Small-fibre neuropathy can be detected in patients with chronic idiopathic axonal polyneuropathy.

BACKGROUND: The main sensory presenting symptoms of chronic idiopathic axonal polyneuropathy (CIAP) are paraesthesias, numbness and burning pain in the feet. Although these symptoms indicate the involvement of small nerve fibres, clinical analysis or electrophysiological investigations have not yet been studied in detail. METHOD: Cardiovascular autonomic tests and cold and heat pain perception threshold tests were performed in 10 patients with CIAP, 10 patients with diabetes mellitus (DM) and 10 healthy volunteers. The results of the DM group were used to see whether the tests were able to detect small-fibre neuropathy in patients with diabetes and pain. RESULTS: Quantitative sensory threshold and autonomic tests showed more frequent abnormal test results in the patients compared to the healthy control group. The proportion of abnormal test results reached significance for the deep breathing tests in both patient groups and for the cold threshold and heat pain test in patients with CIAP. The spectral analysis of RR intervals showed a significant decrease in the high frequency in both patients with DM and CIAP. CONCLUSION: The results of this study demonstrated that small-fibre neuropathy can be detected in patients with CIAP.

Riboflavin-responsive lipid-storage myopathy and glutaric aciduria type II of early adult onset.

A 17-year-old girl with progressive lipid-storage myopathy for 2 years had low muscle carnitine levels. There was no therapeutic response to prednisone and DL-carnitine-HCl. Chemical findings indicated glutaric aciduria type II. Riboflavin therapy and a fat-restricted, carbohydrate-enriched diet resulted in dramatic improvement. Low carnitine concentrations in plasma and muscle were observed in three asymptomatic sisters who had normal urinary excretion patterns. There was impaired mitochondrial beta-oxidation in cultured skin fibroblasts from the index patient and all three siblings.

Evaluation of electrophysiological and clinical tests in an exploratory trial of Org 2766 in motor neuron disease.

Twenty four patients with motor neuron disease (MND) participated in a double-blind, placebo-controlled trial with the ACTH 4-9 analog, Org 2766. Patients were examined three times during an 8 week treatment period, using a summated score for several manually and functionally tested muscles (sum score), myometry, jitter, fibre density (FD), macro motor unit potential (MUP), and supramaximal evoked muscle action potentials. No differences were found between Org 2766 and placebo treated patients. In an open 1 yr follow-up study, 5 out of 13 patients treated with Org 2766 died; the others showed continued progression of weakness. The methods used for assessment of muscle function were compared. The highest interest reliability was obtained in the sum score and myometry. Mean differences that might be detectable were relatively small for the sum score and myometry, and large for FD and MUP. We concluded that clinical function testing and myometry are superior to electromyographic measurements for assessment of changes in MND patients.

Response to intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy with only sensory symptoms.

In an open prospective study we analysed the effect of treatment with intravenous immunoglobulin (IvIg) in three patients with clinically pure sensory neuropathy, two of whom met the clinical, electrophysiological, pathological and cerebrospinal fluid research criteria of the American Academy of Neurology for chronic inflammatory demyelinating polyneuropathy. In all patients, subclinical signs of demyelination were present in motor nerves. Treatment with IvIg resulted in improvement of neurological functions in all three patients and in improvement of the disability score in two of them.

Hypoxic neuropathy versus diabetic neuropathy. An electrophysiological study in rats.

In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypoxic conditions (10% O2) for a 10-week period. Two factors are held responsible for the development of diabetic polyneuropathy: metabolic deterioration and hypoxia. However, until now the relative roles of metabolic deterioration and hypoxia in the development of polyneuropathy have not been settled. To test both explanations further with more sophisticated electrophysiological techniques, the H-reflex (motor and sensory NVC) and the stimulated SF-EMG (measures terminal nerve branch and neuromuscular transmission) were measured in 3 groups of 10 rats, a healthy control group, a diabetic group, and a hypoxic group, every 5 weeks, for 6 months. In the control rats an age-related increase in motor and sensory conduction velocity was found, whereas in the diabetic rats as well as in the hypoxic rats a marked decrease in sensory and a slight decrease in motor nerve conduction velocity was observed. The jitter measured in the stimulated SF-EMG was significantly increased in both the diabetic and the hypoxic group. The results of the present study support the possible role of hypoxia, in addition to metabolic factors, in the development of experimental diabetic neuropathy.

Stomach distension increases efferent muscle sympathetic nerve activity and blood pressure in healthy humans.

Although the enteric nervous system is usually described as a separate and independent entity, animal studies show that gastric distension causes a reflex increase in arterial pressure and a sympathetically mediated increase in heart rate and peripheral vascular resistance. To assess the influence of gastric distension on sympathetic outflow and blood pressure, we recorded muscle sympathetic nerve activity (MSNA) from the peroneal nerve by microneurography in eight healthy volunteers. The stomach was distended by means of a barostat, using a single staircase protocol by which pressure was increased by 2 mmHg every 3 min. Gastric sensory function was assessed at each distension step by using a visual analog scale (VAS) for sensations of fullness, nausea and pain. For comparison, we also performed a cold pressor test. The MSNA increased on barostat-induced gastric distension with an almost concomitant elevation of blood pressure. The increase in both was proportional to the intragastric pressure and both decreased towards initial values after the end of distension. Heart rate increased inconsistently and only at higher distension pressures that were associated with high VAS scores. The opposite was found for the cold pressor test. The results of this study confirm the existence of a functional relationship between gastrointestinal distension and cardiovascular function. Decrease in this gastrovascular response may play a role in postprandial hypotension in the elderly, since the MSNA responses to simulated microgravity decrease with age.

Features of the Guillain-Barré syndrome in mice following intraperitoneal injection of patient serum.

Intraperitoneal injection of serum from a patient with the Guillain-Barré syndrome (GBS) produced GBS-like signs in mice: inadequate respiration and weakness in the legs. We studied the clinical, electrophysiological and pathological features of these mice. Three groups of three mice were injected with patient serum from days 6, 10 and 15 after onset of neurological symptoms. GBS-like signs in mice were observed only with serum from day 6 and improved within 48 h. When serum was frozen and thawed more than once no signs were seen. Electrophysiological measurements of the sciatic nerves of injected and control mice were done before and after serum injection. Five days after injection of patient serum of day 6, the mice showed a significant decrease in the ratio between CMAP amplitude from proximal and distal stimulation and increase in H-M interval from proximal stimulation. These electrophysiological changes returned to normal within 12 days. The sciatic nerve showed no morphological abnormalities. Our results indicate that the observed GBS-like signs in mice are caused by peripheral nerve dysfunction.

Neuro-musculo-skeletal manifestations in primary Sjögren's syndrome.

Primary Sjögren's syndrome is a systemic autoimmune disorder whose main characteristics are dryness of the eyes and mouth, caused by lymphocytic infiltration of the exocrine glands. Patients may also show signs of extraglandular involvement of lung, liver, kidney and vessel walls, as well as of the central and peripheral nervous systems, muscles and joints. This article presents a review of the literature on extraglandular involvement of the peripheral and central nervous systems, muscles and joints. Several data support the hypothesis that vasculitis is the underlying mechanism. The need for an extended inventory of the extraglandular manifestations, preferentially linked to immunoserological and -histological investigations to gain more insight into the aetiology and pathogenesis is stressed. As far as the clinical picture is concerned, myalgia and arthralgia are often reported, but myositis and arthritis are rare. Data about the prevalence of peripheral and central nervous system involvement are conflicting: factors contributing to these differences are discussed. As insight into prognosis and therapy will strongly depend on the diagnostic criteria used, the need for international agreement on these is emphasized.

Autonomic function in patients with hereditary motor and sensory neuropathy type I and Lambert-Eaton myasthenic syndrome.

Noninvasive tests of four autonomic organ systems (vasomotor control, baroreceptor reflexes, sudomotor function and pupillary reflexes) were performed on nine patients with hereditary motor and sensory neuropathy (HMSN) type I and three patients with Lambert-Eaton myasthenic syndrome (LEMS). The results were compared with those of 33 control subjects. Autonomic dysfunction was considered present when at least two of the four organ system tests were abnormal. The three patients with LEMS had abnormal results in two or more different systems, whereas only one of the nine patients with HMSN type I had two abnormal test results. This study demonstrates that autonomic dysfunction is not a common finding in patients with HMSN type I and its presence should alert us to find the cause of this autonomic disorder.

Muscle conduction velocity and morphology after prolonged hypoxemia and diabetes in rats.

One of the electrophysiological abnormalities in the experimental rat model of chronic hypoxia (10% O2) and in the experimental rat model of diabetes is an increase in jitter in the stimulated single fibre EMG, which is thought to result from a primary disorder of the axon with its terminal branches. But muscle fibre alterations that influence the propagation of muscle action potentials can also increase jitter. The contribution of possible changes in muscle conduction velocity and muscle morphology to jitter were investigated in the present study. Muscle conduction velocities were determined and compared with the morphological properties of muscle fibers in muscles of control, chronic hypoxic and terminal-stage diabetic rats. The mean muscle conduction velocities were in the same range in the three groups. The muscle fibre type composition and the mean muscle fibre diameters were about the same in the hypoxic and the control rats, whereas the muscles of the diabetic rats showed a higher percentage of intermediate type muscle fibres, which is suggestive of muscle degeneration, and a smaller mean muscle fibre diameter in comparison with muscles of the hypoxic and the control rats. It is concluded that the similarities between the electrophysiological properties of the muscles despite differences in their morphology, indicate that there is primary axonal degeneration in diabetic hypoxic rats.

Temporary muscle weakness in the early phase of distraction during femoral lengthening. Clinical and electromyographical observations.

Limb lengthening by distraction osteogenesis has a high complication rate. Much of the response of muscle and nerve to distraction is still unknown. Thirteen children, mean age 12.6 yr (8.4-17.3) were surgically treated by the Ilizarov procedure for acquired and congenital femoral limb-length discrepancy. All children showed a decrease in muscle strength in the quadriceps, shortly after the operation, followed by an improvement before distraction started. After an elongation in the early phase of distraction (1 to 2 cm), muscle weakness was again observed and the muscle strength gradually increased after ending of distraction. To provide an explanation for this clinical observation, in one patient (limb lengthening of 4.1 cm) muscle strength measurements were extended with investigations of Hoffman (H) reflex of m. vastus medialis and determination of muscle-fiber conduction velocity of m. vastus lateralis by using the invasive method (IMFCV). The examinations were performed every two weeks during 20 weeks and 12 weeks after removing the cast. A severe decrease in muscle strength of the corrected limb was found after 1.2 cm of distraction with a recovery in muscle strength before lengthening was ended. EMG study showed the same tendency. Denervation was observed as evidence by positive sharp waves and reduced IMFCV findings. Evidence for reinnervation before lengthening was ended, was found by an increased range of velocities consisting of a combination of slow potentials and gradual increase of the velocity of reinnervated fibers (increased Fast/Slow ratio). The latencies of M waves and H-M interval from both legs separated as well after 2.25 cm of distraction. At the end of the follow-up period, the H-M interval reached the preoperative value. It is suggested that these neurogenic changes are an effect of axonal dysfunction and the local effect due to intraoperative trauma and stretching might affect nerve blood flow adversely.

Intramedullary femoral nailing through the trochanteric fossa versus greater trochanter tip: a randomized controlled study with in-depth functional outcome results.

PURPOSE: In a level 1 university trauma center, an explorative randomized controlled study was performed to compare soft tissue damage and functional outcome after antegrade femoral nailing through a trochanteric fossa (also known as piriform fossa) entry point to a greater trochanter entry point in patients with a femoral shaft fracture. MATERIALS AND METHODS: Nineteen patients were enrolled and randomly assigned to two nail insertion groups; ten patients were treated with an Unreamed Femoral Nail(®) (UFN, Synthes(®), Solothurn, Switzerland) inserted at the trochanteric fossa and nine patients were treated with an Antegrade Femoral Nail(®) (AFN, Synthes(®), Solothurn, Switzerland) inserted at the tip of the greater trochanter. The main outcome measures were pain, gait, nerve and muscle function, along with endurance. Magnetic resonance imaging (MRI), electromyography (EMG), and Cybex isokinetic testings were performed at, respectively, 2 and 6 weeks and at a minimum of 12 months after surgery. RESULTS: The MRI and EMG showed, in both groups, signs of iatrogenic abductor musculature lesions (four in the UFN group and four in the AFN group) and superior gluteal nerve injury (five in the UFN group and four in the AFN group). The isokinetic measurements and the patient-reported outcomes showed moderate reduction in abduction strength and endurance, as well as functional impairment with slight to moderate interference with daily life in both groups, with no appreciable differences between the groups. CONCLUSIONS: Anatomical localization of the entry point seems to be important for per-operative soft tissue damage and subsequent functional impairment. However, the results of this study did not show appreciable differences between femoral nailing through the greater trochanter tip and nailing through the trochanteric fossa.

Subclinical diabetic neuropathy: similarities between electrophysiological results of patients with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients share many clinical and biochemical characteristics. However, sural nerve biopsies from patients with advanced and chronic neuropathy show ultrastructural differences between these two groups. We investigated whether at a subclinical stage of the illness, when Type 1 and Type 2 diabetic patients are clinically uniform and the histopathological nerve alterations are not advanced, comparison between the two diabetes groups might show differences in nerve fibre involvement related to the different pathogeneses of the neuropathies. A total of 88 diabetic patients (52 Type 1 and 36 Type 2), with a subclinical form of polyneuropathy were selected. The clinical neurophysiological examination consisted of motor and sensory nerve conduction studies, Hoffmann (H)-reflex, single fibre electromyography and static as well as dynamic pupillometry. With regard to clinical neurophysiological abnormalities, the severity of the polyneuropathy appeared to be equal in both groups. Despite the absence of clinical symptoms the neurophysiological abnormalities were pronounced and it was impossible to differentiate Type 1 diabetic patients from Type 2 diabetic patients on a clinical neurophysiology basis when correcting for differences in age, height, and duration of illness. In the Type 1 diabetic group as well as in the Type 2 diabetic group the autonomic nerve fibres and nerves in the legs were more frequently affected than the thick myelinated nerves in the arms. These findings do not support the assumption that there is a difference in the manifestation of polyneuropathy between Type 1 and Type 2 diabetic patients.

Ocular myasthenia gravis: the diagnostic yield of repetitive nerve stimulation and stimulated single fiber EMG of orbicularis oculi muscle and infrared reflection oculography.

For the diagnosis of ocular myasthenia gravis (ocular MG), testing of the muscles close to the affected ones may be important. The relative importance of several methods: stimulated single fiber EMG (stimulated SFEMG), repetitive nerve stimulation test (RNS) of orbicularis oculi muscle, and infrared reflection oculography (IROG) was investigated. Thirty-two patients in whom a diagnosis of ocular MG was considered on clinical grounds were admitted to the study. Based on the results of the three neurophysiological tests, the patients could be divided in three groups: a first group with an abnormal stimulated SFEMG, and an abnormal RNS and/or abnormal IROG; a second group with only a slightly abnormal stimulated SFEMG; and a third group with normal tests in all three tests. The clinical diagnosis of ocular MG was made in all 11 patients of the first group; in 86% (6 of 7) of the patients of the second group; and in 7% (1 of 14) of the patients of the third group. This study demonstrates that the orbicularis oculi muscle is a suitable muscle for stimulated SFEMG in patients with ocular MG, and that the results obtained with this technique showed a better relation with the clinical diagnosis than those of the two other techniques. We also demonstrate that there is no additional value in studying the jitter with different stimulation rates in patients with suspected ocular MG.

Cold stress provokes sympathoinhibitory presyncope in healthy subjects and hemodialysis patients with low cardiac output.

BACKGROUND: Sudden hypotension in progressive hypovolemia or during hemodialysis is attributed to sudden inhibition of sympathetic activity. Critical ventricular underfilling seems responsible for this paradox, but it is unknown why the transition from sympathoactivation accompanying hypovolemia to sympathoinhibition is so abrupt. We studied whether brief fluctuation of sympathetic activity induced by cold pressor test (CPT) evokes sympathoinhibition if applied during low cardiac output. METHODS AND RESULTS: Fourteen healthy subjects underwent CPT, lower-body negative pressure (LBNP; -45 mm Hg for 60 minutes), or the combination thereof. CPT alone caused vasoconstriction and increased muscle sympathetic nerve activity, followed by uneventful relaxation. When applied during reduced cardiac output, tachycardia, and vasoconstriction induced by prior LBNP for 6 minutes, CPT again caused vasoconstriction, now followed by acute hypotension in 10 subjects, and was associated with vasorelaxation, relative bradycardia, and fall in muscle sympathetic nerve activity. Eight subjects also experienced acute LBNP-induced hypotension in the absence of CPT, but not until 17 +/- 6 minutes of LBNP. We also performed CPT before and in the final phase of hemodialysis in 8 patients. Before dialysis, the patients tolerated CPT uneventfully, but during hemodialysis, CPT provoked acute hypotension in 5 cases, showing similar withdrawal of vasoconstriction. CONCLUSIONS: This is the first study showing that brief cold stress, tolerated well in normal circulatory conditions, can provoke sudden sympathoinhibition and hypotension when applied during decreased cardiac output induced by LBNP or hemodialysis. We suggest that during conditions of a decreased cardiac output, subtle sympathetic relaxation such as follows cold stress triggers self-enhancing relaxation that cannot be controlled.

Antihypoxic treatment at an early stage of diabetic neuropathy: an electrophysiological study with sabeluzole.

Thirty-seven non-IDDM patients at an early stage of polyneuropathy, defined as the presence of symptoms for less than two years, as well as an abnormal perception threshold and/or abnormal thermal discrimination threshold, were treated with sabeluzole, a new antihypoxic drug, or placebo for 1 year in a double-blind, placebo-controlled study. They were examined neurophysiologically every 3 months, when motor (tibial, ulnar) nerve and sensory (sural, ulnar) nerve conduction velocities, H-reflex of the soleus muscle, SF-EMG of the anterior tibial muscle, static and dynamic pupillometry were measured. Statistical analysis did not show significant differences in nerve function between the sabeluzole group and the placebo group. There were also no significant changes within each group over the 1-year period. The results of the present study show no beneficial effect of sabeluzole on peripheral nerve function in patients at an early stage of diabetic polyneuropathy.

Subclinical diabetic polyneuropathy: early detection of involvement of different nerve fibre types.

Nerve conduction studies, tests of autonomic function and terminal nerve branches, and soleus muscle H reflexes were applied to 60 patients with insulin dependent diabetes mellitus who had no clinical symptoms but abnormal vibratory or temperature perception thresholds indicating subclinical neuropathy. In most patients neurophysiological examination yielded a broad spectrum of neural dysfunction. The perception threshold for cold stimuli was sometimes selectively impaired and abnormal pupillometry results were common, suggesting that small fibres are vulnerable in the early stage of diabetic neuropathy. The arms were less frequently and less severely affected than the legs, an effect that may be related to nerve length. The neurophysiological test results did not change in 30 patients followed up for one year.