Assessment of Motor Evoked Potentials in Multiple Sclerosis.

Transcranial magnetic stimulation (TMS) is a noninvasive technique mainly used for the assessment of corticospinal tract integrity and excitability of the primary motor cortices. Motor evoked potentials (MEPs) play a pivotal role in TMS studies. TMS clinical guidelines, concerning the use and interpretation of MEPs in diagnosing and monitoring corticospinal tract integrity in people with multiple sclerosis (pwMS), were established almost ten years ago and refer mainly to the use of TMS implementation; this comprises the magnetic stimulator connected to a standard EMG unit, with the positioning of the coil performed by using the external landmarks on the head. The aim of the present work was to conduct a narrative literature review on the MEP assessment and outcome measures in clinical and research settings, assessed by TMS Methodological characteristics of different TMS system implementations (TMS without navigation, line-navigated TMS and e-field-navigated TMS); these were discussed in the context of mapping the corticospinal tract integrity in MS. An MEP assessment of two case reports, by using an e-field-navigated TMS, was presented; the results of the correspondence between the e-field-navigated TMS with MRI, and the EDSS classifications were presented. Practical and technical guiding principles for the improvement of TMS studies in MEP assessment for MS are discussed, suggesting the use of e-field TMS assessment in the sense that it can improve the accuracy of corticospinal tract integrity testing by providing a more objective correspondence of the neurophysiological (e-field-navigated TMS) and clinical (Expanded Disability Status Scale-EDSS) classifications.

Using Cutaneous Receptor Vibration to Uncover the Effect of Transcranial Magnetic Stimulation (TMS) on Motor Cortical Excitability.

BACKGROUND Little is known about how vibrational stimuli applied to hand digits affect motor cortical excitability. The present transcranial magnetic stimulation (TMS) study investigated motor evoked potentials (MEPs) in the upper extremity muscle following high-frequency vibratory digit stimulation. MATERIAL AND METHODS High-frequency vibration was applied to the upper extremity digit II utilizing a miniature electromagnetic solenoid-type stimulator-tactor in 11 healthy study participants. The conditioning stimulation (C) preceded the test magnetic stimulation (T) by inter-stimulus intervals (ISIs) of 5-500 ms in 2 experimental sessions. The TMS was applied over the primary motor cortex for the hand abductor pollicis-brevis (APB) muscle. RESULTS Dunnett's multiple comparisons test indicated significant suppression of MEP amplitudes at ISIs of 200 ms (P=0.001), 300 ms (P=0.023), and 400 ms (P=0.029) compared to control. CONCLUSIONS MEP amplitude suppression was observed in the APB muscle at ISIs of 200-400 ms, applying afferent signaling that originates in skin receptors following the vibratory stimuli. The study provides novel insight on the time course and MEP modulation following cutaneous receptor vibration of the hand digit. The results of the study may have implications in neurology in the neurorehabilitation of patients with increased amplitude of MEPs.

Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study.

Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.

Brain Sciences Special Issue "Neuromodulation of Cortical Networks in Neurological and Neuropsychiatric Disorders: Potential Clinical Indications and the Biophysiological Impact of Stimulation".

Individuals with neurological and neuropsychiatric disorders face a variety of difficulties that can significantly impact their daily lives [...].

Overt Word Reading and Visual Object Naming in Adults with Dyslexia: Electroencephalography Study in Transparent Orthography.

The study aimed to investigate overt reading and naming processes in adult people with dyslexia (PDs) in shallow (transparent) language orthography. The results of adult PDs are compared with adult healthy controls HCs. Comparisons are made in three phases: pre-lexical (150-260 ms), lexical (280-700 ms), and post-lexical stage of processing (750-1000 ms) time window. Twelve PDs and HCs performed overt reading and naming tasks under EEG recording. The word reading and naming task consisted of sparse neighborhoods with closed phonemic onset (words/objects sharing the same onset). For the analysis of the mean ERP amplitude for pre-lexical, lexical, and post-lexical time window, a mixed design ANOVA was performed with the right (F4, FC2, FC6, C4, T8, CP2, CP6, P4) and left (F3, FC5, FC1, T7, C3, CP5, CP1, P7, P3) electrode sites, within-subject factors and group (PD vs. HC) as between-subject factor. Behavioral response latency results revealed significantly prolonged reading latency between HCs and PDs, while no difference was detected in naming response latency. ERP differences were found between PDs and HCs in the right hemisphere's pre-lexical time window (160-200 ms) for word reading aloud. For visual object naming aloud, ERP differences were found between PDs and HCs in the right hemisphere's post-lexical time window (900-1000 ms). The present study demonstrated different distributions of the electric field at the scalp in specific time windows between two groups in the right hemisphere in both word reading and visual object naming aloud, suggesting alternative processing strategies in adult PDs. These results indirectly support the view that adult PDs in shallow language orthography probably rely on the grapho-phonological route during overt word reading and have difficulties with phoneme and word retrieval during overt visual object naming in adulthood.

Treated and Untreated Primary Progressive Multiple Sclerosis: Walkthrough Immunological Changes of Monocytes and T Regulatory Cells.

The objective of this study was to investigate regulatory T cells (Tregs) and monocytes; specifically, the expression of CTLA-4 (CD152) and FOXP3+ in CD4+CD25+ Tregs and the expression of CD40+ and CD192+ monocyte subpopulations in subjects with primary progressive multiple sclerosis (PPMS). Immunological analysis was conducted on peripheral blood samples collected from the 28 PPMS subjects (15 treated with ocrelizumab and 13 untreated PPMS subjects) and 10 healthy control subjects (HCs). The blood samples were incubated with antihuman CD14, CD16, CD40, and CD192 antibodies for monocytes and antihuman CD4, CD25, FOXP3, and CTLA-4 antibodies for lymphocytes. The study results showed that in comparison to HCs both ocrelizumab treated (N = 15) and untreated (N = 13) PPMS subjects had significantly increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs. Further, ocrelizumab treated PPMS subjects, compared to the untreated ones, had significantly decreased percentages of CD192+ and CD40+ nonclassical monocytes. Increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs in both ocrelizumab treated and untreated PPMS subjects indicates the suppressive (inhibitory) role of Tregs in abnormal immune responses in PPMS subjects. Decreased percentages of CD40+ and CD192+ non-classical CD14+CD16++ monocytes for treated compared to untreated PPMS subjects suggests a possible role for ocrelizumab in dampening CNS inflammation.

Confirmation of CD19+ B-Lymphocyte Depletion Prior to Intake of the Second Dose of Ocrelizumab in Multiple Sclerosis Patients.

The aim of the retrospective study was to compare the immunophenotyping of T-lymphocytes, B-lymphocytes, and natural killer cells before the administration of the first and the second dose of ocrelizumab in 22 patients with multiple sclerosis in a three-year period (2019-2021) at the Department of Neurology of the University Hospital of Split. The values of cell immunophenotyping and protein electrophoresis, as well as laboratory parameters, were investigated. There was no significant decrease in serum albumin and globulins before the second dose of ocrelizumab (p > 0,05). A decrease in the number of T-lymphocytes before administration of the second dose of ocrelizumab was observed, but without statistical significance (p = 0.274). Significant depletion occurred in median CD19+ B-lymphocytes (p < 0.001) before the intake of the second dose of ocrelizumab confirming the primary action of ocrelizumab on the B cell lineage.

Exploring Neurophysiological Mechanisms and Treatment Efficacies in Laryngeal Dystonia: A Transcranial Magnetic Stimulation Approach.

Laryngeal dystonia (LD), known or termed as spasmodic dysphonia, is a rare movement disorder with an unknown cause affecting the intrinsic laryngeal muscles. Neurophysiological studies point to perturbed inhibitory processes, while conventional genetic studies reveal fragments of genetic architecture in LD. The study's aims are to (1) describe transcranial magnetic stimulation (TMS) methodology for studying the functional integrity of the corticospinal tract by stimulating the primary motor cortex (M1) for laryngeal muscle representation and recording motor evoked potentials (MEPs) from laryngeal muscles; (2) evaluate the results of TMS studies investigating the cortical silent period (cSP) in LD; and (3) present the standard treatments of LD, as well as the results of new theoretical views and treatment approaches like repetitive TMS and laryngeal vibration over the laryngeal muscles as the recent research attempts in treatment of LD. Neurophysiological findings point to a shortened duration of cSP in adductor LD and altered cSP duration in abductor LD individuals. Future TMS studies could further investigate the role of cSP in relation to standard laryngological measures and treatment options. A better understanding of the neurophysiological mechanisms might give new perspectives for the treatment of LD.

Psychometric properties of the Croatian version of the Multiple Sclerosis Walking Scale (MSWS-12).

PURPOSE: Walking difficulties in people with multiple sclerosis (pwMS) are one of the most pronounced predictors affecting patients' quality of life. The study objective was to determine the psychometric properties of the Croatian version of the Multiple Sclerosis Walking Scale (MSWS-12) among pwMS in Croatia and to examine the association between MSWS-12 and Depression, Anxiety, and Stress Scale-21 (DASS-21), and Multiple Sclerosis Impact Scale-29 (MSIS-29). MATERIALS AND METHODS: A cross-sectional study included a sample of pwMS (N = 148). Psychometric properties were examined by estimating the validity and reliability of the MSWS-12. The predictive validity of MSWS-12 and demographic and disease-related factors were assessed by a hierarchical regression model using MSIS-29 and DASS-21 as criterion variables. RESULTS: Scale reliability was good for the MSWS-12 scale, expressed by Cronbach's alpha coefficient (α = 0.98). Correlations between MSWS-12 and DASS-21 (0.20-0.27) and between MSWS-12 and MSIS-29 subscales (0.47-0.83) provided initial support for the convergent validity. Factor analysis demonstrated the unidimensional structure of the MSWS-12. CONCLUSIONS: The Croatian version of the MSWS-12 is a reliable, valid, and clinically useful tool for assessing walking impairments in pwMS.Implications for rehabilitationWalking difficulties in people with multiple sclerosis (pwMS) are one of the most pronounced predictors affecting patients' quality of life.Multiple Sclerosis Walking Scale (MSWS-12) is a measure of the disease's impact on walking abilities from the patient's perspective.MSWS-12 is a reliable scale for assessing walking speed, endurance, and gait quality in multiple sclerosis and is validated in several languages (Korean, Italian, Brazilian, and Persian).The Croatian version of the MSWS-12 is a reliable, predictive, and valid tool for screening walking impairments in pwMS.