Motor Unit Number Index of the Upper Trapezius: A Meta-Analysis and Cross-sectional Study of Its Reliability.

Motor unit number index of the upper trapezius (MUNIX-Trapezius) is a candidate biomarker for bulbar lower motor neuron function; however, reliability data is incomplete. To assess MUNIX-Trapezius reliability in controls, we conducted a systematic review, a cross-sectional study (n = 20), and a meta-analysis. We demonstrated a high inter- and intra-rater intraclass correlation (0.86 and 0.94, respectively), indicating that MUNIX-Trapezius is reliable with between-study variability moderated by age and MUNIX technique. With further validation, this measure can serve as a disease monitoring and response biomarker of bulbar function in the therapeutic development for amyotrophic lateral sclerosis.

Ischaemic lumbosacral plexopathy following aortic dissection.

A 57-year-old man was diagnosed with acute myocardial infarction and Stanford type A aortic dissection that had spread to the common iliac arteries. He underwent a Bentall procedure for vascular repair. Immediately after surgery, he developed numbness and severe weakness in his left leg. On examination, he had hypotonia, absent deep tendon reflexes, weakness in the left leg (Medical Research Council (MRC) scale for muscle strength - 0/5 distal, 3/5 proximal) and reduced sensation in the left leg. Electromyography confirmed subacute involvement of the left lumbar and lumbosacral plexus. MR scan of the lumbar plexus showed diffuse muscle oedema involving the left gluteus maximus. We diagnosed ischaemic lumbosacral plexopathy secondary to extensive aorta dissection and internal iliac artery occlusion. We discuss the clinical features of ischaemic plexopathy and the diagnostic approach and review the vascular anatomy of the lumbosacral plexus.

The Intersection Between Cerebellar Ataxia and Neuropathy: a Proposed Classification and a Diagnostic Approach.

Neuropathy is a common associated feature of different types of genetic or sporadic cerebellar ataxias. The pattern of peripheral nerve involvement and its associated clinical features can be an invaluable aspect for narrowing the etiologic diagnosis in the investigation of cerebellar ataxias. In this review, we discuss the differential diagnosis of the intersection between peripheral nerve and cerebellar involvement, and classify them in accordance with the predominant features. Genetics, clinical features, neuroimaging, and neurophysiologic characteristics are discussed. Furthermore, a diagnostic approach for cerebellar ataxia with neuropathy is proposed according to the different clinical characteristics. This is an Educational and Descriptive review with the aim of medical education for the approach to the patients with cerebellar ataxia and neuropathy. The diagnostic approach to the patient with cerebellar ataxia with neuropathy requires a detailed medical history, phenotyping, characterization of disease progression and family history. Neuroimaging features and the neurophysiological findings play pivotal roles in defining the diagnosis. Establishing an organized classification method for the disorders based on the clinical features may be very helpful, and could be divided as those with predominant cerebellar features, predominant neuropathic feature, or conditions with both cerebellar ataxia and neuropathy. Second, determining the mode of inheritance is critical on cerebellar ataxias: autosomal dominant and recessive cerebellar ataxias, mitochondrial or sporadic types. Third, one must carefully assess neurophysiologic findings in order to better characterize the predominant pattern of involvement: damage location, mechanism of lesion (axonal or demyelinating), motor, sensory or sensory motor compromise, large or small fibers, and autonomic system abnormalities.

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.

Non-motor and Extracerebellar Features in Spinocerebellar Ataxia Type 2.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant degenerative disease. Pathological studies have demonstrated not only cerebellar and brainstem atrophy, but substantia nigra, motoneurons, basal ganglia, thalamus, and peripheral nerves involvement. These findings may explain non-motor and extra-cerebellar features in SCA2. We accessed the non-motor symptoms and extra-cerebellar signs in SCA2 patients in order to provide a better understanding on pathophysiological mechanisms and natural history of brain degeneration in the disease. Thirty-three SCA2 patients were evaluated and compared with 26 healthy subjects. We investigated the following variables: sleep disorders, cognitive deficit, olfactory impairment, urinary dysfunction, psychiatric symptoms, cramps, pain, movement disorders, and weight loss. SCA2 had a high frequency of REM sleep behavior disorder (48.48 %, N = 16) as well as excessive daytime sleepiness (42.42 %, N = 14). Chorea was present in 15.15 % (N = 5), dystonia in 27.27 % (N = 9), and parkinsonism in 27.27 % (N = 9). Slow saccadic pursuit was present in 87.87 % (N = 29) and ophtalmoparesis in 78.78 % (N = 26) of patients. Regarding sleep disorders, 18.18 % (N = 6) of patients had restless leg syndrome. Dysphagia was present in 39.39 % (N = 13), weight loss 24.24 % (N = 8), and urinary dysfunction 27.27 % (N = 9). Cramps was present in only 6 % of patients (N = 2). This study highlighted the high frequency of non-motor symptoms and extra-cerebellar signs in SCA2. Our findings demonstrate the widespread of nervous system involvement in SCA2 patients and contribute to better understand the natural history of brain degeneration in this genetic condition.

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.

Pattern of peripheral nerve involvement in Machado-Joseph disease: neuronopathy or distal axonopathy? A clinical and neurophysiological evaluation.

OBJECTIVE: Neuropathy is a well-recognized feature in spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD), but the pattern of neuropathy is still a matter of debate. This study aimed to evaluate peripheral nerve involvement in MJD patients. Neurophysiological and clinical data were analyzed to distinguish neuronopathy from length-dependent distal axonopathy. METHODS: In the present study we evaluated 26 patients with clinical and molecular-proven MJD and investigated their peripheral nerve involvement. Neurophysiological and clinical data were compared and correlated aiming to distinguish neuronopathy from distal axonopathy. RESULTS: The neurophysiological evaluation showed that 42.3% of the patients had polyneuropathy. Among these patients, 81.8% presented neuronopathy. CONCLUSION: We concluded that neuronopathy is the most common form of peripheral nerve involvement in MJD patients.

Ginkgo biloba and cerebral bleeding: a case report and critical review.

Ginkgo biloba is a herbal medication that is often used worldwide. Although side effects are uncommon, G. biloba has been associated with serious bleeding complications, especially intracranial hemorrhage. We report the case of a young woman who made chronic use of G. biloba and suffered from cerebral bleeding without any structural abnormalities. Several studies have pointed to the association between G. biloba and intracranial hemorrhage.