Understanding Neuropathy Features in the Context of Nitrous Oxide Abuse: A Combined Electrophysiological and Metabolic Approach.

BACKGROUND: The incidence of neurological complications associated with nitrous oxide (N2O) abuse, including N2O-induced myelopathy and neuropathy, has risen in the past decade. N2O-induced neuropathy often presents as a subacute axonal pathology; however, demyelinating patterns mimicking Guillain-Barré syndrome have also been observed. This study explores the metabolic pathophysiology of N2O-induced neuropathy, focusing on the alteration in metabolism to provide a deeper understanding of the biochemical pathways influencing the diverse electrophysiological patterns observed. METHODS: We conducted a combined metabolic and electrophysiological exploration of 35 patients who underwent electromyographic exams at our referral center over a three-year period for sensorimotor symptoms linked to recreational N2O use. We collected demographic, clinical, radiological, electrophysiological, and biological data. Patients were categorized into axonal or demyelinating groups based on their electrophysiological patterns, and metabolic parameters were compared. RESULTS: Our cohort predominantly exhibited a length-dependent sensorimotor axonal symmetrical neuropathy affecting the lower limbs. Among the patients, 40% met the demyelinating criteria, with four patients exhibiting conduction blocks. The demyelinating group had a significantly higher peripheral neuropathy disability (PND) score at diagnosis. Elevated homocysteine and methylmalonic acid (MMA) levels were noted in all patients, but these were lower in the demyelinating group. CONCLUSIONS: This study highlights the diverse electrophysiological manifestations of N2O-induced neuropathy and underscores the potential role of metabolic parameters as biomarkers to understand its pathophysiology. Lower hyperhomocysteinemia and MMA levels were observed in demyelinating patterns. In this study, we did not observe further improvement, but it is well-known that demyelinating features have a better prognosis related to the further remyelination. These findings contribute to a better understanding of N2O-related neuropathic damage and could guide future therapeutic interventions based on biochemical-neurophysiological stratifications.

Factors associated with a maternal lower-limb neurological deficit after vaginal delivery.

INTRODUCTION: The etiology of lower-limb neurological deficit after vaginal delivery remains poorly understood. The objective herein was to identify factors associated with this maternal nerve injury after vaginal delivery. MATERIAL AND METHODS: A single-center, case-control (matching 1:4) study. Cases were women with a lower-limb neurological deficit that appeared immediately after vaginal delivery. Controls were randomly selected women who gave birth vaginally during the same period, without any deficit. Finally, to assess the rates of factors associated with these deficits, we studied them using a randomly selected 5% sample of the population with vaginal deliveries. RESULTS: During the 30-month study period, 31 cases were identified among 10 333 women who gave birth vaginally (0.3%, 95% CI 0.20-0.43); 124 controls were also included. After logistic regression, the presence of a neurological deficit after delivery was associated with second-stage labor duration (per hour odds ratio [OR] 3.67, 95% CI 2.09-6.44; OR per standard deviation increase 2.73, 95% CI 1.75-4.25, p < 0.001) and instrumental delivery (OR = 3.24, 95% CI 1.29-8.14, p = 0.012), with no interaction effect (p = 0.56). Extrapolation of these factors to a 5% sample of the overall population of women with vaginal births showed that the rate of these deficits would be very low for women with second-stage labor lasting up to 90 min without instrumental delivery (0.05%) but increased to 1.52% when these factors were combined (OR 33.1, 95% CI 9.4-116.9). CONCLUSIONS: Following vaginal delivery, the onset of a neurological deficit is principally associated with the duration of second-stage labor and instrumental delivery.

Young infants with PMP22 duplication can have minor nerve conduction study abnormalities.

Charcot-Marie-Tooth disease type 1A (CMT1A) is related to PMP22 gene duplication. It is characterized at electrodiagnostic testing (EDX) by diffuse homogeneous signs of demyelination, such as velocity slowing and prolonged distal latencies. These abnormalities are less pronounced in infants under two years old, and the possibility of normal nerve conduction studies (NCS) in infants with CMT1A under one year of age has been questioned. We report three infants who displayed normal or almost normal NCS. EDX abnormalities in CMT1A patients may therefore appear late during development. This may affect early EDX diagnosis in infants and should be considered for upcoming clinical trials.

Neuralgic amyotrophy triggered by hepatitis E virus: a particular phenotype.

The neuralgic amyotrophy may be of difficult diagnosis, due to phenotypic variability, with different initial presentations (upper plexus multiple mononeuropathy, lumbosacral involvement, distal reached, phrenic involvement). To date, there is little guidance on these patients' therapeutic management, especially those for which neuralgic amyotrophy is triggered by hepatitis E virus (HEV-NA). The study aims to identify specific features that characterize patients bearing the neuralgic amyotrophy triggered by HEV. We first describe a new case report of HEV-neuralgic amyotrophy, with delayed diaphragmatic reach. Then, the literature was searched for reports of HEV-NA (n = 39), and neuralgic amyotrophy with phrenic paresis (n = 42) from 1999 to June 2016. Relevant data were retrieved, analyzed and compared with the parameters of idiopathic neuralgic amyotrophy (n = 199) of the largest cohort, described by Van Alfen and Van Engelen in 2006. Compared to the published cohort, HEV-NA patients were more likely to be men (M/F 34/5 vs. 136/63, p = 0.017), with more frequent bilateral symptoms (86.8% cases vs. 28.5%, p < 0.0001) as well as phrenic paresis (18.0 vs. 6.6%, p = 0.028). The clinical improvement is poor, with 15.6% of cases with remission only. A particular phenotype characteristic of the HEV-induced neuralgic amyotrophy has arisen. Our findings call for action in validating the above-mentioned features that illustrate the HEV-NA cases as an early diagnosis would prevent complications, especially the phrenic damage often associated with a worse functional outcome.

Task-dependent changes in late inhibitory and disinhibitory actions within the primary motor cortex in humans.

The objective of the present study was to investigate the time course of long-interval intracortical inhibition (LICI) and late cortical disinhibition (LCD) as a function of the motor task (index abduction, thumb-index precision grip). Motor-evoked potentials were recorded from the first dorsal interosseus (FDI) muscle of the dominant limb in 13 healthy subjects. We used paired-pulse transcranial magnetic stimulation (TMS) paradigms in which a test pulse was preceded by a suprathreshold priming pulse (130% of the resting motor threshold) with varying interstimulus intervals (ISIs). In each task, double pulses were delivered with ISIs ranging from 30% of the corresponding silent period (SP; ~ 45 ms) to 220% of the SP (~ 330 ms). In both tasks, we found that LICI was followed by LCD (namely a period of increased cortical excitability lasting until ~ 200% of the SP). The time-dependent modulation of LICI and LCD differed in the two tasks; LICI was shorter (i.e. disinhibition occurred earlier) and LCD was more intense during precision grip than during index abduction. Long-interval intracortical inhibition disappeared well before the end of the SP in the precision grip task, suggesting that the mechanisms underlying these two inhibitory phenomena are distinct. Our data suggest that disinhibition might reflect adaptation of neural circuit excitability to the functional requirements of the motor task.

Task-dependent changes of motor cortical network excitability during precision grip compared to isolated finger contraction.

The purpose of this study was to determine whether task-dependent differences in corticospinal pathway excitability occur in going from isolated contractions of the index finger to its coordinated activity with the thumb. Focal transcranial magnetic stimulation (TMS) was used to measure input-output (I/O) curves--a measure of corticospinal pathway excitability--of the contralateral first dorsal interosseus (FDI) muscle in 21 healthy subjects performing two isometric motor tasks: index abduction and precision grip. The level of FDI electromyographic (EMG) activity was kept constant across tasks. The amplitude of the FDI motor evoked potentials (MEPs) and the duration of FDI silent period (SP) were plotted against TMS stimulus intensity and fitted, respectively, to a Boltzmann sigmoidal function. The plateau level of the FDI MEP amplitude I/O curve increased by an average of 40% during the precision grip compared with index abduction. Likewise, the steepness of the curve, as measured by the value of the maximum slope, increased by nearly 70%. By contrast, all I/O curve parameters [plateau, stimulus intensity required to obtain 50% of maximum response (S(50)), and slope] of SP duration were similar between the two tasks. Short- and long-latency intracortical inhibitions (SICI and LICI, respectively) were also measured in each task. Both measures of inhibition decreased during precision grip compared with the isolated contraction. The results demonstrate that the motor cortical circuits controlling index and thumb muscles become functionally coupled when the muscles are used synergistically and this may be due, at least in part, to a decrease of intracortical inhibition and an increase of recurrent excitation.

Deficit of sensorimotor integration in normal aging.

Sensorimotor performance declines with normal aging. The present study explored age-related changes in sensorimotor integration by conditioning a supra-threshold transcranial magnetic stimulation pulse with a peripheral nerve shock at different interstimulus intervals. Cortical motor threshold of the abductor pollicis brevis muscle, intracortical inhibition and facilitation were measured. We also assessed the influence of median nerve stimulation on motor cortex excitability at intervals which evoked short- and long-latency afferent inhibition (SAI and LAI, respectively) and afferent-induced facilitation (AIF). We observed a marked decrease of the long latency influence of proprioceptive inputs on M1 excitability in the elderly, with the loss of AIF and LAI. The SAI, motor thresholds and intracortical inhibition and facilitation were not age-related. Decreased sensorimotor performance with aging appears to be associated with a decrease in the influence of proprioceptive inputs on motor cortex excitability at longer intervals (probably via higher order cortical areas).

Myoclonus of peripheral origin: two case reports.

The concept of peripheral myoclonus is not yet fully accepted by the medical community because of the difficulty in establishing a cause-and-effect relationship between trauma and subsequent movement disorders. Here, we report two cases of patients suffering from peripheral myoclonus after nerve injury. The first patient experienced myoclonus of the 4th dorsal interosseous muscle several days after trauma to the elbow. The second patient presented myoclonus of the arm stump (combined with phantom-limb pain) 1 year after amputation. In both cases, central nervous system function (spine and brain imaging, somesthetic evoked potentials, EEG back-averaging) was normal. For the second patient, local infiltration of xylocaine and botulinum toxin into the stump scar rapidly stopped myoclonus and pain. Nerve injury induces ephaptic transmission and ectopic excitation. The physiopathological mechanisms of this type of myoclonus involve a peripheral generator that induces central (spinal) generator activity.

Action-induced clonus mimicking tremor.

Action tremor has been described in cerebellar, task-specific, dystonic, or Holmes tremor. We report 2 patients who developed unilateral kinetic or isometric action tremor of the upper extremity, following cervical spondylotic myelopathy and capsular ischemic stroke. Slight motor weakness and spasticity with exaggerated tendon jerks and passive stretch-induced clonus were present on the same limb. The central motor pathways lesions might have been responsible for a hyperexcitability of the stretch-reflex arc and an enhancement of the coactivation of skeletal muscles through a loss of the descending or segmental control of the spinal reflexes. The unusual topography of the symptoms, their occurrence during motion, and the similar frequency of the passive clonus and the action tremor, led us to hypothesize that both patients had prolonged action-induced clonus, mimicking action tremor. Lesions of the central motor pathways lesions might be responsible for action tremor under certain conditions.

Exhaustive, one-year follow-up of subthalamic nucleus deep brain stimulation in a large, single-center cohort of parkinsonian patients.

OBJECTIVE: To prospectively assess the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) at 12 months after surgery in a series of 100 consecutive patients treated in a single center. The primary objective was to describe the clinical outcome in terms of efficacy and tolerance in STN-DBS patients. A secondary objective was to discuss presurgery clinical characteristics a posteriori as a function of outcome. METHODS: One hundred and three consecutive patients with severe Parkinson's disease received bilateral STN-DBS in our clinic between May 1998 and March 2003. Clinical assessment was performed before and 12 months after surgery and was based on the Unified Parkinson's Disease Rating Scale, Parts II, III, and IV A; the Schwab and England Scale; and cognitive evaluation. Patient-rated overall improvement was also evaluated. RESULTS: Twelve months after surgery, the Unified Parkinson's Disease Rating Scale Part III score decreased by 43%, the Unified Parkinson's Disease Rating Scale Part II score (activities of daily living) fell by 34%, and the severity of dyskinesia-related disability decreased by 61%. The main surgical complications after STN-DBS were as follows: infection (n = 7), intracerebral hematoma (n = 5), electrode fracture (n = 4), and incorrect lead placement (n = 8). We observed cognitive decline and depression in 7.7 and 18% of the patients, respectively. The mean patient-rated overall improvement score was 70.7%. CONCLUSION: The efficacy and safety of STN-DBS in our center's large cohort of Parkinsonian patients are generally similar to the results obtained by other groups, albeit at the lower limit of the range of reported values. In contrast to efficacy, the occurrence of adverse events cannot be predicted. Younger patients with Parkinson's disease (i.e., those younger than 60 yr) often show an excellent response to levodopa. However, in view of our data on overall patient satisfaction and the occurrence of adverse events, we suggest that older patients (but not those older than 70 yr) and less dopa-sensitive patients (but not those with a response <50%) should still be offered the option of STN-DBS.

Effects of pulse width variations in pallidal stimulation for primary generalized dystonia.

BACKGROUND: Various pulse widths (from 60-450 mus) have been used for bilateral pallidal stimulation in generalized dystonia but, to date, no comparison of this parameter's effects is available. OBJECTIVE: To provide an analysis of the differential effects of bilateral short, medium and long stimulus pulse width (PW) on clinical improvement in primary generalized dystonia. METHODS: The most effective therapeutic stimulation parameters were recorded in 22 patients using bilateral pallidal stimulation. Six months after surgery, the effects of bilateral pallidal short (60-90 micros), medium (120-150 micros) and long (450 micros) PWs were studied in 20 of those patients. The effect of the stimulation was assessed by reviewing videotaped sessions by an observer blinded to treatment status (Burke-Fahn-Marsden movement score). Patients were tested on separate days, in random order, for the stimulation conditions (acute effect with the stimulation condition lasting 10 hours). The same contact was used for each stimulation condition. All the electrodes were set at 130 Hz (monopolar stimulation) and the intensity was set individually 10% below the side effect threshold. RESULTS: Median PWs of 60 (short), 120 (medium) and 450 micros (long) were compared,with a mean intensity of 4.46, 3.45 and 2.47 V, respectively. This study failed to demonstrate any significant difference in the movement scale dystonia mean scores depending on PW. CONCLUSION: According to our findings, short duration stimulus PWs are as effective as longer ones during a 10 hour period of observation. Confirmation of this finding for chronic use could be of importance in saving stimulator energy. Moreover, the use of smaller stimulus pulse widths are said to reduce charge injection and increase the therapeutic window between therapeutic effects and side effects.

The comparable size and overlapping nature of upper limb distal and proximal muscle representations in the human motor cortex.

The purpose of this study was to determine the relative size and location of proximal and distal upper limb muscle representations in the human motor cortex. Motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation were recorded in the proximal muscle anterior deltoid (AD) and in the distal muscles extensor carpi radialis (ECR) and first dorsal interosseus (1DI). The coil was moved in steps of 1 cm along a grid drawn on a tight-fitting polyester cap placed on the subject's head. At each location, four stimuli were delivered at 1.2 times the active motor threshold (AMT), and MEPs averaged in real-time. The peak-to-peak amplitude of each muscle's mean MEP was measured at each stimulation site. The area of a muscle's representation was measured by a pixel-counting algorithm. The optimal point of each muscle's areal representation, which corresponds to the locus near which the largest MEPs are obtained, was determined by fitting a 3D Lorentzian function to the data points. The optimal point of distal muscles tended to be situated more laterally along the motor strip than that of proximal muscles. However, there was no statistically significant difference between the size of the areal representations and they overlapped considerably. Additionally, in another five subjects, using a small 45-mm coil placed in a hyper-focal orientation, maps were obtained at a stimulus intensity of 1.1-1.15 times the AMT of the muscle with the lowest threshold, usually the 1DI. Even in this very stringent condition, the mapped representations of the AD, ECR and 1DI overlapped, notwithstanding that sharp demarcations between borders were also apparent. These observations demonstrate that stimulus spread alone does not explain the overlap of muscle representations. These results show that commonly used proximal and distal upper-limb muscles, taken individually, are controlled by motor cortical territories of approximately equal size that significantly overlap despite differences in the location of their optimal points.

Effect of age on anticipatory postural adjustments in unilateral arm movement.

Aging is frequently accompanied by a deterioration in postural control. Accordingly, the elderly adopt postural strategies in order to maintain balance. The purpose of this study was to compare anticipatory postural adjustments in (healthy) 10 young and 10 elderly subjects using electromyography (EMG) and biomechanical parameters. While standing on a force platform, subjects performed voluntary, arm-raising movements under five conditions: self-paced at three different velocities, self-paced with load and an externally triggered, both at maximal velocity. The force platform provided information on vertical torque (T(z)) and center of pressure anteroposterior displacements (COP). EMG activity was recorded from the biceps femoris, quadriceps, tibialis anterior and soleus muscles. Voluntary movements were associated with an early COP backward shift and an anticipatory T(z). At low velocity, elderly subjects did not show any impairment in stability. At maximal velocity, T(z) was delayed in all conditions in the elderly group, whereas COP latency was reduced only in the self-paced condition without load. Despite this decrease in anticipation, the movement was performed at the same velocity as in younger subjects. The elderly adopted various muscle strategies in order to perform the same movement with less stability. In the self-paced condition, elderly subjects used a hip strategy, whereas young subjects used an ankle strategy. In the triggered condition, the strategy corresponded to increased activation of certain thigh muscles, rather than a sequence modification. Hence, local muscle strategies were used to counteract the overall delay in postural preparation revealed by biomechanical parameters.

Vertical torque allows recording of anticipatory postural adjustments associated with slow, arm-raising movements.

BACKGROUND: When performed in the upright position, voluntary arm-raising movements perturb balance. The maintenance of equilibrium requires postural adjustments, some of which can be anticipatory. It is usually suggested that the role of anticipatory postural adjustments is to stabilise the whole body centre of mass. During movements performed at low velocity (i.e. with a lower inertial perturbation), anticipatory postural adjustments have not systematically been detected by classical recording methods (mainly electromyography). The aim of this study was to use vertical torque to characterise anticipatory postural adjustments in slow movement and to determine the significance of this biomechanical parameter. METHODS: Twenty healthy subjects performed self-paced, right arm-raising movements at low and high velocities. Movements were recorded by an optoelectronic system enabling the synchronization of video, force plate and electromyographic data. The force platform provided information on vertical torque and centre of foot pressure anteroposterior displacement. Electromyography activity was recorded from the right anterior deltoid and the bilateral biceps femoris, tibialis anterior and soleus muscles. FINDINGS: Rapid, voluntary, unilateral movements were associated with an early centre of pressure backward shift, anticipatory vertical torque and electromyographic activities. In slow movements, only the anticipatory changes in vertical torque were consistently observed, with the same latency as in rapid movement. INTERPRETATION: The existence of vertical torque in slow movement (when stabilisation of the centre of mass is not necessary) shows that this parameter does not serve to minimise the centre of mass displacement but rather contributes to the generation of arm movement.

Abnormal cortical mechanisms in voluntary muscle relaxation in de novo parkinsonian patients.

This study aimed at elucidating how the cortical mechanism underlying the preparation and the postmovement phase of voluntary hand muscle relaxation is affected in Parkinson's disease. Event-related mu and beta (de)synchronization (ERD/S) related to voluntary muscle contraction and relaxation were recorded in 16 untreated, akineto-rigid, predominantly hemiparkinsonian patients. The results were compared with data from 10 age-matched, healthy subjects. In the muscle relaxation task, the subject held the wrist in an extended position and then let the hand drop by voluntarily relaxing wrist extensor contraction, i.e., without any overt, associated muscle contraction. In the muscle contraction task, subjects performed a self-initiated brief wrist extension. A same pattern of ERD/S was observed in control subjects and parkinsonian patients performing the motor tasks with their less affected limb. In contrast, related to voluntary relaxation performed with the more affected limb, a delayed mu and beta ERD and a disappearance of beta ERS were revealed. These results demonstrate that the pattern of cortical oscillatory activity in a relaxation task is abnormal in parkinsonian patients. The authors suggest that this may be due to anomalous activity in inhibitory motor cortical systems and impaired sensorimotor integration of afferent inputs from muscle and joint receptors.

Basic mechanisms of central rhythms reactivity to preparation and execution of a voluntary movement: a stereoelectroencephalographic study.

OBJECTIVE: To localize the sources of mu, beta and gamma rhythms and to explore the functional significance of their reactivity. METHODS: We used the method of quantification of event-related desynchronization (ERD) and synchronization (ERS) to analyze the reactivity of intracerebral rhythms recorded in stereoelectroencephalography within the sensorimotor areas during the preparation and the execution of a simple self-paced hand movement. We recorded 3 epileptic subjects who were explored before a surgical treatment. RESULTS: An ERD of mu and beta rhythms has been recorded before the movement onset in the precentral gyrus, spreading then to the postcentral gyrus and to the frontal medial cortex. The frontal lateral cortex was inconstantly involved during the movement. The movement offset was followed by an important and focused beta ERS which was found within the pre- and post-central gyrus and the frontal medial cortex. Within the beta band, we observed several narrower bands with different reactivities and locations. Focused gamma reactivity was also found in the precentral and postcentral gyri. CONCLUSIONS: The reactivities of mu and beta rhythms are different but their locations overlap. Mu ERD is a diffuse phenomenon that reflects the activation of all the sensorimotor areas during a simple movement. Beta band is likely to be composed of different rhythms with different functional significance. The primary motor area seems to contain two distinct areas with different reactivity to the movement preparation and execution.