CMAP Amplitude Research Articles

Lack of effect on ambulation of dalfampridine-ER (4-AP) treatment in adult SMA patients

SMA is a genetically determined motor system disorder that results in muscle weakness, selective motor neuron death, muscle atrophy, and impaired functional mobility. In SMA model systems, long-term treatment with 4-aminopyridine (4-AP) has been shown to improve motor function. To assess tolerability and preliminary efficacy of 4-AP on walking ability, endurance and EMG in adult ambulatory SMA patients, we conducted a double blind, placebo control, crossover pilot study with dalfampridine (4-AP, 10 mg BID). The study is comprised of a short-term (2 weeks) treatment arm with 1-week washout and a long-term (6 weeks) treatment arm with a 2-week washout. The primary outcome measure, for which the study was powered, was the 6 min walk test (6MWT, distance and percent fatigue); secondary outcome measures were the Hammersmith Functional Motor Scale Expanded (HFMSE), Manual Muscle Testing (MMT), Myometry with Hand held Dynamometry, HHD) and Quantitative Gait Analyses. We performed electrophysiology, including CMAP and H-reflex, during the short-term treatment trial. The mean age of the 11 participants enrolled was 37.7 ± 11.9 years; 54.5% were male. Dalfampridine was safe and well tolerated and no patient suffered a serious adverse event related to treatment. We observed no statistically significant positive effects of dalfampridine treatment on our primary functional motor outcome (6MWT distance, fatigue). Dalfampridine had a positive effects on H-reflex and H/M ratio but not on CMAP amplitude. The effect on the H-reflex is of interest, as it suggests dalfampridine may enhance neuronal activity, an effect observed in SMA Drosophila and mouse models at doses (mg/kg) not recommended for clinical use. Larger studies with dalfampridine in SMA patients are needed to confirm our findings, especially in light of studies in other populations showing drug effects in only a subset of patients.

Effects of Chronic and Acute Pulmonary Hyperinflation on Phrenic Nerve Conduction in Patients with COPD

In patients with moderate-to-severe Chronic Obstructive Pulmonary Disorder (COPD), pulmonary hyperinflation can occur at rest and increase during episodes of exacerbation. Among other mechanical constraints, changes in position and configuration of the diaphragm are also induced by increased end-expiratory lung volume. Both descent and flattening of diaphragm might damage the phrenic nerves by stretching their fibers. The study aimed to investigate the phrenic nerve conduction in COPD patients in stable conditions and during COPD exacerbation. In a group of 11 COPD patients without relevant comorbidities in stable conditions and subsequently in another group of 10 COPD patients during in-hospital COPD exacerbation and recovery, measurements of functional respiratory parameters and assessment of phrenic nerves motor conduction by bilateral electric stimulation were performed concurrently. Significant increase in phrenic nerves latency (p < 0.05), but similar amplitude of motor compound muscle action potential (cMAP) was observed in stable COPD patients vs. matched controls (p < 0.05). However, in COPD patients with resting pulmonary hyperinflation as reliably detected by substantial Inspiratory Capacity reduction (<80% pred.), the mean bilateral latency was longer vs. COPD patients without pulmonary hyperinflation (p < 0.02). During COPD exacerbation, in contrast with mean latency, the mean amplitude of phrenic nerves cMAP improved at discharge when compared with in-hospital admission (p < 0.05). In stable COPD patients the velocity of phrenic nerve conduction was impaired mostly in the presence of pulmonary hyperinflation, while during COPD exacerbation where dynamic pulmonary hyperinflation abruptly occurs, the reversible decrease of cMAP amplitude does suggest a temporary, acute axonal damage of phrenic nerves, potentially contributing to diaphragmatic dysfunction in these circumstances.

Analysis of Compound Muscle Action Potential of Median and Ulnar Nerves: Possible Anatomical Correlation

Objective: To analyze of shape, amplitude of CMAP of both median and ulnar in normal population and to analyze the anatomical innervations of small muscles of hand in normal cadavers. Design: Cross sectional study. Settings: outpatient settings and department of anatomy at Alexandria University. Participants: 300 normal adults (82 males and 218 females) and 30 normal adult cadavers. Main outcome measures: Motor conduction study of both median and ulnar nerves for the included normal subjects. Surface recording of CMAP from thenar and hypothenar muscles respectively with analysis of the shape of the waveform and amplitude. The nerve supply of both thenar and hypothenar muscles were dissected for the included normal cadavers. The main nerve trunk (median or ulnar), the number of branches, their sizes and their sites of entering into the muscles were recorded. Results: The mean age of the studied population was 37.86 ± 8.83 (age range 19-69). The mean amplitude of the median nerve was significantly higher than that of the ulnar nerve (11.785 ± 5.0, 10.45 ± 2.96 respectively, p=0.0001). The mean distal latency of median nerve was significantly higher than that of ulnar nerve (3.38 ± 0.41 and 2.698 ± 0.40 respectively, p=0.0001). The median nerve had mostly dome shaped CMAP rather than double peaked CMAP with significant difference (p=0.0001), while the shape of CMAP of the ulnar nerve was more frequently double peaked rather than dome shaped with significant difference (p=0.0001). The mean distal latency of the median nerve was significantly longer in those with dome shaped CMAP rather than those with double peak CMAP (p=0.002). Similarly, the mean distal latency of the ulnar nerve was significantly longer in those with dome shaped CMAP compared with those with double peak CMAP (p=0.0001). There were no statistical significant differences between the amplitude of dome shaped CMAP and the double peaked CMAP in either the median or the ulnar nerve. The anatomical results showed that abductor pollicis brevis supplied by the median nerve in 90% of specimens, and by both nerves in 10%. The abductor digiti minimi brevis supplied by the deep branch of the ulnar nerve in 90% and by superficial branch of the ulnar nerve in 10%. There was a connection between the median and ulnar nerves in 50% of specimens. Conclusion: The configuration of the CMAP of the median nerve is mostly dome, whereas that of the ulnar is mostly double peaked. Variability in the pattern of innervations of the small muscle of the hand could be a possible etiological factor.

Diaphragmatic CMAP amplitude from phrenic nerve stimulation predicts functional decline in ALS.

To evaluate phrenic nerve motor amplitude (PhrenicAmp) as an independent predictor of functional decline in amyotrophic lateral sclerosis (ALS). We also assessed both PhrenicAmp and forced vital capacity (FVC) as predictors of functional loss in patients with bulbar dysfunction. We included consecutive ALS patients with PhrenicAmp and FVC at baseline. Participants were evaluated with the revised ALS Functional Rating Scale (ALSFRS-R) at inclusion and at, at least, one subsequent follow-up visit. The outcome measure of functional decline was the percentage reduction in ALSFRS-R from baseline. Bulbar dysfunction was defined by the presence of any relevant symptom on the ALSFRS-R bulbar sub-score. Correlations and mixed-effects regressions were used to study the relationship between functional decline and both PhrenicAmp and FVC baseline evaluations. A total of 249 ALS patients were included; 64.2% of these had bulbar dysfunction. At inclusion, significant correlations were found between PhrenicAmp and FVC (p < 0.001), as well as between each respiratory measure and ALSFRS-R (all p < 0.001). The functional decline at first (median 3months) and second (median 6months) follow-up visits was significantly correlated with baseline values of both respiratory evaluations (all p < 0.01) in the entire ALS population, but only with baseline PhrenicAmp (all p < 0.05) in bulbar dysfunction cases. Regression analysis revealed that PhrenicAmp (all p < 0.05), but not FVC, was a significant independent predictor of functional decline in ALS patients and in those with bulbar dysfunction. Baseline PhrenicAmp is an independent predictor of functional decline in ALS, whether or not bulbar dysfunction is present.

Clinical duration of action of different botulinum toxin types in humans

The Botulinum NeuroToxin (BoNT) comprises several serotypes with distinct properties, mechanisms of action, sensitivity and duration of effect in different species. The serotype A (BoNT/A) is the prevalent neurotoxin applied in human's disease. In this paper we present an overview of the current knowledge regarding the duration of effect and the neuromuscular sprouting of different BoNT serotypes in humans. Then, we report the original results of a study in healthy subjects treated with BoNT/A, B, C and F using different neurophysiological techniques. Twelve healthy volunteers (7 men, 5 women) are treated with BoNT/A, B, C and F or placebo in Abductor digiti minimi (ADM) muscle of the hand. Before and after injections, an extensive neurophysiological study is performed with the CMAP amplitude variation, Multi-Motor Unit Action Potentials (MUAPs) analysis, the Turns/Amplitude ratio of interference pattern (IP) and determination of jitter and Fiber Density (FD) at single-fiber electromyography (SFEMG), at week 2 (w2), 4 (w4), 6 (w6) and 8 (w8). A maximal neuromuscular block is obtained at w2 for all the serotypes. Afterwards, the CMAP trend appear similar for BoNT/A, B, and C while, BoNT/F shows a faster recover. Multi-MUAPs analysis and IP detect mild changes at w2 for all serotypes, except for BoNT/F that shows a greater change since w4. SFEMG have minimal changes in FD while, Jitter increase at w2 with a slower decrease over the time for all BoNTs. In conclusion, BoNT/F has earlier sprouting and complete recovery at w8. Other serotypes present a slower and similar profile. The EMG appear useful to study the functional recovery in humans, and these results should provide new evidence for assessing different serotypes. These findings improve our knowledge regarding the methods to evaluate duration of effects and dose equivalents in different serotypes, that in the future could change the clinicians strategy for disease-tailored BoNT therapies.

Opposing neurological responses to autologous peripheral blood stem cell transplantation in two patients with POEMS syndrome

AbstractPurposeWe present our findings in two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, one with and one without optic disc edema (ODE), after autologous peripheral blood stem cell transplantation.MethodBoth patients underwent an autologous peripheral blood stem cell transplantation. The peripapillary retinal thickness (pRT) was determined by spectral‐domain optical coherence tomography (SD‐OCT) to assess the degree of optic disc edema. The SD‐OCT examinations consisted of a 3.45 mm diameter circular scan centered on the optic disc. The pRT thickness was measured at the baseline and at 12 months after beginning the treatment. The serum level of VEGF was determined by enzyme‐linked immunosorbent assays (ELISAs) at the baseline and at 12 months after beginning the treatment. Neurological examinations, e.g., grip strength and compound muscle action potentials (cMAPs) of the upper limb, were also measured at the baseline and 12 months after the transplantation.ResultThe pRT in the case without ODE was 310 μm at the baseline. At 12 months after the transplantation, the serum levels of VEGF decreased from 7050 to 511 pg/ml, the grip strength increased from 13 kg to 19 kg, and the cMAP amplitudes increased from 4.31 mV to 7.02 mV. On the other hand, the pRT in the case with severe ODE was 1167 μm at the baseline, and it did not change after the transplantation. The serum levels of VEGF decreased from 9060 pg/ml to 99 pg/ml after the transplantation, the grip strength decreased from 32 kg to 29 kg, and the amplitudes of the cMAP decreased from 2.16 mV to 0.32 mV at 12 months after the transplantation.ConclusionThese results suggest that the baseline degree of ODE before an autologous peripheral blood stem cell transplantation might be a predictive marker on the effectiveness of the transplantation on patients with the POEMS syndrome. However, further studies with a larger sample size are needed.Keywords: POEMS syndrome, vascular endothelial growth factor (VEGF), peripapillary retinal thickness (pRT), autologous peripheral blood stem cell transplantation, predictive marker

Repeater F-waves in amyotrophic lateral sclerosis: Electrophysiologic indicators of upper or lower motor neuron involvement?

ObjectiveTo extract insight about the mechanism of repeater F-waves (Frep) by exploring their correlation with electrophysiologic markers of upper and lower motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). MethodsThe correlations of Frep parameters with clinical scores and the results of neurophysiological index (NI), MScanfit MUNE, F/M amplitude ratio (F/M%), single and paired-pulse transcranial magnetic stimulation (TMS), and triple stimulation technique (TST) studies, recorded from abductor digiti minimi (ADM) and abductor pollicis brevis (APB) muscles of 35 patients with ALS were investigated. ResultsFrep parameters were correlated with NI and MScanfit MUNE in ADM muscle and F/M% in both muscles. None of the Frep parameters were correlated with clinical scores or TST and TMS measures. While the CMAP amplitudes were similar in the two recording muscles, there was a more pronounced decrease of F-wave persistence in APB, probably heralding the subsequent split hand phenomenon. ConclusionOur findings suggest that the presence and density of Freps are primarily related to the degree of lower motor neuron loss and show no correlation with any of the relatively extensive set of parameters for upper motor neuron dysfunction. SignificanceFreps are primarily related to lower motor neuron loss in ALS.

Isoquercitrin promotes peripheral nerve regeneration through inhibiting oxidative stress following sciatic crush injury in mice.

Oxidative stress has been recognized to play a crucial role in the pathogenesis of peripheral nerve injury. Isoquercitrin (quercetin-3-glucoside) is a flavonoid that exhibited many biological activities, including anti-oxidative effect. However, it is unclear whether isoquercitrin has protective effects on peripheral nerve injury. Mice treated by isoquercitrin were used as a case group, and mice injected with saline was the control group. Sciatic behavioral function was assessed using SFI and CMAPs were measured by electrophysiology. Schwann cells proliferation and migration were tested using EdU staining and Transwell migration chambers respectively. The expression of oxidative stress related factors were detected by qRT-PCR and Western blotting. In present study, our results demonstrated that isoquercitrin (20 mg/kg/day) treatment achieved significantly higher SFI and higher amplitude of CMAP, promoted the nerve regeneration and remyelination, increased the production of GAP43, NF200, MAG and PMP22, alleviated target muscle atrophy and autophagy, and suppressed the expression of ATG7, PINK1 and Beclin1 in soleus muscles after sciatic nerve crush. In vitro studies found that isoquercitrin promoted the axonal regeneration of DRGs neurons, the proliferation and migration of Schwann cells, and the expression of proliferating cell nuclear antigen (PCNA) in Schwann cells. The administration of isoquercitrin at 40 and 320 µM showed a dose dependent, and high doses of isoquercitrin (160 and 320 µM) showed better performance in promoting axonal regeneration of DRGs neurons, and the proliferation and migration of Schwann cells than low dose of isoquercitrin (40 µM). Furthermore, isoquercitrin significantly inhibited oxidative stress through reducing the production of Nox4 and Duox1, and promoting the expression of Nrf2 and SOD2 in soleus muscles after sciatic nerve crush. Isoquercitrin may promote motor functional recovery and nerve regeneration following peripheral nerve injury though inhibition of oxidative stress, which highlighted the therapeutic values of isoquercitrin as a neuroprotective drug for peripheral nerve repair applications.

Evaluation of surgical outcomes of obstetric brachial plexus birth injury: clinical and electrophysiological study

BackgroundObstetric brachial plexus birth injury (OBPBI) is a relatively common form of birth injury that might lead to a weighty physical disability. Early microsurgical intervention for properly selected patients will result in maximal functional benefit that couldn’t be otherwise obtained. However, the outcomes of different microsurgical techniques need to be further evaluated and compared.AimTo evaluate the outcomes of different microsurgical techniques performed in patients with OBPBI.Patients & MethodsTwenty-eight patients with OBPBI meeting the criteria for surgical intervention were included in the study. Preoperative and one year postoperative clinical and electrophysiological assessments were done.ResultsThirteen (46.4%) of the studied patients were males and 15 (53.6%) were females. The mean age of patients in the study was 8.64 months ± 4.40; ranging between (3.0 – 16.0 months),7 patients had Horner syndrome.C5 and C6+/-C7 roots affection was the most frequent lesion ,patients who underwent neurotization recovered earlier than patients who underwent nerve grafting ,on the other hand nerve grafting resulted in more significant postoperative improvement after a 12 months follow up period.ConclusionsThe current study provided additional evidence that the earlier the surgical intervention in OBPBI, the better the outcomes. Neurotization results in earlier functional recovery in patients with OBPBI than nerve grafting reconstructive techniques. On the other hand, nerve grafting was superior to neurotization regarding the degree of improvement. Postoperative electrophysiological follow-up can be done using the CMAP amplitude and AUC percentages reflecting the percentage of viable axons.

The impairment of excitation-contraction coupling in icu-acquired weakness

The aim of this study is to elucidate the impairment of excitation-contraction (E-C) coupling in ICU-acquired weakness (ICUAW) using a unique electrophysiologic method in patients received the intensive care in ICU. We examined 9 patients with ICUAW and 10 normal controls. We performed successive recordings of electrophysiological tests after ICU admission. First, CMAPs of abductor hallucis muscle (AH) and sural SNAPs were recorded using a conventional method. In addition, the tibial nerve was stimulated at the popliteal fossa using a supramaximal rectangular pulse to record CMAPs from soleus muscle (SOL). Simultaneously, movement-related potential (MRP) was recorded using an accelerometer (SV1101) taped at the base of hallux and calculated E-C coupling time (ECCT) based on the latency differences between soleus CMAP and MRP. MRPs as well as CMAP amplitudes of AH and SOL were significantly smaller in patients than in controls. Also, ECCTs and CMAP durations of AH were significantly longer in patients than in controls. Nine patients were subdivided into 6 patients with critical illness myopathy (CIM) and 3 patients with critical illness polyneuropathy (CIP) based on the sural SNAP abnormality. All CIM patients consistently showed significantly prolonged ECCTs, and 5 CIM patients showed significantly decreased MRPs. These abnormalities occurred within several days after ICU admission. The E-C coupling may be impaired in the very early stages of CIM. Noninvasive measurement of MRP and ECCT is easy to perform, and may be an useful indicator of muscle involvement in the early stages of ICUAW.

Glycemic Control and Clinico-Electrophysiological Severity of Diabetic Polyneuropathy

Background: Diabetic polyneuropathy (DPN) has a significant positive correlation with poor glycemic&#x0D; control (HbA1c ≥7%). The clinical, biochemical and electrophysiological parameters of DPN in Bangladeshi citizens have not yet been explored elaborately&#x0D; Objective: The purpose of the study was to detect and categorize status of glycemic control of Bangladeshi people and to analyze its impact on clinical severity of DPN using Toronto Clinical Scoring System (TCSS) and electrophysiological severity by modified Michigan diabetic neuropathy score (MDNS).&#x0D; Methodology: This observational study was carried out on diabetic patients having probable DPN by purposive sampling, attending Neurology OPD of Dhaka Medical College Hospital, Dhaka, Bangladesh and Bangladesh Institute of Research &amp; Rehabilitation in Diabetes, Endocrine &amp; Metabolic Disorder (BIRDEM) Hospital, Dhaka, Bangladesh from July 2014 to June 2016. Clinical parameters were recorded and DPN was graded as “no neuropathy”, “mild”, “moderate” and “severe” neuropathy by the Toronto Clinical Scoring System (TCSS). A standard nerve conduction study was performed on each patient and electrophysiological grading according to modified Michigan diabetic neuropathy score (MDNS) was done. Diabetic status of patients was classified into “controlled” (HbA1c &lt;7.0%) and “uncontrolled” (HbA1c ≥7.0%) groups and HbA1c level and the clinical &amp; electrophysiological severity scores were compared and were analyzed.&#x0D; Results: Mean age of the patients was 57.2±9.37 years. 51.0% cases were males and 49% cases were females. The mean HbA1c in the study population was 7.6±0.94% and 56.0% patients had HbA1c≥ 7% .Motor nerve conduction studies revealed that both CMAP amplitudes and MNCV in the ulnar, peroneal and tibial nerves were reduced significantly in patients of uncontrolled (HbA1c≥7%) DM (p&lt;0.001). Sensory nerve conduction studies revealed significant reduction in SNAP amplitudes of median and ulnar sensory and sural nerves in the uncontrolled group (p&lt;0.001). Electrophysiologically, 65.43% patients had mixed sensory-motor neuropathy (p&lt;0.00001). Clinically severe DPN patients were higher (45.2%) within the uncontrolled (HbA1C ≥7%) group (p&lt;0.00001). Similarly, severity in electrophysiological grading was more in patients with uncontrolled DM (48.8%) (p&lt;0.00001).&#x0D; Conclusions: Neuropathic severity, either clinically or electrophysiologically, was associated with higher values of HbA1c.&#x0D; Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 177-184

Role of Electroneurography as a Prognostic Indicator for Bell’s Palsy Patients

The aim of this study was to evaluate the role of electroneurography test in the prediction of outcome of patients with Bell's palsy(BP).Methods: This Cohort study was carried out in the electrophysiological unit of Rheumatology and Rehabilitation department, at Zagazig University Hospitals on 30 adult patients with Bell's palsy. All 30 subjects were assessed clinically by sunnybrook facial nerve grading score (SBS) and electrophysiologicaly by electroneurography (ENoG) test first evaluation was done within 7th-10th day from onset, the second evaluation at 20 days and the follow up visit was at 30th to assess the clinical grading system (SBS).Results: There was statistically highly significant increase in SBS with increase follow up time. There was statistically highly significant decrease in CMAP amplitude more than 50% difference from healthy side in both frontalis and mentalis when comparing 1st with 2nd evaluation. At one month, 20 patients (66.7%) had good recovery, while 10 patients (33.3%) had poor recovery according to the Sunnybrook scale. Multiple logistic regression analysis showed that the most significant predictive indicator of BP recovery was ENoG degeneration index. The receiver operating characteristics (ROC) curves showed ENoG degeneration index of 74.6% as a critical cutoff value of non-recovery, with the sensitivity 95% and specificity 90%.Conclusion: This study showed that ENoG degeneration index has an important role as a significant prognostic indicator for predicting of recovery of Bell’s palsy. Sunnybrook score can be used as an additional tool in predicting non-recovery in the clinical evaluation

P63-S Insidious neuromuscular deterioration in polio survivors demonstrated by CMAP scan analysis

Background This study aimed to explore the subtle motor unit(MU) changes in asymptomatic muscles of poliomyelitis survivors (PS) using CMAP Scan analysis. Material and method Nineteen PS cases and 21 controls were recruited. CMAP Scan recordings were obtained from asymptomatic thenar and hypothenar muscles. CMAP Scan parameters indicating nerve excitability [stimulus intensities producing 50%, 95% and 5% of the CMAP amplitude (SI%5, SI%50, SI%95), absolute range width (ARW) (SI%95-SI%5), relative width (RW) (SI95 − SI5)/SI5], all step parameters and D50 which reflect the MU motor unit loss and reinnervation were analyzed. The new motor unit number estimation (MUNE) method, MscanFit was also calculated. Results There were no significant differences in ages, maximum CMAP amplitudes and MScanFit MUNE between the groups. PS group median and ulnar D50 values (46.76 ± 10.98, 46.19 ± 12.42 respectively) were lower than control group (37.21 ± 17.37, 36.44 ± 11.99) (p Conclusions CMAP Scan can show reduced axonal excitability and reveal insidious MU loss and reinnervation in presumably unaffected muscles of PS, regardless of the decrease in CMAP amplitudes or a significant reduction in MUNE values.

P22-T The correlation between clinical, electrodiagnostic findings and prodromal symptoms in patients with Bell’s palsy

Objective The aim of this study was to investigate what prodromal symptoms are occurring and associated with occurrence and clinical severity of Bell’s palsy using House-Brackmann facial nerve grading system (HBS). An additional aim was to evaluate whether the result of electrodiagnostic examination reflects HBS and what prodromal symptoms are related with poor outcome. Method The investigation included 51 patients with Bell’s palsy. To clinically assess the severity of Bell’s palsy, HBS was used. To evaluate the facial nerve damage, the CMAP amplitude were measured and the percent amplitude reduction was calculated by comparing the affected side with the healthy side. A self-reported questionnaire was conducted about prodromal sympto. Results The most common prodromal symptoms were postauricular pain (66.7%), tongue sensory decline (41.1%), blepharospasm (33.3%) in order of frequency. All of these symptoms were significantly associated with onset of Bell’s palsy and the most powerful risk factor was postauricular pain (p 0.001). A CMAP difference of more than 70% were significantly associated with postauricular pain, tongue sensory decline and blepharospasm (p Conclusion This study indicates that patients with Bell’s palsy can have a variety of prodromal symptoms including systemic, sensory, opthalmic, auricular symptoThrough this, can predict the clinical, electrodiagnostic prognosis and postauricular pain was the most powerful risk factor on occurrence of Bell’s palsy.

P41-T Distal nerve excitability block in severe paraproteinemic demyelinating neuropathy

We present a rare case of a 55-year-old male who came to our attention due to the pronounced degree of injury to the peripheral nerves and a decrease in the excitability of their distal segments. Patient had a predominantly distal, chronic (5 years duration), slowly progressive, symmetric, predominantly sensory impairment (hypoaesthesia with hyperpathia) with sensory ataxia and mild weakness. Serum immunoelectrophoresis revealed an IgM-kappa monoclonal protein. CSF protein level was elevated at 3.5 g/L. NCS demonstrated a pronounced demyelinating sensorimotor peripheral neuropathy. Median, ulnar and sural sensory responses were not registered. Sympathetic skin response latencies were 1.8 ms (palm) and 2.3 ms (sole). Blink reflex latencies were prolonged up to 64 ms (R1) and 80 ms (R2). Motor NCS showed a pronounced prolongation of the distal CMAP latencies and conduction velocities decrease: median nerve – 61.0 ms and 9.0 m/s, ulnar – 44.0 ms and 10.0 m/s, peroneal – 58.5 ms and 9 m/s, tibial – 74.0 ms and 10 m/s respectively, femoral – 21.5 ms, facial – 34.2 Terminal latency indexes were smaller than 0.25. CMAP amplitudes was significantly reduced. Attention was drawn to the fact that the proximal CMAP area was greater than distal one. The reduction in CMAP area after distal simulation, as compared to proximal stimulation, was calculated as: (proximal CMAP – distal CMAP) × 100%/proximal CMAP. We called this diagnostic criterion the distal nerve excitability block. This criterion for the tibial and the median nerves was 85.5% and 58.3%, respectively.

O-29 CMAP scan and MScanFit MUNE during Wallerian degeneration after nerve transactions

Background Wallerian degeneration (WD) includes complex physiological changes in the distal portion of the axon which follow a severe injury. The aim of this study was to advance our earlier observations with MUNE studies during early stages of WD by evaluating the CMAP Scan curve and MScanFit MUNE in the same period. Materials and methods Twelve patients with acute nerve transections at the forearm (7 median, 5 ulnar) were recruited. First electrophysiological studies, performed at 9–72 h after the insult, were followed by serial studies at 1–2 day intervals until CMAP amplitudes reached at zero. At each session, CMAP Scan curves were recorded, their quantitative parameters and the new MUNE method, MScanFit, were calculated. The results were grouped according to the recording time after injury (before and after the 48th hour). They were compared with those of healthy controls and amyotrophic lateral sclerosis (ALS) patients. Results Excitability of axons was reduced in patients with transected nerves, as compared controls and ALS patients, irrespective of the recording time. In most of the patients, MUNE values decreased during the follow-up as a result of relatively more pronounced reduction of CMAP amplitudes as compared to mean unit sizes. While steps occurred in 8 patients, D50 remained unchanged during the follow-up. Conclusions These suggest higher ability of MScanFit, as compared to other MUNE methods, in discriminating the changes caused by functional instability of neuromuscular junction. Occasional steps in the early WD deserve some arguments on their possible mechanisms.

Split-Hand Syndrome in Amyotrophic Lateral Sclerosis: Differences in Dysfunction of the FDI and ADM Spinal Motoneurons.

The F-wave test allows for the non-invasive assessment of spinal motoneuron excitability. We investigated the difference in spinal motoneuron dysfunction between the first dorsal interosseous (FDI) and abductor digit minimi (ADM) muscles by investigating F-waves and to assess the contribution of spinal mechanisms to split-hand syndrome in patients with amyotrophic lateral sclerosis (ALS). Sixty-five consecutive ALS patients and twenty age- and gender-matched healthy controls (HCs) were enrolled. Motor nerve conduction studies and F-waves were performed bilaterally on median and ulnar nerves in all subjects. HCs revealed prominently longer F-wave latencies, lower chronodispersion, mean F-wave amplitude, and mean and maximal F/M amplitude ratio (P < 0.001) in the FDI compared to the ADM. However, no significant differences in almost all F-wave parameters between the FDI and ADM were observed in ALS patients with affected hands except the minimal and mean F-wave latency. These data suggest that excitability is greatly changed in the spinal motoneurons innervating the FDI. Furthermore, the mean F-wave amplitude (r = 0.454, P = 0.002) of the FDI was significantly correlated with the FDI/ADM CMAP amplitude ratio in ALS patients with affected hands but not of the ADM. Our findings suggested that the dysfunction of spinal motoneurons between the FDI and ADM was different in ALS, and spinal motoneuron dysfunction was associated with development of the split-hand phenomenon.

The split hand in amyotrophic lateral sclerosis: a possible role for the neuromuscular junction

Objective: We investigated the neuromuscular junction as a possible factor leading to the split-hand phenomenon in amyotrophic lateral sclerosis (ALS). Methods: Thenar and hypothenar muscles were studied in 91 healthy control subjects and 39 ALS patients matched for age and gender. We investigated neuromuscular transmission using repetitive nerve stimulation (RNS) at 2 Hz in ulnar and median nerves in the right hand, recording from abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. In the ALS patients, these muscles were clinically and electrophysiologically normal, without neurogenic change. Sixteen ALS patients were re-studied 6 months later. The CMAP amplitude and area percent decrement in RNS was analyzed in each muscle. Results: In controls, the decrement to RNS was significantly greater in APB > FDI > ADM (p < 0.001). In older subjects, the CMAP amplitude decreased with age, but the decrement was increased only in ADM. At the baseline study the CMAP amplitude was similar in all three muscles in control and ALS patients. In the ALS patients, the decrement during RNS was greater in APB (p = 0.014) and FDI (p < 0.001) than in controls, but there was no difference for ADM (0.68). In the 16 ALS patients, reevaluated 6 months later CMAP amplitude and area percent decrement changed significantly in all three muscles, but the reduction in CMAP amplitude was much greater in APB and FDI than in ADM. Conclusions: These physiological differences in distal motor nerve function in normal small hand muscles may influence vulnerability to neurogenic change in ALS. These findings support a role for a peripheral factor in the split-hand phenomenon.

Abstract 36: Viability and Signal Transduction with the Composite Regenerative Peripheral Nerve Interface (C-RPNI)

PURPOSE: There have been many advancements in the field of neuroprosthetics for functional restoration following limb loss. However, devices that provide prosthetic users with intuitive, simultaneous motor control and somatosensory feedback have not yet been realized. Critical to the evolution of this ideal bioprosthetic device is the development of a reliable, biologic human-machine interface that facilitates transmission of both efferent motor signals for device control, and afferent somatosensory information. The Composite Regenerative Peripheral Nerve Interface (C-RPNI) is a novel biologic interface that demonstrates promise in this role. The C-RPNI is a surgical construct composed of a transected, mixed peripheral nerve implanted between a composite free graft consisting of de-epithelialized glaborous skin and skeletal muscle. The purpose of the present study was to investigate the viability and bidirectional signal transduction capabilities of the C-RPNI. METHODS: C-RPNIs were surgically implanted on the end of transected common peroneal nerves of thirty F344 rats using de-epithelialized dermal grafts harvested from glaborous skin of isogenic donor rat hindpaws and free skeletal muscle grafts from the animal’s contralateral limb. Thirty animals underwent endpoint testing at three months (n=15) and at six months (n=15). Electrophysiologic testing was performed to determine both the in vivo efferent and afferent signal transduction capabilities of C-RPNIs following electrical stimulation. C-RPNI constructs were also harvested for histologic evaluation at both three- and six-month study endpoints. RESULTS: C-RPNI constructs remained viable over the study period with regeneration and revascularization evident on histologic analysis. At both three and six months, electrical stimulation of proximal peroneal nerve evoked efferent signals (CMAPs) and muscle contractions that were measured from the free muscle graft component of the C-RPNI. The average CMAP amplitude recorded from the muscle was 6.3 ± 1.4 mV at three months and 6.1 ± 1.6 mV at six months. The average conduction velocity was 11.0 ± 2.7 m/sec at three months and 12.0 ± 2.0m/sec at six months. Electrical stimulation of the dermal side of the C-RPNI evoked afferent signals (CSNAPs) in the proximal peroneal nerve at both three and sixth months. The average peak-to-peak CSNAP amplitude was 391.6 ± 145.0 µV at three months and 267.1 ± 143.8 µV at six months. The average conduction velocity with an average conduction velocity was 11.6 ± 3.0 m/sec at three months and 9.6 ± 2.4 m/sec at six months. CONCLUSIONS: C-RPNI constructs remained viable with preserved innervation for six months following implantation. Recorded efferent motor signals and evoked afferent signals remained robust over time. The C-RPNI facilitates bidirectional signal transduction of both efferent motor signals and afferent sensory signals. This confirmation of bidirectional signal transduction in the C-RPNI validates the potential role of the C-RPNI in human-machine interfacing.

Abstract 112: Vegf-receptor Inhibitor Impedes Macrophage Function At The End Target Muscle After Nerve Injury

PURPOSE: Recovery in peripheral nerve injuries is limited by the critical time point beyond which muscle denervation is irreversible. A major component of functional recovery is muscle reinnervation, which depends on terminal Schwann cells (tSCs) at the neuromuscular junction (NMJ). The hallmark feature of the tSC response to injury is cytoplasmic process elongation that guides axon growth. In response to injury, macrophages secrete Vascular Endothelial Growth Factor (VEGF) which may induce angiogenesis to support tSC process extension. We hypothesize that VEGF inhibition impedes tSC function at the NMJ, which in turn will impede reinnervation of the end target muscle. METHODS: Sciatic nerve transection with immediate repair was performed in C57BL/6 mice. To evaluate whether VEGF inhibition impedes end target muscle reinnervation, Cabozantinib, a VEGF Receptor-2 (VEGFR-2) inhibitor, was administered to mice via oral gavage for seven days following nerve injury to suppress VEGF secretion. For the control group, saline was given for the same duration. Mice were sacrificed on 14, 21, 28 and 42 days after injury (n = 3 per time point), and the leg muscles were harvested. Immunohistochemical stains for NF200 (axon marker), S100 (Schwann cell marker), VEGF, CD68 (macrophage marker), and bungarotoxin (BTX, motor endplate marker) were used on extensor digitorum longus and tibialis anterior muscle sections. Functional innervation was determined by two methods: 1) immunohistochemical staining with NF-200 for axonal reinnervation into motor endplates marked by BTX in whole muscle mounts and 2) electrophysiological stimulation of the sciatic nerve to test tibialis anterior CMAP amplitude. RESULTS (PRELIMINARY): After nerve injury, extracellular and intracellular VEGF expression increased significantly at postoperative day (POD) 3 compared to non-injured muscle, and then peaked at POD 12. At two weeks (POD14) after injury, motor end plates were 41.2% fully innervated and 37.1% partially innervated in the control group, while the Cabozantinib group had only 7.5% fully innervated and 4.3% partially innervated motor end plates. VEGF expression at POD 14 was greatly different between the two groups (11.48 percent pixels vs 3.49 percent pixels, p <0.001). By POD 21, however, 97% of the motor end plates in the Control group and 93.2% in the Cabozantinib group had reached full innervation. Axonal sprouting between motor end plates was more prevalent in the control group (46.9% vs 18.5%). VEGF expression decreased in both groups by POD 21 and POD 28, while CD68 positive cells co-stained with VEGF remained significantly higher in the control group at POD 28. Electrophysiological stimulation at 10 Hz showed significant differences at POD 21 (t test, mean difference 2.151 mV, p = 0.047) but no differences at POD 42 (t test -0.822, p = 421). CONCLUSIONS: Drug induced VEGF inhibition had a marked but temporary effect on the functional recovery of denervated muscle after nerve injury. Although the differences between the two experimental groups became nonsignificant over time, the effects seen at the neuromuscular junction of the target muscles highlighted the unrecognized role of VEGF in macrophages on the functional recovery after nerve injury.