A double-blind randomised placebo-controlled evaluation of three doses of botulinum toxin type A (Dysport) in the treatment of spastic equinovarus deformity after stroke.

BACKGROUND/OBJECTIVES: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport) in post-stroke calf spasticity. METHODS: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. RESULTS: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002-0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators' and patients' assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. CONCLUSION: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed.

[Isolated, unilateral paresis of the phrenic nerve after pneumonia and pleurisy]. / Isolierte, unilaterale Parese des N. phrenicus nach Pneumonie und Pleuritis.

Unilateral diaphragmatic paralysis has many causes. Tumor and trauma are the two most frequent identifiable causes. Infectious processes involving the lung and/or mediastinum may result in temporary or permanent diaphragmatic paralysis. We report the case of an 81-year old man who suffered from right-sided pneumonia followed by a period of several months with exertion dyspnea. Radiological examinations showed an elevated right diaphragm, abnormal restrictive lung function, and impaired diaphragmatic muscle strength. The neurophysiological studies provided evidence of a partial phrenic nerve lesion. We discuss the differential diagnosis of isolated phrenic nerve lesions with particular regard to infections.

Systematic muscle building exercises in the rehabilitation of stroke patients.

The effects of targeted strength training in patients with muscle weakness of central origin following cerebrovascular accidents has hardly been investigated to date. This prospective non-randomized study of 56 patients was designed to shed light on the effects of strength building exercises on muscle tone and on the gain in muscle strength achieved with them. All patients underwent a full residential neurologic rehabilitation program for 4 weeks, which included an exercise program for restoring the extensor strength of the legs and the supporting strength of the arms by leg and arm presses. Throughout the rehabilitation program muscle spasticity was evaluated clinically and maximal muscle strength on completion of the exercise program was compared to baseline. The extensor strength of the legs increased by 31.0 (+/- 26.7)% by 40.2 (+/- 15)%. significant for both variables. The extent of strength gain was positively correlated with the intensity and the number of exercising units. Muscle tone, which was abnormally high at baseline, did not further increase in any one case. The results of this study showed that targeted strength training significantly increased muscle power in patients with muscle weakness of central origin without any negative effects on spasticity.

[Sertraline in the treatment of post-stroke depression--results of an open multicenter study]. / Sertralin in der Behandlung der Post-Stroke-Depression--Ergebnisse einer offenen Multicenterstudie.

BACKGROUND: The aim of the study is to test the tolerability and efficacy of 50 mg Sertralin in the treatment of Post-Stroke depression (PSD). METHODS: Open-label, 3-months study of in- and outpatients. Evaluation of the 5-Item WHO-Wellbeing Index, the Clinical Global Impression test (CGI) and documentation of the subjective evaluation of tolerability and efficacy by patients and examining doctors. PATIENTS: 267 out of 287 patients (150 women, 137 men; mean age 68.6 +/- 12.1 years with a range from 27 to 100 years) took part in the study over a 12 months period. RESULTS: Eight patients had to stop the study because of side-effects. The WHO-Wellbeing Index improved from a baseline value of 26.7 +/- 17.1 to 45.0 +/- 18.3 after 4 weeks (p < 0.001), and to 57.2 +/- 19.5 after 12 weeks (p < 0.001). The CGI after 12 weeks gave evidence of an improvement in 252 patients (88%). No change of PSD was seen in 10 patients (3%), and deterioration of PSD was observed in 5 patients (2%). The duration between onset of treatment and improvement was 13.3 +/- 6 days. CONCLUSIONS: A single dose of 50 mg Sertralin is well tolerated in patients with PSD. The WHO-Wellbeing Index and the CGI gave evidence of significant improvement of PSD in the majority of examined patients participating in this open-label study.

Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin's disease.

Acquired neuromyotonia is characterized by hyperexcitability of motor nerves resulting in continuous muscle fiber activity. It occurs most often as a paraneoplastic syndrome in patients with cancers of the immune system. Antibodies against voltage-gated potassium channels (VGKCs) have been detected in some patients. Peripheral neuropathy is sometimes present. We report on a patient with Hodgkin's lymphoma in complete remission who developed paresthesias followed by neuromyotonia with bulbar involvement. Peripheral sensorimotor neuropathy was diagnosed electrophysiologically and evidence of axonal degeneration and demyelination was detected by sural nerve biopsy. The patient's complaints, including dysarthria, improved after carbamazepine treatment.

Evaluation of a German version of the Rivermead Mobility Index (RMI) in acute and chronic stroke patients.

The English Rivermead Mobility Index (RMI) has been proposed as a simple, valid and reliable measure in stroke rehabilitation. A German version was established and validated in two centres. In centre A 46 acute (median: 3.0 days after onset) and in centre B 151 chronic (median: 88.0 days after onset) stroke patients participated. Interrater reliability of the German RMI was tested in 12 subjects in the acute stage of stroke and was found to be statistically significant (r = 0.98, P < 0.0001). In centre A, a statistically significant correlation was found between the German RMI and the 10-m walk time at baseline (r = 0.73, P < 0.0001) and after three weeks (r = 0.92, P < 0.0001). In centre B, the German RMI correlated significantly with the motor part of the Functional Independence Measure (motor-FIM) on admission (r = 0.78, P < 0.0001) and after three weeks (r = 0.79, P < 0.0001), respectively. The change of the RMI correlated significantly with the change in 10-m walk time in acute patients (r = 0.87, P < 0.0001) and with the change in motor-FIM in chronic patients (r = 0.54, P < 0.0001). A moderate ceiling-effect was detected in the chronic study population. The German RMI appears to be a reliable, valid and responsive measure for mobility disability in acute and chronic stroke patients.

Long-term outcome of critical illness polyneuropathy.

The aim of this study was to describe the outcome of patients with critical illness polyneuropathy (CIP). Twenty-six patients with CIP were studied to determine the clinical and electrophysiological profile 13-24 months after the onset of CIP. Seven patients refused to participate in the study; 6 patients died within the 1st year. Eleven of the 13 survivors showed clinical evidence of polyneuropathy. Five of these patients also had mononeuropathies, including peroneal and ulnar nerves. The quality of life was markedly impaired in all patients. Nerve conduction studies, including limb motor and sensory nerve conductions, bilateral phrenic nerve onset latencies, and bilateral diaphragmatic compound muscle action potentials, were abnormal in all patients. Incomplete recovery within 1-2 years after the onset of disease occurs frequently in patients with CIP.

Repetitive phrenic nerve stimulation in myasthenia gravis.

OBJECTIVE: In patients with MG it may be difficult to determine whether respiratory insufficiency is due to a defect in neuromuscular transmission. We therefore studied the clinical value of repetitive electrical stimulation of the phrenic nerve. METHODS: Repetitive phrenic nerve stimulation at 3 Hz was performed in 25 patients with MG. We recorded from the ipsilateral hemidiaphragm with surface electrodes before and after exercising the diaphragm for 10 and 90 seconds. The percent decrement of the negative peak (NP) area between the first and the fifth or sixth diaphragmatic compound muscle action potential (DCMAP) was analyzed and results compared with those from 10 healthy individuals. RESULTS: The mean +/- standard deviation percent change of the NP area in healthy individuals was -2.1 +/- 4.2%, with a normal cutoff of > or = 11%. Twelve patients (48%) had an abnormal decrement of DCMAP--9 had a decrement when the diaphragm was rested, 3 only after fatiguing of the diaphragm. The mean percent change in the 12 patients was 20% at rest, -18% after 10 seconds of exercise, and -23% after 90 seconds of exercise-a pattern consistent with MG. Repetitive stimulation of the accessory nerve with recording of the trapezius CMAP (TCMAP) was abnormal in nine patients (36%). The three patients with abnormal decrement of the DCMAP despite normal TCMAP had symptoms of dyspnea. CONCLUSIONS: Repetitive phrenic nerve stimulation studies are a promising tool in the diagnosis of respiratory muscle weakness in MG and should be part of electrophysiologic studies in patients with undiagnosed respiratory failure.

Neuralgic amyotrophy with phrenic nerve involvement.

Phrenic nerve involvement is a rare feature in patients with neuralgic amyotrophy (Parsonage-Turner syndrome). We report four patients who initially presented with severe dyspnea in the absence of lung disease. All patients had a history of infectious disease or surgery and of pain of sudden onset in the shoulder region. Weakness of the proximal arm was observed in only one. Radiographic and pulmonary function studies, phrenic nerve conduction studies, and needle electromyogram (EMG) of the diaphragm documented diaphragmatic paralysis which was unilateral in one patient, bilateral in two patients, and recurrent on alternating sides in another one. Follow-up studies remained abnormal for up to 4 years. Neuralgic amyotrophy with phrenic nerve involvement should be considered in patients presenting with severe, unexplained dyspnea of sudden onset.

Clinical and electrophysiological findings in critical illness polyneuropathy.

Sixty two patients with critical illness polyneuropathy (CIP) were studied prospectively to determine the clinical and electrophysiological profile, to assess the prognostic value of respiratory electrophysiology in determining the duration of ventilation and to analyze the role of neuromuscular blocking agents (NMBA) and steroids. Limb motor and sensory nerve conductions, bilateral phrenic nerve onset latencies, bilateral diaphragmatic compound muscle action potentials (CMAP), unilateral diaphragmatic needle electromyography (EMG), limb muscle EMG, time on the ventilator, time in the intensive care unit (ICU), dosage of NMBA and steroids were analyzed in 62 patients. The diagnosis of CIP was made by clinical criteria, electrophysiological criteria and exclusion of any other condition suspicious of an axonal neuropathy. The results of phrenic nerve conduction studies and diaphragmatic EMG were compared to normal mean values in 25 healthy subjects. The most common finding in our study were reduced CMAPs and abnormal spontaneous activity in muscle, occuring in 100%. Forty per cent had reduced CMAPs but normal sensory nerve action potentials (SNAP). These patients had normal CK-levels and normal findings, unspecific changes, type 2 fibre atrophy or denervation atrophy on muscle biopsy. Seventy seven per cent of patients had abnormal diaphragmatic CMAPs and spontaneous activity in the diaphragm indicating denervation of the diaphragm is common in CIP. There was no statistically significant relationship to the dosage of NMBA and steroids, and the respiratory electrophysiological studies, duration of ventilation and stay in the ICU.

Electrophysiological respiratory studies in the critical care unit.

Respiratory electrophysiological studies are useful in the investigation and monitoring of respiratory failure. Phrenic nerve conduction studies and needle electromyography of the diaphragm are invaluable in establishing the diagnosis, determining the severity, and following the progression of peripheral respiratory muscle dysfunction. In addition to these established methods, repetitive phrenic nerve stimulation is of diagnostic value in patients with neuromuscular transmission defects and dyspnea. The diagnosis of impaired central respiratory drive can often be accomplished by the newly-developed techniques of transcortical magnetic stimulation of the motor cortex with recording of the diaphragm and phrenic nerve somatosensory evoked potentials. These studies are of particular value in critically ill patients where both the central and peripheral lesions may impair respiration.

Migrant sensory neuropathy: report of 5 cases and review of the literature.

There are only a few case descriptions of migrant sensory neuropathy. We report the clinical, laboratory, and electrophysiological findings observed in 5 patients whose presentation conformed with Wartenberg's description of a chronic, disseminated migrant sensory mononeuritis. In one patient, intermittent cranial motor nerve involvement occurred as well. The sural nerve biopsy in this patient showed changes suggestive of focal ischemic nerve damage and electron microscopy confirmed a vasculopathy.

[Electrophysiology of respiration]. / Die Elektrophysiologie der Atmung.

Neurological respiratory insufficiency may be the primary cause of admission to an intensive care unit or may develop during care in an intensive care ward. Severe respiratory insufficiency due to nervous system causes either involves a lack of central drive or weakness of the respiration muscles. The former are induced by a wide variety of encephalopathies and the latter by diseases of anterior horn cells, peripheral nerve, the neuromuscular junction, or muscles of the chest wall or diaphragm. In an intensive care unit, it is often not possible clinically to determine whether there is a lack of central drive or a neuromuscular problem. It is now possible by electrophysiological methods to pinpoint the site of nervous system cause of respiratory insufficiency. This review will describe the various electrophysiological techniques currently available and describe how they have been successfully applied in investigating some conditions that cause severe respiratory failure.

Central and peripheral respiratory electrophysiological studies in myotonic dystrophy.

Acute and chronic respiratory failure is a common and potentially life-threatening feature in patients with myotonic dystrophy (MD). The causes may be varied, and can involve both the central and peripheral nervous system. To evaluate the incidence of respiratory muscle involvement and the function of the central motor inspiratory pathway to phrenic motor neurons we performed magnetic stimulation of the cortex and cervical spinal cord, phrenic nerve conduction studies and needle EMG of diaphragm and intercostal muscles in 25 patients with MD. The results were compared with those from 35 healthy subjects. In addition, pulmonary function tests, blood gas analyses and static mouth pressures were evaluated. Abnormalities in response to magnetic stimulation, including a reduced compound muscle action potential (CMAP) from the diaphragm and increased excitability threshold, indicated impaired central inspiratory drive in 20% of cases. Phrenic nerve conduction showed a reduced diaphragmatic CMAP amplitude in 20%, and a delayed negative peak onset latency in 4% of cases. Abnormalities in diaphragm and intercostal muscle needle EMG were found in 76% of cases, these were mainly myotonic discharges (68%) and a decrease in the number of active motor units (36%). Patients with abnormal respiratory electrophysiological parameters had a significantly lower functional vital capacity (FVC; P = 0.005). The duration of the disease correlated negatively with diaphragmatic CMAP amplitude to phrenic nerve, but not magnetic, stimulation. Our results demonstrate that the involvement of the central inspiratory pathway is common in MD patients. Central and peripheral electrophysiological studies of the diaphragm should be considered in the diagnosis and management of patients with MD and dyspnoea.

The cortical representation of somatosensory evoked potentials of the phrenic nerve.

Respiratory electrophysiological studies are of essential value in diagnosing and managing patients with respiratory failure, but assessment of the sensory phrenic nerve fibres has been neglected. We recorded phrenic nerve somatosensory evoked potentials (SSEPs) by combining neurophysiological and neuroimaging techniques in three healthy subjects. Evoked potentials of the phrenic nerve showed the highest amplitude at CP3, determined by the modified 10-20 EEG system, and occurred at a constant latency, PI at 12.0 +/- 0.6 ms, and NI at 17.3 +/- 0.8 ms. Single photon emission computer tomography (SPECT) performed during phrenic nerve stimulation revealed focal neuronal activation in the somatosensory pathways. Intravenously administered Tc-99m Ethyl Cysteinate Dimer (ECD) was used as a blood flow tracer to obtain baseline and activated images. After image registration, baseline images were compared voxel-by-voxel with the activation images. The mean inter-subject summation image of the activated state was compared with that of the baseline state using ten normal subjects. The extent of the total voxel volume increase on the mean images of the 3 activated SPECT images was 0.7%, and a mean signal increase of 22%. For further anatomic localization of regional increases in signal, the magnetic resonance image (MRI) scan of each subject was registered and superimposed on the activated stage SPECT image. This method may be used clinically to study the pathophysiology of impaired central respiratory drive.

Brain mapping of median nerve somatosensory evoked potentials with combined 99mTc-ECD single-photon emission tomography and magnetic resonance imaging.

Single-photon emission tomography (SPET) was performed during electrical median nerve stimulation and used to detect focal neuronal activation in the somatosensory pathways. Intravenously administered technetium-99m ethyl cysteinate dimer (ECD) was used as a blood flow tracer to obtain baseline and activated images in each of three subjects. After image registration, baseline images were compared voxel by voxel with the activation images. In addition, the mean summation of the activated-state images of the subjects was compared with the mean summation of the baseline-state images of ten normal subjects. Discrete brain regions occupying 0.9%-1.6% of total brain volume showed an increase in signal from 33.6% to 35.0%. For further anatomical localization of regional increases in signal, the MRI scan of each subject was registered and superimposed on the activated-state SPET image. This method may be used to localize lesions in various disorders of the central nervous system.