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.

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.

Effect of gastric distension on cardiovascular parameters: gastrovascular reflex is attenuated in the elderly.

Stretching the stomach wall in young healthy subjects causes an increase in muscle sympathetic nerve activity and in blood pressure, the gastrovascular reflex. We compared healthy elderly subjects with healthy young subjects to find out whether the gastrovascular reflex attenuates in normal ageing and we studied whether there was a difference in autonomic function or gastric compliance that could explain this possible attenuation. Muscle sympathetic nerve activity, finger blood pressure and heart rate were continuously recorded during stepwise isobaric gastric distension using a barostat in eight healthy young (6 men and 2 women, 27 +/- 3.2 years, mean +/-s.e.m.) and eight healthy elderly subjects (7 men and 1 woman, 76 +/- 1.5 years). Changes in cardiac output and total peripheral arterial resistance were calculated from the blood pressure signal. The baseline mean arterial pressure and muscle sympathetic nerve activity were higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity increase during the cold pressor test was lower in the elderly group (P = 0.005). During stepwise gastric distension, the elderly subjects showed an attenuated increase in muscle sympathetic nerve activity compared to the young subjects (P < 0.01). The older group tended to show a higher increase in mean arterial pressure (P = 0.08), heart rate (P = 0.06) and total peripheral arterial resistance (P = 0.09) The cardiac output rose slightly in both groups without significant difference between groups. The fundic compliance did not differ between groups. We conclude that stepwise gastric distension caused an increase in muscle sympathetic nerve activity in both groups, but the increase in the elderly was attenuated.

Observer variations in short period spectral analysis of heart rate variability.

25% of the corresponding mean LF/HF ratio. The smallest interobserver variations were found for the 'fixed frequency' method. The data showed that it is advantageous to select the 3-min ECG periods but not to select the frequency regions. Selection of the latter led to an increase in interobserver variation. The results of this study give a realistic impression of the intrasubject and interobserver variation to be expected when measuring the LF/HF ratio. This variation is considerable.

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.

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.

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure.

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

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.

Differences between hereditary motor and sensory neuropathy type 2 and chronic idiopathic axonal neuropathy. A clinical and electrophysiological study.

To evaluate whether chronic idiopathic axonal polyneuropathy (CIAP) should be considered as hereditary motor and sensory neuropathy type 2 (HMSN type 2), we compared the clinical features of 48 patients with CIAP with those of 47 patients with HMSN type 2. In addition, we studied electrophysiological data in 20 patients with CIAP and in 20 patients with HMSN type 2. We found, in patients with HMSN type 2, that the initial symptoms were predominantly motor and that weakness and handicap were more severe and skeletal deformities more frequent, compared with those of CIAP patients. Electrophysiologically, the tibialis anterior muscle showed more denervation in patients with HMSN type 2, consistent with the predominance of motor symptoms. There was no important effect of age of onset on clinical features in HMSN type 2 patients. We conclude that in an individual patient with a sensory or sensorimotor idiopathic axonal polyneuropathy and no family history of polyneuropathies, the diagnosis HMSN type 2 is unlikely. However, if motor symptoms predominate, the diagnosis of HMSN type 2 should be considered.

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.

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.

A new variant of sensory ataxic neuropathy with autosomal dominant inheritance.

We describe a Dutch family with sensory ataxia in two generations, late onset of symptoms (over the age of 40 years) and slow progression. Clinical, electrophysiological and sural nerve biopsy findings revealed a sensory polyneuropathy due to axonal degeneration of myelinated nerve fibres in four of five investigated siblings. Other neurological abnormalities in the affected family members consisted only of mild eye movement disturbances, probably due to cerebellar involvement. Five other family members were investigated and found unaffected. As the disease is inherited from the affected father to his sons and daughters, this is the first description of a probably autosomal dominant form of late onset hereditary sensory neuropathy with predominant sensory ataxia and minor other neurological abnormalities.

Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study.

The effect of high dose intravenous immunoglobulin (IVIg) treatment was studied in six patients with multifocal motor neuropathy (MMN). All patients responded to treatment (0.4 g/kg for five consecutive days) in an open trial. The effect of IVIg treatment was confirmed for each patient in a single patient, double blind, placebo controlled trial. Four patients received two IVIg treatments and two placebo treatments, and two patients received one IVIg and one placebo treatment in a randomised order. Five out of six patients responded to IVIg but not to placebo. One patient responded to IVIg in the same manner as to placebo treatment. Thus IVIg treatment can lead to improvement of muscle strength in patients with MMN.

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.

Randomized double-blind placebo-controlled trial to evaluate the effect of the ACTH4-9 analogue ORG 2766 in IDDM patients with neuropathy.

In this study we report a randomized double-blind, placebo-controlled trial to evaluate the effect of ORG 2766 in IDDM patients with peripheral neuropathy. Sixty-two patients were selected based on the following criteria: abnormal vibration perception threshold above the 95th-percentile adjusted for age and/or abnormal warm temperature threshold, both measured in the right hand. The patients were randomized into two treatment groups after baseline studies: Group 1 was treated with placebo and Group 2 was treated with 3 mg of the ACTH4-9 analogue ORG 2766 every 24 h. The total study period was 1 year. After 1 year of treatment there was a significant improvement in vibration threshold in Group 1 compared to Group 2. No other parameters improved in the study period. The number of patients selected may have been too small to detect a more important treatment effect. We conclude from this study that ORG 2766 can improve vibration threshold, indicating large myelinated fibre function, but does not affect any of the other neurophysiological function tests.

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.

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.

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.