Training in MS: influence of two different endurance training protocols (aquatic versus overland) on cytokine and neurotrophin concentrations during three week randomized controlled trial.

BACKGROUND: The influences of exercising on cytokine response, fatigue and cardiorespiratory values are important aspects of rehabilitation in persons with multiple sclerosis (PwMS). Exercise performed within these programs is often practised in water but the effects of immersion on PwMS have not been systematically investigated. OBJECTIVE: The objective of this study is to determine differences in cytokine and neurotrophin concentrations, fatigue and cardiorespiratory values in response to 3 week endurance training conducted on a cycle ergometer or an aquatic bike. METHODS: A randomized controlled clinical trial was conducted in 60 MS patients (Expanded Disability Status Scale range 1.0-6.5). Resting serum levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Interleukin-6, soluble receptor of IL-6 and tumor necrosis factor alpha, and concentrations in response to cardiopulmonary exercise test (CPET), fatigue and cardiorespiratory values were determined at entry and discharge. Subjects performed daily 30 minute training at 60% of VO2max. RESULTS: Cytokines and neurotrophins showed no significant differences between groups over the training intervention. Within the water group BDNF resting and post-CPET concentrations (p<0.05) showed a significant increase and NGF tended to increase after the training intervention. Short-term effects on BDNF (CEPT) tended to increase at the start and significantly thereafter (p<0.05). No changes occurred in the land group. Other cytokines and fatigue scores remained unchanged over the training period. Cardiorespiratory values improved significantly over time within both groups. CONCLUSION: This study indicates that aquatic training activates BDNF regulation and can be an effective training method during rehabilitation in PwMS.

Factors influencing patient satisfaction with the first diagnostic consultation in multiple sclerosis: a Swiss Multiple Sclerosis Registry (SMSR) study.

BACKGROUND: Patient satisfaction is predictive of adherence, malpractice litigation and doctor-switching. OBJECTIVE: To investigate which factors of the first diagnostic consultation (FDC) influence patient satisfaction and which topics persons with multiple sclerosis (PwMS) thought were missing. METHODS: Using retrospective patient-reported data of the Swiss Multiple Sclerosis Registry from PwMS with relapsing disease onset, we fitted ordered logistic regression models on satisfaction with FDC, with socio-demographic and FDC features as explanatory factors. RESULTS: 386 PwMS diagnosed after 1995 were included. Good satisfaction with the FDC was associated with a conversation more than 20 min [multivariable odds ratio, 95% confidence interval 3.9 (2.42; 6.27)], covering many topics [1.35 (1.19; 1.54) per additional topic], the presence of a significant others [1.74 (1.03; 2.94) ], and shared decision making [3.39 (1.74; 6.59)]. Not receiving a specific diagnosis was main driver for low satisfaction [0.29 (0.15; 0.55)]. Main missing topics concerned long-term consequences (reported by 6.7%), psychological aspects (6.2%) and how to obtain support and further information (5.2%). CONCLUSIONS: A conversation of more than 20 min covering many MS relevant topics, a clear communication of the diagnosis, the presence of a close relative or significant other, as well as shared decision making enhanced patient satisfaction with the FDC. ClinicalTrials.gov Identifier: NCT02980640.

Telerehabilitation for persons with multiple sclerosis. A Cochrane review.

A wide range of telerehabilitation interventions are trialled in persons with multiple sclerosis (pwMS). However, the evidence for their effectiveness is unclear. Aim of the review was to systematically assess the effectiveness and safety of telerehabilitation intervention in pwMS, the types of approaches that are effective (setting, type, intensity) and the outcomes (impairment, activity limitation and participation) that are affected. The search strategy comprised: Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Review Group Specialised Register (up to 9 July, 2014). Relevant journals and reference lists of identified studies were screened for additional data. Selected studies included randomized and controlled clinical trials that compared telerehabilitation intervention/s in pwMS with a control intervention (such as lower level or different types of intervention, minimal intervention; waiting-list controls, no treatment or usual care; interventions given in different settings). Best evidence synthesis was based on methodological quality using the GRADEpro software. Nine RCTs (N.=531 participants, 469 included in analyses) investigated a variety of telerehabilitation interventions in adults with MS. The interventions evaluated were complex, with more than one rehabilitation component and included physical activity, educational, behavioural and symptom management programmes. All studies scored "low" on the methodological quality assessment. Evidence from included studies provides 'low-level' evidence for reduction in short-term disability (and symptoms) such as fatigue. There was also "low-level" evidence supporting telerehabilitation in the longer term for improved functional activities, impairments (such as fatigue, pain, insomnia); and participation. There were limited data on process evaluation (participants'/therapists' satisfaction) and no data available for cost effectiveness. There were no adverse events reported as a result of telerehabilitation intervention. There is limited evidence to date, on the efficacy of telerehabilitation in improving functional activities, fatigue and quality of life in adults with MS. There is also insufficient evidence to support what types of telerehabilitation interventions are effective, and in which setting. More robust trials are needed to build evidence for the clinical and cost effectiveness of these interventions.

Effectiveness of telerehabilitation interventions in persons with multiple sclerosis: A systematic review.

BACKGROUND: Telerehabilitation, a service delivery model using telecommunications technology to provide therapy at a distance, is used in persons with multiple sclerosis (pwMS), but evidence for their effectiveness is yet to be determined. OBJECTIVE: To investigate the effectiveness and safety of telerehabilitation intervention pwMS. METHOD: A comprehensive literature search was conducted using medical and health science electronic databases. Three reviewers selected potential studies and independently assessed the methodological quality. A meta-analysis was not possible due to heterogeneity amongst included trials, and a qualitative analysis was performed for best evidence synthesis. RESULTS: Ten RCTs and 2 observational studies (n=564 participants) investigated a wide variety of telerehabilitation intervention in pwMS, which included: physical activity; educational, behavioural and symptom management programmes. All studies scored "low to moderate" on the methodological quality assessment implying high risk of bias. Overall, the review found low level evidence for the effectiveness of telerehabilitation on reducing short-term disability and reducing and/or improving symptoms, such as fatigue. There was low level evidence suggesting some benefit of telerehabilitation in improving functional activities; improving symptoms in the longer-term; and psychological outcomes and quality of life. There is limited data on safety, process evaluation and no data on cost-effectiveness of telerehabilitation. CONCLUSIONS: A wide range of telerehabilitation is used in pwMS, however, the quality of evidence on these interventions was low. More robust trials are needed to build evidence about these interventions.

Impact of neurorehabilitation on disability in patients with acutely and chronically disabling diseases of the nervous system measured by the Extended Barthel Index.

To study the impact of rehabilitation on disability in an unselected patient group with acutely and chronically disabling neurologic diseases, the Extended Barthel Index (EBI) was determined at the beginning and at the end of the rehabilitation stay in all patients admitted to our Neurorehabilitation Centre in Valens, Switzerland. Patients who reached the highest possible EBI score at entry ("ceiling effect"), with a short stay (<1 week), or with a deterioration due to other medical complications were excluded. Finally EBI data of 743 patients could be analyzed. The mean EBI at entry was 45 and 51 at discharge. The mean increase of the EBI score per week was 1.1 (SD, 1.7). The change of the EBI score was analyzed independently in patients with acute neurologic diseases admitted in the postacute phase (acute group) and patients with chronically disabling neurologic diseases (chronic group). As expected, the increase of the EBI score was higher in the acute group than in the chronic group; 80.8% of the acute group patients and 42.5% of the chronic group patients showed an increase of the EBI score at discharge. Both groups showed a significant EBI gain with a marked shift to higher EBI scores at discharge. The mean gain per week was 1.6 in the acute group and 0.5 in the chronic group, respectively. Analysis of EBI changes considering the different underlying diseases showed the highest increase in patients with stroke and traumatic brain injury.

Fitness to drive with neurological disabilities.

To restore the ability to drive is one aim of the rehabilitation of patients with neurological disabilities. In some instances, an evaluation is required to judge a patient's fitness to drive in today's traffic. Forty-three patients of the neurorehabilitation unit of the Valens Clinic were assessed by a standard traffic psychological test protocol and a control drive. In 88%, there was agreement between the judgments based on each procedure. Four patients had failed either the psychological tests or the control drive but not both. Six patients had failed the psychological test and the control drive. Two drove nevertheless, and three patients stopped driving. Nineteen of 32 patients cleared to drive were followed up. Eleven drove without accidents or traffic fines. The traffic psychological tests and control drive yield complementary information on the fitness to drive. However, the assessments need to be improved. New generations of interactive driving simulators may refine the fitness to drive evaluation and become useful tools in driving rehabilitation.

Constantin von Monakow's formative years in Pfäfers.

Constantin von Monakow was the first professor of neurology in Switzerland and founder of the Swiss Neurological Society and of the Swiss Archives of Neurology and Psychiatry. He gained worldwide reputation as a neuroscientist mainly through his monumental work on neuropathology and cortical localization. His concept of diaschisis has been verified only in recent years by modern network concepts and imaging techniques. The basis of his work was developed with ingenious animal experiments and careful clinico-pathological comparisons during his early years, which he spent as assistant physician in the psychiatric clinic at St. Pirminsberg in Pfäfers, Canton St. Gallen, Switzerland from 1878 to 1885.

Cognitive and affective disturbances in multiple sclerosis.

The emotional and relationship problems associated with MS have not always been fully appreciated by the medical profession, which has tended to concentrate on the physical aspects of this disease. Yet the psychological problems of MS often cause more suffering than physical effects.

Detection of anterior horn lesions by MRI in central European tick-borne encephalomyelitis.

We report a case of central European tick-borne encephalitis with cervical myelitis presenting clinically as a lower motor neuron syndrome of the upper limbs with proximal asymmetrical pareses and atrophies. There were no sensory deficits nor signs of lesions of the spinal pathways or signs of encephalitis or meningitis. The affected motor fibers of the upper limbs were electrically inexcitable, but sensory findings were normal. Electromyography of the paralyzed muscles revealed pathological denervation activity without voluntary activation. The initial magnetic resonance imaging (MRI) showed a large hyperdense lesion in the anterior part of the cervical cord from C3 to T1. Despite the fact that MRI changes disappeared completely within 6 weeks the patient showed only little improvement in the paralyzed muscles after 6 months. To our knowledge, these MRI changes in patients with tick-borne encephalitis, consistent with an isolated anterior horn lesion, have never been reported previously. The course may have been aggravated by an initial antibiotic treatment with cephalosporins.

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.

Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study.

OBJECTIVE: To quantify temperature induced changes (=Uhthoff phenomenon) in central motor conduction and their relation to clinical motor deficits in 20 multiple sclerosis (MS) patients. METHODS: Self-assessment of vulnerability to temperature and clinical examination were performed. We used motor evoked potentials to measure central motor conduction time (CMCT) and applied the triple stimulation technique (TST) to assess conduction failure. The TST allows an accurate quantification of the proportion of conducting central motor neurons, expressed by the TST amplitude ratio (TST-AR). RESULTS: Temperature induced changes of TST-AR were significantly more marked in patients with prolonged CMCT (P=0.037). There was a significant linear correlation between changes of TST-AR and walking velocity (P=0.0002). Relationships were found between pronounced subjective vulnerability to temperature and (i) abnormal CMCT (P=0.02), (ii) temperature induced changes in TST-AR (P=0.04) and (iii) temperature induced changes in walking velocity (P=0.04). CMCT remained virtually unchanged by temperature modification. CONCLUSIONS: Uhthoff phenomena in the motor system are due to varying degrees of conduction block and associated with prolonged CMCT. In contrast to conduction block, CMCT is not importantly affected by temperature. SIGNIFICANCE: This is the first study quantifying the Uhthoff phenomenon in the pyramidal tract of MS patients. The results suggest that patients with central conduction slowing are particularly vulnerable to develop temperature-dependent central motor conduction blocks.

Lethality of pentazocine and tripelennamine combinations in mice housed individually and in groups.

Lethality of 80 mg/kg pentazocine alone; 40 mg/kg tripelennamine alone; 20 mg/kg tripelennamine in combination with 40, 60, and 80 mg/kg pentazocine; and 40 mg/kg tripelennamine in combination with 10, 20, and 40 mg/kg pentazocine was determined in mice housed individually and in groups. Results indicate that the lethality of pentazocine and tripelennamine combinations in mice is (1) dose-dependent, (2) potentiated relative to either drug alone, and (3) greater in group-housed than in individually-housed animals.

Parachloroamphetamine toxicity in mice: influence of body weight, sex and dose.

Five doses of d,l-para-chloroamphetamine (0.0, 15,0, 30.0, 45.0 and 60.0 mg/kg) were used to challenge 10 groups of 16 male and 10 groups of 16 female CF-1 mice weighing either 16 to 25 g or 40 to 55 g. Twenty-four hours after intraperitoneal injection, rates of lethal toxicity were assessed. Effects for body weight and dose were found. In addition, a sex by dose interaction was demonstrated. It was hypothesized that the influence of weight might be related to thermoregulatory processes, since as weight rises, surface-to-volume ratios decline, and with them the efficiency of heat exchange. Caution is suggested in the interpretation of ontological studies of drug response.

Severe traumatic brain injury--epidemiology and outcome after 3 years.

In 1987 80 patients living in the region of St Gallen, Switzerland, suffered from head injury with neuroradiologically visible intracranial lesions (annual incidence 20/100,000). One-quarter died during the first month after injury, and six others during the following 3 years. All except three of the 45 survivors interviewed and examined after 3 years had symptoms and functional impairment related to injury: neuropsychological (78%), behavioural (58%), neurological (53%), and related to bone or soft tissue trauma (36%). Half of the patients suffered from headache. Although these impairments caused little disability--only 5% of the patients had a Glasgow Outcome Score of 2 or 3--handicap in social life was reported in half of them and only 13 of 29 working before the accident were able to resume their former work. The consequences for long-term management of these patients are discussed.

[Multiple sclerosis--what should be done?]. / Multiple Sklerose--was tun?

Major progress in MS-research has been achieved in recent years concerning diagnosis and differential diagnosis, pathogenetic mechanisms and prognostic indicators. Symptomatic treatment and prevention of complications help to improve quality of life and to prolong expected duration of life. Treatment trials intended to influence the course of the disease must still be considered experimental. Comprehensive rehabilitation remains the cornerstone of long-term management in MS. First results of carefully designed placebo-controlled double-blind studies, however, justify the expectation, that more efficient measures to influence the course of the disease will be available in the near future.

[Leg pain--the contribution of the neurologist]. / Beinschmerzen--der Beitrag des Neurologen.

Pain syndromes in the lower limbs are a particular challenge for the clinical neurologist. Pain may be due to various disorders of the central and peripheral nervous system or muscles of different etiologies. There is a continuum from slightly unpleasant sensory disturbances to nociception. Differential diagnosis must be sought according to topological and pathophysiological interpretation of the clinical findings. This will determine the necessary diagnostic requirements and therapeutic procedures. Within the central nervous system lesions of the nociceptive projections of the spinal cord or brain may lead to pain in the lower limbs. Furthermore, different pathologies of the peripheral nervous system (root, plexus, peripheral nerve) or muscles can cause pain. Finally, pain syndromes are known in clinical syndromes with disturbances of the muscle tone (extrapyramidal syndromes, spasticity) and secondary to postural problems in patients with muscular dysbalance due to paralysis.

[Magnetic resonance tomography and multiple sclerosis]. / Magnetresonanztomographie (MRI) und multiple Sklerose (MS).

Magnetic resonance tomography (MRI) is the imaging technique of first choice in diseases of the white matter of the central nervous system (CNS) including multiple sclerosis (MS). The signal changes observed are not specific, however, and have to be evaluated critically in the clinical context. The most difficult problems of differential diagnosis arise from other inflammatory diseases of the CNS like cerebral lupus, neurosarcoidosis, Behçet's syndrome and other vasculitides. MRI allows for the first time in vivo studies of the blood-brain barrier which is so important in MS pathogenesis. A great potential for MRI is in monitoring putative therapies in MS.

[Developments in neurology from the 19th to the 20th century with special reference to various contributions from Switzerland]. / Die Entwicklung der Neurologie vom 19. zum 20. Jahrhundert mit besonderer Berücksichtigung einiger Beiträge aus der Schweiz.

Several modern concepts of the nervous system have developed since the last century: Their influence on modern neurology is traced by notes from biographies and the work of leading Swiss neurologists and neurobiologists. 1. Psychiatrists working in neuroanatomy: Auguste Forel, Constantin von Monakow, Bernhard Aloys von Gudden and Eduard Hitzig. 2. Anatomists who influenced the development of the "neurone-theory": Rudolf Albert von Kölliker and Wilhelm His Senior. 3. A practising physician developing "interactionism" as a basis for neurorehabilitation: Heinrich Simon Frenkel. 4. Behavioural aspects considered within a general framework of neurobiology: Walter R. Hess. 5. Neurosurgery: Hugo Krayenbühl.

[Rehabilitation in multiple sclerosis]. / Rehabilitation bei multipler Sklerose.

Rehabilitation is the only effective treatment in multiple sclerosis (MS), as long as the cause of this commonest neurological disease of younger adults is not known. No medical treatment constantly influences the course of the disease. Methods for restitution of functional impairments, for improvement of abilities and for adaptation of daily life according to constraints caused by disability and handicap are applied with the goal of enlarging personal free space. Inadequate prevention of complications is often the cause for apparent progressive deterioration of the disease. Efficient symptomatic therapies have helped to increase life expectancy and to improve quality of life of MS patients in recent years.

[Gait analysis--a prerequisite for general movement analysis]. / Ganganalyse--eine Voraussetzung für eine allgemeine Bewegungsanalyse.

Our system for analysis of gait is a combined visualisation of angular velocities in any joint with dynamic measurements of pressure at the sole while walking in a natural surrounding. Infrared reflectors are attached to chosen parts of the body. Their position in space is sampled over time and transferred to an easily manageable personal computer that visualizes motion in progression as angular velocities. Pressure at the sole is measured by pressure sensors. The magnitude of force is expressed as calibrated circular areas following the dynamic course of gait. The system is accurate and easily operated. The time necessary for measurements and evaluation of data as well as the costs render an application in daily clinical work acceptable.