Somatosensory evoked potentials and transcranial color Doppler monitoring in subarachnoid hemorrhage.

OBJECTIVES: The outcome of patients with subarachnoid hemorrhage (SAH) is broadly influenced by the complications that may result from the hemorrhage. We describe a series of subjects, in which neurophysiological monitoring executed by simultaneous recording of somatosensory evoked potentials (SEPs) and transcranial color Doppler (TCD) was performed to reveal possible, early complications following acute SAH. MATERIALS AND METHODS: We described the absolute and interhemispheric values of SEPs from the upper limb and TCD examinations of the cerebral arteries in 13 subjects with acute SAH. RESULTS: In cases with middle cerebral artery (MCA) vasospasm, N20 SEP amplitude absolute values for the hemisphere involved in the vasospasm were much lower than the contralateral ones. The N20 amplitude ratio reduction correlated with reciprocal of MCA mean flow velocity values detected within each patient. In the subjects with early ischemic damage following SAH, the affected hemisphere showed N20 amplitude drop; in addition, the relationship between SEPs and TCD findings was missing. CONCLUSION: Our findings emphasize the utility of simultaneous evaluation of SEPs and TCD in SAH follow-up, since the two methods reflect different pathomechanisms of possible secondary brain damage in aneurysmal SAH.

Changes in corticomotor pathway excitability after exercise training in Parkinson's disease.

BACKGROUND: Altered corticospinal excitability in Parkinson's disease (PD) is related to many of the motor signs. OBJECTIVE: We examined whether the recruitment properties of the corticospinal pathway to hand muscles are changed after 8 weeks of specialized upper limbs exercise in PD. METHODS: Seven PD subjects were enrolled. Upper limb exercise was achieved by using a specially designed device. The input-output (I-O) curves were obtained by transcranial magnetic stimulation (TMS). The conduction of peripheral axons and H reflex was also recorded. UPDRS scale, part-III motor examination was used to assess the motor symptom. Clinical and neurophysiological data were obtained before and after 2-month exercise training. RESULTS: After 2-month exercise training, the UPDRS score was significantly improved. Threshold, slope, and V50 (i.e., the stimulus intensity required to obtain a response 50% of the maximum) of the I-O curve were unchanged, whereas the plateau value was significantly higher. CONCLUSIONS: Exercise training affects the larger motoneurons, that is those activated at higher TMS stimulation intensity. These motoneurones are related to the large, type II motor units. Clinical improvement after exercise may depend upon restoration of the recruitment of the large motor unit, i.e., those necessary to perform rapid and strong movements, known to be deficient in PD.

A new mutation in DNM2 gene in a large Italian family.

The Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with great clinical and genetic heterogeneity. Mutations in DNM2 have been associated with CMT dominant intermediate B (CMTDIB). However, mutations in the same gene are known to induce also axonal CMT (CMT2M) or centronuclear myopathy. Moreover, the ability of effectively and simultaneously sequencing different CMT-related genes by next-generation sequencing approach makes it possible to detect even the presence of modifier genes that sometimes give reason of clinical variability in the context of complex phenotypes. Here, we describe an Italian family with very variable severity of phenotype among members harboring a novel DNM2 gene mutation which caused a prevalent CMT2M phenotype. The contemporary presence of a de novo variant in PRX gene in the most severely affected family member suggests a possible modulator effect of the PRX variant thus highlighting the possible impact of modifier genes in CMT.

Reference values for distal motor conduction of the tibial nerve: Effects of demographic and anthropometric measures.

INTRODUCTION: In this study we collected reference values for the across-tarsal-tunnel conduction of the motor tibial nerve (mTN). METHODS: The mTN compound muscle action potentials (CMAPs) from the abductor hallucis muscle were obtained by stimulating below/above the malleolus and the popliteal fossa. The effect of weight, height, body mass index (BMI), foot and leg length, sex, and age were evaluated using univariate and multivariate correlation analyses, and predictive equations for each mTN conduction parameter were developed. RESULTS: On the basis of data from 185 subjects, there were differences between women and men in all anthropometric parameters and for some nerve conduction values. Through multivariate analysis, age, but not sex, was found to have a significant impact. Height affected both distal and proximal conduction velocity. BMI affected CMAP amplitude. DISCUSSION: mTN conduction is influenced by various demographic and anthropometric factors. For all intrinsic factors, height demonstrated the greatest effect on mTN conduction across the tarsal tunnel.

SPG8 mutations in Italian families: clinical data and literature review.

BACKGROUND: Spastic paraplegia type 8 (SPG8) is an autosomal-dominant form of hereditary spastic paraplegia (AD-HSP) caused by a mutation in the KIAA0196 gene. SPG8 accounts for 1% of less of all AD-HSP and the genotype-phenotype correlation remains poorly understood. METHODS: We report the first clinical and genetic description of SPG8 disease in Italian patients. We identified four new mutations in KIAA0196 gene. These variants were identified using a multigene targeted resequencing HSP panel. We took this opportunity to review the pertinent literature. RESULTS: Age at disease onset was in the third or fourth decade of life. Stiffness of the lower limb with spastic gait, walking impairment, and decreased vibration sense were common early symptoms. Subjects of two families had bladder control abnormalities. Unlike previous reported cases, Italian SPG8 subjects have pure form of spastic paraparesis without cranial nerve involvement, and onset is in adult life. DISCUSSION: By a clinical point of view, it is hard to differentiate SPG8 from the SPG4, in which bladder and vibration sense dysfunctions are frequent signs. The differential diagnosis with other forms of AD-HSPs seems relatively easier if one considers the early-onset manifestations in SPG3A and the peripheral nervous system and cerebellar involvement seen in SPG31.

Diagnostic Accuracy of Sensory Clinical Findings of the Hand Dorsum and of Neurography of the Dorsal Ulnar Cutaneous Nerve in Ulnar Neuropathy at the Elbow.

OBJECTIVE: The main objective is to investigate the diagnostic accuracy and the relation of touch sensation and subjective sensory symptoms in the medial aspect of the hand dorsum, and neurography of the dorsal ulnar cutaneous nerve (DUCN) in ulnar neuropathy at the elbow (UNE). Secondary objective is to report the electrophysiological occurrence of anatomical variant of sensory innervation of the medial aspect of the hand dorsum from superficial radial nerve (SRN). DESIGN: Prospective, cohort study. SETTING: Electromyography laboratory. PARTICIPANTS: Consecutive participants (N=282), those with UNE (n=81) and those without UNE (n=201), were enrolled. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Accuracy and agreement between sensory clinical findings of the medial hand dorsum and neurography of DUCN in UNE diagnosis. RESULTS: DUCN neurographic and sensory findings had high specificity and relatively low sensitivity. Normal or abnormal sensory nerve action potential (SNAP) of DUCN matched with normal or abnormal touch sensation of the medial aspect of hand dorsum. Abnormal DUCN SNAP was related to the clinical severity of UNE and to the axonal damage of the ulnar nerve. Anatomical variant of the innervation of hand dorsum from SRN was demonstrated in 31 of 564 hands (6.2%) belonging to 26 of 282 participants (9.2%). If the variant was present, DUCN SNAP of the same side was more frequently absent or of low amplitude. CONCLUSIONS: The utility of DUCN neurography and sensory findings of the medial aspect of the dorsum of the hand is limited in the diagnosis of UNE. However, if DUCN SNAP is absent or low in amplitude, it is advisable to check the presence of the anatomical variant of the innervation of the medial aspect of the hand dorsum from SRN.

Major motor-functional determinants associated with poor self-reported health-related quality of life in myasthenia gravis patients.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which disabling muscle weakness may affect health-related quality of life (HRQoL). The aim of this study was to investigate which common motor-functional deficits and corresponding severity are most determinant of poor HRQoL in these patients. In 41 patients, the dichotomized first item of the Italian Myasthenia Gravis Questionnaire (IMGQ), categorizing patients who report "good" and "poor" HRQoL, was chosen as dependent-outcome variable. All items composing the myasthenia gravis-specific scale (MG-ADL), i.e. talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to rise from chair, double vision, and eyelid droop were acquired as independent variables and dichotomized. Stepwise backward LR multivariable logistic regression analysis was performed. In addition, the main characteristics of patients were compared. MG-ADL items "chewing" ≥1, i.e. "fatigue chewing solid food", and "breathing" ≥2, i.e. "shortness of breath at rest" proved to be significant determinants. Higher dose of corticosteroid therapy was significantly (p = 0.027; r s  = -0.35), correlated with poor HRQoL. At diagnosis, a decremental response to repetitive nerve stimulation (RNS) from the abductor pollicis brevis was significantly more frequent in patients with poor HRQoL. In conclusion, impaired "chewing" and "breathing" functions indicate the need for careful planning of rehabilitation, re-education and patient management. Moreover, decremental response to RNS at diagnosis may identify patients at risk for poor HRQoL.

Associations Between Body Anthropometric Measures and Severity of Carpal Tunnel Syndrome.

OBJECTIVE: To assess the associations between carpal tunnel syndrome (CTS) severity and selected anthropometric and obesity indexes. DESIGN: We performed a case-control study. Clinical and electrophysiological severity of CTS was classified as mild, moderate, or severe based on validated scales. Body and hand anthropometric characteristics were measured at the time of the electrodiagnostic study. We estimated the relative risk ratios (RRRs) of CTS severity by fitting multinomial logistic regression models adjusted by age and sex. In addition, we fitted multivariable models, including age, sex, wrist ratio, hand ratio, body mass index (BMI), and waist/stature ratio. SETTING: Electromyography laboratories. PARTICIPANTS: Consecutive patients (N=1087), those with CTS (n=340) and those without CTS (n=747), were enrolled. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Associations between CTS severity and selected anthropometric and obesity indexes. RESULTS: We observed associations between many anthropometric indexes and CTS severity. Among obesity indexes, the waist/stature ratio, and among hand anthropometric indexes, the wrist/palm ratio, showed the highest RRRs for the clinical and electrophysiological severity scales. The RRRs of severe CTS (adjusted for age and sex) for the wrist/palm ratio were 3.5 for the clinical scale and 2.4 for the electrophysiological scale. The RRRs of severe CTS for the waist/stature ratio were 2.3 for the clinical scale and 2.0 for the electrophysiological scale. In the multivariable models, both BMI and the waist/stature ratio were associated with the outcomes. CONCLUSIONS: Different configurations of the body and, in particular, the hand and wrist system may influence the occurrence and severity of CTS. Multiple obesity indexes, possibly including the waist/stature ratio, should be considered when investigating the association between body composition and CTS. Future studies should determine whether in obese subjects with CTS the weight and waist circumference loss produces an improvement in CTS symptoms and recovery of distal conduction velocity of the median nerve.

Sensory axons excitability changes in carpal tunnel syndrome after neural mobilization.

Increased mechanosensitivity of the median nerve in carpal tunnel syndrome (CTS) has been demonstrated during upper limb tension test 1 (ULTT1) when the nerve is passively elongated. However, the neurophysiological changes of the sensory axons during stressing activities are unknown. The aim of present study was to verify possible changes in the excitability of median nerve afferent axons following nerve stress in elongation, in subjects with and without CTS. Eight CTS hands and eight controls were selected. Recruitment properties of the median nerve were studied by analyzing the relationship between the intensity of electrical stimulation and the size of motor response, before and after intermittent-repetitive neural mobilization. Only in CTS hands, after the intervention, the stimulus-response curve was strikingly abnormal: both plateau and slope values were significantly lower. During anatomical stress across the median nerve in elongation, compressive forces may exert mechanical traction on the median nerve, since it is 'tethered' at the carpal tunnel, resulting inactivation of Na(+) channels at the wrist, or impairment of energy-dependent processes which affect axonal conduction block. We conclude that in entrapment neuropathies, neural mobilization during nerve elongation may generate conduction failure in peripheral nerve. Our study supports specific considerations for patient education and therapeutic approaches.

Hand muscles corticomotor excitability in hereditary spastic paraparesis type 4.

Transcranial magnetic stimulation (TMS) studies on the pathways to the upper limbs have revealed inconsistent results in patients harboring mutations in SPAST/SPG4 gene, responsible for the commonest form of hereditary spastic paraplegia (HSP). This paper is addressed to study the corticomotor excitability of the pathways to the upper limbs in SPG4 subjects. We assessed the corticomotor excitability of hand muscles in 12 subjects belonging to 7 unrelated SPG4 families and in 12 control subjects by stimulus-response curve [input-output (I-O) curve]. All the parameters of the recruitment curve (threshold, V50, slope and plateau) did not differ significantly from those of the controls. Presence of upper limb hyper-reflexia did not influence the results of I-O curve. Considering the multiplicity of possible genes/loci accounting for pure HSPs, performing TMS analyses could be helpful in differential diagnosis of pure HSPs in the absence of other clinical or neuroimaging tools.

Factors associated with Edinburgh Cognitive and Behavioural ALS Screen (ECAS) alteration at time of diagnosis, in amyotrophic lateral sclerosis.

BACKGROUND: Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a validated assessment designed to screen cognitive functions and behavioral disorders in amyotrophic lateral sclerosis (ALS). Objective of this study is to determine the factors associated with ECAS impairment in a cohort of ALS patients without a co-morbid diagnosis of dementia, at the time of diagnosis. METHODS: We enrolled 71 non-demented ALS patient. We collected clinical and demographic data, ALS familiarity, analysis of the most commonly mutated genes in ALS, ALS Milano Torino Staging System and ALS Functional Rate Scale revised scores, progression rate; finally, we recorded whether symptoms onset involved spinal or bulbar area. The alteration of the ECAS was estimated based on age and education-adjusted-validated cut off for each of the items included in ECAS. A multivariable regression analysis was done. RESULTS: The significant determinants of ECAS alterations were: bulbar onset in both ALS-specific test and total ECAS score; bulbar onset and familiarity in ALS-non-specific test; finally, familiarity and diagnosis delay in ALS-behavioral test. All the subjects carrying C9orf72 mutations had alteration of both total ECAS score and ALS-specific tests. DISCUSSION: At diagnosis, bulbar-onset ALS, family history, diagnosis delay and C9orf72 hexanucleotide repeat expansion may contribute to impairment of ECAS.

Chronic inflammatory demyelinating polyneuropathy after SARS-CoV2 vaccination: update of the literature and patient characterization.

Since the beginning of worldwide vaccination against COVID-19 disease, some reports have revealed a possible relationship between SARS CoV2 vaccination and chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed the available evidences regarding this topic, adding three new cases to those reported so far, with the purpose to outline the characteristics of these post-vaccinal CIDP. Seventeen subjects were studied. A total of 70.6% of CIDP cases were related to viral vector vaccines, most occurring after the administration of the first dose. CIDPs that occurred after the second dose (17%) were temporally associated with mRNA vaccines. The clinical course and electrophysiology of all patients met the criteria for acute-subacute CIDP (A-CIDP). Administration of the viral vector vaccine was significantly correlated with a higher probability of having cranial nerve impairment (p = 0.004). The electrophysiological phenotype, laboratory and imaging data, and first-line therapies were substantially similar to those of the classical CIDP. The take-home message of the present paper is that the SARS CoV2 vaccine, especially the AstraZeneca vaccine, may be associated with inflammatory neuropathies with acute onset, often indistinguishable from Guillain-Barré syndrome (GBS). Hence, the importance of tracked prospectively patients with GBS occurred post-SARS-CoV2 vaccine. Distinguishing GBS from A-CIDP is crucial because treatment strategies and long-term prognosis are different.

Study of total duration of distal compound muscle action potential in demyelinating and axonal Guillain-Barre' syndrome.

OBJECTIVES: Electrophysiology plays a crucial role in Guillain-Barré syndrome (GBS) diagnosis and subtype classification. The aim of our study was to assess the potential role of distal compound muscle action potential (dCMAP) for early differentiation between acute inflammatory demyelinating polyneuropathy (AIDP) and axonal GBS. METHODS: We retrospectively reviewed the medical records of 24 subjects with AIDP and 18 subjects with axonal GBS. We built up receiver operating characteristic curves for total dCMAP duration and negative phase of dCMAP duration, in order to derive cut-off values able to differentiate between AIDP and axonal GBS. RESULTS: The total duration of dCMAP was significantly prolonged in AIDP compared to axonal GBS. AUCs, odds ratio and positive predictive values were higher for total duration than for negative peak duration. Nerve conduction parameters in the lower limbs were more sensitive than those in the upper limbs in distinguishing AIDP from axonal GBS. DISCUSSION: Total duration of dCMAP dispersion may capture an adjunctive component of distal demyelination, not measured by the more traditional parameters and may thus represent a useful tool for early differentiation between AIDP and axonal GBS.

Diagnosis and Management of Seronegative Myasthenia Gravis: Lights and Shadows.

Myasthenia gravis (MG) is an antibody-mediated neuromuscular disease affecting the neuromuscular junction. In most cases, autoantibodies can be detected in the sera of MG patients, thus aiding in diagnosis and allowing for early screening. However, there is a small proportion of patients who have no detectable auto-antibodies, a condition termed "seronegative MG" (SnMG). Several factors contribute to this, including laboratory test inaccuracies, decreased antibody production, immunosuppressive therapy, immunodeficiencies, antigen depletion, and immune-senescence. The diagnosis of SnMG is more challenging and is based on clinical features and neurophysiological tests. The early identification of these patients is needed in order to ensure early treatment and prevent complications. This narrative review aims to examine the latest updates on SnMG, defining the clinical characteristics of affected patients, diagnostic methods, management, and therapeutic scenarios.

Purtscher-like retinopathy in a patient with systemic tacrolimus vasculopathy.

INTRODUCTION: Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathogenesis has not been totally defined yet. Most frequent cause of Purtscher-like retinopathy is acute pancreatitis, but it may be triggered by other systemic or toxic conditions. We report herein a case of Purtscher-like retinopathy in the context of systemic tacrolimus vasculopathy. CASE REPORT: A 56-years old male with history of kidney transplant was referred to local emergency room because of a global worsening of health conditions, with fatigue, muscular pain and diuresis contraction. During hospitalization the patient came to our attention for sudden and severe visual acuity impairment in both eyes. Extensive ophthalmological assessment, optical coherence tomography (OCT) and fluorescein angiography (FA) were performed disclosing a marked drop in best corrected visual acuity (BCVA) (20/200 in the right eye and 10/400 in the left eye) caused by a bilateral severe occlusive retinal microangiopathy complicated by diffuse retinal ischaemia and neovascular glaucoma. Muscular biopsy showed a necrotizing myopathy with autoimmune features, as indicated by conspicuous upregulation of MHC-I complex and microangiopathic changes, consistent with tacrolimus toxicity. Tacrolimus administration was interrupted, and intravenous glucocorticoids were administered. The large areas of retinal ischemia and neovascular glaucoma were treated with pan-retinal photocoagulation and intravitreal injections of bevacizumab with complete regression of iris neovascolarization. BCVA measured 20/200 in both eyes at last follow-up visit, 20 months after symptoms onset. CONCLUSIONS: Purtscher-like retinopathy should be suspected in patients under treatment with calcineurin inhibitors especially in case of sudden and severe bilateral visual impairment.

Sex differences in neuromuscular disorders.

The prevalence, onset, pathophysiology, and clinical course of many neuromuscular disorders (NMDs) may significantly differ between males and females. Some NMDs are more frequently observed in females, and characterized to show a higher grade of severity during or after the pregnancy. Meanwhile, others tend to have an earlier onset in males and exhibit a more variable progression. Prevalently, sex differences in NMDs have a familiar character given from genetic inheritance. However, they may also influence clinical presentation and disease severity of acquired NMD forms, and are represented by both hormonal and genetic factors. Consequently, to shed light on the distinctive role of biological factors in the different clinical phenotypes, we summarize in this review the sex related differences and their distinctive biological roles emerging from the current literature in both acquired and inherited NMDs.

Anti-Cytosolic 5'-Nucleotidase 1A in the Diagnosis of Patients with Suspected Idiopathic Inflammatory Myopathies: An Italian Real-Life, Single-Centre Retrospective Study.

BACKGROUND: Anti-cytosolic 5'-nucleotidase 1A (anti-cN1A) antibodies were proposed as a biomarker for the diagnosis of inclusion body myositis (IBM), but conflicting specificity and sensitivity evidence limits its use. Our study aimed to assess the diagnostic accuracy of anti-cN1A in a cohort of patients who underwent a myositis line immunoassay for suspected idiopathic inflammatory myopathies (IIM). We also assessed the agreement between two testing procedures: line immunoassay (LIA) and enzyme-linked immunoassay (ELISA). MATERIALS AND METHODS: We collected retrospective clinical and serological data for 340 patients who underwent a myositis antibody assay using LIA (EUROLINE Autoimmune Inflammatory Myopathies 16 Ag et cN-1A (IgG) line immunoassay) and verification with an anti-cN1A antibody assay using ELISA (IgG) (Euroimmun Lubeck, Germany). RESULTS: The serum samples of 20 (5.88%) patients (15 females, 5 males, mean age 58.76 ± 18.31) tested positive for anti-cN1A using LIA, but only two out of twenty were diagnosed with IBM. Seventeen out of twenty tested positive for anti-cN1A using ELISA (median IQR, 2.9 (1.9-4.18)). CONCLUSIONS: Our study suggests excellent concordance between LIA and ELISA for detecting anti-cN1A antibodies. LIA may be a rapid and useful adjunct, and it could even replace ELISA for cN1A assay. However, the high prevalence of diseases other than IBM in our cohort of anti-cN1A-positive patients did not allow us to consider anti-cN1A antibodies as a specific biomarker for IBM.