Fatigue is one of the most common and most disabling symptoms of multiple sclerosis (MS). Although numerous studies have tried to reveal it, no definite pathogenesis factor behind this fatigue has been identified. Fatigue may be directly related to the disease mechanisms (primary fatigue) or may be secondary to non-disease-specific factors. Primary fatigue may be the result of inflammation, demyelination, or axonal loss. A suggested functional cortical reorganization may result in a higher energy demand in certain brain areas, culminating in an increase of fatigue perception. Higher levels of some immune markers were found in patients with MS-related fatigue, whereas other studies rejected this hypothesis. There may be a disturbance in the neuroendocrine system related to fatigue, but it is not clear whether this is either the result of the interaction with immune activation or the trigger of this process. Fatigue may be secondary to sleep problems, which are frequently present in MS and in their turn result from urinary problems, spasms, pain, or anxiety. Pharmacologic treatment of MS (symptoms) may also provoke fatigue. The evidence for reduced activity as a cause of secondary fatigue in MS is inconsistent. Psychological functioning may at least play a role in the persistence of fatigue. Research did not reach consensus about the association of fatigue with clinical or demographic variables, such as age, gender, disability, type of MS, education level, and disease duration. In conclusion, it is more likely to explain fatigue from a multifactor perspective than to ascribe it to one mechanism. The current evidence on the pathogenesis of primary and secondary fatigue in MS is limited by inconsistency in defining specific aspects of the concept fatigue, by the lack of appropriate assessment tools, and by the use of heterogeneous samples. Future research should overcome these limitations and also include longitudinal designs.

Within-session practice effect on paced auditory serial addition test in multiple sclerosis.

The paced auditory serial addition test (PASAT) is increasingly used in multiple sclerosis (MS) studies. Since these studies rely on repeated assessments with relatively short inter-test intervals, practice effects can be a confounding factor. We examined intra-session PASAT practice effects in 70 relapsing remitting (RR) and 40 secondary progressive (SP) patients. The average number of correct answers increased from 39.6+/-11.7 in the first PASAT run to 43.8+/-11.4 in the second run for the RR group, and from 39.1+/-11.6 to 41.8+/-13.3 in the SP group. PASAT scores showed a consistent decrease when comparing the second half of each test to the first half for both patient groups, and for both runs. Items for which the answer was a number greater than 9 had the same discrimination ability as other test items, but were significantly more difficult. A simulation of ;single-button' responses supported the use of the simplified scoring method which is currently used in fMRI studies. Our results demonstrate a within-session PASAT practice effect in MS, as well as a fatigability effect for both patient groups.

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.

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.

P300 and treatment effect of modafinil on fatigue in multiple sclerosis.

To evaluate the value of visual and auditory P300 for predicting the response of multiple sclerosis-related fatigue to modafinil treatment, 33 patients were treated with 100 mg modafinil once daily for 4 weeks, following a 4-week baseline phase and an optional 8-week extension phase. The main clinical outcome parameter was a decrease in the fatigue visual analogue score (VAS) before and after 4 weeks of treatment. Patients with shorter auditory P300 latency at baseline were more likely to benefit from modafinil treatment. Auditory P300 latency predicted treatment response with a specificity of 76% and a sensitivity of 75% at a cut-off latency of 350 ms. Visual P300 latency could not be used to predict treatment response. Baseline auditory P300 latency predicted treatment response, whereas visual P300 latency did not. Clinical improvement did not correlate with changes in either visual or auditory P300.