[What is new in symptomatic MS treatment: Part 3-bladder dysfunction]. / Neues zur symptomatischen MS-Therapie: Teil 3 ­ Blasenfunktionsstörungen.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKNMS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of bladder dysfunction will be discussed.

[New aspects of symptomatic MS treatment: Part 4-sexual dysfunction and eye movement disorders]. / Neues zur symptomatischen MS-Therapie: Teil 4 ­ Störungen der Sexualfunktion und der Augenbewegungen.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKNMS) in 2014, several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in several individual contributions. In this article the symptoms of sexual dysfunction and eye movement disorders are discussed.

[New aspects of symptomatic MS treatment: Part 6 - cognitive dysfunction and rehabilitation]. / Neues zur symptomatischen MS-Therapie: Teil 6 ­ kognitive Störungen und Rehabilitation.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis ("Klinisches Kompetenznetz Multiple Sklerose", KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in several individual contributions. In this article the symptoms of cognitive disorders and the growing impact of rehabilitation are discussed.

[New aspects of symptomatic MS treatment: Part 5 - fatigue]. / Neues zur symptomatischen MS-Therapie: Teil 5 ­ Fatigue.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in a series of 6 individual contributions. In this article the symptom of fatigue is discussed.

Patient education programme on immunotherapy in multiple sclerosis (PEPIMS): a controlled rater-blinded study.

OBJECTIVE: To investigate the effectiveness of a multi-component evidence-based education programme on disease modifying therapies in multiple sclerosis. DESIGN: Controlled trial with two consecutive patient cohorts and a gap of two months between cohorts. SETTING: Three neurological rehabilitation centres. SUBJECTS: Patients with multiple sclerosis within rehabilitation. INTERVENTIONS: Control group (CG) participants were recruited and received standard information. Two months later, intervention group (IG) participants were recruited and received a six-hour nurse-led interactive group education programme consisting of two parts and a comprehensive information brochure. MAIN MEASURES: Primary endpoint was "informed choice", comprising of adequate risk knowledge in combination with congruency between attitude towards immunotherapy and actual immunotherapy uptake. Further outcomes comprised risk knowledge, decision autonomy, anxiety and depression, self-efficacy, and fatigue. RESULTS: A total of 156 patients were included (IG=75, CG=81). The intervention led to significantly more participants with informed choice (IG: 47% vs. CG: 23%, P=0.004). The rate of persons with adequate risk knowledge was significantly higher in the IG two weeks after the intervention (IG: 54% vs. CG: 31%, P=0.007), but not after six months (IG: 48% vs. CG: 31%, P=0.058). No significant differences were shown for positive attitude towards disease modifying therapy (IG: 62% vs. CG: 71%, P=0.29) and for disease modifying therapy status after six months (IG: 61.5% vs CG: 68.6%, P=0.39). Also no differences were found for autonomy preferences and decisional conflict after six months. CONCLUSION: Delivering evidence-based information on multiple sclerosis disease modifying therapies within a rehabilitation setting led to a marked increase of informed choices.

[What is new in symptomatic MS treatment: Part 2-gait disorder and spasticity]. / Neues zur symptomatischen MS­Therapie: Teil 2 ­ Gangstörung und Spastik.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of gait disorders and spasticity will be discussed.

[What is new in symptomatic MS treatment: Part 1-introduction and methodical approach, ataxia and tremor]. / Neues zur symptomatischen MS­Therapie: Teil 1 ­ Einleitung und methodisches Vorgehen, Ataxie und Tremor.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the topic will be introduced, the methodical approach will be explained, and the treatment of ataxia and tremor will be discussed.

[Monitoring of blood parameters under course-modified MS therapy : Substance-specific relevance and current recommendations for action]. / Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie : Substanzspezifische Relevanz und aktuelle Handlungsempfehlungen.

With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force "Provision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.

[Current aspects of therapy conversion for multiple sclerosis]. / Aktuelles zur Therapieumstellung bei Multipler Sklerose.

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

Spasticity in patients with multiple sclerosis--clinical characteristics, treatment and quality of life.

AIMS: To gain real-life data on demographic and clinical characteristics, treatment patterns, treatment satisfaction and quality-of-life of multiple sclerosis-related spasticity (MSS) in Germany. MATERIAL AND METHODS: MObility ImproVEment (MOVE 1), a cross-sectional burden-of-disease study, combines retrospective 12-month chart documentation with questionnaires for both, patients and physicians. Data were collected at office-based neurologists, MS outpatient clinics and rehabilitation centres in Germany. Structured documentation forms, questionnaires and validated instruments were used for data collection. Patients with mild to severe MSS were included. Participants documented the clinical characteristics, impact of MSS on daily living, quality-of-life, treatment patterns and satisfaction with available drug treatment stratified by severity of MSS. Severity was assessed by patients and physicians. RESULTS: Of 419 patients enrolled at 42 centres from 4/2011 to 9/2011, 414 were available for analysis (mean age: 48.5 years; female: 64%). Most disturbing symptoms associated with spasticity reported by physicians and patients were stiffness (74%) and mobility restrictions (66%). Mean EQ-5D score fell from 0.6 to 0.3 with increasing severity of spasticity, while percentage of subjects with spasticity-related impairment of activities every day rose from 10% in patients with mild to 85% in patients with severe spasticity. At time of enrolment, 55% of patients received pharmacotherapy and 78% physiotherapy. These percentages increased with increasing severity (drugs: 39-84%; physiotherapy: 65-86%). Overall, 41% of physicians and 36% of patients were partial dissatisfied or dissatisfied with the effectiveness of available anti-spastic pharmacotherapy. CONCLUSIONS: Spasticity and its symptoms impair personal well-being and quality-of-life. Treatment of spasticity with drugs and physiotherapy is common, but satisfaction with the currently available anti-spastic pharmacotherapy is low.

Health-related quality of life as an independent predictor of long-term disability for patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Predictive factors of long-term disability in patients with relapsing-remitting multiple sclerosis (RR-MS) are well known, but the weight of these factors does not explain the entire change of disability. Few studies have examined the predictive value of quality of life (QoL). OBJECTIVES: To determine the value of the initial level of QoL to predict changes in the disability status of patients with MS and to determine if specific-MS questionnaires predict more accuracy in these changes than generic questionnaires. DESIGN: multicenter, multi-regional, and longitudinal study. Main inclusion criteria: patients with RR-MS subtype and an Expanded Disability Status Scale (EDSS) score lower than 7.0. Sociodemographic and clinical data were recorded at baseline. Every 6 months up to month 24, QoL (MusiQoL and SF-36) was recorded. At 24 months, individuals were defined into two 'disability change' groups: the worsened and not worsened patients. RESULTS: Five-hundred and twenty-six patients were enrolled: 386 (83.7%) not worsened and 75 (16.3%) worsened patients at 24 months. The activity of daily living and the relationship with healthcare workers dimensions of MusiQoL questionnaire were independent predictors of change in the EDSS score after 24 months. The physical-functioning dimension of the SF-36 questionnaire predicted independently disability change after 24 months. CONCLUSIONS: Patient-reported baseline QoL levels provide additional prognostic information on MS disability beyond traditional clinical or sociodemographic factors. These findings reinforce the importance of incorporating a patient's evaluation of their own QoL level during patient monitoring and the assessment of treatment effects.

[Importance and treatment of spasticity in multiple sclerosis : results of the MOVE 1 study]. / Bedeutung und Behandlung der Spastik bei Multipler Sklerose : Ergebnisse der MOVE-1-Studie.

BACKGROUND: The impact of spasticity induced by multiple sclerosis (MS) on patients and the applied treatment options have so far been insufficiently studied. METHODS: This was a multicentre, retrospective, nationwide study of the care situation of MS spasticity in Germany from the perspective of both patients and physicians. RESULTS: In this study 414 patients (mean age 48.6 years, 64.3 % women) from 42 centres were analyzed: 27 % suffered from mild, 44 % from moderate and 29 % from severe spasticity. The most common comorbidities were depression and anxiety (25.6 %) and 94.9 % suffered from concomitant symptoms (e.g. fatigue and bladder disorders). The severity of spasticity and its consequences were assessed by both patients and physicians and 54.8 % of physicians were dissatisfied with available treatment options. The most frequently cited disadvantages of currently available antispastic treatment were adverse effects (95.2 %) und insufficient effectiveness (88.1 %) and one third of patients sought help by self-medication. CONCLUSIONS: This initial assessment of MS-induced spasticity in Germany showed that patients experienced severe impairment due to spasticity. Available treatment options were assessed as dissatisfying.

[MusiQol: international questionnaire investigating quality of life in multiple sclerosis: validation results for the German subpopulation in an international comparison]. / MusiQol: Internationaler Fragebogen zur Erfassung der Lebensqualität bei Multipler Sklerose : Validierungsergebnisse der deutschen Subpopulation im internationalen Vergleich.

BACKGROUND: The existing health-related quality of life questionnaires on multiple sclerosis (MS) only partially reflect the patient's point of view on the reduction of activities of daily living. Their development and validation was not performed in different languages. That is what prompted the development of the Multiple Sclerosis International Quality of Life (MusiQoL) Questionnaire as an international multidimensional measurement instrument. This paper presents this new development and the results of the German subgroup versus the total international sample. PATIENTS AND METHODS: A total of 1,992 MS patients from 15 countries, including 209 German patients, took part in the study between January 2004 and February 2005. The patients took the MusiQoL survey at baseline and at 21±7 days as well as completing a symptom-related checklist and the SF-36 short form survey. Demographics, history and MS classification data were also generated. Reproducibility, sensitivity, convergent and discriminant validity were analysed. RESULTS: Convergent and discriminant validity and reproducibility were satisfactory for all dimensions of the MusiQoL. The dimensional scores correlated moderately but significantly with the SF-36 scores, but showed a discriminant validity in terms of gender, socioeconomic status and health status that was more pronounced in the overall population than in the German subpopulation. The highest correlations were observed between the MusiQoL dimension of activities of daily living and the Expanded Disability Status Scale (EDSS). CONCLUSION: The results of this study confirm the validity and reliability of MusiQoL as an instrument for measuring the quality of life of German and international MS patients.

Costs and quality of life of multiple sclerosis in Germany.

This cost-of-illness analysis based on information from 2973 patients with multiple sclerosis (MS) in Germany is part of a Europe-wide study on the costs of MS. The objective was to analyze the costs and quality of life (QOL) related to the level of disease severity. Patients from six centres (office- and hospital-based physicians) and patients enrolled in a database were asked to participate in the survey; 38% answered a mail questionnaire. In addition to details on the disease (type of disease, relapses, level of functional disability), the questionnaire asked for information on all resource consumption, medical, non-medical, work absence, informal care, as well as QOL (measured as utility). The mean age of the cohort was 45 years, and 18% of patients were 65 years of age or older. Forty-seven percent of patients had mild disease (Expanded Disability Status Scale [EDSS] score 0-3), 36% had moderate disease (EDSS score 4-6.5) and 12% had severe disease (EDSS score > or =7). The mean EDSS score in the sample was 3.8 (median 4.0), with a mean utility of 0.62. Costs and utility are highly correlated with disease severity. Workforce participation decreases from 73% in very early disease to less than 10% in the very late stages, leading to a tenfold rise in productivity losses in the late stages of disease. Hospitalisation and ambulatory visits rise by a factor of 5-6 between early and late disease; investments and services increase from basically no cost to euro 2700; and informal care increases by a factor of 27 for patients with an EDSS score of 7 and by a factor of 50 for patients at the very severe end of the EDSS scale (8-9). Hence, total mean costs per patient are determined essentially by the distribution of the severity levels in the sample, increasing from approximately euro 18 500 at an EDSS score of 0-1 to euro 70 500 at an EDSS score of 8-9. The same is true for utility, which decreases from 0.86 to 0.10 as the disease becomes severe. However, the utility loss compared to the general population is high at all levels of the disease, leading to an estimated loss of 0.2 quality-adjusted life-years per patient. Relapses are associated with a cost of approximately euro 3 000 and a utility loss of 0.1 during the quarter in which they occur. Compared with a similar study performed in 1999, resource consumption, with the exception of drugs, is somewhat lower. This is most likely due to a difference in the severity distribution of the two samples and to changes in health-care consumption overall in the country, such as the introduction of diagnosis-related groups (DRGs, Fallpauschalen).

Eyeball pressure testing in the evaluation of serious bradyarrhythmias in Guillain-Barré syndrome.

OBJECTIVE: To investigate the usefulness of eyeball pressure testing (EP) as an indicator for impending serious bradyarrhythmias in patients with Guillain-Barré syndrome (GBS) and its relationship to motor disability. BACKGROUND: Autonomic dysfunction is a common complication in GBS and accounts for a significant number of deaths. Serious bradyarrhythmias are thought to occur only in severe cases but are difficult to predict. METHODS/DESIGN: In 13 consecutive patients with GBS aged 29 to 70 years, 156 EP (6 to 19 per patient) were done serially for up to 1 year. Bilateral moderate pressure was manually applied and sustained for 25 seconds or until abnormal bradycardia developed, defined as heart rate below 40 beats per minute. Disability was graded by a score from 0 to 5 (DS). RESULTS: Four of 13 patients (DS 2/2/3-4/5) showed abnormal sensitivity to EP at least once. In two of them, vagal overreactivity could be demonstrated repeatedly, which gradually resolved within 4 and 10 days. In one patient with a rapid progressive course requiring early cardiopulmonary resuscitation, a highly abnormal EP could be recorded until 1 day after heart arrest. Another patient (DS 3-4) with abnormal EP required cardiac pacing twice because of significant bradycardia. The only other event necessitating pacing occurred in a severely disabled patient (DS 5-4) who never showed abnormal EP. CONCLUSIONS: Vagal overreactivity could be demonstrated in approximately 30% of our patients. It was not restricted to severe motor impairment and was also present in mild-to-moderately disabled patients. In this regard, EP may be a simple and useful bedside test to indicate an increased risk of developing serious bradyarrhythmias in patients with GBS.

Distal muscular dystrophy of Miyoshi type. Report of two cases and review of the literature.

Miyoshi myopathy (MM) is a rare distal myopathy that mainly occurs in Japan. And that is characterized by prominent involvement of the gastrocnemius muscles. Here we report two patients, brother and sister, from a German family. Onset of the disease was at the age of 20 and 22 years, respectively. In both siblings, there was an early and predominant involvement of the gastrocnemius muscles. Creatine kinase activity was elevated 37- to 95-fold above normal. Electromyography revealed fibrillations, positive sharp waves and a myopathic pattern, particularly in the distal muscles of the lower limbs. Histology of the gastrocnemius muscles showed myopathic changes consistent with muscular dystrophy. Occurrence in these two siblings but in no other family members was indicative of an autosomal-recessive inheritance. Our report indicates that MM may also be found in Germany, and that it should be considered in the differential diagnosis of distal myopathies.

Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance.

Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS), but clinical studies disagree on the frequency and type of abnormalities in autonomic function tests. Orthostatic dizziness (OD) has been reported in up to 49% of patients, but the pathophysiological mechanisms are poorly understood. This study investigated cardiovascular reflex tests and their association with OD in patients with MS in order to examine the hypothesis that the sympathetic nervous system is specifically involved in these patients. Forty patients with clinically active relapsing-remitting (n = 27) and secondary progressive MS (n = 13), aged 35.0+/-8.5 years, were studied by parasympathetic (heart rate responses to the Valsalva maneuver, deep breathing, and active change in posture) and sympathetic function tests (blood pressure responses to active change in posture and sustained handgrip), and by spectral analysis of heart rate variability during rest and during standing. Results were compared to those obtained in 24 healthy volunteers, aged 29.4+/-7.2 years. A standardized questionnaire was used to evaluate symptoms of orthostatic intolerance. Abnormal responses on at least one cardiovascular reflex test were observed in 40% of MS patients, compared to 17% of the control group, with a statistically significant involvement of the sympathetic vasomotor system. Orthostatic intolerance was reported in 50% of patients (controls: 14%, P<0.006). Subgroup comparison of patients with and without OD suggests that orthostatic intolerance results from impaired sympathetic vasoconstriction. These results provide further evidence that the sympathetic nervous system is involved in patients with MS.

Clinical outcome of sural nerve biopsy: a retrospective study.

Sural nerve biopsy is a valuable tool in establishing the diagnosis and investigating the underlying causes of peripheral neuropathies. Few investigations have been carried out in which the sequelae of this procedure have been described systematically. We studied the short-term adverse reactions in 110 patients and the long-term outcome of sural nerve biopsy in a subgroup of 54 patients after 5-32 months. Long-lasting sensory deficits were reported in 93%, dysaesthesia in 19% and mild persistent pain in 33% of the 54 patients. No significant differences were found between patients followed for 1-2 years and those followed for more than 2 years in the frequency and distribution of hypaesthesia and anaesthesia. However, dysaesthesia was less frequent after more than 2 years (6/32 vs 1/16), and persistent pain completely subsided within our observation period. We conclude that disabling sequelae regress and finally subside over time. If we assume that returning for follow-up visits may cause bias towards more severely affected patients, the overall prognosis may be even better.

Norepinephrine transporter gene (NET) variants in patients with panic disorder.

Several lines of evidence suggest that catecholamines, especially norepinephrine, are implicated in the etiology and/or symptomatology of panic disorder (PD). At the cellular level, functional noradrenergic neurotransmission depends on synaptic reuptake of norepinephrine as mediated by the norepinephrine transporter (NET). A pharmacological target of agents with an established anti-panic efficacy, e.g. tricyclic antidepressants, the NET is of particular interest in PD. We investigated the NET gene for the presence of 6 naturally occurring exonic sequence variants, 5 of which give rise to amino acid substitutions (Val69Ile, Thr99Ile, Val245Ile, Val449Ile and Gly478Ser) in a population of 87 patients with PD and 89 healthy controls. Except for a silent substitution (G1287A), overall frequencies of variant alleles were low (< or =0.016). None of the variants under study was found to be associated with PD regardless of an additional diagnosis of agoraphobia.

Twenty-four-hour heart rate power spectrum for evaluation of autonomic dysfunction in Guillain-Barré syndrome.

Long-term fluctuations of the heart rate have an important prognostic impact after myocardial infarction, in patients with chronic heart failure and even in elderly subjects. Autonomic dysfunction is a common complication in patients with Guillain-Barré syndrome, and particularly vagally-mediated bradyarrhythmias require early recognition for immediate initiation of appropriate preventive therapy. This study aimed at investigating (1) whether the 24-h heart rate power spectrum (HRPS) could be used as a measure of autonomic dysfunction also in patients with GBS, and (2) whether the slope of the regression line of power on frequency of the 24-h HRPS could indicate potentially fatal bradyarrhythmias in these patients. In 13 patients with GBS, the heart rate was continuously recorded in the intensive care unit during the early stages of the disease, averaged at 1-min intervals and stored for 4 to 82 days. The HRPS (n = 76, 2 to 14 per patient, median 5) was calculated by Fourier analysis of 24-h recordings and logarithmically transformed. The slope was estimated by regression analysis of log(power) on log(frequency) between 10(-4) and 4x10(-3) Hz demonstrating an inverse power law behaviour in all 76 HRPS. The slope of the regression line ranged from -0.66 to -2.18, and was significantly steeper in patients with tachycardia (median -1.51, interquartile range -1.35 to -1.71) than in those with vagal overreactivity (median -1.14. -1.02 to -1.23) who are suspected to be at risk for fatal arrhythmias. Correlation analysis suggested that the slope was moderately associated with the spectral components of 5-min epochs, but not significantly to standard tests of autonomic hypofunction. Patients with and without vagal overreactivity were better discriminated by the 24-h HRPS than by conventional measures of autonomic function. Therefore, the 24-h HRPS may be a useful adjunct to autonomic nervous system testing, and might be a promising tool to predict serious bradyarrhythmias in patients with GBS.