Effect of time of day on walking capacity and self-reported fatigue in persons with multiple sclerosis: a multi-center trial.

BACKGROUND: Many persons with multiple sclerosis (PwMS) report increased fatigue in the afternoon and evening compared with the morning. It is commonly accepted that physical capacity also decreases as time of day progresses, potentially influencing the outcomes of testing. OBJECTIVE: The objective of this article was to determine whether self-reported fatigue level and walking capacity are influenced by time of day in PwMS. METHODS: A total of 102 PwMS from 8 centers in 5 countries, with a diverse level of ambulatory dysfunction (Expanded Disability Status Scale [EDSS] <6.5), participated. Patients performed walking capacity tests and reported fatigue level at three different time points (morning, noon, afternoon) during 1 day. Walking capacity was measured with the 6-Minute Walk Test (6MWT) and the 10-m walk test performed at usual and fastest speed. Self-reported fatigue was measured by the Rochester Fatigue Diary (RFD). Subgroups with mild (EDSS 1.5-4.0, n = 53) and moderate (EDSS 4.5-6.5, n = 49) ambulatory dysfunction were formed, as changes during the day were hypothesized to depend on disability status. RESULTS: Subgroups had different degree of ambulatory dysfunction (p < 0.001) but reported similar fatigue levels. Although RFD scores were affected by time of day with significant differences between morning and noon/afternoon (p < 0.0001), no changes in walking capacity were found in any subgroup. Additional analyses on subgroups distinguished by diurnal change in self-reported fatigue failed to reveal analogous changes in walking capacity. CONCLUSIONS: Testing of walking capacity is unaffected by time of day, despite changes in subjective fatigue.

Renin and the complications of acute myocardial infarction.

To determine whether plasma renin activity in addition to catecholamines could be used as risk indicators, these parameters were measured in 19 patients with acute myocardial infarction. During the course of hospitalization, five patients developed ventricular fibrillation and three, cardiogenic shock. On admission, heart rate, plasma norepinephrine, epinephrine, and renin levels of these eight patients were significantly higher than those of the other patients with uncomplicated course. Peak creatine kinase MB activity was positively related to initial plasma renin activity (r = 0.62, p less than 0.01). Thus, the patients with the highest sympathetic activity following an acute myocardial infarction also had the highest plasma renin levels. They seem particularly prone to develop large infarcts and life-threatening complications.

An extreme form of the hyperdynamic syndrome in septic shock.

We classified 41 patients in septic shock on the basis of cardiac index (CI) after volume expansion with plasma protein solution, in order to obtain adequate filling pressures. Five had decreased CI (less than 3.5 1/min per m2), 31 had moderately increased CI (3.5 - 7.0 1/min per m2) and 5 had extreme hyperdynamic shock with CI superior to 7.0 1/min per m2. Among the patients with increased CI, those with extreme hyperdynamic state (EHS) had lower total systemic and pulmonary arteriolar resistances (370 vs 658 and 52 vs 119 dynes X s X cm-5, respectively) and a higher stroke index (67 vs 46 ml/m2), in spite of similar right atrial pressures. In this latter group, blood lactate was higher (6.5 vs 2.1 mmol/l), acidosis was more severe and coagulation disorders more pronounced; all five patients maintained an extremely high CI until death, which supervened after a brief episode of sinus bradycardia. A similar clinical course was rarely observed in the remaining moderately hyperdynamic group, in which mortality rate was significantly lower (35%). Three of five patients with EHS (compared to 2 of 31 in the moderately hyperdynamic group) had liver cirrhosis, the fourth died of fulminant meningococcemia and the fifth had prolonged polymicrobial bacteremia before adequate treatment was begun. Thus, underlying liver disease or particularly severe and uncontrolled infection seems to predispose to EHS. It is concluded that septic shock with extremely high cardiac output and excessively low peripheral resistances represents a distinct subset with more severe metabolic and coagulation disorders, an unusual hemodynamic evolution and a particularly poor prognosis.

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

[The mind and epilepsy: opinions and viewpoints over the course of time]. / Psyche und Epilepsie: Meinungen und Ansichten im Wandel der Zeit.

Among the very few diseases that can be traced back to ancient times none has stimulated human phantasy as much as epilepsy, and the many names given to epilepsy reflects the different trends of thinking on the topic over the past two and a half thousand years. The ancient Greek believed epilepsy to be a sacred disease with the body being invaded by a God. The view that demons and evil spirits rather than Gods were responsible for the disease prevailed throughout the middle ages, influenced by Christian thinking. This led people with epilepsy to be treated, as the mentally ill, with contempt and pity. Up to the latter half of the 19th century epilepsy remained an integral part of psychiatry. The concept of the epileptic personality, stating that the behaviour and consequently the seizures themselves came from a constitutional hereditary psychopathic make-up, was deeply entrenched. The process of distinguishing epilepsy from insanity began with the development of neurology as a new and independent discipline, helped by the discovery of electroencephalography EEG and potent antiepileptic drugs. It became more widely accepted that most epileptic patients have normal mental states. It was argued that the psychiatric consequences of having epilepsy depended on the existence of pathological brain lesions, side-effects of inadequate drugs and the psychological stress of living with a chronic and debilitating disease.

[Mental suffering IN patients with parkinsonism]. / Les souffrances psychiques des malades parkinsoniens.

Comprehensive treatment of patients with parkinson's disease demands that not only motoric dysfunctions but also psychosocial aspects have to be considered. The scope of this review is to cover not only the frequent dementia and depressive states associated with this disease, but also the drug-induced behavioral abnormalities, insomnia, conflicts with those providing care and implications for professional activities. The fundamental pathophysiological and psychopathological mechanisms are explained and illustrated by examples.

[Pain in multiple sclerosis. Clinical aspects and therapy]. / Schmerzen bei Multipler Sklerose. Klinik und Therapie.

Although pain is not considered a typical symptom of multiple sclerosis, more than 50% of patients with MS present with pain syndromes. In the setting of an incurable disease, symptom control and particularly pain control is very important in achieving a better quality of life. For paroxysmal pain syndromes such as trigeminal neuralgia or painful tonic seizures, carbamazepine and other anticonvulsive drugs are the cornerstone of treatment. On the other hand, drugs are not always effective in treating the various chronic pain syndromes such as dysesthetic extremity pain or leg spasms. In these conditions, individualized regular physiotherapy may relieve pain.

[Neglect--the frequently neglected syndrome of neglect]. / Neglekt--das oft vernachlässigte Syndrom der Vernachlässigung.

In daily clinical practice "neglect" is the term for a syndrome following a right parietal lesion with inability of the patient to concentrate on events on the left side. A patient is described who was admitted for headaches and in whom neurologic investigation revealed left sided neglect as the only sign. A glioma of the right hemisphere was found. The clinical search for neglect is described and possible mechanisms are discussed. Neglect is regarded as a disturbance of directed attention. The arguments in favour of attributing dominance for this function to the right hemisphere are presented.

SaGAS, the Short and Graphic Ability Score: an alternative scoring method for the motor components of the Multiple Sclerosis Functional Composite.

The timed performances of the 10-m timed walk (TMTW) and the nine-hole peg test (NHPT) of 881 consecutive patients with multiple sclerosis (MS) undergoing a rehabilitation stay, were expressed as a logarithmic function of time in two subscores to form a composite score called the Short and Graphic Ability Score (SaGAS). The subscores (sS) were constructed in such a way that any interval of 0.5 unit corresponds to a change of 25% in the tests. The SaGAS was computed as the mean of four subscores: SaGAS = (2 x TMTWsS + NHPTsS right hand + NHPTsS left hand). With the aid of a nomogram, the timed values of the tests are easily transformed into the corresponding subscores, which are then displayed graphically to facilitate follow-up over time. The correlation coefficients between the SaGAS and the two motor components of the MS Functional Composite (MSFC) (r = 0.987), the Expanded Disability Status Scale (EDSS)(r = -0.83), the Nottingham EADL Index (r = 0.80) and the Rivermead Mobility Index (RMI) (r = 0.90) were all statistically significant (P < 0.001), supporting the validity of the measure. SaGAS had a similar sensitivity to the RMI, but was significantly more sensitive than the EDSS in detecting changes occurring during the rehabilitation stay (14.9% versus 5.0%; P < 0.001) and over a one-year follow-up (35.3% versus 19.7%; P < 0.001). Compared with the motor components of the MSFC, with which it shares several features, SaGAS has several advantages: it does not depend on the stratification of the study population; it does not skew the results of the NHPT towards improvement at the lower end; and it offers an independent assessment of both hands. SaGAS is a simple, intuitive, nonphysician-based measure, which could provide consistent scoring in future clinical trials.

A novel score for predicting the mortality of septic shock patients.

OBJECTIVE: To establish a prognostic scoring system for septic shock patients. DESIGN: The clinical, biological, and hemodynamic data of these patients were retrospectively explored to select variables independently associated with outcome. According to the risk of death, ratings from 0 to 2 points were attributed to each value. SETTING: Medical intensive care service of a 1,000-bed tertiary care university medical center. PATIENTS: Eighty-eight patients in septic shock in whom hemodynamic measurements were performed using pulmonary artery flotation catheters. RESULTS: Fourteen clinical, biological, and hemodynamic variables were selected and rated for each patient. A Simplified Septic Shock Score, available immediately after admission and catheterization, was established by adding the rates of these variables. The mean Simplified Septic Shock Score was 2.5 +/- 1.7 (SD) in 43 survivors and 6.5 +/- 2.3 in 45 nonsurvivors (p less than .0001). Some underlying diseases and characteristics of infections also correlated with the outcome. Further ratings from 0 to 2 points were attributed to these conditions. A Complete Septic Shock Score was calculated by adding these rates to the Simplified Septic Shock Score. The Complete Septic Shock Score had a slightly better prognostic value than the Simplified Septic Shock Score, but it could be determined only after the availability of the microbiological data. The mean Complete Septic Shock Score was 3.1 +/- 1.9 in survivors and 8.4 +/- 2.6 in nonsurvivors (p less than .0001). Both Simplified and Complete Septic Shock Scores showed better association with patient outcome than the Simplified Acute Physiology Score or the Acute Physiology and Chronic Health Evaluation (APACHE II) score. CONCLUSIONS: The Simplified and the Complete Septic Shock Scores are simple scoring systems that appear to predict the outcome of septic shock patients more accurately than general scoring systems, such as the Simplified Acute Physiology Score and APACHE II score. These septic shock scores might be useful in assessing the severity of septic shock patients.

Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study.

OBJECTIVE: Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity. METHODS: During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B started with placebo for seven days, crossed to the active period (14 days) and closed with a three-day placebo period (active drug dose escalation and placebo sham escalation as in group A). Measures used included daily self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk, nine-hole peg test, paced auditory serial addition test (PASAT), and the digit span test. RESULTS: In the 50 patients included into the intention-to-treat analysis set, there were no statistically significant differences associated with active treatment compared to placebo, but trends in favour of active treatment were seen for spasm frequency, mobility and getting to sleep. In the 37 patients (per-protocol set) who received at least 90% of their prescribed dose, improvements in spasm frequency (P = 0.013) and mobility after excluding a patient who fell and stopped walking were seen (P = 0.01). Minor adverse events were slightly more frequent and severe during active treatment, and toxicity symptoms, which were generally mild, were more pronounced in the active phase. CONCLUSION: A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.