[Polyneuropathy in older individuals]. / Polyneuropathie im Alter.

The peripheral nervous system is subject to changes during the aging process, e.g., deep tendon reflexes decrease, as proprioception does. In contrast, polyneuropathies have to be distinguished from age-associated changes as independent diseases with etiologies similar to those in younger ages. Incidence of polyneuropathies is reported about 118/100,000, the overall prevalence in the general population is estimated to be about 1% and rises to up to 7% in the elderly. Etiology includes metabolic disorders, primary inflammatory polyneuropathies, systemic disorders and vasculitic neuropathies. Due to the age-specific increase of the prevalence of certain etiologies, neuropathies associated with diabetes, malignancy, and monoclonal gammopathies are even more common in older patients. However, the proportion of cryptogenic neuropathies, e.g. neuropathies without obvious cause, increases also with age. In older age, polyneuropathies additionally impair mobility and increase the risk of falling, thus the assessment of functional abilities is mandatory. It is essential to try to identify the underlying cause by a systematic approach including history, clinical investigation, neurophysiological and lab exams. Treatment of polyneuropathies is based on therapy of underlying conditions and requires management of neuropathic pain in the majority of cases. Physiotherapy and rehabilitation target pain relief and sustaining activities of daily living.

Secondary myopathy due to systemic diseases.

BACKGROUND: Some systemic diseases also affect the skeletal muscle to various degrees and with different manifestations. This review aimed at summarizing and discussing recent advances concerning the management of muscle disease in systemic diseases. METHOD: Literature review by search of MEDLINE, and Current Contents with appropriate search terms. RESULTS: Secondary muscle disease occurs in infectious disease, endocrine disorders, metabolic disorders, immunological disease, vascular diseases, hematological disorders, and malignancies. Muscle manifestations in these categories include pathogen-caused myositis, muscle infarction, rhabdomyolysis, myasthenia, immune-mediated myositis, necrotising myopathy, or vasculitis-associated myopathy. Muscle affection may concern only a single muscle, a group of muscles, or the entire musculature. Severity of muscle affection may be transient or permanent, may be a minor part of or may dominate the clinical picture, or may be mild or severe, requiring invasive measures including artificial ventilation if the respiratory muscles are additionally involved. Diagnostic work-up is similar to that of primary myopathies by application of non-invasive and invasive techniques. Treatment of muscle involvement in systemic diseases is based on elimination of the underlying cause and supportive measures. The prognosis is usually fair if the causative disorder is effectively treatable but can be fatal in single cases if the entire musculature including the respiratory muscles is involved, in case of infection, or in case of severe rhabdomyolysis. CONCLUSION: Secondary muscle manifestations of systemic diseases must be addressed and appropriately managed. Prognosis of secondary muscle disease in systemic diseases is usually fair if the underlying condition is accessible to treatment.

Neurophysiological effects of needle trauma and intraneural injection in a porcine model: a pilot study.

BACKGROUND: Neurophysiological data are lacking in the research of nerve injury during regional anaesthesia. The aim of this pilot study was to establish a large animal model in order to test the hypothesis that needle trauma alone or in combination with intraneural injection would result in measurable nerve injury. METHODS: The experimental set-up was elaborated in four pre-test animals. In the remaining animals (n = 11), 22 sciatic nerves were randomly assigned to one of four groups: needle trauma (n = 5) generated by ultrasound-guided forced needle advancement; intraneural injection of 2.5 ml saline (n = 6); intraneural injection of 5 ml saline (n = 6); extraneural injection of 5 ml saline (n = 5) as control group. Compound muscle action potential (CMAP) amplitudes as well as latencies were taken as outcome parameter and monitored over 180 min. Sonographic assessments were performed simultaneously. RESULTS: Following needle trauma and intraneural injection, CMAP amplitudes declined significantly over 180 min (P < 0.001). The control group showed no electrophysiological alterations. At 60 min, decreases in amplitude were significant after needle trauma (P = 0.04) and intraneural injection of 2.5 ml (P = 0.045), and highly significant after injection of 5 ml (P = 0.006) when compared to controls. Sustained nerve swelling was observed after intraneural injection, but not after needle trauma and perineural injection. CONCLUSIONS: Isolated mechanical trauma caused by forced needle advancement alone or in combination with intraneural injection of saline was followed by a significant decline in CMAP amplitudes indicating conduction block due to disruption of myelin or axon loss (pseudo-conduction block).

Iatrogenic lesions of peripheral nerves.

Iatrogenic nerve lesions (INLs) are an integral part of peripheral neurology and require dedicated neurologists to manage them. INLs of peripheral nerves are most frequently caused by surgery, immobilization, injections, radiation, or drugs. Early recognition and diagnosis is important not to delay appropriate therapeutic measures and to improve the outcome. Treatment can be causative or symptomatic, conservative, or surgical. Rehabilitative measures play a key role in the conservative treatment, but the point at which an INL requires surgical intervention should not be missed or delayed. This is why INLs require close multiprofessional monitoring and continuous re-evaluation of the therapeutic effect. With increasing number of surgical interventions and increasing number of drugs applied, it is quite likely that the prevalence of INLs will further increase. To provide an optimal management, more studies about the frequency of the various INLs and studies evaluating therapies need to be conducted. Management of INLs can be particularly improved if those confronted with INLs get state-of-the-art education and advanced training about INLs. Management and outcome of INLs can be further improved if the multiprofessional interplay is optimized and adapted to the needs of the patient, the healthcare system, and those responsible for sustaining medical infrastructure.

7th International Immunoglobulin Conference: Interlaken Leadership Awards.

The Interlaken Leadership Awards (ILAs), established in 2010, are monetary grants pledged annually by CSL Behring to fund research into the use of immunoglobulin (Ig) therapy, especially into its use in neurological disorders. Five recipients of the 2011/2012 Awards were invited to present their research at the 7th International Immunoglobulin Conference. Dr Honnorat reports on paraneoplastic neurological syndromes (PNS). His multi-centre Phase II trial, currently under way, will assess the efficacy of IVIg therapy in treating PNS in the first 3 months of treatment. Dr Geis shows improved disease scores after IVIg treatment in a mouse model of neuromyelitis optica (NMO). It is hoped that these promising results will translate well into human NMO. Dr Schmidt studied IVIg therapy in an mdx mouse model for Duchenne muscular dystrophy (DMD). He reports that motor function improved and myopathic changes in skeletal muscles and creatine kinase release were decreased. Dr Gamez presents the design and rationale for a Phase II clinical trial investigating the preoperative use of IVIg therapy in myasthenia gravis patients to prevent post-operative myasthenic crisis. Dr Goebel reports results from studies elucidating the immune-mediated pathogenesis of complex regional pain syndrome (CRPS), the successful IVIg therapy in a proportion of CRPS patients, and the development of a model for predicting which patients are more likely to respond to Ig therapy.

7th International Immunoglobulin Conference: Interlaken Leadership Awards.

The research presented in this section explores novel applications of immunoglobulin (Ig) therapy in neurological disorders. The results from the upcoming and ongoing trials of Drs Honnorat and Gamez are expected to provide meaningful insights into the treatment of two serious and disabling diseases. The results already being reported from the work of Drs Schmidt and Geis in animal models seem promising, but further proof-of-concept research is warranted to translate their significance to human diseases. Dr Goebel's work in developing animal models of complex regional pain syndrome (CRPS) may provide new insights into predicting which CRPS patients could respond to Ig therapy or other immunotherapies. The work being made possible by a number of the Interlaken Leadership Awards may provide fundamental insights in understanding neurological disorders and improving quality of life for the patients who suffer from them.

Prognosis and prognostic factors in non-traumatic acute-onset compressive mononeuropathies--radial and peroneal mononeuropathies.

BACKGROUND AND PURPOSE: Little is known about the natural history of non-traumatic compressive mononeuropathies. To improve patient management, prognostic factors and outcome in patients with non-traumatic peroneal and radial mononeuropathies were studied. METHODS: Retrospective clinical, electrophysiological and sonographic data of patients with non-traumatic peroneal and radial mononeuropathies were evaluated. Clinical, electrophysiological and sonographic evaluations had to take place 2-12 weeks after symptom onset and follow-up had to be for >6 months. RESULTS: Twenty-five patients with peroneal mononeuropathy and 58 with radial mononeuropathy were included. Mean follow-up was 8.9 ± 2.4 months. Approximately 90% of patients recovered to a muscle strength of British Medical Research Council grade 4 or 5. Multiple logistic regression analysis revealed conduction block on nerve conduction studies, younger age and less severe initial weakness as indicators for a good prognosis. Peripheral nerve ultrasound was not prognostic in the 40 patients where it was available. CONCLUSIONS: The present study shows a good prognosis for spontaneous recovery after non-traumatic acute-onset compressive peroneal and radial mononeuropathies. Patients with denervation on needle electromyography, older age and severe initial weakness have a poorer prognosis and should be closely monitored to facilitate timely surgery whenever weakness persists. Peripheral nerve ultrasound seems to be of limited prognostic value in these mononeuropathies.

Pompe disease in Austria: clinical, genetic and epidemiological aspects.

In this study, we performed a survey of infantile and late-onset Pompe disease (IOPD and LOPD) in Austria. Paediatric and neuromuscular centres were contacted to provide a set of anonymized clinical and genetic data of patients with IOPD and LOPD. The number of patients receiving enzyme replacement therapy (ERT) was obtained from the pharmaceutical company providing alglucosidase alfa. We found 25 patients in 24 families, 4 IOPD and 21 LOPD with a resulting prevalence of 1:350,914. The most frequent clinical manifestation in LOPD was a lower limb-girdle phenotype combined with axial weakness. Three patients were clinically pauci- or asymptomatic and were diagnosed because of persistent hyperCKemia. Diagnostic delay in LOPD was 7.4 ± 9.7 years. The most common mutation was c.-32-13T > G. All IOPD and 17 symptomatic LOPD patients are receiving ERT. Standardized follow-up was only available in six LOPD patients for the 6-min walk test (6minWT) and in ten for the forced vital capacity (FVC). Mean FVC did not decline (before ERT; 63.6 ± 39.7%; last evaluation during ERT: 61.9 ± 26.9%; P = 0.5) while there was a trend to decline in the mean distance covered by the 6minWT (before ERT: 373.5 ± 117.9 m; last evaluation during ERT: 308.5 ± 120.8 m; P = 0.077). The study shows a lower prevalence of Pompe disease in Austria than in other European countries and corroborates a limb-girdle phenotype with axial weakness as the most common clinical presentation, although asymptomatic hyperCKemia may be the first indication of LOPD.

Cortical motor activation patterns following hand transplantation and replantation.

We studied cortical activation patterns by functional MRI in a patient who received bilateral hand transplantation after amputation 6 years ago. In the early post-operative period, the patient who had had the hand transplantation revealed strong activation of a higher motor area, only weak activation of the primary sensorimotor motor cortex and no activation of the primary somatosensory cortex. At one-year follow-up, a small increase in primary sensorimotor motor cortex activation was observed. Activation of the primary somatosensory cortex was only seen at the 2-year follow-up. Transplantation after long-standing amputation results in cortical reorganisation occurring over a two-year period.

Neuromuscular complications in cancer.

Cancer is becoming a treatable and even often curable disease. The neuromuscular system can be affected by direct tumor invasion or metastasis, neuroendocrine, metabolic, dysimmune/inflammatory, infections and toxic as well as paraneoplastic conditions. Due to the nature of cancer treatment, which frequently is based on a DNA damaging mechanism, treatment related toxic side effects are frequent and the correct identification of the causative mechanism is necessary to initiate the proper treatment. The peripheral nervous system is conventionally divided into nerve roots, the proximal nerves and plexus, the peripheral nerves (mono- and polyneuropathies), the site of neuromuscular transmission and muscle. This review is based on the anatomic distribution of the peripheral nervous system, divided into cranial nerves (CN), motor neuron (MND), nerve roots, plexus, peripheral nerve, the neuromuscular junction and muscle. The various etiologies of neuromuscular complications - neoplastic, surgical and mechanic, toxic, metabolic, endocrine, and paraneoplastic/immune - are discussed separately for each part of the peripheral nervous system.

Cortical motor activation patterns following hand transplantation and replantation.

We studied cortical activation patterns by functional MRI in a patient who received bilateral hand transplantation after amputation 6 years ago and in a patient who had received unilateral hand replantation within 2 hours after amputation. In the early postoperative period, the patient who had had the hand transplantation revealed strong activation of a higher motor area, only weak activation of the primary sensorimotor motor cortex and no activation of the primary somatosensory cortex. At 1-year follow-up, a small increase in primary sensorimotor motor cortex activation was observed. Activation of the primary somatosensory cortex was only seen at the 2 year follow-up. By contrast, after hand replantation, the activation pattern was similar to that of the uninjured hand within 6 weeks. This included activation of the primary sensorimotor motor cortex, higher motor areas and primary somatosensory cortex. Transplantation after long-standing amputation results in cortical reorganization occurring over a 2-year period. In contrast, hand replantation within a few hours preserves a normal activation pattern.

Comparison of second lumbrical and interosseus latencies with standard measures of median nerve function across the carpal tunnel: a prospective study of 450 hands.

The second lumbrical-interosseus distal motor latency (2LI-DML) was compared prospectively in 450 hands. Median nerve function was assessed by standard motor and sensory electrophysiological tests. In a control group of 100 hands the upper limit of normal for the 2LI-DML was 0.5 ms. In all hands studied the correlation coefficients of 2LI-DML were higher with sensory nerve tests than with motor studies. Carpal tunnel syndrome (CTS) was diagnosed clinically in 276 hands, and 174 showed no clinical signs of CTS. The 2LI-DML was prolonged in 269 of the 276 hands, with clinical signs of CTS and normal in 170 of 174 non-CTS hands. Thus the 2LI-DML resulted in a sensitivity of 97.5%. On the other hand, combining the standard tests yielded a sensitivity of 98.5 %. In 31 of 36 additional hands a lumbrical response was recorded, although motor and sensory responses form standard median nerve conduction studies were absent, and the 2LI-DML was substantially prolonged. The 2LI-DML therefore represents a highly sensitive, fast, easy-to-perform, and cost-efficient method to study median nerve function across the wrist and may help to localize the lesion in cases in which standard electrophysiological methods fail.

Load-dependence of fatigue related changes in tremor around 10 Hz.

OBJECTIVES: The aim of the study was to investigate the effects of different loads on tremor around 10 Hz during fatiguing contractions. METHODS: Eighteen healthy volunteers performed sustained isometric knee extensions at 30%, 50% and 70% maximum voluntary contraction (MVC). During the fatiguing contractions, mechanical recordings were made with a high-resolution force sensor. Tremor-power was calculated for the 6-20 Hz frequency window as a function of time normalized to endurance time. RESULTS: Initial tremor power was different between the high and low load tasks. Changes of tremor with contraction time differed between the three tasks, in that tremor of the 30% MVC contraction showed the least decrease throughout the sustained contraction, whilst that of the 50% and 70% MVC showed progressively higher decreases. At failure, all 3 contractions merged to the same tremor level. CONCLUSION: Load-dependent, fatigue-related 6-20 Hz tremor changes during sustained submaximum voluntary contractions seem mainly the consequence of recruitment of new units and fatigue-related properties of the high threshold motor units of muscles.

Neurological status, sleep apnea frequency and blood oxygenation in six weeks old infants.

A study was carried out to investigate the correlation between sleep apnea frequency, blood oxygenation and neurological condition in 21 infants at six weeks of age with inconspicuous medical history. Polygraphic recordings of respiratory behaviour and transcutaneous blood gas monitoring lasted for at least five hours. To quantify the results of the neurological examination we established a neurological optimality score (NOS). We found statistically significant correlations between several indexes of apneas and indexes of blood oxygenation and NOS. Thus, a reduced NOS was strongly correlated with higher apnea frequencies and with pronounced drops of transcutaneous PO2-values. In addition all but one infant who were diagnosed as having a sleep apnea syndrome showed a greater than ten percent reduction of NOS. Some pathophysiological considerations to explain our findings are put forward and the possible role of the neuromodulator adenosine is emphasized.

Arm tremor and precision of hand force control in a short and long term flight on the MIR-Space-Station.

To determine whether long and short time exposure of man in 0g alters normal physiological tremor patterns we recorded arm tremor using an accelerometer as well as hand forces and tremor during constant isometric contraction using a load cell. Arm tremor was decreased during both flights in amplitude and frequency. Shortly after the long term flight arm tremor amplitude was increased, indicating adaptive changes in the tonic reflex loop. Isometric hand tremor remained unchanged during the long and short time flight demonstrating that the contractile properties of hand muscles remained constant. Precision of hand force was decreased until the half duration of the long term flight.

Significance of peripheral afferent input to the alpha-motoneurone pool for enhancement of tremor during an isometric fatiguing contraction.

The objective of this study was to investigate the contribution of peripheral afferent input to the enhancement of isometric tremor during a sustained submaximal isometric contraction. It was hypothesised that during muscle fatigue, when excitatory drive is high, peripheral afferent input may augment oscillations in the stretch reflex arc and result in bursting motor-unit activity and increased tremor. Nine healthy subjects maintained isometric plantar flexions at 30% of their maximum voluntary contraction until the limit of endurance, under three test conditions. Two paradigms were used to reduce afferent input to the triceps surae alpha-motoneurone pool: (1) continued vibration of the Achilles tendon, and (2) ischaemic partial block of the tibial nerve. These were compared to a control experiment, in which there was no intervention. By recording H-reflexes from the gastrocnemius and soleus muscles, it was possible to assess the effectiveness of reducing the afferent input. When H-reflex suppression had stabilised, the fatiguing contraction was commenced and tremor was computed from the continuously recorded torque signal. Superimposed maximum twitches were elicited as indirect measures of excitatory drive. The increase in tremor root mean square throughout the fatiguing contraction was significantly less for both the vibration and ischaemic conditions. Furthermore, tremor mean power frequency decreased significantly with endurance time in the control experiment, while no significant change was seen in the other two experimental conditions. It is concluded that the enhancement of isometric tremor seen during a fatiguing submaximal isometric contraction is facilitated by peripheral afferent input to the alpha-motoneurone pool.

Myo-electric signals from two extrinsic hand muscles and force tremor during isometric handgrip.

The objective of the present study was to investigate the myo-electric signs of muscle fatigue and the isometric force tremor of two extrinsic hand muscles, extensor digitorum communis and flexor digitorum superficialis, during isometric power grip. In addition, the synergy between flexor and extensor muscles and hand differences in a right-handed population have been studied. During isometric hand-dynamometry the myo-electric signal was recorded using surface electrodes and isometric force tremor was recorded using a special load cell. Eight subjects participated in this study and contractions were performed at 20%, 40%, 60% and 80% of maximal voluntary contraction (MVC) with left and right hands. The decrease of mean power frequency (MPF) with duration of contraction was greater in the left extensor as compared to the ipsilateral flexor muscle. No differences in the decrease in MPF with the duration of the contraction were found between the right extensor and flexor muscles. Isometric force tremor root mean square did not change during contractions at a given contraction level. Isometric tremor amplitude increased from 20% to 60% MVC and decreased at higher contraction levels. Tremor amplitude was higher in the left hand at all contraction levels but 60% MVC. These data would suggest differences in fatiguability and muscle fibre composition between the dominant and nondominant hand, which may be due to preferred use. The significance of force tremor for the evaluation of recruitment order and muscle fatigue is discussed.