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.

Spirituality, Religiosity and Nationalism from the Perspective of Public and Global Mental Health.

Despite the intensive globalization and an attractive idea of human cosmopolitism the world is still divided into rival nations and religions, with confronting ethics and many war conflicts across the globe producing and perpetuating huge mental health problems. Radicalism, malignant nationalism, pathological religiosity and violent extremism and terrorism are important issues from the public and global mental health perspective. Public and global mental health research can inform preventive strategies and interventions against malignant nationalism, pathological religiosity and violent extremism. Healthy spirituality, sound religiosity and normal nationalism may contribute significantly to public and global mental health and promotion of empathic civilization. The aim of this paper is to address, stress and support mutual understanding and creative cooperation between religions and nations in promotion of public and global mental health, research, patient care and education.

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.

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.

Transcranial Magnetic Stimulation Measures, Pyramidal Score on Expanded Disability Status Scale and Magnetic Resonance Imaging of Corticospinal Tract in Multiple Sclerosis.

Probing the cortic ospinal tract integrity by transcranial magnetic stimulation (TMS) could help to understand the neurophysiological correlations of multiple sclerosis (MS) symptoms. Therefore, the study objective was, first, to investigate TMS measures (resting motor threshold-RMT, motor evoked potential (MEP) latency, and amplitude) of corticospinal tract integrity in people with relapsing-remitting MS (pwMS). Then, the study examined the conformity of TMS measures with clinical disease-related (Expanded Disability Status Scale-EDSS) and magnetic resonance imaging (MRI) results (lesion count) in pwMS. The e-field navigated TMS, MRI, and EDSS data were collected in 23 pwMS and compared to non-clinical samples. The results show that pwMS differed from non-clinical samples in MEP latency for upper and lower extremity muscles. Also, pwMS with altered MEP latency (prolonged or absent MEP response) had higher EDSS, general and pyramidal, functional scores than pwMS with normal MEP latency finding. Furthermore, the RMT intensity for lower extremity muscles was predictive of EDSS functional pyramidal scores. TMS/MEP latency findings classified pwMS as the same as EDSS functional pyramidal scores in 70-83% of cases and were similar to the MRI results, corresponding to EDSS functional pyramidal scores in 57-65% of cases. PwMS with altered MEP latency differed from pwMS with normal MEP latency in the total number of lesions in the brain corticospinal and cervical corticospinal tract. The study provides preliminary results on the correspondence of MRI and TMS corticospinal tract evaluation results with EDSS functional pyramidal score results in MS.

Expression of CD40 and CD192 in Classical Monocytes in Multiple Sclerosis Patients Assessed with Transcranial Magnetic Stimulation.

Expression of CD40 and CD192 markers in different monocyte subpopulations has been reported to be altered in people with MS (pwMS). Also, functional connectivity of the corticospinal motor system pathway alterations has been proved by transcranial magnetic stimulation (TMS). The study objective was to investigate the expression of CD40 and CD192 in classical (CD14++CD16-), intermediate CD14++CD16+ and non-classical (CD14+CD16++) blood monocyte subpopulations in pwMS, undergoing neurophysiological TMS assessment of the corticospinal tract integrity by recording motor-evoked potentials (MEPs). Radiological examination on lesion detection with MRI was performed for 23 patients with relapsing-remitting MS treated with teriflunomide. Then, immunological analysis was conducted on peripheral blood samples collected from the patients and 10 healthy controls (HC). The blood samples were incubated with anti-human CD14, CD16, CD40 and CD192 antibodies. Next, pwMS underwent neurological testing of functional disability (EDSS) and TMS assessment with recording MEPs from upper and lower extremity muscles. The results show that in comparison to HC subjects, both pwMS with normal and altered MEP findings (prolonged MEP latency or absent MEP response) had significantly decreased surface receptor expression measured (MFIs) of CD192 and increased CD40 MFI in classical monocytes, and significantly increased percentages of classical and total monocytes positive for CD40. Knowing CD40's pro-inflammatory action, and CD192 as a molecule that enables the passing of monocytes into the brain, decreased CD192 in classical monocytes could represent a beneficial anti-inflammatory parameter.

The comparison of mechanical thrombectomy and symptomatic therapy on early outcome of acute ischemic stroke in patients older than 80 years: A retrospective cohort study.

OBJECTIVE: Multiple randomized trials have confirmed that endovascular thrombectomy (ET) is an effective treatment method for patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). However, patients older than eighty years of age show worse functional outcomes and higher mortality rates after ET. Our retrospective study aimed to confirm the efficacy of ET in older patients and identify characteristics or variables that can be associated with a better or worse outcome of ET. METHODS: The data of 102 patients with AIS aged 80 years or older were retrospectively collected from January 2019 to September 2020 from the Clinical University Hospital of Split (Department of Neurology). All patients had the AIS caused by occlusion of the M1 segment of the middle cerebral artery (MCA), 51 of them were treated with ET, and 51 of them received general supportive measures (symptomatic therapy - ST group). Detailed demographic information about age, gender, previous diseases (stroke risk factors), baseline National Institute of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS), as well as NIHSS and mRS at discharge, were collected. In addition, concomitant use of recombinant tissue-type plasminogen activator, symptom onset to hospital admission time, time from admission to groin puncture, thrombectomy duration, and thrombolysis in cerebral infarction scale (TICI) recanalization grading scores were collected. RESULTS: Rates of functional independence (mRS score 0-2) were significantly higher among elderly patients treated with ET than with ST (14 vs. 8% respectively, Z = 1.98, p < 0.05). Mortality in the ET group was 33%, while in the ST group was 41%, and no statistically significant difference was found. TICI 2b and 3 negatively correlate with thrombectomy duration (r = -0.39; p < 0.05). Patients with a good outcome had significantly better TICI scores (86% of patients had TICI 2b and 3) and lower NIHSS at admission (12.6 ± 5.4 vs. 16.4 ± 3.6 in the group with poor outcome, p < 0.01). Hypertension (HTN) showed to be an independent predictor of poor clinical outcome (OR 4, p = 0.03, CI 1.11-14.35). CONCLUSIONS: Outcomes of ET among older adults are better than among the older adults treated with ST. The lower NIHSS at the admission, shorter duration of ET, and better TICI could be the predictors of good ET outcome, while HTN could be a predictor of poor outcome. Better patient selection and more studies of ET in the elderly are needed.

Symptom-Level Disability Status Assessed with an Electronic Unsupervised Patient-Reported Expanded Disability Status Scale (ePR-EDSS) in Multiple Sclerosis Patients-The Example of Croatia.

The present study aimed to apply an electronic, unsupervised patient-reported Expanded Disability Status Scale (ePR-EDSS) to investigate disability severity in people with multiple sclerosis (pwMS) as a case study in Croatia in 2021, including demographic and comorbidity characteristics and multiple sclerosis (MS) disease-related factors. The cross-sectional study was conducted as an online survey from 4 October 2021 to 31 December 2021. Symptom-level disability status was assessed with ePR-EDSS for MS capturing MS-related disability across the spectrum of severity.The study enrolled 147 pwMS patients, of which 84% were women. The mean age ± standard deviation in the sample was 41.1 ± 11.3, and the mean disease duration was 8.5 ± 7.4 years, with a median EDSS score of 3.0 (range, 0−8). The distribution of the participants according to clinical forms of MS was as follows: 71% had relapsing-remitting MS, 13% had primary progressive MS, 4% had secondary progressive PMS, and 12% did not provide information on their MS type. Twenty-nine point two percent (29.2%) of the participants had comorbidities in addition to MS. EDSS scores indicate significant differences with regard to age (t = −3.51, p < 0.001), gender (χ2 = 8.04, p < 0.01), and immunomodulatory drug use (χ2 = 5.89, p < 0.05). An ePR-EDSS analysis of disability symptoms showed a significant difference in symptoms with regard to strength, sensation, coordination, vision, fatigue, mobility, and overall wellness among MS types. Participants with PPMS and SPMS were older on average, had higher EDSS, and had more pronounced symptoms of disability measured with ePR-EDSS compared to those with RRMS. Application of ePR-EDSS shows it to be a reliable eHealth tool for clinical assessment of pwMS disability status, and future studies should correlate it with standard self-report scales capturing MS symptoms such as fatigue, depression, anxiety, and stress.

Validation of the fatigue severity scale in Croatian population of patients with multiple sclerosis disease: Factor structure, internal consistency, and correlates.

BACKGROUND: Fatigue is a common symptom in people with multiple sclerosis (MS) and is evaluated and monitored with self-report questionnaires. The objective of this study was to determine the psychometric properties of the Croatian version of the Fatigue Severity Scale (FSS) in people with MS. MATERIAL AND METHODS: This is a retrospective cohort study conducted as an online survey from December 16, 2020, until January 13, 2021. A total of 179 people with MS and 999 control subjects completed FSS and self-administered questionnaires capturing information of demographic, education level, disease-related variables (duration of the disease, MS type, the expanded disability status scale (EDSS), and Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the FSS scale in people with MS. RESULTS: The Croatian version of the FSS had excellent internal consistency (Cronbach's α value 0.93). Factor analysis demonstrated a unidimensional structure. The concurrent validity of the FSS appeared to be satisfactory due to the significant differences between people with MS and control subjects (p < .05). The correlations between FSS and MSIS-29 physical (r = 0.60) and psychological (r = 0.50) subscale results confirmed the convergent validity of the FSS scale. Results also indicated that the best cut-off score is between 4 and 5 with a relatively high sensitivity and specificity. CONCLUSIONS: The Croatian version of FSS was shown to have excellent psychometric properties in people with MS and can be used in the research and clinical settings evaluating fatigue in people with MS in Croatia.

Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in Patients with Multiple Sclerosis: Factor Structure, Reliability, Correlates, and Discrimination.

Sleep disturbances and poor sleep are a common complaint in the population with multiple sclerosis (MS) disease. The most commonly reported scale is the Pittsburgh Sleep Quality Index (PSQI), measuring seven components of sleep quality. Yet, till today, the PSQI instrument has not been validated in people with multiple sclerosis (pwMS). The objective of our study was to add precision in sleep quality assessment by investigating the psychometric properties of PSQI (factor structure, reliability, validity based on relations with other variables, cut-off scores) in pwMS. The cross-sectional study included data on a total of 87 patients with MS and 216 control subjects. Demographic information, education level, and MS-related variables were ascertained. Psychometric properties were examined by estimating the validity, including factor structure, metric invariance, and relations with other MS- and non-MS-related variables, reliability, and discrimination ability of the PSQI. The Croatian version of the PSQI had a two-factor structure which demonstrated loading and partial intercept invariance between pwMS and the control group. The global score and both subscales had high internal consistencies (McDonald's omega and Cronbach's alpha coefficients) in pwMS and showed expected relations with demographic and MS-related variables. PwMS differed significantly in the PSQI global score from the control groups, although receiver operating characteristics (ROC) curve analysis did not indicate a clear cut-off point. The PSQI is a reliable and valid scale and can be applied in clinical settings for assessing sleep quality in pwMS.

Information Processing Speed Assessed with Letter Digit Substitution Test in Croatian Sample of Multiple Sclerosis Patients.

Cognitive impairment is a common complaint in people with multiple sclerosis (pwMS). The study objective was to determine the psychometric properties of the letter digit substitution test (LDST) that measures information processing speed and to investigate the impact of relevant predictors of LDST achievement in pwMS. The design was cross-sectional. The study included 87 pwMS and 154 control subjects. The validity of LDST was examined, and a hierarchical regression model was used to explore relevant predictors of LDST success. The LDST had excellent construct validity, as expressed by differences between pwMS and control subjects. Convergent validity of the LDST was supported by a significant moderate correlation with the expanded disability status scale (EDSS) (ρ = -0.36; p < 0.05) and a significantly strong correlation with the multiple sclerosis impact scale (MSIS-29) physical subscale (r = -0.64; p < 0.01). The LDTS score well differentiated the pwMS considering age, education, EDSS, disease duration, comorbidity, and medication therapy. Using the LDST as a criterion variable in pwMS results showed consistent evidence for the age, education, and EDSS impact on LDST performance. The best cut-off score of ≤35 discriminated the control and MS group. LDST proved to be a valid test for assessing information processing speed in pwMS.

Psychometric Properties of the HADS Measure of Anxiety and Depression Among Multiple Sclerosis Patients in Croatia.

Depression and anxiety are common complaints in patients with multiple sclerosis (MS). The study objective was to investigate the factor structure, internal consistency, and correlates of the Croatian version of the Hospital Anxiety and Depression Scale (HADS) in patients with MS. A total of 179 patients with MS and 999 controls were included in the online survey. All subjects completed the HADS and self-administered questionnaires capturing information of demographic, education level, disease-related variables, and the Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the HADS in patients with MS. The two HADS subscales (anxiety and depression) had excellent internal consistencies (Cronbach's α value 0.82-0.83), and factor analysis confirmed a two-factor structure. The convergent validity of the HADS subscales appeared to be good due to the significant correlations between HADS and MSIS-29. Receiver operating characteristic (ROC) analysis indicates that the HADS subscales have a significant diagnostic validity for group differentiation. Hierarchical regression analysis using MSIS-29 subscales as criterion variables showed consistent evidence for the incremental validity of the HADS. The HADS is a reliable and valid self-assessment scale in patients with MS and is suggested to be used in clinical monitoring of the psychiatric and psychological status of patients with MS.

Obstructive Sleep Apnea Syndrome: A Preliminary Navigated Transcranial Magnetic Stimulation Study.

PURPOSE: An increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS. SUBJECTS AND METHODS: After acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18-28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed. RESULTS: The study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (ρ=-0.47) with MEP amplitude percentage deviation in OSAS patients. CONCLUSION: The nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.