The feasibility and technical aspects of trigemino-cervical reflex elicitation in humans under general anesthesia.

OBJECTIVE: To analyze the feasibility, neurophysiological aspects, stimulation patterns, and topographic distribution of trigemino-cervical reflex (TCR) components in humans under general anesthesia. METHODS: This prospective observational study enrolled 20 participants who underwent posterior fossa surgery, surgical proceduresin thecraniovertebral junction,or spinal cord surgery. TCR responses were simultaneously recorded in the sternocleidomastoid (SCM) and trapezius muscles after electrical stimulation of the supraorbital and infraorbital nerves. TCR responses were recorded preoperatively and intraoperatively using single-pulse and multipulse (trains of 2-7 electrical stimuli) stimulation, respectively. Two stimulus duration patterns were evaluated: 0.2-0.5 ms and 0.5-1.0 ms. RESULTS: Intraoperatively, short- and long-latency TCR components were obtained in the SCM ipsilateral to the stimulation with variable recordability. Short-latency responses were the most commonly recorded components. A longer stimulus duration (0.5-1.0 ms) seems to favor the elicitation of TCR responses under general anesthesia. CONCLUSIONS: Short-latency components recorded in the SCM ipsilateral to the stimulation could be regularly elicited under general anesthesia when a larger stimulus duration (0.5-1.0 ms) was applied. SIGNIFICANCE: This is the first study to demonstrate the elicitation of TCR components in humans under general anesthesia. This neurophysiological technique can potentially optimize intraoperative neurophysiological monitoring during brainstem surgery.

Technical Aspects of Eliciting Trigeminocervical and Trigeminospinal Reflexes in Humans: A Scoping Review.

SUMMARY: This scoping review aims to summarize the technical strategies for obtaining trigeminocervical reflex (TCR) and trigeminospinal reflex (TSR) responses. Studies published on TCR or TSR elicitation in humans through electrical stimulation of trigeminal nerve branches were eligible for this scoping review. The data of interest included stimulation parameters, site of stimulation, recording parameters, and the feasibility of TCR and TSR elicitation, in healthy participants. Short-latency TCR responses were regularly obtained in both anterior and posterior neck muscles after electrical stimulation of the supraorbital and infraorbital nerves under voluntary muscle activation. However, without voluntary muscle activation, we found evidence of elicitation of short-latency TCR components only in the posterior neck muscles after supraorbital or infraorbital nerve stimulation. Long-latency TCR responses were regularly obtained in the anterior and posterior neck muscles in studies that evaluated this technique, regardless of the trigeminal branch stimulation or muscle activation status. Short-latency TSR components were not obtained in the included studies, whereas long-latency TSR responses were regularly recorded in proximal upper limb muscles. This scoping review revealed key heterogeneity in the techniques used for TCR and TSR elicitation. By summarizing all the methodological procedures used for TCR and TSR elicitation, this scoping review can guide researchers in defining optimized technical approaches for different research and clinical scenarios.

Immune-mediated inflammatory polyneuropathy overlapping Charcot-Marie-Tooth 1B.

Charcot Marie Tooth (CMT) due to myelin protein zero (MPZ) mutations, may cause a wide variation of phenotypes, depending on the localization of the mutation within the gene. Among the most common phenotypes are: an infantile onset disease with extremely slow nerve conduction velocities (CMT1B) and an adult onset phenotype with nerve velocities in the axonal range (CMT2I). We reported a patient with CMT1B (MPZ p.Ser63del mutation) which developed an overlapping immune mediated polyradiculoneuropathy with recurrent episodes of quadriparesis and cranial nerve involvement. We observed reversible conduction block on serial neurophysiologic studies, non-uniform demyelination and good clinical response to prednisone and cyclophosphamide, as evidenced by objective functional recovery. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-like characteristics have not yet been described associated with a MPZ p.Ser63del mutation. This description adds evidence indicating that a defective structural myelin protein may predispose peripheral nerves to immune attacks.

Motor unit number index (MUNIX) in myopathic disorders: Clinical correlations and potential pitfalls.

Our aim was to study motor unit number index (MUNIX) in myopathic disorders. We studied 11 patients with myopathy, and healthy controls. We obtained MUNIX, compound muscle action potential (CMAP), motor unit size index (MUSIX) and alpha (α, power exponent from MUNIX equation) measurements from three different muscles. MUNIX and CMAP were significantly lower in one muscle. This MUNIX decrease may not be related to motor neuron loss, but rather to muscle fiber atrophy. MUSIX and α did not change and may be useful in determining whether the MUNIX decrease is indeed due to motor unit loss.

Tonic pupils: an unusual autonomic involvement in chronic inflammatory demyelinating polyneuropathy (CIDP).

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neuropathy which affects mainly large myelinated axons and has a typically mild autonomic dysfunction mainly from postganglionic nerve fiber involvement. CASE REPORT: We report here an acute onset CIDP initially diagnosed as Guillain-Barré syndrome (GBS), unresponsive to treatment with intravenous immunoglobulin (IVIg), which later responded to plasmapheresis and corticoids. The patient had a markedly distal demyelination, prominent cranial nerve involvement and, interestingly, bilateral fixed dilated pupils. Despite complete clinical recovery, this neurological sign remained. CONCLUSIONS: Tonic pupils have previously been described in different neurologic conditions, including GBS, but not yet in acute onset CIDP or in variants with predominantly distal demyelination. It differs from the classical Adie's pupil because it lacks the light-near dissociation. This case report expands the range of possible autonomic signs in acute onset CIDP, which could help physicians establish optimal treatment strategies earlier on.

Optimal E2 (reference) electrode placement in fibular motor nerve conduction studies recording from the tibialis anterior muscle.

INTRODUCTION: In this study we aimed to determine the contribution of the E2 (reference electrode) to the compound muscle action potential (CMAP) amplitude during fibular motor recording to the tibialis anterior (TA) when E2 is placed over routine referential vs. alternative sites. METHODS: The CMAP was obtained from 10 healthy subjects, using the active electrode (E1) over sites routinely used as E2 for the TA, whereas the E2 was over the contralateral knee. The same procedure was performed with the E1 over alternative E2 sites. RESULTS: Significant electrical signal was captured over routine E2 placement sites. Among the tested alternative E2 sites, the ipsilateral patella (especially its medial aspect) was the most electrically silent. DISCUSSION: Using alternative E2 sites with near isoelectric recordings can optimize near-field potential measurement in the fibular motor recording to the TA and represents a more accurate way of measuring nerve and muscle function. Muscle Nerve 59:249-253, 2019.

Motor unit number index and neurophysiological index as candidate biomarkers of presymptomatic motor neuron loss in amyotrophic lateral sclerosis.

INTRODUCTION: Our objective was to determine the utility of motor unit number index (MUNIX) and neurophysiological index (NI) as surrogate biomarkers of disease progression in limbs without clinical signs of lower motor neuron (LMN) involvement from patients with slowly progressive amyotrophic lateral sclerosis (ALS). METHODS: Patients with slowly progressive ALS and at least 1 clinically unaffected limb were prospectively enrolled. Clinical signs of LMN loss and results from hand-held dynamometer (HHD), revised ALS Functional Rating Scale (ALSFRS-R), mean-MUNIX (from 3 different muscles), and NI were longitudinally recorded. RESULTS: Eighteen patients with 43 presymptomatic muscles were evaluated. Twenty-seven muscles remained clinically unaffected during study, with stable ALSFRS-R subscores and HHD measures. However, a significant decline in mean-MUNIX and NI was detected. DISCUSSION: Mean-MUNIX and NI were more sensitive than clinical measures at detecting LMN loss in presymptomatic limbs from patients with slowly progressive ALS. Therefore, these electrophysiological biomarkers should be included in early study phases as meaningful outcome measures. Muscle Nerve 58: 204-212, 2018.

Why averaging multiple MUNIX measures in the longitudinal assessment of patients with ALS?

OBJECTIVE: To assess the impact of averaging multiple MUNIX trials on the follow-up of patients with amyotrophic lateral sclerosis (ALS). METHODS: We determined the percent relative change (%RC) of MUNIX, in healthy subjects and patients with ALS, by subtracting the MUNIX value in the second visit from the first. Both the mean of a set of three MUNIX (mean-MUNIX) and the first MUNIX sample (single-MUNIX) were evaluated. Then, we studied the sensitivity to detect relative changes over time and the statistical dispersion of the %RC from these two parameters. RESULTS: We found that the mean-MUNIX %RC has lower mean coefficient of variation than the single-MUNIX %RC in all muscles. The mean-MUNIX also resulted in more ALS patients with significant %RC, i.e., outside reference limits. CONCLUSION: The mean-MUNIX resulted in less dispersed values of %RC in patients with ALS and thus, increased the precision of the technique. The mean-MUNIX resulted also in an increase in the sensitivity to track changes over time in these patients. SIGNIFICANCE: The mean-MUNIX should be considered in any ALS follow-up study as a more reliable approach and as a way of potentially reducing the sample size needed for the study.

Improving the reproducibility of motor unit number index.

INTRODUCTION: Reproducibility is an important aspect of any method intended to be a marker of disease progression. In this study we investigated approaches for improving motor unit number index (MUNIX) reproducibility. METHODS: We used the intraclass correlation coefficient (ICC) and the coefficient of variation (CV) to study reproducibility in healthy subjects. We tested reproducibility between test and retest of a single MUNIX from 3 different muscles (S-MUNIX) and also of the mean of a set of 3 measurements from these same muscles (M-MUNIX). RESULTS: M-MUNIX was more reproducible than S-MUNIX. The CV showed a greater improvement than the ICC in all 3 muscles. CONCLUSIONS: M-MUNIX may be a valuable approach for following motor unit loss, because it is more replicable than MUNIX. This may be especially relevant in amyotrophic lateral sclerosis patients, in whom MUNIX variability is higher than in healthy individuals. Muscle Nerve, 2016 Muscle Nerve 55: 635-638, 2017.

Effects of the stimulus phase on the air-conducted ocular vestibular evoked myogenic potential in healthy subjects.

OBJECTIVE: The study aimed to examine the effect of the stimulus phase of air-conducted sound on ocular vestibular evoked myogenic potentials (oVEMPs). METHODS: oVEMPs were recorded after air-conducted sounds (500Hz, 4ms duration), presented with initial condensation (positive), rarefaction (negative), and alternant polarities from 12 healthy subjects. RESULTS: Most responses showed a bifid n10 peak separated by ∼1.9ms. The most prominent sub-peak after condensation was shorter than the most prominent sub-peak after rarefaction; however, the first sub-peak was shorter after the rarefaction stimuli. When a third sub-peak appeared, it occurred before the most prominent sub-peak after condensation and after the most prominent sub-peak after rarefaction. The latency difference between this third sub-peak and the closest sub-peak was shorter than the difference among the others sub-peaks, in both cases; the oVEMPs after alternating stimuli was an amalgam of the responses to the different stimuli. CONCLUSIONS: The findings suggest that the negative to positive change of the stimulus was the main event responsible for the stimulation, and that when a third sub-peak appeared it was related to the initiation or the end of the stimulus. SIGNIFICANCE: These findings suggested that the oVEMP response, obtained by air conducted sound, was secondary to stimulation of the same type of afferent vestibular unit, independent of the stimulus polarity.

MUNIX: Reproducibility and clinical correlations in Amyotrophic Lateral Sclerosis.

OBJECTIVE: To study the reproducibility, diagnostic yield to detect denervation, and clinical correlations of the Motor Unit Number Index (MUNIX) in subjects with Amyotrophic Lateral Sclerosis (ALS). METHODS: MUNIX evaluation was performed in three muscles twice on the same day to assess reproducibility. Cut-off values for the MUNIX were based on data from 51 healthy subjects (controls) to evaluate the sensitivity of the technique to detect denervation in 30 subjects with ALS. RESULTS: The method had good reproducibility. The variability was greater in the ALS group. In 23 ALS subjects (77%), low MUNIX values were detected. Most of the muscles with low MUNIX had also low compound muscle action potential (CMAP) and strength, but these parameters were normal in 9% of muscles. According to ROC curve analysis, MUNIX was generally accurate (AUC=0.9504) for discriminating between healthy individuals and subjects with at least one denervated muscle. CONCLUSIONS: MUNIX variability was higher in the ALS group. The method showed good diagnostic performance for the detection of denervation in a sample of patients with ALS. SIGNIFICANCE: This study demonstrated that in addition to being a quantitative tool MUNIX can detect denervation in subjects with ALS.

Expression of praxis induction on cortical excitability in juvenile myoclonic epilepsy.

OBJECTIVE: This study aimed to evaluate the effects of praxis induction on sensorimotor cortical and transcallosal excitability in juvenile myoclonic epilepsy (JME). METHODS: A total of 36 subjects (18-62years) were included. The JME group was screened by video-electroencephalography neuropsychological protocol and divided into JME without praxis induction [JME-WI (n=12)], JME with praxis-induced seizures or epileptiform discharges [JME-PI (n=10)], and healthy controls (n=14). Motor and somatosensory cortical excitability and transcallosal pathways were evaluated through single-pulse transcranial magnetic stimulation (sTMS) and somatosensory evoked potentials (SEPs). RESULTS: Motor and transcallosal excitabilities tested with sTMS were not different in the motor-dominant or non-dominant hemisphere among groups. Significant differences were found in cortical SEP amplitudes in the P27 component of the non-dominant hemisphere (p=0.03, Cohen's d=0.98), N35 in the dominant hemisphere (p=0.04, Cohen's d=0.96), and P27-35 interpeak amplitude in both somatosensory cortices of the JME-PI group (p=0.03, Cohen's d=0.96; p=0.02, Cohen's d=1.05) when compared with healthy controls. Giant SEPs were observed in two (16.7%) and five (50%) patients of the JME-WI and JME-PI groups, respectively. Cortical latencies did not reveal differences. CONCLUSIONS: Praxis induction was associated with enhanced excitability in the somatosensory cortex of JME patients. SIGNIFICANCE: These findings may help clarifying the less favorable therapeutic response in the JME-PI group and indicate identifying praxis induction as an important determinant in differentiating between JME patients.

Pattern of Peripheral Nerve Involvement in Spinocerebellar Ataxia Type 2: a Neurophysiological Assessment.

Peripheral neuropathy is frequent in spinocerebellar ataxia type 2 (SCA2), but the pattern and characteristics of nerve involvement are still an unsettled issue. This study aimed to evaluate the prevalence, extent, and distribution of nerve involvement in SCA2 patients through neurophysiological studies. Thirty-one SCA2 patients and 20 control subjects were enrolled in this study. All subjects were prospectively evaluated through electromyography, including nerve conduction, needle electromyography in proximal and distal muscles of the upper and lower limbs, and sural radial amplitude ratio (SRAR). We aimed to differentiate distal axonopathy from diffuse nerve commitment, characterizing neuronopathy. Nerve involvement was observed in 83.6 % (26 individuals) of SCA2 patients. Among these, 19 had diffuse sensory abnormalities on nerve conduction predominantly on the upper limbs, with diffuse chronic denervation on needle electromyography and elevated SRAR values. Four individuals had only diffuse sensory involvement, and 2 had only motor involvement on needle evaluation and normal nerve conduction. These were interpreted as neuronopathy due to the diffuse distribution of the involvement. One individual had distal sensory axonopathy, with lower limb predominance. In this study, we found neuronopathy as the main pattern of nerve involvement in SCA2 patients and that motor involvement is a frequent feature. This information brings new insights into the understanding of the pathophysiology of nerve involvement in SCA2 and sets some key points about the phenotype, which is relevant to guide the genetic/molecular diagnosis.

Cervical and ocular vestibular evoked potentials in Machado-Joseph disease: Functional involvement of otolith pathways.

INTRODUCTION: Machado-Joseph disease is defined as an autosomal dominant ataxic disorder caused by degeneration of the cerebellum and its connections and is associated with a broad range of clinical symptoms. The involvement of the vestibular system is responsible for several symptoms and signs observed in the individuals affected by the disease. We measured cervical and ocular vestibular evoked myogenic potentials in a sample of Machado-Joseph disease patients in order to assess functional pathways involved. METHODS: Bilateral measures of cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) were obtained from 14 symptomatic patients with genetically proven Machado-Joseph disease and compared with those from a control group of 20 healthy subjects. RESULTS: Thirteen (93%) patients showed at least one abnormal test result; oVEMP and cVEMP responses were absent in 17/28 (61%) and 11/28 (39%) measures, respectively; and prolonged latency of cVEMP was found in 3/28 (11%) measures. Of the 13 patients with abnormal responses, 9/13 (69%) patients showed discordant abnormal responses: four with absent oVEMP and present cVEMP, two with absent cVEMP and present oVEMP, and three showed unilateral prolonged cVEMP latencies. CONCLUSION: Both otolith-related vestibulocollic and vestibulo-ocular pathways are severely affected in Machado-Joseph disease patients evaluated by VEMPs.

Neurophysiological studies and non-motor symptoms prior to ataxia in a patient with machado-joseph disease: trying to understand the natural history of brain degeneration.

Spinocerebellar ataxia type 3 or Machado-Joseph disease is the most common spinocerebellar ataxia. In this neurological disease, anatomical, physiological, clinical, and functional neuroimaging demonstrate a degenerative process besides the cerebellum. We performed neurophysiological and neuroimaging studies-polysomnography, transcranial sonography, vestibular-evoked myogenic potential, single-photon emission computed tomography (SPECT) with (99m)Tc-TRODAT-1, and a formal neuropsychological evaluation in a patient with sleep complaints and positive testing for Machado-Joseph disease, without cerebellar atrophy, ataxia, or cognitive complaints. Polysomnography disclosed paradoxical high amplitude of submental muscle, characterizing REM sleep without atonia phenomenon. Transcranial sonography showed hyperechogenicity of the substantia nigra. There was an absence of vestibular-evoked myogenic potentials on both sides in the patient under study, in opposite to 20 healthy subjects. Brain imaging SPECT with (99m)Tc-TRODAT-1 demonstrated a significant lower DAT density than the average observed in six healthy controls. Electroneuromyography was normal. Neuropsychological evaluation demonstrated visuospatial and memory deficits. Impairment of midbrain cholinergic and pontine noradrenergic systems, dysfunction of the pre-synaptic nigrostriatal system, changes in echogenicity of the substantia nigra, and damage to vestibulo-cervical pathways are supposed to occur previous to cerebellar involvement in Machado-Joseph disease.

Neuroimaging features in congenital trichomegaly: the Oliver-McFarlane syndrome.

A 23-year-old woman presented to our hospital with 9 months history of progressive ataxia, visual loss since childhood due to retinitis pigmentosa and primary amenorrhea. On examination, there were also sparse scalp hair, very long and curled upwards eyelashes and short stature. Oliver-McFarlane syndrome was suspected. Brain MRI disclosed cerebellar atrophy and hyperintense signal in corticospinal tracts on FLAIR and T2-weighted images. Therefore, brain imaging must be thoroughly investigated in patients with suspected Oliver-McFarlane syndrome, in order to determinate whether cerebellar atrophy and hyperintense signal in corticospinal tracts are part of this neurological condition.

Current perception threshold and reaction time in the assessment of sensory peripheral nerve fibers through sinusoidal electrical stimulation at different frequencies

INTRODUCTION: The Perception Sensory Threshold (ST) for sinusoidal current stimuli at 5, 250, and 2,000 Hz is commonly used in the assessment of peripheral nerve fibers (C, Aδ, and Aβ, respectively). However, the neuroselectivity of these frequencies is far from consensus. In addition, Reaction Time (RT) measurements suggest that 2,000 Hz stimuli excite Aβ-fibers, 250 Hz Aβ- or Aδ-fibers, as well as 5 Hz Aβ-, Aδ- or C-fibers. Therefore, we suppose that the sinusoidal current neuroselectivity may be better observed if ST and RT parameters are jointly evaluated. In addition, we have investigated whether there are other sets of frequencies that could be used. METHODS: Thus this work investigates ST and RT for stimuli with frequency ranging from 1 to 3,000 Hz, on 28 healthy subjects aged from 19 to 44 years old (27.1±5.49). ST and RT dissimilarity among different frequencies was evaluated applying bi-dimensional Fisher Quadratic Discriminant. RESULTS: The lowest classification error (3.6%) was obtained for 1, 250, and 3,000 Hz. Error for 5, 250, and 2,000Hz was 16.7%. Stimulation frequency at 1 Hz evoked more sensations related to C-fibers (53% of reports) than to Aβ-fibers (36%). However, this behavior did not repeat itself at 5 Hz (only 21% of perceptions were related to C-fibers against 64% to Aβ-fibers). Sensations related to Aβ-fibers prevailed for the highest frequencies presented to the subjects (2,000 Hz - 82% and 3,000 Hz - 93%). Mean RT values showed a decreasing trend with frequency. CONCLUSION: These results suggest that frequencies 1, 250, and 3,000 Hz are more neuroselective than 5, 250, and 2,000 Hz for the evaluation of peripheral sensitive fibers. Furthermore, they show RT usefulness.

Electrophysiological evaluation of the pudendal nerve and urethral innervation in female stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Although still a matter of debate, stress urinary incontinence (SUI) may be accompanied by damage to urethral and pelvic floor innervations, thus promoting dysfunctions of the urethral support and sphincteric closure mechanisms. The aim of this study was to analyze the pelvic floor and urethral innervations through pelvic electrophysiological tests to identify whether neurological alterations interfere with urinary continence and urethral functional activity. METHODS: This prospective study included 52 women, 33 with clinically and urodynamically proven SUI and 19 continent volunteers matched for age, height, parity, and number of vaginal deliveries by the propensity score method. The patients were divided according to the severity of urinary loss evaluated by measuring abdominal leak point pressure (ALPP). Pudendal nerve terminal motor latency (PNTML), pudendal somatosensory evoked potential (SSEP) latencies, urethral and clitoral sensory thresholds, and urethroanal reflex latency were tested. RESULTS: SUI and control subjects did not differ in PNTML, SSEP latency, and clitoral sensory thresholds. However, reduced responsiveness to urethral electrosensitivity and prolonged urethroanal reflex latency were detected in most incontinent patients. In addition, urethral electrosensitivity was altered in suspected intrinsic sphincteric dysfunction. CONCLUSIONS: Urethral afferent pathways can be altered in women with SUI and may play an important role in evoking intrinsic sphincteric dysfunction.