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In this investigation we study the impact of Guillain-Barré syndrome (GBS) on psychological distress, depressive symptoms, and health status of patients during the first year after GBS. At 3, 6, and 12 months, patients were given the General Health Questionnaire, the Sickness Impact Profile, and the Center for Epidemiologic Studies Depression Scale. Eighty-five patients participated. Psychological distress and depressive symptoms were present but improved between 3 and 6 months. At 12 months the psychosocial health status was still impaired. Patients who perceived their physical residua to be moderately to seriously disruptive and patients with muscle ache and cramps had worse scores on all scales. It can be concluded that most of the improvement occurred in the first 6 months. Psychosocial health status, however, was still impaired at 1 year, but depressive symptoms played no role. Treatment of muscle ache and cramps, and the disruptive effect of physical residua should be seriously considered. Muscle Nerve, 2010. [ABSTRACT FROM AUTHOR]

Objective: To investigate the course of anxiety, depression and disease-related distress of patients with multiple sclerosis (MS) and their partners in the first years after diagnosis., Methods: The Hospital Anxiety and Depression Scale (HADS) and Impact of Event Scale (IES) were completed at baseline, six-month, one- and two-year follow-up in 101 recently diagnosed patients and 78 partners. The Expanded Disability Status Scale (EDSS) was assessed annually., Results: Mean time since diagnosis at baseline was 7.8 (SD 6.5) months. Mean anxiety scores of patients and partners did not change during the two years of follow-up and remained higher than that observed in the general population at all assessments (P < 0.05). The high levels of disease-related distress at baseline were lower at follow-up. Of the patients and partners with high anxiety scores at baseline (HADS anxiety > or = 8), 69% also had high scores at any time during follow-up, compared to 26% in those with low baseline anxiety scores. For severe distress at follow-up, these percentages were 41 and 14%. The sensitivity and specificity of baseline anxiety screening for the prediction of high anxiety or distress scores at follow-up were 55 and 85%., Conclusion: MS patients and their partners continued to have high levels of anxiety and distress in the first years after diagnosis. Screening for anxiety after diagnosis can be used to predict levels of anxiety and distress during two-year follow-up.

Objective: To study the impact of Guillain-Barré Syndrome (GBS) on the psychosocial functioning of the closest relative and on family functioning during the first year after GBS., Method: At 1 (=T1), 3 (=T3), 6 (=T6), and 12 months (=T12) after the onset of GBS, relatives of patients received the General Health Questionnaire (GHQ28) and the Family Assessment Device (FAD). Sixty-three relatives returned the GHQ28 at all four designated intervals. At T1 the relatives also received a questionnaire that contained questions on the impact on their daily life. The answers to these questions yielded a Daily Living Impact index. From the 110 relatives, 86 returned this questionnaire., Results: 72% of the 86 relatives reported one or more problems in daily living. At T1 the scores of the GHQ subscales ranged from normal to mildly disturbed. The relatives showed significant improvement in their somatic complaints and anxiety during the first half year. Social dysfunction remained somewhat less than normal, severe depression was not found. At T1 and T3 the scores of the GHQ28 and some subscales differed significantly depending on the severity of the functional status of the patient, but not at T6 and T12. Relatives of patients with severe residua at 1 month score worse on the GHQ28 and most subscales at 6 months. The FAD was normal at all moments measured., Conclusions: Psychological morbidity of close relatives is significantly higher in the first months after the onset of GBS. The patient's condition has an important impact on the psychosocial functioning of close relatives. Therefore, a family approach is recommended to neurologist and other medical personnel during the first period of the disease. Also patient support groups may play a beneficial role for the relatives of GBS patients.

Objective: Fatigue is a major complaint in patients with immune mediated polyneuropathies. Despite apparently good physical recovery after Guillain-Barré syndrome (GBS), many patients remain restricted in daily and social activities, and have a decreased quality of life. In this trial, the effect of amantadine on severe fatigue related to GBS was studied., Methods: During the pre-treatment phase, all patients were monitored for 2 weeks. Only patients with severe fatigue, defined as a mean fatigue score of > or = 5.0 on the Fatigue Severity Scale (FSS), were randomised for this double blind, placebo controlled, crossover study. Primary outcome measure was improvement of at least 1 point on the FSS. Secondary outcome measures were impact of fatigue, anxiety and depression, handicap, and quality of life., Results: In total, 80 patients with GBS were randomised, of whom 74 were included for analysis. Fatigue appeared to be reduced already during the pre-treatment phase (p = 0.05), probably due to increased attention provided to the patients. No significant differences in any of the primary and secondary outcome measures were found., Conclusions: Amantadine was not superior to placebo. Because fatigue remains a serious complaint, other studies evaluating new treatment options are strongly recommended.

Background: Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS)., Aims: To halt disease progression in aggressive MS by a bone marrow transplantation (BMT) protocol aimed at maximum T cell suppression., Methods: Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen--cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source., Results: Median follow up was 36 months (range, 7-36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases., Conclusions: This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.

Objectives: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA., Methods: This was a prospective study with 73 RR MS patients followed for an average of 1.7 years with frequent neurological examination and blood sampling. Antibodies to various EBV proteins were measured by ELISA and plasma EBV DNA was measured by PCR., Results: All MS patients had IgG antibodies to EBV (viral capsid antigen (VCA) and/or EBV nuclear antigen (EBNA)), irrespective whether samples were taken at stable disease or exacerbation. A significantly elevated percentage of the patients (48%) had antibodies against EBV antigens (early antigen, EA) that indicate active viral replication, compared with the age matched healthy controls (25%). Antibodies against a control herpesvirus, cytomegalovirus, were similar between the two groups. The percentage of EA positive individuals and EA titres did not differ between stable disease or exacerbation. Anti-VCA IgM was positive in three cases, unrelated to disease activity. Using a highly sensitive PCR on 51 samples taken at exacerbation visits, only three patients were found to have one timepoint with viraemia, and this viraemia was unrelated to disease activity. Of special note was the fact that anti-EA seropositive patients remained seropositive during follow up, with stable titres over time. We hypothesised that these patients may constitute a subgroup with higher disease activity, due to the triggering effect of a chronic attempt of the virus to reactivate. The EA positive group did not differ from the EA negative with respect to clinical disease activity or other characteristics. However, in the EA positive group, analysis with gadolinium enhanced MRI indicated more MRI disease activity., Conclusions: There was no evidence for increased clinical disease activity in the subgroup of MS patients with serological signs of EBV reactivation. However, the observation that chronic EBV reactivation may be associated with increased inflammatory activity as assessed by gadolinium enhanced MRI lesions should be reproduced in a larger and independent dataset.

Objective: To analyze how the patient himself perceives his physical and social situation 1 year after Guillain-Barre syndrome (GBS)., Material and Method: The Dutch patients who participated in an international multicenter trial were asked to complete a self-administered questionnaire containing questions on their physical status at homecoming and at 12 months, as well as questions dealing with various aspects of their social condition., Results: Ninety patients participated. Up to 72% had sensory disturbances and loss of power in part of the arms and up to 89% in part of the legs at homecoming. At 12 months, a significant improvement had occurred, but residua were perceived in 36 and 67%, respectively. The residua ranged from irritating to seriously disturbing in up to 49%, and only 33% felt completely cured. Furthermore, 32% had changed their work due to GBS, 30% did not function at home as well as before and 52% had altered their leisure activities., Conclusion: One year after the onset of GBS, a considerable number of patients still perceived a decrease of power and sensation with an often disturbing effect. GBS had an evident impact on daily life and social well-being., (Copyright Blackwell Munksgaard 2005.)

Objective: The aim of the study was to investigate the impact of perception of prognostic risk on anxiety, depression, and disease-related distress in patients with multiple sclerosis (MS)., Study Design and Setting: Perceived risk and perceived seriousness of the 2-year, 10-year, and lifetime prognosis of wheelchair dependence, disability status, anxiety, depression, and disease-related distress were assessed in 101 patients. Distress was measured as the intrusion and avoidance of MS-related thoughts and feelings., Results: Patients with higher perceptions of 2-year, 10-year, or lifetime risk were bothered by more intrusion of MS-related thoughts and feelings. Only higher perception of the 2-year risk of wheelchair dependence was significantly related with higher levels of anxiety, depression, and avoidance. Similarly, higher perception of the seriousness of wheelchair dependence was consistently associated with more intrusion and avoidance, but only perceived seriousness of the 2-year prospect of wheelchair dependence was significantly correlated with anxiety and depression. All relations were independent of clinically assessed disability status., Conclusion: Perceptions of the short-term risk and seriousness of wheelchair dependence were significantly related to anxiety, depression, and disease-related distress in patients with MS. These findings underscore the importance of informing patients with chronic disorders about the short-term prognosis of important long-term consequences of disease.

Objectives: Studies demonstrating reduced quality of life and psychological well-being in multiple sclerosis (MS) have typically investigated patients within more advanced stages of disease. The aim of the present paper was to evaluate the emotional burden and quality of life of recently diagnosed MS patients and their partners., Methods: Data on health-related quality of life (SF-36), anxiety and depression (Hospital Anxiety and Depression Scale) and disease-related distress (Impact of Event Scale) were obtained in 101 patients and their partners (n=78)., Results: On average 8 months after diagnosis (range 0-24 months), 34% of the patients and 40% of the partners had clinically high levels of anxiety, and 36% of the patients and 24% of the partners had levels of severe distress. Scores of anxiety, depression and distress were higher in patients with more functional limitations (Expanded Disability Status Scale=3.0). Quality of life was significantly poorer in patients compared with controls, particularly among those with higher disability., Conclusions: Both patients and their partners demonstrated high levels of anxiety and distress in the early period after the diagnosis. These findings indicate careful attention by health care professionals to identify those who may benefit from further psychological support.

Objective: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis., Design: Longitudinal, prospective cohort study., Setting: Outpatient clinic of department of neurology in the Netherlands., Participants: Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded., Main Outcome Measure: The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events., Results: Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress., Conclusion: Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis.

The ability of a scale to detect clinical relevant changes over time, i.e., its "responsiveness," may help clinicians to choose among valid and reliable measures. Therefore, we investigated the responsiveness' rank ordering (best to worse) of six selected valid and reliable scales, namely the Medical Research Council (MRC)-sumscore, sensory-sumscore, grip-strength (Vigorimeter), nine-hole peg, ten-meters walking, and a disability-sumscore, in immune-mediated polyneuropathies. Patients with newly diagnosed Guillain-Barré syndrome (n = 7) or chronic inflammatory demyelinating polyneuropathy (n = 13) were examined over 52 weeks. Responsiveness of each scale was measured using different methods (effect-size, standardized response mean score, Wilcoxon matched-pairs signed-rank, and a newly devised Schmitz's distribution-free responsiveness score), and the obtained scores in each method were plotted against the follow-up period, thus allowing area-under-the-curve calculations (higher area-under-the-curve indicating better responsiveness). Also, longitudinal correlations were performed between the scales' values and patients' own clinical judgments (deteriorated, unchanged, improved) (higher correlation = better responsiveness). A consistent rank ordering was observed in each technique with the disability-sumscore, MRC-sumscore, and Vigorimeter being among the best responsive scales. Hence, the primary use of these measures is suggested in studies of immune-mediated polyneuropathies., (Copyright 2003 Wiley Periodicals, Inc.)

Background: In the World Health Organisation (WHO) International Classification of Impairments, Disabilities, and Handicaps (ICIDH), it is suggested that various levels of outcome are associated with one another. However, the ICIDH has been criticised on the grounds that it only represents a general, non-specific relation between its entities., Objective: To examine the significance of the ICIDH in immune mediated polyneuropathies., Methods: Four impairment measures (fatigue severity scale, MRC sum score, "INCAT" sensory sum score, grip strength with the Vigorimeter), five disability scales (nine hole peg test, 10 metres walking test, an overall disability sum score (ODSS), Hughes functional grading scale, Rankin scale), and a handicap scale (Rotterdam nine items handicap scale (RIHS9)) were assessed in 113 clinically stable patients (83 with Guillain-Barré syndrome, 22 with chronic inflammatory demyelinating polyneuropathy, eight with a gammopathy related polyneuropathy). Regression analyses with backward and forward stepwise strategies were undertaken to determine the correlation between the various levels of outcome (impairment on disability, impairment on handicap, disability leading to handicap, and impairment plus disability on handicap)., Results: Impairment measures explained a substantial part of disability (R(2) = 0.64) and about half of the variance in handicap (R(2) = 0.52). Disability measures showed a stronger association with handicap (R(2) = 0.76). Combining impairment and disability scales accounted for 77% of the variance in handicap (RIHS9) scores., Conclusions: In contrast to some suggestions, support for the ICIDH model is found in the current study because significant associations were shown between its various levels in patients with immune mediated polyneuropathies. Further studies are required to examine other possible contributors to deficits in daily life and social functioning in these conditions.

Objective: To determine the long-term impact of Guillain-Barré syndrome (GBS) on work and private life of patients and their partners., Methods: Three to six years after the onset of GBS 150 patients who participated in the Dutch Guillain-Barré trial received a questionnaire specifically drafted for this study to survey their present psychosocial status. Furthermore, their present physical status was established., Results: A total of 122 patients participated. Thirty-one percent showed moderate to serious physical residua after a functional assessment. Due to GBS, 38% of the patients who held a job had to change it, 44% altered their leisure activities, 37% of the patients did not function as well at home as before GBS and 39% reported a change in their partners' lives. Almost half of the patients still had negative comments on their present psychosocial situation., Conclusion: GBS has a serious long-term impact on the patients' work and private life and that of their partners.

Anti-galactocerebroside (GalC) antibodies are reported to be present in GBS patients with preceding Mycoplasma pneumoniae (MP) infection. We investigated the presence of anti-GalC reactivity in serum of a large group of GBS patients using ELISA and compared this with healthy controls and individuals with an uncomplicated MP infection. Anti-GalC antibody reactivity was present in 12% of the GBS patients. Furthermore, anti-GalC antibodies were associated with MP infections, a relatively mild form of the disease and demyelinating features. Anti-GalC antibodies cross-reacted with MP antigen. In conclusion, anti-GalC antibodies in GBS patients may be induced by molecular mimicry with MP.

Objectives: To determine whether quality of life complements traditional outcome measures in immune-mediated polyneuropathies using the Medical Outcome Study 36-item short-form health status scale (SF-36). The validity, reliability, and responsiveness of the SF-36 were also analyzed., Methods: SF-36 and three other measures (Medical Research Council sumscore, sensory sumscore, and Hughes functional scale) were assessed in 114 stable patients (83 with Guillain-Barré syndrome (GBS), 23 with chronic inflammatory demyelinating polyneuropathy (CIDP), eight with a gammopathy-related polyneuropathy) and serially in 20 patients with recently diagnosed GBS (n = 7) or CIDP (n = 13) with changing conditions. The SF-36 values were compared with reported healthy Dutch community scores (controls). The SF-36 validity and reliability were examined by correlation and regression studies with the other measures and by calculating its internal consistency. The standardized response mean and effect size techniques were applied to determine its responsiveness., Results: In the stable group, all SF-36 scores were substantially lower (indicating worse clinical condition) compared with control subjects (p < 0.0001). Improvement in the longitudinal group resulted in a gradual shift of all SF-36 scores toward normal values. Acceptable validity and internal consistency values and moderate to good standardized response mean and effect size scores were demonstrated for the SF-36. The Medical Research Council sumscore and sensory sumscore explained SF-36 values only partially., Conclusion: The SF-36 as a generic health status complemented traditional strength and sensory measures in patients with immune-mediated polyneuropathies and appears to be a potentially valuable instrument for measuring quality of life in these conditions.

Objectives: To determine the validity, reliability, and responsiveness of a new overall disability sum score in immune mediated polyneuropathies., Methods: Three impairment measures (MRC sum score, sensory sum score, grip strength (Vigorimeter)) and three disability scales (an overall disability sum score (ODSS), Hughes' functional scale (f score), Rankin scale) were assessed in a cross sectional group of 113 clinically stable patients (83 with Guillain-Barré syndrome, 22 with chronic inflammatory demyelinating polyneuropathy (CIDP), eight with a gammopathy related polyneuropathy). The ODSS was also used serially in 20 patients with recently diagnosed Guillain-Barré syndrome (n = 7) or CIDP (n = 13) and changing clinical conditions. Multiple regression studies were performed to compare the impact of impairment disturbances (independent variables) on the various disability scales (dependent variable)., Results: Moderate to good construct validity (stable group: Spearman's rank test (absolute values), r = 0.41-0.79; longitudinal group: multiple correlation coefficient, R = 0.69-0.89; p < 0.006 for all associations) and reliability (intraclass correlation coefficient, R = 0.90-0.95; p < 0.0001) were demonstrated for the ODSS. Its SRM values were high (> 0.8), indicating good responsiveness. Impairment measures accounted for a higher variance proportion of the ODSS compared with the f score and Rankin (R = 0.64 v 0.56 and 0.45, respectively)., Conclusions: All clinimetric requirements were met by the overall (arm and leg) disability sum score in immune mediated polyneuropathies. Its use is therefore suggested in evaluating immune mediated polyneuropathies.

One of the characteristics of multiple sclerosis is the unpredictable occurrence of exacerbations and remissions. These fluctuations in disease activity are related to alterations in (auto-)immune activity. Exacerbations lead to short-term morbidity, but may also influence long-term disability. This longitudinal study in 73 patients with relapsing-remitting multiple sclerosis assessed the contribution of systemic infections to the natural course of exacerbations. In addition, we analysed whether infections lead to an increase in the number of gadolinium-enhancing lesions. A total of 167 infections and 145 exacerbations were observed during 6466 patient weeks. During a predefined at-risk period (ARP) of 2 weeks before until 5 weeks after the onset of a clinical infection (predominantly upper airway infections), there was an increased risk of exacerbations (rate ratio 2.1), which is in accordance with previous studies. Exacerbations with onset during the ARP led more frequently to sustained deficit [increase of > or =1 Expanded Disability Status Scale (EDSS) point or > or =0.5 above EDSS 5.5 for >3 months] than exacerbations with onset outside the ARP, with a rate ratio of 3.8. Minor and major exacerbations were equally distributed between the ARP and non-ARP onset groups. ARP exacerbations were associated with significantly higher plasma levels of the inflammatory marker soluble intracellular adhesion molecule 1 than non-ARP exacerbations, indicating relatively enhanced immune activation during ARP relapses. Three serial MRI scans were performed after the onset of an infection over a 6-week period. There was no difference in the number of gadolinium-enhancing lesions between the three time points. In conclusion, exacerbations in the context of a systemic infection lead to more sustained damage than other exacerbations. There is no indication that this effect occurs through enhanced opening of the blood-brain barrier.

A new handicap measure, the Rotterdam nine-item handicap scale, was developed and its validity, reliability, and responsiveness evaluated in patients with immune-mediated polyneuropathies. We evaluated 113 stable patients, of whom 83 had Guillain--Barré syndrome (GBS), 22 had chronic inflammatory demyelinating polyneuropathy (CIDP), and 8 had a gammopathy-related polyneuropathy. We also studied 20 patients with recently diagnosed GBS (n = 7) or CIDP (n = 13) and changing clinical conditions (longitudinal group). Significant discriminatory validity and correlation with the Rankin scale were demonstrated for the Rotterdam nine-item handicap scale (stable group: Spearman's test, r = minus sign.76 to minus sign.78; longitudinal group: intraclass correlation coefficient, r =.83; P <.0001). Also, good reliability (r =.89--.98; P <.0001) and high responsiveness values (standardized response mean values >.8) were obtained for the Rotterdam nine-item handicap scale. In contrast to the Rankin scale, the Rotterdam scale not only provided information regarding mobility but also highlighted physical independence, occupation, and social integration. These results illustrate the clinical usefulness of the Rotterdam nine-item handicap scale under these conditions., (Copyright 2002 Wiley Periodicals, Inc.)

Objective: Twenty-eight percent of patients with the Guillain-Barré syndrome remain able to walk unaided. Studying patients with the mild form of Guillain-Barré syndrome can further contribute to knowledge of the spectrum of the syndrome and explore whether this subgroup may need treatment with IV immunoglobulin., Methods: Patients fulfilling the National Institute of Neurologic and Communicative Disorders and Stroke criteria for Guillain--Barré syndrome were included in a nationwide survey over a 2-year period. Clinical characteristics and serum samples were collected prospectively. In addition, a questionnaire was completed concerning the course and outcome of the disease., Results: A total of 139 patients were included. Nineteen of the patients (14%) included were mildly affected, and 120 (86%) were severely affected. Infections with Epstein-Barr virus were found more frequently in mildly affected patients (p = 0.02). Antiganglioside antibodies were less frequently found in the mildly affected patients (p = 0.03). The degree of severity of the disease between mildly and severely affected patients was different on the day of admission (p < 0.01). Thereafter, the groups showed a remarkably similar rate of progression. Thirty-eight percent of mildly affected patients report problems in hand function and an inability to run at 3 and 6 months (all women, p = 0.02)., Conclusion: The difference in severity of Guillain--Barré syndrome seems to be determined in an early phase of the disease. Preceding infections and antiganglioside antibodies may influence the initial immune attack, determining the severity of the disease. The presence of residual signs in patients with mild disease may advocate the use of early treatment in mildly affected patients.

Anti-ganglioside antibodies are consistently found in Guillain-Barré syndrome (GBS) patients from different geographical parts of the world. Several studies indicated differences in relative frequencies of anti-ganglioside reactivity and isotype distribution between GBS patients from Asia and from Europe. We investigated antibody reactivity against the gangliosides GM1, GM1b and GalNAc-GD1a in GBS patients from Japan and The Netherlands in two different laboratories. The proportion of GBS patients with anti-ganglioside antibodies did not differ between the two countries. GBS patients from The Netherlands more frequently had cross-reacting anti-GalNAc-GD1a/anti-GM1b antibodies and a stronger IgM anti-ganglioside response. Our findings indicate that geographical determined factors, dependent on either the host or the triggering infectious agent, determine the isotype distribution and fine specificity of anti-ganglioside antibodies in GBS patients.

Background: Previously, mainly retrospective and a few important prospective studies postulated the role of sepsis or systemic inflammatory response syndrome (SIRS), multiple organ failure, and the use of medication as causative factors for the development of critical illness polyneuropathy and myopathy (CIPNM). This study aimed to identify the risk factors in the development of CIPNM., Methods: Prospectively, we studied 98 patients who were on artificial respirators for the development of CIPNM. The Acute Physiology and Chronic Health Evaluation (APACHE) III score, presence of SIRS, and sepsis severity score at entry; the dosage of midazolam, vecuronium, and steroids at entry and day 7 of artificial respiration; and the use of aminoglycosides at entry were related with time to CIPNM or time of last follow-up. The Kaplan-Meier method and log-rank test were used., Results: Thirty-two patients (33%) developed CIPNM. After multivariate analysis, it was found that the APACHE III score and the presence of SIRS were significantly related with risk for the development of CIPNM. No significant relation was found for the use of midazolam, vecuronium, or steroids. Based on a risk index from a Cox regression model with APACHE III score and presence of SIRS as outcomes, three groups could be constructed with low-, medium-, and high-risk patients for the development of CIPNM., Conclusions: The APACHE III score, a quantitative index of disease severity based on clinical and laboratory physiologic data, is a valuable predictor for the development of CIPNM in patients in the intensive care unit. Together with the presence of SIRS, it can be used to estimate the risk of developing CIPNM for patients on artificial respirators.

Background: Shoulder complaints in scaffolders are very common and may result in permanent disability., Methods: We present two case reports of patients who developed acute shoulder complaints. After lifting weights up to 50 kg both patients suffered an isolated lesion of the long thoracic nerve resulting in serratus anterior paralysis., Results: Physical signs are unilateral winging of the scapula and loss of strength in the arm. A combined effect of pressure and stretching of the nerve resulted in an occupational injury with a different prognosis of reversibility in both patients., Conclusion: Shoulder pads in the overall and limiting the weight to carry may prevent future injuries., (Copyright 2001 Wiley-Liss, Inc)

Background: The number of patients with Guillain-Barré syndrome (GBS) who have been observed in Curaçao, the Netherlands Antilles, may be increasing., Methods: Clinical and serologic data were obtained from records of patients admitted between 1987 and 1999 and fulfilling National Institute of Neurological and Communicative Disorders and Stroke criteria for GBS. When possible, serum and stool samples were collected. The results were compared with a large Dutch epidemiologic study., Results: The authors identified 49 patients, an overall crude incidence rate (IR) in Curaçao of 2.53/100,000 inhabitants (95% CI 1.87 to 3.35) (Dutch study 1.18, rate ratio (RR) of 2.14, p < 0.001). The IR in Curaçao increased from 1.62 in 1987 to 1991 to 3.10 in 1992 to 1999, RR 5.22 (95% CI 2.48 to 10.2, p = 0.02). The IR showed a curvilinear shape within a year. In comparison with the Dutch group, patients from Curaçao had a more severe course of the disease, with a mortality rate of 23% (3.4% in the Dutch group, p < 0.001), a higher percentage of preceding gastroenteritis (p < 0.001), and less sensory involvement (p < 0.001). In 8 of 10 serum samples, evidence was found for a recent infection with Campylobacter jejuni., Conclusions: The authors found a steady increase in incidence of GBS over the years in association with a more pronounced seasonal preponderance and a more severe course. The clinical characteristics suggest a role for C jejuni.

In order to document the sensory deficit still present several years after onset of Guillain-Barré syndrome (GBS) and to determine if the sensory residua have a disrupting effect on daily life, 122 patients were asked to cooperate in a neurological examination and to complete a questionnaire three to six years after onset. On functional assessment 84 patients had no or only minor neurological symptoms or signs, 24 patients showed moderate recovery and 14 patients were left with severe residual signs. On neurological examination, residual sensory deficit was found in the arms of 38 % of the patients and in the legs of 66 % of the patients. Sensory disturbance was experienced as moderate to severe in the arms of 27 % of the patients and in the legs of 40 % of the patients. Muscle aches and cramps were still present in 48 %. There was a statistically significant relation between muscle aches and cramps and objective residual sensory deficit but not with residual weakness. Furthermore, in the group of patients with a pure motor GBS, significantly fewer people suffered from muscle aches and cramps than in the remaining patients (p=0.04). Twenty-five percent of patients changed jobs after their illness, and 44% gave up some leisure activities. It can be concluded that many patients still suffer from sensory deficit, and a considerable number experience these as moderately to seriously disruptive, especially in the legs. Muscle aches and cramps seems to be related to sensory rather than motor dysfunction.

A comparative study was made in Japan and The Netherlands of the presence of preceding Campylobacter jejuni infections in Guillain-Barré syndrome (GBS). It was conducted in two laboratories using different serological criteria. The Japanese results showed no significant difference in the frequency of C jejuni infection between the Japanese (17/88, 19%) and Dutch (21/132, 16%) patients with GBS. The Dutch investigation showed a higher frequency in Dutch patients (45/132; 34%) than in Japanese patients(20/88; 23%), but the difference did not reach significance. Although the frequencies of preceding C jejuni infection have been reported to be higher in Asian countries than in western countries, the findings of this collaborative study show that the incidence of antecedent C jejuni infection in GBS in Japan is not higher than in The Netherlands and that serological assays vary considerably between laboratories.

Campylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopolysaccharides (LPS) and gangliosides. We used purified LPS fractions from five Campylobacter strains to induce antiganglioside responses in rabbits. The animals that received injections with LPS from GBS-associated strains developed anti-GM1 and anti-GA1 antibodies. Animals injected with LPS from one MFS-related C. jejuni strain produced anti-GQ1b antibodies. Rabbits that were injected with Penner O:3 LPS had a strong anti-LPS response, but no antiganglioside reactivity was observed. The antiganglioside specificity in the rabbits reflected the specificity in the patients from whom the strains were isolated. In conclusion, our results indicate that an immune response against GBS- and MFS-associated C. jejuni LPS results in antiganglioside antibodies. These results provide strong support for molecular mimicry as a mechanism in the induction of antiganglioside antibodies following infections.

The authors assessed the referral pattern and outcome in patients with Guillain-Barré syndrome (n = 266) after the introduction of intravenous immunoglobulin (IVIg). Fewer patients were transferred from small to large hospitals after the introduction of IVIg (p = 0.05). This did not result in a worse outcome in patients treated in small centers. The introduction of IVIg has led to a better use of different levels of health care facilities.

Background: Diagnostic criteria for the Guillain-Barré syndrome (GBS) have been available since 1978. Since then, several variants have been described. More recently, a distinction has been made between pure motor forms, severe sensory forms, primary axonal and primary demyelinating varieties. Associations of clinical characteristics, and specific infections and the presence of antiganglioside antibodies have been found. For further studies on GBS, it is therefore necessary to reconsider the available diagnostic criteria and add additional criteria for subclassification., Methods: A panel of (20) experts was formed. The literature representing the recent developments in GBS subclassification was reviewed. Following a consensus protocol, diagnostic and classification criteria were formulated., Results: The diagnosis of GBS can usually be made on clinical characteristics. A schedule for subclassification has been made to cover also the clinical variants in a systematic manner.

We describe an outbreak of Campylobacter jejuni enteritis involving three family members of whom one developed Guillain-Barré syndrome (GBS). The patients' serum reacted strongly with several gangliosides and with the lipopolysaccharide (LPS) fractions from the C. jejuni strains isolated from his family members. Only low titer anti-ganglioside antibodies were found in his siblings. HLA-typing did not indicate a locus associated with auto-antibody production. Comparing the immune response in GBS patients and C. jejuni enteritis patients can be of great value in determining the additional factors that lead to post-Campylobacter GBS. Ganglioside mimicry alone is necessary but not sufficient for the induction of anti-ganglioside antibodies. Other susceptibility factors are required to induce an anti-neural immune response.

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy. Two thirds of GBS patients are unable to walk at their most severe state of disease. Respiratory insufficiency and autonomic failure are probably the main causes of death. Optimal general care, physiotherapy and the availability of intensive care facilities at short distance are of great importance. Randomized controlled trials show that intravenous immune globulin (IVIg) and plasma exchange (PE) are equally effective in reducing the time to functional recovery. The combination of PE followed by IVIg, is not significantly better than IVIg or PE alone. Corticosteroids alone are not effective in GBS. Approximately 10% of GBS patients deteriorate after initial improvement or stabilization following IVIg or PE treatment, and often require repeated treatment. These "treatment related clinical fluctuations" are more frequently seen in relatively young patients with severe motor and sensory involvement associated with a preceding and possibly ongoing cytomegalovirus infection. Predominantly motor GBS is frequently preceded by a Campylobacter jejeuni infection. Diarrhea prior to GBS is associated with a worse predicted outcome. Further confirmation is needed to determine whether this is especially the case in those patients treated with PE. GBS patients who are unable to walk without assistance, and who are still within their first 2 weeks of the disease, need to be treated. One PE study showed that patients who are only mildly disabled showed positive progress from two plasma exchange sessions. Presently, due to its wide availability, ease of administration, and favorable side-effect profile, IVIg is considered to be the first-line treatment for patients with GBS. Current investigations are trying to determine if IVIg used in combination with methylprednisolone is even more effective in treating GBS.

In a longitudinal prospective study a muscle biopsy was taken from 30/32 (33%) of the 98 patients who developed critical illness polyneuropathy and myopathy (CIPNM). Neuropathic changes were found in 37%, myopathic in 40%, and a combination in 23% of the biopsies. The immunohistopathology showed macrophages and Th-cells in 40% and 60% of the muscle biopsies respectively. Small mainly perivascular infiltrates contained macrophages and Th-cells. ICAM-1, VCAM and MAC were found on the vascular endothelium in 58%, 53% and 79% respectively. In all biopsies there was an upregulation of both HLA-I and HLA-DR. Proinflammatory cytokines and TNFalphaR75 were also produced locally (IL-1beta in 71%, IFN-gamma in 40%, IL-12 in 73%, TNFalphaR75 in 90%). The anti-inflammatory cytokine IL-10 was simultaneously expressed in 96% of the biopsies. HLA-DR, TNFalphaR75 and IL-10 differed significantly when compared with control muscle biopsies. Our data provide evidence that small numbers of activated leukocytes producing both pro- and anti-inflammatory cytokines infiltrate skeletal muscle of CIPNM patients. We propose that the local balance of leukocyte activities is of importance in the pathophysiology of muscle weakness in CIPNM.

Lipopolysaccharides (LPS) from Campylobacter jejuni strains isolated from patients with Guillain-Barré syndrome (GBS) display molecular mimicry with GM1. We immunized rabbits with C. jejuni LPS from GBS-associated strains containing a GM1-like epitope. All animals produced high titre anti-LPS antibodies that were cross-reactive with GM1. We conclude that C. jejuni strains from GBS patients are able to induce antibodies that cross-react with gangliosides and LPS. This study further confirms the role of molecular mimicry in the induction of anti-ganglioside antibodies in GBS patients.

The interobserver and intraobserver reliability of the Rydel-Seiffer (RS) graduated tuning fork was evaluated in 113 patients with a clinically stable immune mediated polyneuropathy (83 patients who had had Guillain-Barré syndrome (GBS) in the past, 22 with a chronic inflammatory demyelinating polyneuropathy (CIDP), and eight with a polyneuropathy associated with a gammopathy of undetermined significance). Additionally, the responsiveness of this instrument was serially investigated in 20 patients with recently diagnosed GBS or CIDP and changing clinical conditions. The measures were done in triplicate at eight different locations in the limbs and the values were compared with the recently published vibration threshold reference values. Good interobserver and intraobserver agreements (quadratic weighted kappa=0.67-0.98) and high responsiveness values (standardised response mean scores>0.8) were demonstrated for the RS tuning fork. These results provide, in addition to literature findings, further evidence for incorporation of this easily applicable instrument in routine neurological examination.

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Objective: To investigate whether anti-GM2 antibodies in patients with Guillain-Barré syndrome (GBS) are induced by molecular mimicry with cytomegalovirus (CMV)., Background: Antibodies against ganglioside GM2 are frequently present in the serum from GBS patients with an antecedent infection with CMV., Methods: The authors detected inhibition of anti-GM2 reactivity after incubation of GM2-reactive serum samples with fibroblasts infected with a GBS-associated CMV strain. Control sera consisted of GQ1b-reactive samples, and control antigens included uninfected fibroblasts and fibroblasts that were infected with other herpes viruses., Results: Serum immunoglobulin M reactivity with GM2 was decreased in a dose-dependent manner after incubation with CMV-infected fibroblasts. Incubation of anti-GM2-positive serum samples with uninfected fibroblasts and fibroblasts infected with varicella zoster virus did not inhibit anti-GM2 reactivity, whereas this reactivity was slightly decreased after incubation with herpes simplex virus type 1 in one patient. Antibodies against ganglioside GQ1b did not react with CMV-infected fibroblasts., Conclusions: CMV-infected fibroblasts express gangliosidelike epitopes that recognize specifically anti-GM2 antibodies. These results support the hypothesis that antiganglioside antibodies in CMV-infected GBS patients are induced by molecular mimicry between GM2 and antigens that are induced by a CMV infection.

GM1b is a minor ganglioside in human peripheral nerves. Serum anti-GM1b antibodies frequently are present in patients with Guillain-Barré syndrome (GBS). In this collaborative study, we investigated the antecedent infections, clinical features, and response to treatment of GBS patients with anti-GM1b antibodies. Of 132 GBS patients who participated in the Dutch GBS trial that compared the effect of intravenous immunoglobulins and plasma exchange, 25 (19%) patients had anti-GM1b antibodies. IgM antibodies were present in 14, IgG antibodies in 15, and both isotypes in 4 patients. The 25 patients with anti-GM1b antibodies had a clinical pattern distinct from that of the other 107 GBS patients. They more often had an episode of gastrointestinal illness and frequently showed serological evidence of recent infection by Campylobacter jejuni. The anti-GM1b-positive subgroup was marked by more rapidly progressive, more severe, and predominantly distal weakness. Cranial nerve involvement and sensory deficits were less common in the patients with anti-GM1b antibodies. The presence of anti-GM1b antibodies was associated with slower recovery. The clinical manifestations predominantly were associated with anti-GM1b antibodies of the IgG isotype. Fourteen (56%) of the 25 patients with anti-GM1b antibodies also had anti-GM1 antibodies. The group of patients with both antibodies was clinically more homogeneous and had a more rapidly progressive, pure motor neuropathy. The subgroup of anti-GM1b-positive GBS patients responded well to treatment with immunoglobulins but not to plasmapheresis. The distinctive clinical features of the patients with anti-GM1b antibodies show that acute motor neuropathy represents a specific subgroup within GBS and that recognizing these patients may have consequences as to the choice of therapy.

Objectives: Assessment of the long-term effect of uvulopalatopharyngoplasty (UPPP) on snoring, excessive daytime sleepiness, and nocturnal oxygen desaturation index (ODI) in patients with obstructive sleep apnea syndrome., Study Design: Evaluation of snoring, excessive daytime sleepiness, and ODI in patients treated by UPPP earlier., Materials and Methods: Patients (n = 58) with a follow-up period of 11 to 74 months (median, 34 mo) were included in this study. Snoring and excessive daytime sleepiness were scored on specially designed semiquantitative scales. In all patients ODI was calculated from pulse-oximetry combined with polysomnography at base line and by polygraphy (MESAM 4) during follow-up in 38 patients. Long-term response was compared with 6-month response in the same cohort., Results: There was a long-term improvement of snoring in 63% of patients, no change in 23%, and a deterioration in 14% (P < .00001). Overall snoring increased slightly between 6 months and long-term follow-up. There was an improvement of excessive daytime sleepiness in 38%, no change in 27%, and a deterioration in 35% (P = .80). Excessive daytime sleepiness showed a relapse to preoperative levels between 6 months and long-term follow-up. The median improvement of ODI was -1 (95% interpercentile range, 73-51) and was not significant (P = .35). In 5 of 13 patients in whom ODI at baseline exceeded 20, ODI was reduced to less than 20. In 4 of the 38 patients ODI was reduced to less than 5. The improvement of ODI decreased significantly between 6 months and long-term follow-up (P = .03). No relation was found between body mass index, Mueller maneuver, X-cephalometry, and long-term outcome. An additional finding was that the ODI decreased after UPPP in combination with tonsillectomy, compared with a slight increase after UPPP alone; the difference was significant (P = .008)., Conclusion: The response to UPPP for obstructive sleep apnea syndrome decreases progressively over the years after surgery. UPPP in combination with tonsillectomy was more effective than UPPP alone.

Objective: To perform a psychometric evaluation of the inflammatory neuropathy cause and treatment (INCAT) sensory sumscore (ISS) in sensory-motor immune-mediated polyneuropathies. This new sensory scale was evaluated to strive for uniformity in assessing sensory deficit in these disorders., Methods: The ISS comprises vibration and pinprick sense plus a two-point discrimination value and ranges from 0 (normal sensation) to 20 (maximum sensory deficit). Before its clinical use, a panel of expert neurologists concluded that the ISS has face and content validity. The construct validity of the ISS was investigated by correlation and regression studies with additional scales (Nine-Hole Peg Test, 10-Meter Walking Test, a disability sumscore). All scales were applied in 113 patients with a stable neurologic condition (83 patients who experienced Guillain-Barre syndrome [GBS] in the past, 22 with chronic inflammatory demyelinating polyneuropathy [CIDP], 8 patients with a monoclonal gammopathy associated polyneuropathy), and 10 patients with recently diagnosed GBS or CIDP with changing clinical conditions. Reliability of the ISS was evaluated in the stable patients. Its responsiveness was investigated in the patients examined longitudinally., Results: A moderate to good validity was obtained for the ISS (stable group: r = 0.38 to 0.56, p < or = 0.006; longitudinal group: R = 0.60 to 0.82, p < or = 0.007, except for the association with the 10-Meter Walking Test [p = 0.08]). Acceptable internal consistency, and inter- and intraobserver reliability were demonstrated for the ISS (alpha = 0.68 to 0.87; R = 0.85 to 0.89, p < 0.0001). Standardized response mean scores for the ISS were high (> or =0.8), indicating good responsiveness., Conclusions: All psychometric requirements are provided for the the inflammatory neuropathy cause and treatment sensory sumscore. The use of this scale is therefore suggested for bedside evaluation of sensory deficit in the individual patient with a sensory-motor immune-mediated polyneuropathy as well as in clinical trials.

Objective: Assessment of incidence rates of Guillain-Barré syndrome (GBS) in the Netherlands over a 10-year period; investigation of a relationship between possible seasonality in GBS and the occurrence of preceding infections; and determination of distinctive characteristics in patients with GBS who are only mildly affected (able to walk unaided at nadir)., Method: Records of patients with GBS admitted between 1987 and 1996 from all 45 hospitals in the southwest Netherlands were evaluated, covering a population of 4.2 million inhabitants., Results: A total of 476 patients met National Institute for Neurological and Communicative Disorders and Stroke criteria for GBS. This resulted in a crude incidence rate (IR) of 1.18/100,000 inhabitants. This IR increased linearly with age (p < 0.001). Men were more frequently affected than women (p < 0.001). No seasonal preponderance for GBS, nor for any of the preceding infections, was found. Patients under 50 years of age (p < 0.001) and men (p = 0.01) were more frequently found in the mildly affected group. In both groups a preceding infection was reported in 70% of the cases. In the severely affected group, serologic evidence for infection with Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, or Mycoplasma pneumoniae was found more frequently than in the mildly affected group (41% versus 16%, p = 0.001)., Conclusions: Overall IR in the Netherlands are similar to those found in other studies. The incidence increases linearly with age and men are more frequently affected than women. Distinctive characteristics for mildly and severely affected patients were found regarding age, sex, and preceding infections. This suggests that other infectious agents or host factors may be involved in mild forms of GBS.

Background: The cause of Guillain-Barré syndrome (GBS) is inflammation of the peripheral nerves which corticosteroids would be expected to benefit., Objectives: To examine the efficacy of corticosteroids in hastening recovery and reducing the long term morbidity from Guillain-Barré syndrome (GBS)., Search Strategy: Search of the Cochrane Neuromuscular Disease Group register for randomised trials and enquiry from authors of trials and other experts in the field., Selection Criteria: Types of studies: quasi-randomised or randomised controlled trials, Types of Participants: patients with GBS of all ages and all degrees of severity Types of interventions: any form of corticosteroid or adrenocorticotrophic hormone Types of outcome measures: Primary: improvement in disability grade on a commonly used seven point scale four weeks after randomisation Secondary: time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for those ventilated), mortality, proportion of patients dead or disabled (unable to walk without aid) after 12 months, improvement in disability grade after six months, improvement in disability grade after 12 months, proportion of patients who relapse, and proportion of patients with adverse events related to corticosteroid treatment, Data Collection and Analysis: We identified six randomised trials. One author extracted the data and the other checked them. We obtained some missing data from investigators., Main Results: The six eligible trials included a total of 195 corticosteroid treated patients and 187 control subjects. One trial of intravenous methylprednisolone accounted for 243 of the total 382 subjects studied (63%). This trial did not show a significant difference in any disability related outcome between the corticosteroid and placebo groups. There was no significant difference between the corticosteroid and control groups for the primary outcome measure, improvement in disability grade four weeks after randomisation. The weighted mean difference of the three trials for which this outcome was available showed no difference. The actual figure was 0.01 (95% CI -0.27 to 0.29) grade in favour of the corticosteroid group. There was also no significant difference between the groups for most of the secondary outcome measures. However in the largest trial hypertension developed less often in the intravenous methylprednisolone group (2/124, 1.6%) than in the control group (12/118, 10.2%), a significant difference in favour of corticosteroid treatment (relative risk 0.20, 95% CI 0.04 to 0.66)., Reviewer's Conclusions: Corticosteroids should not be used in the treatment of Guillain-Barré syndrome. If a patient with Guillain-Barré syndrome needs corticosteroid treatment for some other reason its use will probably not do harm. The effect of intravenous methylprednisolone combined with intravenous immunoglobulin in Guillain-Barré syndrome is being tested with a randomised trial.

Objective: To investigate the presence of anti-GalNAc-GD1a antibodies in patients with Guillain-Barré syndrome (GBS) and to determine the relation of anti-ganglioside antibodies with clinical features., Background: The GBS is heterogeneous with regard to clinical manifestations, antecedent infections, and the presence and specificity of anti-ganglioside antibodies. Recently, antibodies to minor gangliosides have been identified in serum from GBS patients., Methods: The authors used ELISA to detect anti-ganglioside antibodies in 132 GBS patients and then correlated results with a database containing information on antecedent infections and clinical parameters., Results: Anti-GalNAc-GD1a antibodies could be detected in 19 (14%) GBS patients. The presence of anti-GalNAc-GD1a antibodies was related to antecedent Campylobacter jejuni infection (p<0.001). GBS patients with anti-GalNAc-GD1a antibodies had a rapidly progressive, more severe, and predominantly distal weakness. Furthermore, they had less sensory loss, paresthesia, and cranial nerve involvement. In most patients, this reactivity was independent of reactivity to GM1. Dividing patients into separate groups based on their reactivity to GalNAc-GD1a and GM1 enabled the authors to delineate more homogeneous subgroups with regard to clinical features., Conclusions: This study provides further evidence for the hypothesis that antecedent infections and the specificity of subsequent anti-neural antibody responses determine the clinical manifestations in GBS patients.

Objectives: To determine the prevalence and severity of ongoing fatigue and to investigate the internal consistency, reliability, and validity of the Fatigue Severity Scale (FSS) in patients with immune-mediated polyneuropathies., Methods: The FSS was assessed in 113 patients who either experienced Guillain-Barré syndrome in the past or currently have a stable, chronic, inflammatory demyelinating polyradiculoneuropathy or a polyneuropathy associated with a monoclonal gammopathy of undetermined significance, and in 113 age- and sex-matched healthy controls. Data on four additional scales (Medical Research Council sumscore, functional grading scale [f-score], INCAT sensory sumscore, medical outcome study 36-items health survey [SF-36]) were obtained in all patients. SF-36 also was assessed in 59 controls., Results: "Severe" fatigue (FSS scores > or =95th percentile values in controls) was present in 80% of the patients. Fatigue was not significantly related to general strength, sensory deficits, f-score, and duration of symptoms. Severe fatigue was reported in 81% to 86% of patients with normal strength or sensation. Eighty percent of the patients (controls, 12%) reported their fatigue being among the three most disabling symptoms. SF-36 health status scores in the patient group were significantly lower than the obtained values of the controls and partially related to the FSS scores. Good internal consistency, significant reliability, and validity were obtained for the FSS., Conclusion: Fatigue is a major symptom in patients with immune-mediated polyneuropathies and may persist for years after apparent recovery. The Fatigue Severity Scale seems appropriate for assessing fatigue in these patients because good internal consistency, reliability, and validity were demonstrated.

Objective: To determine the influence of clinical, laboratory, and electrodiagnostic factors on the prognosis of Guillain-Barré syndrome (GBS)., Background: Identification of prognostic factors may lead to better selection of patients with a poor prognosis for new therapeutic trials., Methods: The authors studied 147 patients with GBS who participated in the Dutch GBS trial comparing the effect of IV immunoglobulins with plasma exchange (PE). Outcome was measured at 8 weeks because half of the patients had recovered independent locomotion by then and at 6 months, the endpoint of the study., Results: Multivariate logistic regression revealed the following factors predicting outcome (inability to walk independently) at 8 weeks: a preceding gastrointestinal illness (yes, no), age (> or =50, <50 years), Medical Research Council sum score (<40, > or =40) at the start of treatment, and-described for the first time-a recent cytomegalovirus (CMV) infection (yes, no). At 6 months, the same clinical factors were found, but an initial rapid progression of weakness also appeared to be a prognostic factor. Analysis of treatment interactions revealed that the effect of diarrhea was more pronounced in the PE-treated group., Conclusions: The main predictors of outcome in GBS are clinical factors. Diarrhea is an important poor predictor of outcome, especially for the PE-treated group, and a recent CMV infection predicts delayed early recovery.

Three to six years after onset of Guillain-Barré syndrome, 63% of 122 patients showed one or more changes in their lifestyle, work, or leisure activities, or in the life of their partners. The changes were influenced by an impaired final functional outcome, along with loss of power and poor condition, although physically recovered patients showed these changes as well.

Objectives: The effect of interferon-beta1a (INF-beta1a; Rebif) was studied in patients with chronic motor neuropathies not improving after conventional treatments such as immunoglobulins, steroids, cyclophosphamide or plasma exchange., Methods: A prospective open study was performed with a duration of 6-12 months. Three patients with a multifocal motor neuropathy and one patient with a pure motor form of chronic inflammatory demyelinating polyneuropathy were enrolled. Three patients had anti-GM1 antibodies. Treatment consisted of subcutaneous injections of IBF-beta1a (6 MIU), three times a week. Primary outcome was assessed at the level of disability using the nine hole peg test, the 10 metres walking test, and the modified Rankin scale. Secondary outcome was measured at the impairment level using a slightly modified MRC sumscore., Results: All patients showed a significant improvement on the modified MRC sumscore. The time required to walk 10 metres and to fulfil the nine hole peg test was also significantly reduced in the first 3 months in most patients. However, the translation of these results to functional improvement on the modified Rankin was only seen in two patients. There were no severe adverse events. Motor conduction blocks were partially restored in one patient only. Anti-GM1 antibody titres did not change., Conclusion: These findings indicate that severely affected patients with chronic motor neuropathies not responding to conventional therapies may improve when treated with INF-beta1a. From this study it is suggested that INF-beta1a should be administered in patients with chronic motor neuropathies for a period of up to 3 months before deciding to cease treatment. A controlled trial is necessary to confirm these findings.

In the Miller Fisher syndrome (MFS) variant of the Guillain-Barré syndrome, weakness is restricted to extraocular muscles and occasionally other craniobulbar muscles. Most MFS patients have serum antibodies against ganglioside type GQ1b of which the pathophysiological relevance is unclear. We examined the in vitro effects of MFS sera, MFS IgG, and a human monoclonal anti-GQ1b IgM antibody on mouse neuromuscular junctions (NMJs). It was found that anti-GQ1b antibodies bind at NMJs where they induce massive quantal release of acetylcholine from nerve terminals and eventually block neuromuscular transmission. This effect closely resembled the effect of the paralytic neurotoxin alpha-latrotoxin at the mouse NMJs, implying possible involvement of alpha-latrotoxin receptors or associated downstream pathways. By using complement-deficient sera, the effect of anti-GQ1b antibodies on NMJs was shown to be entirely dependent on activation of complement components. However, neither classical pathway activation nor the formation of membrane attack complex was required, indicating the effects could be due to involvement of the alternative pathway and intermediate complement cascade products. Our findings strongly suggest that anti-GQ1b antibodies in conjunction with activated complement components are the principal pathophysiological mediators of motor symptoms in MFS and that the NMJ is an important site of their action.

Objective: To provide clinically useful vibration threshold normal values., Methods: The graduated Rydel-Seiffer tuning fork was evaluated in 198 healthy controls and 59 patients with a polyneuropathy. The measures were done in triplicate at four locations: the distal interphalangeal joint of the index finger, ulnar styloid process, interphalangeal joint of the hallux, and internal malleolus. The values obtained with this tuning fork in healthy controls and patients with polyneuropathy were compared with the values of an electronic device, the Vibrameter., Results: Vibration sense was better perceived in the arms compared with the legs. There was a significant age related decline of vibration sense at all locations. The values from the Rydel-Seiffer tuning fork and the Vibrameter were significantly correlated in both groups. The sensitivity of these two instruments for the four sites examined in the polyneuropathy group ranged from 29-76% and 31-73%, respectively and was the highest at the hallux for both instruments., Conclusion: This study provides clinical useful normal values of vibration threshold for the Rydel-Seiffer tuning fork. This is a simple and easily applicable instrument that assesses vibration sense semiquantitatively and should therefore have a place in routine neurological examination.