The Rise Slope of the Compound Sensory Nerve Action Potential in Normal and Pathological Human Nerves.

In spite of the diagnostic importance of the early phase of the sensory nerve action potential (SNAP), reliable electrodiagnostic metrics for this part of the recorded waveform are lacking. The average rise slope of the SNAP appreciates the steepness of the initial negative deflection of the waveform, which might be a useful metric for the first part of the potential. Sural nerve sensory neurography was performed in patients with various axonal neuropathies, and median nerve sensory studies were carried out in patients with carpal tunnel syndrome. Age-matched healthy individuals served as controls. The rise slope was compared to conventional SNAP parameters such as conduction velocity, latency, duration, and rise time. Overall, 537 sensory studies were prospectively analyzed. The rise slope of the sural SNAP demonstrated superior classification performance in terms of sensitivity (92.5%), specificity (97%), and area under the receiver operating characteristic curve (0.986), as compared to conventional SNAP parameters. Its diagnostic power was similarly excellent in median nerve studies, whereas here a slightly better classification performance was obtained by SNAP latency and conduction velocity. The average rise slope appears to do justice to the tight interplay between amplitude and rise time of the initial negative spike deflection, outperforming many conventional measures. This composite metric proved high diagnostic potency in particular with regard to axonal sensory nerve dysfunction.

Diagnostic Accuracy of Muscle Biopsy and Electromyography in 123 Patients with Neuromuscular Disorders.

BACKGROUND/AIM: Diagnostic accuracy of muscle biopsy and electromyography (EMG) in patients with myopathy varies widely among studies. The goal of this study was to examine the diagnostic accuracy of each method in the diagnosis of patients with suspected myopathy, and determine the level of agreement between the two methods. PATIENTS AND METHODS: The files of all patients with a presumed myopathy were retrospectively reviewed. All patients with detailed muscle biopsy and EMG data were included. RESULTS: A total of 123 patients were included. Accuracy of biopsy was 80.4% compared to 70.7% for EMG. Biopsy was sensitive and specific in all neuromuscular disorders. EMG was accurate in neurogenic disorders. Biopsy and EMG agreement was 70.7%. CONCLUSION: Muscle biopsy is more accurate than EMG in patients with myopathy. Muscle biopsy-EMG discordance can be attributed to different muscle sampling and to disorders with both neurogenic and myopathic features, such as acquired and mitochondrial myopathies.

Quantification of sweat gland innervation in patients with Fabry disease: A case-control study.

INTRODUCTION: Hypohidrosis and heat intolerance, frequently reported by men and women with Fabry disease (FD), is thought to be related not only to the deposition of globotriaosylceramide (Gb3) in eccrine sweat glands, but also to reduced sweat gland sympathetic innervation. METHODS: We performed a case-control study to compare the density of sweat gland innervation between patients with FD and healthy controls by examining lower leg skin punch biopsies. We used a standardized grid of circles superimposed upon the immunofluorescent specimen to create a simple pattern of circles over the sweat gland. Nerve fibers that crossed within the circles were manually counted ("crossed circles"). Nerve fibers that touched the edge of the circle but did not enter were spared ("uncrossed circles"). The percentage of crossed circles from all circles was determined. RESULTS: Biopsy specimens were available of 37 FD patients (median age 44 years, 19-67; n = 18 men) and 16 controls (median age 48 years, 24-83, n = 7 men). Totally there were 153 sweat glands from FD patients and 63 from controls, in which innervation was quantified. While mean sweat gland innervation per biopsy did not differ between the entire FD cohort and controls, data stratification for the reported sweating phenotype revealed a stepwise lower innervation in women with FD and hypohidrosis (n.s.) and anhidrosis (p < .05) compared to women reporting normal sweating. CONCLUSION: Sweat gland innervation is reduced in women with FD and anhidrosis compared to female patients without sweating impairment. Loss of sweat gland innervation may play a role in FD associated anhidrosis, at least in women.

Decreased Axon Flare Reaction to Electrical Stimulation in Patients With Chronic Demyelinating Inflammatory Polyneuropathy.

PURPOSE: In chronic inflammatory demyelinating polyradiculopathy (CIDP), the impairment of unmyelinated nerve fibers appears unexpected. The measurement of the electrically induced axon flare reflex is a clinical test to assess the peripheral C-nociceptor function. In this study, we compared the flare area in patients suffering from CIDP with healthy subjects. METHODS: We examined 18 patients fulfilling the criteria for CIDP (11 men, mean age 51.8 years, SD 15.1) and 18 age-matched adult healthy volunteers (control group) (11 men, mean age 51.9 years, SD 15.8). The flare responses were elicited by transcutaneous electrical stimulation and recorded by laser Doppler imaging. RESULTS: There was a significant reduction of electrically induced maximum flare area in the foot dorsum of patients with CIDP (t-value 2.08, P = 0.04) which proved to be length-dependent measured by a numerical index comparing the results with the forearm and thigh. The repeatedmeasures ANOVA revealed statistically significant smaller flare areas in all body regions for the CIDP group (P < 0.001). CONCLUSIONS: The axon flare reaction to electrical stimulation was decreased in patients with chronic demyelinating inflammatory polyneuropathy. The evaluation of the axon flare response can be proposed as a noninvasive objective functional test to detect an impaired C-fiber function in CIDP patients with the advantages of simplicity of the procedure, time economy, and objectivity.

Early phase interference between low-intensity running and power training in moderately trained females.

PURPOSE: The aim of the study was to investigate the effects of low-intensity running performed immediately after lower-body power-training sessions on power development. METHODS: Twenty young females participated in 6 weeks, 3/week, of either lower body power training (PT) or lower body power training followed by 30 min of low-intensity running (PET) eliciting 60-70 % of maximal heart rate. The following were measured before and after the training period: counter-movement jump, isometric leg press force and rate of force development (RFD), half squat 1-RM, vastus lateralis fiber type composition and cross sectional area, resting intramuscular fiber conduction velocity (MFCV), and heart rate during the modified Bruce treadmill test. RESULTS: Counter-movement jump height and peak power increased after PT (10.7 ± 6.2 and 12.9 ± 18.7 %, p < 0.05) but not after PET (3.4 ± 7.6 and 5.11 ± 10.94 %, p > 0.05). Maximum isometric force, RFD, and half squat 1-RM increased similarly in both groups. Muscle fiber type composition was not altered in either group. Muscle fiber cross sectional area increased only after PT (17.5 ± 17.4, 14.5 ± 10.4, 20.36 ± 11.3 %, in type I, IIA, and IIX fibers, respectively, p < 0.05). Likewise, mean MFCV increased with PT only (before: 4.53 ± 0.38 m s(-1), after: 5.09 ± 0.39 m s(-1), p = 0.027). Submaximal heart rate during the Bruce treadmill test remained unchanged after PT but decreased after PET. CONCLUSION: These results suggest that low-intensity running performed after lower-body power training impairs the exercise-induced adaptation in stretch-shortening cycle jumping performance (vertical jump height, peak power), during the first 6 weeks of training, which may be partially linked to inhibited muscle fiber hypertrophy and muscle fiber conduction velocity.

LRP4 antibodies in serum and CSF from amyotrophic lateral sclerosis patients.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) and myasthenia gravis (MG) are caused, respectively, by motor neuron degeneration and neuromuscular junction (NMJ) dysfunction. The membrane protein LRP4 is crucial in the development and function of motor neurons and NMJs and LRP4 autoantibodies have been recently detected in some MG patients. Because of the critical role in motor neuron function we searched for LRP4 antibodies in ALS patients. METHODS: We developed a cell-based assay and a radioimmunoassay and with these we studied the sera from 104 ALS patients. RESULTS: LRP4 autoantibodies were detected in sera from 24/104 (23.4%) ALS patients from Greece (12/51) and Italy (12/53), but only in 5/138 (3.6%) sera from patients with other neurological diseases and 0/40 sera from healthy controls. The presence of LRP4 autoantibodies in five of six tested patients was persistent for at least 10 months. Cerebrospinal fluid samples from six of seven tested LRP4 antibody-seropositive ALS patients were also positive. No autoantibodies to other MG autoantigens (AChR and MuSK) were detected in ALS patients. No differences in clinical pattern were seen between ALS patients with or without LRP4 antibodies. CONCLUSIONS: We infer that LRP4 autoantibodies are involved in patients with neurological manifestations affecting LRP4-containing tissues and are found more frequently in ALS patients than MG patients. LRP4 antibodies may have a direct pathogenic activity in ALS by participating in the denervation process.

Inappropriate surgeries in amyotrophic lateral sclerosis: a still considerable issue.

Owing to the variety of its clinical presentations, amyotrophic lateral sclerosis (ALS) may mimic several neurological syndromes and even lead to inappropriate surgical procedures. We wished to assess the impact of unnecessary surgical treatments among ALS patients, and therefore we retrospectively reviewed medical records of 164 consecutive ALS patients. We collected data on the clinical presentation of ALS at onset, the initial symptom that led the patients to seek medical care, the timing of diagnosis and surgical procedures attributed to the onset of symptoms. Results showed that among 164 consecutive patients with ALS, 13 (7.9%) were surgically treated as a consequence of false diagnosis. Despite this, these patients showed no statistically significant difference in time of diagnosis compared to non-operated patients. In conclusion, a small but not negligible number of ALS patients are misdiagnosed. The diagnostic pathway of these patients includes often specialists other than neurologists who should be more aware of this disease in order to avoid inappropriate surgical treatments and provide the patients the appropriate diagnostic and therapeutic procedure by referring them promptly to a neurologist.

Objective assessment of C-fiber function by electrically induced axon reflex flare in patients with axonal and demyelinating polyneuropathy.

INTRODUCTION: A simple test to evaluate the peripheral C-fiber function is the measurement of axon reflex flare area. In this study, we compared the flare area in healthy subjects and in two groups of patients with predominantly axonal or demyelinating polyneuropathy. MATERIALS AND METHODS: We examined 42 control subjects and 33 patients. The flare responses were elicited by the application of transcutaneous electrical stimulation and recorded by laser Doppler imaging. RESULTS: There was a significant reduction of electrically induced flare area in both groups of neuropathy patients (P < 0.001; analysis of covariance). Interestingly, patients with an axonal neuropathy had a significantly stronger reduction of flare size as compared to patients with demyelinating neuropathy (P = 0.03). CONCLUSIONS: The evaluation of the axon flare response in the arm can be used as a screening test of impaired C-fiber function in polyneuropathy patients with the advantages of simplicity of the procedure and time economy.

Double seronegative myasthenia gravis with anti-LRP 4 antibodies.

About 10% of patients with generalized myasthenia gravis do not have detectable antibodies to acetylcholine receptor or muscle specific kinase (double seronegative myasthenia). The presence of anti-low density lipoprotein receptor-related protein 4 antibodies (LRP4 Abs) has recently been reported in variable proportion of double seronegative cases. We report the presenting characteristics of two double seronegative myasthenic patients from Greece with anti-LRP4 antibodies shortly after disease onset. The first patient, a 52-year-old male, presented with a one month history of isolated neck extensor weakness; the second patient is a 52-year-old female with three months history of ocular-bulbar-cervical myasthenic weakness. Both patients presented with mild severity and responded promptly and adequately to pyridostigmine. In the female patient thymic residual tissue was detected on CT of the mediastinum. She underwent thymectomy, and histological examination revealed follicular hyperplasia. This is the first clinical report of the presenting features of newly diagnosed myasthenia with anti-LRP4 antibodies. The clinical and therapeutic implications of the anti-LRP4 antibody positivity remain to be clarified.

MUAP values of two facial muscles in normal subjects and comparison of two methods for data analysis.

INTRODUCTION: This study aimed to obtain normal MUAP values in 2 facial muscles and to compare the results of different analysis methods. METHODS: The frontalis muscle of 36 and the mentalis muscle of 28 normal subjects were examined, and mean and outlier values of all MUAP parameters were calculated with the automatic method. Next, manual editing of the recorded raw data provided new sets of values for comparison. RESULTS: The frontalis muscle MUAPs have significantly shorter duration, smaller amplitude and a lower number of turns and phases compared with those of mentalis. Higher MUAP duration values in the frontalis were the only significant difference after the comparison of the different analysis methods. CONCLUSIONS: The set of normal values for frontalis and mentalis in this study could be useful in routine practice. Careful manual editing of the frontalis MUAPs is recommended for more accurate determination of their duration.

Turns-amplitude analysis in normal and myopathic facial muscles.

The purpose of this study was to assess turns/amplitude analysis (TAA) as an objective alternative to conventional qualitative electromyography (EMG) for detection of myopathy in facial muscles. Normal values of TAA parameters were calculated in the frontalis and mentalis muscles of 26 control subjects. We estimated the slope of the regression line of mean amplitude/turn values (MA) plotted against the number of turns/second (NT) and the resulting clouds. The 95% confidence limits of the cloud data were drawn as an ellipse. The sensitivity of TAA was determined from a group of 35 myopathic patients and specificity from a second group of 25 control subjects. Significant differences for every TAA parameter were found between frontalis and mentalis. Cumulative sensitivity and specificity of TAA for frontalis and mentalis were 74.6%, 56.5%, and 73.3%, 70.8%, respectively. With at least two of the aforementioned criteria abnormal, the sensitivity and specificity for frontalis and mentalis were 61.3%, 82.6%, and 56.7%, 100.0%, respectively.

Plasticity in human motor cortex is in part genetically determined.

Brain plasticity refers to changes in the organization of the brain as a result of different environmental stimuli. The aim of this study was to assess the genetic variation of brain plasticity, by comparing intrapair differences between monozygotic (MZ) and dizygotic (DZ) twins. Plasticity was examined by a paired associative stimulation (PAS) in 32 healthy female twins (9 MZ and 7 DZ pairs, aged 22.6±2.7 and 23.8±3.6 years, respectively). Stimulation consisted of low frequency repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with a single pulse transcranial magnetic stimulation (TMS) for activation of the abductor pollicis brevis muscle (APB). Corticospinal excitability was monitored for 30 min following the intervention. PAS induced an increase in the amplitudes of the motor evoked potentials (MEP) in the resting APB, compared to baseline. Intrapair differences, after baseline normalization, in the MEP amplitudes measured at 25-30 min post-intervention, were almost double for DZ (1.25) in comparison to MZ (0.64) twins (P =0.036). The heritability estimate for brain plasticity was found to be 0.68. This finding implicates that genetic factors may contribute significantly to interindividual variability in plasticity paradigms. Genetic factors may be important in adaptive brain reorganization involved in motor learning and rehabilitation from brain injury.

Clinical and neurophysiological study of peroneal nerve mononeuropathy after substantial weight loss in patients suffering from major depressive and schizophrenic disorder: Suggestions on patients' management.

BACKGROUND: Peroneal nerve is susceptible to injuries due to its anatomical course. Excessive weight loss, which reduces the fatty cushion protecting the nerve, is considered a common underlying cause of peroneal palsy. Other predisposing factors, such as prolonged postures, traumas of the region or concomitant pathologies (for example diabetes mellitus) contribute to the nerve damage. This study aims to reveal the multiple predisposing factors of peroneal nerve mononeuropathy after substantial weight loss that coexist in psychiatric patients and to make suggestions on their management. METHODS: Nine psychiatric inpatients, major depressive or schizophrenic, with foot drop underwent a complete clinical neurological and neurophysiological examination. All had excessive weight loss, which was completed in a short period of time and had not resulted from a well-balanced low-calorie diet, but was due to their psychiatric illness. Data regarding predisposing factors to peroneal nerve mononeuropathy were gathered, such as habitual leg crossing, squatting or other prolonged postures. RESULTS: The clinical examination and the neurophysiological evaluation in all patients were indicative of a focal lesion of the peroneal nerve at the fibular head. CONCLUSION: Patients with major depressive and schizophrenic disorders gather multiple predisposing factors to peroneal palsy, adequate to classify them at a high risk group. The better focus of the attendant medical and nursing staff on this condition, the early clinical and neurophysiologic evaluation and surgical interventions may enable an improved management and prognosis of these patients.

Dropped head syndrome as prominent clinical feature in MuSK-positive Myasthenia Gravis with thymus hyperplasia.

MuSK-positive Myasthenia Gravis is in most cases clinically characterized by a progressive course with severe oculobulbar involvement or prominent neck, shoulder and respiratory muscle weakness. It is also distinguished from other forms of myastehnia through its lack of germinal centers or lymphocytic infiltrates in the thymic tissue. We present the case of a MuSK-positive female myasthenic patient with over four years slowly progressive weakness of the neck extensor muscles in the presence of thymus hyperplasia and discuss its uncommon and markedly focal clinical and electrophysiological features, as well as the excellent course under medication with pyridostigmine and prednisone, especially after thymectomy.

Urinary frequency in a case of Neuro-Behcet disease involving the brainstem - clinical, electrophysiological and urodynamic features.

Micturitional disturbances are reported in 5-20% of patients with Behcet disease (BD) affecting the central nervous system. However, corresponding data regarding urodynamic and electrophysiological findings are limited. A patient with known BD presented with dysarthria, diplopia and urinary frequency (36 times/day). MRI revealed an extensive lesion involving the lateral and tegmental pons, reaching the pontomedullary junction. Auditory evoked potentials indicated a left-side lesion between superior olivary nucleus and superior colliculus. Blink reflex examination indicated a location caudal to the left trigeminal root. Pudendal nerve somatosensory evoked potentials and transcranial magnetic stimulation of the perineal muscles were slightly affected. Bulbocavernosus reflex latencies were normal. EMG of the bulbocavernosus muscles showed a normal maximal voluntary contraction activity. Urodynamic studies revealed normal urine volume, maximum flow rate and residual volume. After intravenous administration of methylprednisolone diplopia and dysarthria resolved within 3 weeks. Urinary frequency remained almost unchanged for the first 8 weeks, but clearly improved during the following months. We assume that the present case of urinary frequency is the result of vasculitic lesion affecting the pontine micturition inhibitory area on the ground of Neuro-Behcet disease.

Impaired interhemispheric inhibition in amyotrophic lateral sclerosis.

The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) remains unknown. Neurophysiological studies provide evidence of hyperexcitability of the motor cortex or of impairment of inhibitory intrahemispheric modulation of the corticomotoneuron in ALS. In this paper, we used TMS to elicit transcallosal inhibition of the motor cortex in ALS patients in order to investigate whether interhemispheric inhibitory mechanisms subserved by callosal fibres are also disturbed in ALS. Twenty-five patients with ALS and 18 controls were recruited for the study. Resting Motor Threshold (RMT), Silent Period (SP) and interhemispheric inhibition (IHI) were recorded. No significant difference was detected regarding RMT or the duration of SP between patients and controls. IHI was detected in all controls. IHI was totally absent in eight patients, in another eight patients IHI did not reach a significant level and in the remaining nine patients was normal. The degree of IHI was significantly lower in ALS patients than in controls (p = 0.001). In conclusion, altered IHI in ALS patients is in line with the general pattern of reduced corticomotoneuron inhibition, being thus, one of the factors which may lead to chronic overexcitation of pyramidal cells.

A combined urodynamic and electrophysiological study of diabetic cystopathy.

AIMS: The aim of this study is to compare urodynamics and electrophysiological studies in the diagnosis of diabetic cystopathy. MATERIALS AND METHODS: In this prospective study are included twenty six patients with diabetes mellitus diagnosed at least since 5 years; 17 patients with diabetes type II and 9 with type I. They were divided in two groups in respect to lower urinary tract symptoms (LUTS) and signs suggestive of lower urinary tract dysfunction (LUTD) according to the ICS standardization. Patients with LUTS/LUTD were included in Group A and patients without LUTS/LUTD in Group B. Patients underwent different studies: urodynamic, somatosensory evoked potentials (SSEP) of tibial and pudendal nerves, bulbocavernosus reflex (BCR), bulbocavernosus muscles' electromyography and motor evoked potentials after transcranial magnetic stimulation to indirectly investigate bladder's innervation. RESULTS: Abnormal urodynamics were found in 13 patients of group A (92.9%) and in 5 of group B (47.1%). This difference was statistically significant (P=0.009). Abnormally prolonged latency of P40 of tibial SSEP was found in 11 patients of group A (78.6%) and in 4 of group B (33.3%) and this difference was also statistically significant (P=0.04). Differences between the two groups concerning: i) peripheral polyneuropathy; ii) pudendal SSEP, iii) dysfunction of central nervous system and iv) abnormal BCR were not statistically significant. CONCLUSION: The study of tibial SSEP is an easily performed test and it is well correlated to abnormal urodynamics in diabetic patients with and without LUTD/LUTS.

Large and small fiber neuropathy in chronic alcohol-dependent subjects.

The aim of the present study was to evaluate the occurrence of large and small fiber neuropathy among alcohol-dependent subjects and to correlate neuropathy with the pattern of alcohol abuse, age of the subjects, nutritional status, and biochemical parameters. The study sample comprised 98 consecutive alcohol-dependent subjects without signs of malnutrition treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic in an inpatient basis. Polyneuropathy (PN) was graded using the neuropathy symptoms score and neurologic disability score, conduction velocity studies, and quantitative sensory tests. Seventy-seven men and 21 women aged 27-70 years took part in the study. PN was diagnosed in 57 subjects (58.2%). PN of both large and small fibers was found in 25 patients (25.5%); exclusively small fiber neuropathy was observed in 12 (12.2%) and exclusively large fiber neuropathy in 20 patients (20.4%). Neuropathy was significantly correlated with the age of the subjects, duration of alcohol abuse, liver dysfunction, macrocytosis, and blood sugar levels upon admission. PN was significantly more frequent in males than in females. The two groups of exclusively large and exclusively small fiber neuropathy did not differ significantly in any clinical and laboratory parameter. Subclinical neuropathy (stage 1) was observed in 11.2%, which also did not differ significantly in any clinical and laboratory parameter from the stage 2 PN group subjects. Our findings indicate the direct toxic effect of alcohol on peripheral nerve fibers as the main etiologic factor of alcoholic PN. Long-standing hyperglycemia may be another contributing factor. Impaired vitamin B(12) utilization may be also involved.

Iliopsoas: a new electromyographic technique and normal motor unit action potential values.

OBJECTIVE: To describe a reliable technique of needle electrode examination and present the normal values of motor unit action potential (MUAP) parameters in iliopsoas muscle. METHODS: Thirty-one normal subjects underwent quantitative electromyographic (QEMG) examination of the iliopsoas muscle, following an ultrasonographically confirmed technique of needle electrode insertion and sampling. The leg under examination was flexed, abducted and externally rotated at the hip joint and also flexed at the knee joint. A slight flexion at the hip joint was used to uncover iliopsoas from the overlying sartorius. This provides enough space at the inguinal region between the sartorius and the femoral neurovascular bundle. Mean and outlier values of MUAP parameters and polyphasia were calculated. RESULTS: Our technique was easy to perform and secure in sampling iliopsoas. The mean +/- SD values for MUAP duration, amplitude, area, area to amplitude ratio, phases and turns were 11.5 +/- 1.35 ms, 419 +/- 71.5 microV, 633 +/- 142.7 microV ms, 1.57 +/- 0.25, 3.1 +/- 0.32, and 2.9 +/- 0.44, respectively. Lower and upper outlier limits for duration, amplitude, area and area to amplitude ratio were 3.6/20.7 ms, 150/930 microV, 100/1567 microV ms, and 0.35/3.07. Mean polyphasia was 12.6% (range 0-30%). CONCLUSIONS: The suggested EMG technique helped to distinguish iliopsoas from sartorius and at the same time increased the accessibility of its anterior surface. Normal values and outlier limits of the MUAP parameters of iliopsoas have been quantitatively established. SIGNIFICANCE: This new technique and the normal MUAP values might prove helpful for the examination of iliopsoas, important in the assessment of many neuropathic and, especially, myopathic processes.