Concentric needle jitter analysis of the genioglossus muscle in patients with motor neuron disease.

OBJECTIVES: Difficulty relaxing the genioglossus muscle makes the evaluation of spontaneous activity problematic in patients with motor neuron disease (MND). We performed jitter analysis using conventional disposable concentric needle electrodes (CNEs) of the voluntarily activated genioglossus muscle in patients with and without MND to detect the denervation-reinnervation process. METHODS: CNE jitter analysis was performed at the genioglossus muscle in 21 MND(+) patients and 22 MND(-) subjects. The jitter analysis was considered abnormal if the jitter values exceeded these limits for the mean consecutive difference (MCD) or the individual MCD in more than 10% of readings. RESULTS: Seventeen MND(+) patients (81%) had at least three abnormal individual jitter values whereas denervation findings were obtained in eleven of them during the needle electromyographic examination at genioglossus muscle. None of the MND(-) subjects showed CNE jitter abnormality. CONCLUSION: CNE jitter analysis of genioglossus muscle may provide an useful information that may be suggestive of a diagnosis of MND/ALS.

Effects of Clozapine on Cortical Inhibition: A Transcranial Magnetic Stimulation Follow-up Study.

BACKGROUND: Preclinical and clinical investigations have revealed deficits in cortical inhibition in individuals with schizophrenia. Transcranial magnetic stimulation, a commonly used noninvasive measurement technique, is used for assessing these deficits. Limited research has been conducted on the effects of antipsychotic medications on cortical inhibition. This study aimed to evaluate the effects of clozapine on cortical inhibition with transcranial magnetic stimulation longitudinally and compare it with unaffected controls. METHODS: Ten patients who started clozapine were assessed at baseline, with 8 reassessed after 4 months. Eight age- and sex-matched unaffected controls were included. Psychopathology, neurocognitive performance, formal thought disorder, and disability were assessed, and the cortical excitability parameters (resting motor threshold, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, and short-latency afferent inhibition [SAI]) were measured at baseline and four months after clozapine treatment. RESULTS: Resting motor threshold, ICF, and SAI were significantly different between patients and controls at baseline, whereas resting motor threshold, SAI, and ICF became similar to controls after clozapine with only ICF having a trend for significance. Clozapine prolonged cortical silent period significantly in the patients. CONCLUSIONS: This is the first study to investigate the effect of clozapine on SAI, a potential cholinergic biomarker, and the first follow-up study to investigate the relationship between the effects of clozapine on cortical inhibition and cognition. Clozapine seems to cause an increase in cortical inhibition through GABAergic and possibly cholinergic mechanisms. However, additional follow-up studies with larger sample sizes are required to reach more robust conclusions.

Winged Scapula: Clinical and Electrophysiological Features and Common Causes Based on 20 Years of Experience in a Referral Center in Turkey.

PURPOSE: Winged scapula (WS) is a functionally disabling problem and it occurs because of neurogenic causes frequently. The authors aimed to assess WS patients by physical and electrodiagnostic examinations as well as some further investigations and define the common causes of WS. METHODS: The authors reviewed clinical and neurophysiological findings of 52 patients who were referred for electrodiagnostic examination because of WS in the period of 20 years. RESULTS: The mean age was 39 (range, 11-73) years and 32 were male patients. Right side was involved in 60% of patients (n = 31). According to electrodiagnostic examinations, 44 patients (85%) had neurogenic causes; 29 spinal accessory nerve palsy (17 occurred after surgical procedure), nine long thoracic nerve palsy (four occurred after strenuous activity), two dorsal scapular nerve (both neuralgic amyotrophy), one long thoracic nerve and spinal accessory nerve (relevant with strenuous trauma), one spinal accessory nerve and dorsal scapular nerve palsies (after surgical procedure and radiotherapy), one C5-7 radiculopathy (avulsion), and one brachial plexopathy (obstetric trauma). Five patients (10%) had muscle-related findings (four facio-scapulo-humeral dystrophy and one Duchenne muscular dystrophia) and three patients (5%) had normal findings (bone-joint related). CONCLUSIONS: This study presents a relatively large series of patients with WS because of several causes from a referral tertiary EMG laboratory. The authors found that spinal accessory nerve palsy after neck surgery is the most common cause and long thoracic nerve palsy is the second common cause of unilateral WS. Electrodiagnostic examinations should be performed in WS patients to establish exact diagnosis and reveal some coexistence of WS causes.

Multimodal integration and modulation of visual and somatosensory inputs on the corticospinal excitability.

OBJECTIVE: Corticospinal excitability may be affected by various sensory inputs under physiological conditions. In this study, we aimed to investigate the corticospinal excitability by using multimodal conditioning paradigms of combined somatosensory electrical and visual stimulation to understand the sensory-motor integration. METHODS: We examined motor evoked potentials (MEP) obtained by using transcranial magnetic stimulation (TMS) that were conditioned by using a single goggle-light-emitting diode (LED) stimulation, peripheral nerve electrical stimulation (short latency afferent inhibition protocol), or a combination of both (goggle-LED+electrical stimulation) at different interstimulus intervals (ISIs) in 14 healthy volunteers. RESULTS: We found MEP inhibition at ISIs of 50-60 ms using the conditioned goggle-LED stimulation. The combined goggle-LED stimulation at a 60 ms ISI resulted in an additional inhibition to the electrical stimulation. CONCLUSIONS: Visual inputs cause significant modulatory effects on the corticospinal excitability. Combined visual and somatosensory stimuli integrate probably via different neural circuits and/or interneuron populations. To our knowledge, multimodal integration of visual and somatosensory inputs by using TMS-short latency inhibition protocol have been evaluated via electrophysiological methods for the first time in this study.

Immunotherapy Provides Electrophysiological Recovery and Excellent Clinical Response in Sjogren's Syndrome-Linked Quite Severe Autonomic Neuropathy.

INTRODUCTION: The autonomic system is frequently affected in Sjogren's syndrome (SS), but presentation with severe autonomic neuropathy is infrequent. Herein, we present a patient with primary SS-linked autonomic neuropathy, which is significantly clinic and electrophysiological responsive to immunotherapy. CASE REPORT: A 29-year-old female patient was admitted to our neurology department with recurrent syncope, postural light-headedness, and weight loss. Neurological examination revealed tonic pupils. The baseline composite autonomic symptom score-31 was 51 (0 to 75), and baseline functional ability score was 10 (0 to 100%). In the follow-up, syncope episodes that frequently develop during the day required the patient to lie in the supine position in bed all day and were triggered even by coming to a slightly sitting position. Neurophysiologic testing showed evidence of cardiovagal and sudomotor impairment. The patient was diagnosed with SS after detailed investigations. A 5-day course of intravenous immunoglobulin (IVIg) was given, and she continued IVIg once a month. After 6 months, she could walk long distances without support, and gastrointestinal complaints and syncopes had significantly decreased. After ~1.5 years, she had a composite autonomic symptom score-31 score of 11 and a functional ability score of 80%. Control heart rate variability analysis showed a significant improvement in the values of SD of the RR interval and root mean square of successive RR interval differences. CONCLUSIONS: In SS-linked severe autonomic neuropathy, immunotherapy can provide electrophysiological recovery in addition to excellent clinical response.

Multimodal assessment of intensive care unit-acquired weakness in severe stroke patients.

BACKGROUND: Intensive care unit-acquired weakness (ICUAW) defines generalized muscle weakness seen in critically ill patients in the absence of other causative factors. Herein, we aimed to evaluate ICUAW in stroke patients by electrodiagnostic testing, histopathology, and assessment of respiratory complex activities (RCA), to define the frequency of ICUAW in this patient group, and to reach new parameters for early prediction and diagnosis. METHODS: We prospectively recruited twenty-four severe acute stroke patients during a sixteen-month period. In addition to serial nerve conduction studies (NCS), we performed muscle biopsy and RCA analysis on the non-paretic side when ICUAW developed. Patients undergoing orthopedic surgery without metabolic and neuromuscular diseases constituted the control group for RCA. Survival and longitudinal data were analyzed by joint modeling to determine the relationship between electrophysiological parameters and ICUAW diagnosis. RESULTS: Eight patients (33%) developed ICUAW, and six of them within the first two weeks. Extensor digitorum brevis, abductor digiti minimi (ADM), rectus femoris and vastus medialis (VM) compound muscle action potential (CMAP) amplitudes showed a significant decrease in the ICUAW group. VM CMAP amplitude (BIC = 358.1574) and ADM CMAP duration (BIC = 361.1028) were the best-correlated parameters with ICUAW diagnosis. The most informative electrophysiological findings during the entire study were obtained within the first 11 days. Muscle biopsies revealed varying degrees of type 2 fiber atrophy. Complex I (p = 0.003) and IV (p = 0.018) activities decreased in patients with ICUAW compared to controls. CONCLUSION: VM CMAP amplitude and ADM CMAP duration correlate well with ICUAW diagnosis, and may aid in the early diagnosis.

Neurologic manifestations in children with COVID-19 from a tertiary center in Turkey and literature review.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory disease and multisystem inflammatory syndrome in children (MIS-C) are main clinical presentations in children, numerous neurological manifestations are being described increasingly. We aimed to investigate new onset neurological symptoms associated with SARS-CoV-2 in pediatric patients in order to establish a possible relationship as well as to understand the underlying pathophysiological mechanisms between SARS-CoV-2 infection and neurological findings. METHODS: We analyzed retrospectively children who had neurologic manifestations temporally associated with SARS-CoV-2 infection at Hacettepe University Ihsan Dogramaci Children's Hospital. We performed a literature search between March 20, 2020 and March 30, 2021. Articles that report children with COVID-19 related neurological manifestations were included. RESULTS: We have observed 15 consecutive cases with new onset neurological manifestations along with confirmed SARS-CoV-2 infection. Age at hospitalization ranged from three months to 17 years. Ten patients had central nervous system involvement, and most common manifestation was encephalopathy (5/10), which is also one of the most common manifestations of the patients mentioned in the relevant 39 articles we reviewed. CONCLUSION: Children with COVID-19 can present with neurologic findings such as encephalopathy, seizures, cerebrovascular events as well as abnormal eye movements. Clinical suspicion and awareness are required to show the association between neurologic manifestations and COVID-19.

Isolated spinal cord granulomatous angiitis: a case report and review of the literature.

INTRODUCTION: Isolated spinal cord angiitis (ISCA) is very rare disease. But, it is frequently encountered in the differential diagnosis of atypical spinal cord syndromes. CASE PRESENTATION AND REVIEW OF THE LITERATURE: We present a 31-year-old male who presented with progressive paraparesis, and diagnosed with pathologically confirmed ISCA. Longitudinal cystic transverse myelitis was documented in spinal MRI. He responded well to cyclophosphamide and steroid combination, and no relapse was noted during the 4-year follow-up. A standard systematic analysis of the germane literature disclosed 15 more ISCA cases. In total 16 cases (mean age: 46.5, 10 males), ISCA was diagnosed with pathological evaluation in all (Biopsy in 11, Autopsy in 5). MRI lesion is characterized by usually multisegmental longitudinal and sometimes cystic expansile lesions. In seven cases, it was described as "(pseudo)tumoral" by the authors. Albeit absence of elevation of CSF protein/WBC or "compatible" spinal MRI lesion may aid to exclude ISCA to some extent, pathological confirmation is currently necessary for the diagnosis. In 11 cases, ISCA was treated similar to primary supratentorial vasculitis. Mortality rate is 31%. DISCUSSION: ISCA diagnosis, a typical example of which we have presented here, can only be established by tissue examination. However, noninvasive diagnostic criteria are critically needed. Our data suggest that this can only be possible with multinational multicenter prospective registry.

Cystinosis beyond kidneys: gastrointestinal system and muscle involvement.

BACKGROUND: Cystinosis is a multisystemic disease resulting from cystine accumulation primarily in kidney and many other tissues. We intended to study the evolution of less commonly seen extrarenal complications of cystinosis in a group of patients who have periods without cysteamine treatment. METHODS: Gastrointestinal and muscular complications of cystinosis were studied in a group of 21 patients. RESULTS: Twenty one patients were included in the study. Among them, 14 were homozygous and 3 were compound heterozygous for CTNS mutations. The median age of diagnosis was 15 months (range; 5 months-14 years) and the mean age at last visit was 11.3 ± 6.5 years. Nine patients (42%) had end stage renal disease at a mean age of 10.6 years (6.5-17 years). Abdominal ultrasonography and portal vein doppler ultrasonography were performed in19 patients, 14 of them (74%) had hepatomegaly, 10 patients (53%) had granular pattern or heterogeneity of liver. Only one patient had high transaminase levels and liver biopsy showed cystine crystals in the liver. Eleven patients (58%) had borderline or increased portal vein minimum and maximum flow velocities. One patient had CK level of 9024 U/L and electromyographic study showed active myopathic involvement. Two patients were found to have gastroesaphageal reflux only and 4 patients were found to have esophageal remnants in addition to reflux. CONCLUSIONS: In addition to renal functions, extrarenal organs may be affected from cystine accumulation even in childhood, especially in patients who are incompliant to treatment, resulting in complications such as swallowing difficulty, hepatomegaly and portal hypertension.

Tracking Pain in Resting State Networks in Patients with Hereditary and Diabetic Neuropathy.

INTRODUCTION: Chronic pain is associated with maladaptive plastic changes in the brain. It is usually more prominent in acquired pathologies of nerve fibers as in diabetic neuropathy despite less severe degeneration than hereditary neuropathies. Based on clinical differences concerning pain perception, we hypothesized that functional connectivity analysis would reveal distinct patterns in resting-state networks in these groups. METHODS: Ten diabetic patients with painful neuropathy (5F/5M; mean age=50.10±6.05 years), 10 patients with hereditary neuropathy (5F/5M; mean age=37.80±14.01 years), 18 age-and gender-matched healthy controls (eight for painful diabetic neuropathy and 10 for hereditary neuropathy) and seven diabetic controls without painful neuropathy were enrolled in the study. All subjects (n=45) underwent a 5-min resting-state scan in a 3T magnetic resonance scanner. The images were analyzed with seed-based functional connectivity method. The group-level maps of the default mode network and insula-cingulate network were identified for each group. RESULTS: Patients with hereditary neuropathy displayed increased connectivity between left insula and left anterior cingulate cortex and inversely correlated activity between left insula and left inferior parietal lobule compared to their controls. In patients with painful diabetic neuropathy, the major findings were the increased connectivity between left anterior cingulate cortex and posterior cingulate cortex/precuneus, and the increased connectivity between medial prefrontal cortex and left medial temporal region compared to their controls. CONCLUSION: This study revealed that hereditary and diabetic painful neuropathy patients exhibit different patterns of functional connectivity. The clinical differences in these groups regarding the presence of neuropathic pain may relate to this difference in cortical organization.

Electrophysiologic evaluation of facial nerve functions after oxaliplatin treatment.

PURPOSE: This study analyzes the effect of oxaliplatin treatment on the facial nerve. The facial nerve is the most commonly paralyzed cranial motor nerve because it advances through a long, curved bone canal. Electroneurography and blink reflex are the electrophysiological measurements used for evaluating facial nerve function. Oxaliplatin is a cytotoxic agent used in adjuvant or palliative systemic therapy for colorectal cancer treatment. METHODS: This study was performed on 20 individuals who were at least 18 years old at Hacettepe University Ear Nose Throat Department, Audiology and Speech Disorders Unit, and Neurology Division EMG Laboratory as they received oxaliplatin treatment from Hacettepe University Oncology Hospital. Electroneurography and blink-reflex values were recorded and examined. The parameters taken during the second and fourth months were compared for this purpose. RESULTS: This study shows that the prolongation of distal latencies of compound muscle action potential is statistically significant, the amplitudes showed no difference. The ENoG results were analyzed, the prolongation of latency measurements between pre-treatment and the fourth month after treatment were statistically significant. The blink-reflex results showed that comparison with the baseline values, the prolongation of latencies in R1 measurements between pre-treatment, the second month, and the fourth month were significant. CONCLUSIONS: The facial nerve is affected asymptomatically by oxaliplatin treatment. During oxaliplatin treatment, the evaluation of facial nerve function could be beneficial for patients by improving their quality of life. Electroneurography and blink-reflex tests can be used in the early evaluations of different medicines to determine their neurotoxicity.

Cardiac autonomic function evaluation in pediatric and adult patients with congenital myasthenic syndromes.

Cardiac autonomic dysfunction has been examined in myasthenia gravis but not in congenital myasthenic syndromes (CMS). We aimed to evaluate cardiac autonomic functions in genetically defined CMS. Patients diagnosed with and under treatment for CMS were reviewed for 24-hour cardiac rhythm monitoring. Heart rate variability (HRV) measures were defined as: SDNN, mean of the standard deviations for all R-R intervals; SDNNi, standard deviation of all R-R intervals in successive five-minute epochs; RMSSD, square root of the mean of squared differences between successive R-R intervals. Ten patients with mutations in the epsilon subunit of the acetylcholine receptor (AChRε) and five patients with mutations in the collagen-like tail of asymmetric acetylcholinesterase (ColQ) were included. Median age at evaluation was 17 (2.5-46) years. In the AChRε group, RMSSD values; and in the ColQ group, SDNN, SDNNi and RMSSD values were significantly lower than those of healthy subjects. This first extensive report examining HRV in CMS showed alterations in patients with ColQ mutations and, to a lesser extent, in the group with AChRε mutations. This might indicate an increased risk of cardiac arrhythmias. We suggest cardiological follow-up in CMS, and consideration of any potential cardiovascular effects of therapeutic agents used in management.

Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Swallowing Function and Quality of Life of Post-stroke Patients.

Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive techniques, which is used to modulate cortical regions in patients with stroke. The aim of this single blind, controlled study was to investigate the effect of rTMS on swallowing function and quality of life of mono-hemispheric post-stroke patients with dysphagia. Twenty-eight patients were randomized and split between study and control group. Each group received conventional dysphagia rehabilitation 3 days a week for 4 weeks, and study group also received 1 Hz rTMS to unaffected hemisphere in the final week. The descriptive information was noted. The clinical and radiological swallowing evaluation and quality of life assessment have been performed at four different times including before and after the treatment, 1 month and 3 months after the treatment. At baseline, no significant differences were observed between groups in terms of demographic and clinical features (p > 0.05). Swallowing function and quality of life of the patients were statistically improved in both groups towards the third month (p < 0.05). Swallowing function was comparable between two groups. However, a significant improvement was observed on appetite, fear of eating, and mental health parameters of quality of life assessment in the study group compared to the control group (p < 0.05). In conclusion, despite positive changes in some aspects of quality of life, rTMS did not enhance the swallowing function when compared conventional dysphagia rehabilitation. Therefore, the application of 1 Hz rTMS should be reconsidered to improve swallowing function in the chronic period.

Alteration of the affective modulation of the startle reflex during antidepressant treatment.

Whereas the amplitude of the startle reflex varies with stimulus valence in the normal population, a lack of this affective modulation has been reported in patients with major depressive disorder. The present study sought to clarify blunted startle modulation as a feature of depression by comparing 16 patients diagnosed with major depression prior to and after 2 weeks of SSRI treatment, and 16 healthy controls. The affect-modulated startle reflex paradigm and the Self-Assessment Manikin were used to probe affective reactivity. In addition, a preliminary analysis of change in affective reactivity pattern was performed with depressed patients who could be assessed in the eighth week of treatment (n = 13). The control group showed a linear trend in response across valence categories, which was stable over sessions. Blunted affective reactivity was observed only in the patients and persisted after 2 weeks of treatment. Nevertheless, a linear trend could be detected in the eighth week of treatment. These findings confirm that the affective reactivity is blunted in depression and provide initial evidence for the lack of change in the early phase of SSRI antidepressant treatment. Nevertheless, in a small group, the emergence of a linear trend in response was evident later with treatment. Large-scale studies are required to assess the relation between the treatment response and the change in affective modulation of the startle reflex, as a potential biomarker.

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation.

OBJECTIVE: This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. MATERIALS AND METHODS: We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. RESULTS: Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. CONCLUSION: Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects.

The genetic work-up of arthrogryposis is challenging due to the diverse clinical and molecular etiologies. We report a-183/12-year-old boy, from a 2nd degree consanguineous family, who presented at 36/12 years with hypotonia, distal laxity, contractures, feeding difficulties at birth. He required surgery for progressive scoliosis at 16 years of age, and walked independently since then with an unstable gait and coordination defects. His latest examination at 18 years of age revealed a proprioceptive defect and loss-of-joint position sense in the upper limbs. Somatosensory evoked potentials supported bilateral involvement of dorsal column-medial lemniscal sensory pathways and nerve conduction studies revealed a mild axonal neuropathy. Muscle biopsy showed myopathic changes with neonatal myosin expression. Mendeliome sequencing led to the discovery of a recessive stop mutation in piezo-type mechanosensitive ion channel component 2 (PIEZO2, NM_022068, c.1384C>T, p.R462*). PIEZO2 is a nonselective cation channel, expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs. Dominant PIEZO2 mutations were described in patients with distal arthrogryposis type 5 and Marden-Walker syndrome. Sensory ataxia and proprioception defect with dorsal column involvement together with arthrogryposis, myopathy, scoliosis and progressive respiratory failure may represent a distinct clinical phenotype, and indicate recessive mutations in PIEZO2.