The comparative effectiveness of fingolimod, natalizumab, and ocrelizumab in relapsing-remitting multiple sclerosis.

BACKGROUND: Fingolimod, natalizumab, and ocrelizumab are commonly used in the second-line treatment of relapsing-remitting multiple sclerosis (RRMS). However, these have only been compared in observational studies, not in controlled trials, with limited and inconclusive results being reported. A comparison of their effect on relapse and disability in a real-world setting is therefore needed. OBJECTIVES: The objective of this study was to compare the efficacy of fingolimod, natalizumab, and ocrelizumab in reducing disease activity in RRMS. METHODS: This multicenter, retrospective observational study was carried out with prospectively collected data from 16 centers. All consecutive RRMS patients treated with fingolimod, natalizumab, and ocrelizumab were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores, and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), time to first relapse, and disability accumulation were compared. RESULTS: Propensity score matching retained 736 patients in the fingolimod versus 370 in the natalizumab groups, 762 in the fingolimod versus 434 in the ocrelizumab groups, and 310 in the natalizumab versus 310 in the ocrelizumab groups for final analyses. Mean ARR decreased markedly from baseline after treatment in all three treatment groups. Mean on-treatment ARR was lower in natalizumab-treated patients (0.09, 95% confidence interval (CI), 0.07-0.12) than in those treated with fingolimod (0.17, 0.15-0.19, p<0.001), ocrelizumab (0.08, 0.06-0.11), and fingolimod (0.14, 0.12-0.16, p=0.001). No significant difference was observed in mean on-treatment ARR between patients treated with natalizumab (0.08, 0.06-0.11) and ocrelizumab (0.09, 0.07-0.12, p=0.54). Compared to fingolimod, the natalizumab and ocrelizumab groups exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients at year 1. No significance differences in disability accumulation were determined between the therapies. CONCLUSION: Natalizumab and ocrelizumab exhibited similar effects on relapse control, and both were associated with better relapse control than fingolimod. The effects of the three therapies on disability outcomes were similar.

Surface electromyographic activity of submental muscles during different types of swallow-specific tasks: A comparative study.

BACKGROUND: Repetitive performance of a motor task has been proposed to increase the ability to perform that motor task. Therefore, exercise training including swallow-specific task may be an optimal training to improve swallowing function. OBJECTIVES: To determine the submental muscles activity during different types of swallow-specific tasks (effortful swallow, ES; tongue-hold swallow, THS; swallow with Kinesio taping, SwKT; and head extension swallowing exercise, HESE) compared to normal swallow (NS), and also compare these tasks within themselves. METHODS: Thirty-five healthy adults participated in this prospective experimental study with one participant group. The surface electromyography (sEMG) was used to evaluate submental muscles activity while performing swallow-specific tasks. RESULTS: While the greatest submental muscles activity was revealed during the ES, HESE, NS and THS tasks, respectively, the lowest was obtained during SwKT. When compared to NS, ES caused a statistically greater submental muscles activity (p1  = .000 and p2  = .000), although SwKT revealed a lower submental muscles activity (p1  = .002 and p2  = .000). When swallow-specific tasks were compared within themselves, ES caused the highest muscles activity (p < .005) than all other tasks, and HESE caused higher muscles activity than THS and SwKT (p < .005). CONCLUSION: Different swallow-specific tasks can cause increased or decreased submental muscles activity compared to NS task. Since ES and HESE are superior in selective submental muscles, they appear to be more promising in terms of submental muscles gains in long-term exercise training.

Retrospective analysis of effectiveness of fingolimod in real life setting in Turkey (REFINE).

BACKGROUND: During multiple sclerosis (MS) treatment different modes of action such as lateral (interferon beta to glatiramer acetate or glatiramer acetate to interferon beta) or vertical (interferon beta/glatiramer acetate to fingolimod) drug switch can be performed. This study aims to investigate the clinical effectiveness of switching from the first-line injectable disease modifying treatments (iDMTs) to fingolimod (FNG) compared to switching between first-line iDMTs. METHODS: This is a multicenter, observational and retrospective study of patients with relapsing-remitting MS who had lateral and vertical switch. The observation period included three key assessment time points (before the switch, at switch, and after the switch). Data were collected from the MS patients' database by neurologists between January 2018 and June 2019. The longest follow-up period of the patients was determined as 24 months after the switch. RESULTS: In 462 MS patients that were included in the study, both treatments significantly decreased the number of relapses during the postswitch 12 months versus preswitch one year while patients in the FNG group experienced significantly fewer relapses compared to iDMT cohort in the postswitch 12 months period. FNG cohort experienced fewer relapses than in the iDMT cohort within the postswitch 2 year. The mean time to first relapse after the switch was significantly longer in the FNG group. DISCUSSION: The present study revealed superior effectiveness of vertical switch over lateral switch regarding the improvement in relapse outcomes. Patients in the FNG cohort experienced sustainably fewer relapses during the follow-up period after the switch compared the iDMT cohort. Importantly, switching to FNG was more effective in delaying time to first relapse when compared with iDMTs.

Best Practice Recommendations for Stroke Patients with Dysphagia: A Delphi-Based Consensus Study of Experts in Turkey-Part I: Management, Diagnosis, and Follow-up.

Dysphagia is one of the most common and important complications of stroke. It is an independent marker of poor outcome after acute stroke and may become chronic after the acute period and continues to affect all aspects of the patient's life. Patients with stroke may encounter any of the medical branches in the emergency room or outpatient clinic, and as in our country, there may not be specialists specific for dysphagia, such as speech-language pathologists (SLP), in every hospital. This study aimed to raise awareness and create a common opinion of medical specialists for stroke patients with dysphagia. This recommendation paper has been written by a multidisciplinary team and offers 45 recommendations for stroke patients with dysphagia. It was created using the eight-step Delphi round via e-mail. This study is mostly specific to Turkey. However, since it contains detailed recommendations from the perspective of various disciplines associated with stroke, this consensus-based recommendation paper is not only a useful guide to address clinical questions in practice for the clinical management of dysphagia in terms of management, diagnosis, and follow-up, but also includes detailed comments for these topics.

Best Practice Recommendations for Stroke Patients with Dysphagia: A Delphi-Based Consensus Study of Experts in Turkey-Part II: Rehabilitation.

Dysphagia is one of the most common and important complications of stroke. It is an independent marker of poor outcome following acute stroke and it continues to be effective for many years. This consensus-based guideline is not only a good address to clinical questions in practice for the clinical management of dysphagia including management, diagnosis, follow-up, and rehabilitation methods, but also includes detailed algorithms for these topics. The recommendation paper has been written by a multidisciplinary team and offers 117 recommendations for stroke patients with dysphagia. While focusing on management principles, diagnosis, and follow-up in the 1st part (45 items), rehabilitation details were evaluated in the 2nd part (72 items).

Infliximab-induced retrobulbar optic neuritis in a patient with ankylosing spondylitis.

Objective: To present a case with infliximab-induced retrobulbar optic neuritis. Case description: A 58-year-old woman presented to our clinic with a two-day history of blurred vision in her right eye. She had numerous uveitis attacks previously, and she was on infliximab treatment for ankylosing spondylitis. Her best-corrected visual acuity was counting fingers and 20/25 in the right and left eye, respectively. Optic discs seemed healthy in fundoscopic examination. The right optic nerve showed high signal intensity on magnetic resonance imaging (MRI). Infliximab treatment was discontinued and systemic steroid therapy was started. After the treatment her best-corrected visual acuity improved to 20/20 in her right eye. Conclusion: Infliximab is a chimeric human-murine monoclonal antibody used in autoimmune diseases. Optic neuritis is a rare but important side effect of infliximab. Thus, infliximab-induced optic neuritis should be kept in mind for patients receiving infliximab treatment.

Anorexia nervosa and Wernicke Korsakoff's syndrome: atypical presentation by acute psychosis.

A 16-year-old girl was admitted to the emergency department because of acute changes in mental state such as paranoid and nihilistic delusions, confabulations, and distortions of body schema perception. Her history was compatible with anorexia nervosa in that she had lost more than 17 kg in weight over one and a half years. Her body mass index was 14. She was diagnosed with Wernicke Korsakoff's syndrome and was given intravenous thiamine at 250 mg/day. Response was dramatic for nystagmus and gait incoordination but not for other symptoms. After dosage was increased to 750 mg/day all symptoms including psychosis improved. With her increase in food consumption, secondary deterioration was observed and diagnosed as refeeding syndrome. After proper replacements she was completely normal in the 9th month, and her weight was 55 kg. This patient was interesting for the presenting symptoms (psychosis), and improvement by high doses of thiamine replacement, and also for refeeding syndrome during this period.

The relationship between insulin resistance and hypercoagulability in acute ischemic stroke.

AIM: Insulin resistance has effects on the coagulation system, which is important in the acute phase of infarct. We examined the relationships between insulin resistance, hemostatic markers and stroke severity in acute ischemic stroke patients. METHODS: Protein C (PC), protein S (PS), fibrinogen, von Willebrand factor and antithrombin III (AT III) were studied in 75 acute ischemic stroke patients with and without insulin resistance. RESULTS: The PC and PS levels of insulin-resistant patients were significantly lower than those of non-insulin-resistant patients (PC: 87 ± 19.23 vs. 97.89 ± 13.3%, p = 0.007; PS: 84.75 ± 15.72 vs. 93.21 ± 15.02%, p = 0.02), and both of the anticoagulants were correlated with the homeostasis model assessment (HOMA; r = -0.339, p = 0.003 and r = -0.481, p = 0.000, respectively). Additionally, the NIH Stroke Scale (NIHSS) score correlated negatively with PS (r = -0.329, p = 0.004) and AT III levels (r = -0.235, p = 0.04). The parameters with positive correlations with NIHSS were fibrinogen (r = 0.270, p = 0.019), fasting glucose (r = 0.358, p = 0.008) and HOMA (r = 0.286, p = 0.013). CONCLUSIONS: The significant associations between insulin resistance and hemostatic markers may be relevant to stroke severity by causing a procoagulant tendency in acute ischemic stroke.

Hereditary thrombophilic factors in stroke due to cerebral infarct.

BACKGROUND: The stroke is the third most common cause of all deaths. In new studies, the importance of hereditary thrombophilic factors on stroke is emphasized. The aim of this study is to determine the role of hereditary thrombophilic factors including factor V Leiden A1691G (FVL), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations in patients with stroke because of cerebral infarct. METHODS: Twenty-four patients with stroke and 53 controls with risk factor for stroke were enrolled. Polymerase chain reaction was used to detect these mutations. RESULTS: Heterozygote FVL mutation in 2 (8.3%) patients and MTHFR mutation in 10 (41.7%) patients were detected. In the control group, there were 2 (3.8%) patients with heterozygote FVL mutation and 15 (28.3%) patients with MTHR mutation. Both FVL and MTHFR gene mutations were detected in 1 patient and 2 controls, respectively. Prothrombin gene mutation was not found in 2 groups. There were not statistically significant differences for all 3 mutations in-between 2 groups (P > 0.05). Odds ratios were 0.431 (0.074-2.504, 95% CI) for FVL mutation and 0.553 (0.221-1.381, 95% CI) for MTHFR mutation, respectively. CONCLUSION: Although our study group was small, hereditary thrombophilic factors might not be risk factors for stroke because of cerebral infarct.

A Custom-made Pupillometer System for Characterizing Pupillary Light Response.

OBJECTIVES: This paper presents the design and construction of a viable pupillometer system and demonstrates its merits with extensive validation tests. MATERIALS AND METHODS: A web camera was modified by removing its infrared filter and mounted on a chin rest. Light emitting diodes (LEDs) operating at infrared and visible spectra were integrated to provide background and light stimulus, respectively. The LEDs were controlled by a microprocessor board. Stimulation was presented using a periodic paradigm with variable period and duty cycle. Videos of both pupils were recorded at 30 frames/second and processed offline using software developed in-house. The overall system was validated with data gathered from individuals with healthy vision under different stimulation paradigms. Temporal variations in pupil size were determined and analyzed statistically. RESULTS: The analysis revealed that the pupil sizes were accurately measured from the video frames provided that reflections from both infrared and visible lights remain outside the pupil. The system achieved moderate to excellent repeatability scores (87.8 and 86.8% for short 1 second and long 2 second pulses, respectively), which demonstrated its effectiveness and confirmed that it can be used reliably as a pupillometer. CONCLUSION: The proposed pupillometer system produces useful, quantitative data characterizing pupillary light response. However, further development and implementation are needed to potentially turn it into a low-cost alternative for other studies involving the autonomic nervous system, cognitive function, drug metabolism, pain response, psychology, fatigue, and sleep disorders.

Proximal femoral conductions in patients with lumbosacral radiculoplexus neuropathy.

OBJECTIVES: Lumbosacral radiculoplexus neuropathy (DLRPN) is a rare form of neuropathy observed in diabetic and rarely non-diabetic patients. Pathophysiology and lesion location are not clearly understood. Our aim was to analyze proximal and distal femoral conductions in patients with DLRPN. METHODS: Six patients with DLRPN, 14 patients with diabetic polyneuropathy and 25 healthy subjects were included in the study. We performed L3 monopolar root stimulation and femoral nerve trunk stimulation at the inguinal region and calculated lumbar plexus conduction time by subtracting the latency of compound muscle action potential (CMAP) of the vastus medialis evoked by femoral nerve stimulation from the latency of CMAP of vastus medialis evoked by L3 root stimulation. Additionally peak to peak amplitudes and areas of CMAPs were analyzed. RESULTS: Electrophysiological examination showed that there was an axonal involvement in all patients with DLRPN. Prolonged lumbar plexus conduction time (in five extremities), and prolonged distal latency of the femoral nerve (in five extremities) probably due to secondary demyelination were also observed. Similar abnormalities were not observed in the diabetic polyneuropathy group. CONCLUSIONS: DLRPN may affect different localizations on the peripheral nerves. L3 root stimulation may have an important role in the electrodiagnosis of DLRPN.

Epilepsy and seropositivity rates of Toxocara canis and Toxoplasma gondii.

PURPOSE: Increased seropositivity for Toxoplasma gondii and Toxocara canis have been observed in epileptic patients. Our aim is to determine whether there is any relationship between these agents and epilepsy in our cryptogenic epilepsy group. MATERIAL AND METHODS: We studied specific IgG antibodies against T. gondii and T. canis in 100 cryptogenic epileptic patients and 50 healthy volunteers that had no history of epilepsy in their first degree relatives. We studied T. gondii and T. canis-specific IgG antibody serum levels and compared the values of these two groups. RESULT: We found similar T. gondii and T. canis serum IgG antibodies in patients with cryptogenic epilepsy and in the control group, even though the control group included more animal owners. CONCLUSION: We did not show any relationships between epilepsy and positive T. gondii and T. canis serology in our epileptic patients.

Oxidative stress in acute ischemic stroke.

Oxidative stress plays an important role in acute ischemic stroke pathogenesis. Free radical formation and subsequent oxidative damage may be a factor in stroke severity. Serum levels of nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) were measured within the first 48 h of stroke in 70 patients. The levels were also correlated with the clinical outcomes using Canadian Neurological Scale (CNS) scores. The results were compared with a control group consisting of 70 volunteers with similar stroke risk factors. Serum NO, MDA and GSH levels were significantly elevated in acute stroke patients. CNS score was negatively correlated with both MDA and NO levels. However, no statistically significant correlation between GSH levels and CNS scores was detected. Our results suggest deleterious effects of oxidative stress on clinical outcome in acute ischemic stroke. The elevation of GSH levels may be an adaptive mechanism during this period.

Association of central pontin myelinolysis and extra-pontin myelinolysis in diabetic patient.

Central pontin myelinolysis and extra-pontin myelinolysis (CPM/EPM) implies the clinical picture after rapid recovery of hyponatremia or hyponatremia alone. SPM/EPM picture can occur without hyponatremia. Findings such as dysarthria, dysphagia, tetraparesia/plegy accompanies the clinical table. Our case was also diabetic, but there were no electrolyte imbalance in admission. The presence of diarrhea in medical history of the patient might indicate a short-term undetected electrolyte imbalance. In our diabetic case that has borderline metabolic status and lack of any detected electrolyte imbalance, we decided to present SPM/EPM table together with literature information.

Insomnia and dementia: is agomelatine treatment helpful? Case report and review of the literature.

The treatment of sleep disorders in Alzheimer's disease (AD) may be quite challenging in elderly patients because of drug side effects or interactions and comorbid local or systemic diseases. Here, we report a patient with AD, who was suffering from severe insomnia and depression. We ordered agomelatine for the treatment of insomnia in this patient, and it was quite helpful not only for insomnia but also for depression and for the cognitive symptoms related with dementia. Our aim was to share these observations for similar patients.

Sympathetic skin response in idiopathic and diabetic carpal tunnel syndrome.

BACKGROUND: In carpal tunnel syndrome (CTS), certain changes were expected in sympathetic skin response (SSR) because median nerve carries postganglionic unmyelinated fibres. PURPOSE: To investigate the median and ulnar SSR in idiopathic and diabetic CTS without autonomic dysfunction in hands and to find possible relations with electrophysiological features of these diseases. PATIENTS AND METHODS: SSRs were elicited by electrical stimulation on the supraorbital nerve and recorded from the median and ulnar territories in the hand from 20 diabetic patients with only CTS (29 hands), 24 idiopathic CTS patients (42 hands) and 13 normal subjects (26 hands). Hands with ulnar neuropathy at the wrist without symptoms and normal hands of unilateral CTS were excluded. In addition to classical parameters and comparative methods, SSR waveform changes and percentile method was used in finding abnormality. RESULTS: Median SSRs had significant delayed latency compared to ulnar latency in both CTS patients but this was not important clinically (1.38/1.37 s for idiopatic CTS; 1.43/1.36 s for diabetic CTS). Median and ulnar SSR amplitude, area, median/ulnar latency difference, amplitude and area ratio were compared and only median/ulnar latency difference and median/ulnar latency ratio were found different between the three groups. Four idiopathic CTS hands were outside of the limits or absent (9.5%). SSR waveforms were significantly different from normal subjects in CTS patients. P type SSR replaced M type in idiopathic CTS and N type in diabetic CTS. CONCLUSIONS: Findings regarding SSR parameters suggest that unmyelinated C fibers were affected in CTS. These values were not useful because they were too small. Data on SSR were not normally distributed and the percentile method seems to be more convenient for finding any abnormality in clinical practice. Also, SSR waveform analysis could give us valuable data and should add to the SSR examination parameters.

Evoked potentials and disability in multiple sclerosis: A different perspective to a neglected method.

UNLABELLED: Evoked potentials and disability in multiple sclerosis: a different perspective to a neglected method. OBJECTIVE: Because evoked potentials (EP) are reflections of the functional integrity of sensory-motor systems, they are expected to reflect the abnormality in patients with disabilities and handicaps and also be in correlation with scales. This assumption was tested. METHODS: Patients with multiple sclerosis (MS) and myelopathy (M) and normal controls were investigated by EP, Multiple Sclerosis Walking Scale-12, timed 25-foot walk test and extended disability status scale (EDSS). EP results were converted to ordinal values, and correlations of these values with scales were calculated. Sensitivity and specificity analysis of EP parameters was also performed. RESULTS: Total EP scores revealed high rates of abnormality in both groups, but MS revealed a different correlation pattern from M. The SEP+MEP summed score showed high sensitivity and specificity for MS and this was also correlated with the MS-related disability-ambulation scales including EDSS. The most specific parameter was the minimum M latency in the MEP study. CONCLUSIONS: Four extremity recordings of EP with the use of more parameters than usual and ordinal expression of results seem to be benefical in MS. Although this study was cross sectional in nature, results indicated that EP might be useful in clinical follow up.

Diagnostic value of "dysphagia limit" for neurogenic dysphagia: 17 years of experience in 1278 adults.

OBJECTIVE: Neurogenic dysphagia (ND) is a prevalent condition that accounts for significant mortality and morbidity worldwide. Screening and follow-up are critical for early diagnosis and management which can mitigate its complications and be cost-saving. The aims of this study are to provide a comprehensive investigation of the dysphagia limit (DL) in a large diverse cohort and to provide a longitudinal assessment of dysphagia in a subset of subjects. METHODS: We developed a quantitative and noninvasive method for objective assessment of dysphagia by using laryngeal sensor and submental electromyography. DL is the volume at which second or more swallows become necessary to swallow the whole amount of bolus. This study represents 17 years experience with the DL approach in assessing ND in a cohort of 1278 adult subjects consisting of 292 healthy controls, 784 patients with dysphagia, and 202 patients without dysphagia. A total of 192 of all patients were also reevaluated longitudinally over a period of 1-19 months. RESULTS: DL has 92% sensitivity, 91% specificity, 94% positive predictive value, and 88% negative predictive value with an accuracy of 0.92. Patients with ALS, stroke, and movement disorders have the highest sensitivity (85-97%) and positive predictive value (90-99%). The clinical severity of dysphagia has significant negative correlation with DL (r=-0.67, p<0.0001). CONCLUSIONS: We propose the DL as a reliable, quick, noninvasive, quantitative test to detect and follow both clinical and subclinical dysphagia and it can be performed in an EMG laboratory. SIGNIFICANCE: Our study provides specific quantitative features of DL test that can be readily utilized by the neurologic community and nominates DL as an objective and robust method to evaluate dysphagia in a wide range of neurologic conditions.

Sub-acute sensory neuronopathy as a preceding sign of recurrence in colon carcinoma.

Subacute sensory neuronopathy is a paraneoplastic syndrome, which occurs mostly in lung, breast, ovarian malignancies and lymphoma. A 75-yr-old woman who was at the twentieth month of her postoperative follow-up owing to colon adenocarcinoma admitted with subacute sensory neuronopathy. Six months later from the first, neuropathic symptoms liver metastases developed. To the best of our literature review subacute sensory neuronopathy as a preceding sign of recurrence in colon adenocarcinoma has not previously been reported. We conclude that, in the case of subacute sensory neuronopathy without an obvious underlying etiological factor, an occult malignity should always be researched in clinical practice.

Iron deficiency anemia and restless legs syndrome: is there an electrophysiological abnormality?

OBJECTIVE: The pathogenesis of restless legs syndrome (RLS) is unknown. Although iron deficiency anemia (IDA) is related with RLS, the mechanism of this relationship is still unknown. Therefore, we decided to examine some neurophysiological parameters that reflect the function of brainstem, spinal cord and peripheral nervous system. MATERIALS AND METHODS: 34 patients diagnosed with IDA at the hematology department were questioned with a structured battery for RLS and additional symptoms. Of those, 14 patients had symptoms of RLS, while remaining 20 had no signs of this disorder. In both groups, electrophysiological examination including motor and sensory nerve conduction, F-responses, H-reflex, blink-reflex, and mixed nerve silent periods was performed. RESULTS: Neurological examination of all patients was normal. The two groups were identical for age and sex, and the difference between both groups concerning motor and sensory nerve conduction, F-wave, H-reflex, blink-reflex, and mixed nerve silent periods was insignificant. CONCLUSION: Results suggest that IDA does not cause electrophysiological changes in the peripheral nerves, spinal cord and brainstem, and therefore, measurement of these parameters in IDA patients does not seem effective for the confirmation of RLS.