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Stability is the ability of a drug substance or drug product to remain within established specifications to maintain its identity, strength, quality, and purity throughout the retest or expiration dating periods. Physical, chemical data are generated as a function of time and storage conditions. The purpose of this study is design to evaluate of the stability life of Miconazole muco-adhesive tablets in experiential formula. Tablets used in the Stability study were prepared in three different batches with same preparing percentages. Long-term testing was cover a 180 days duration for three different batches at the time of study. Prepared tablets were storied under conditions of high relative humidity and temperatures that applies particularly to solid stability tests. The prepared samples were analyzed according USP 27 methods of analysis. Assays were performed by HPLC while the dissolution was performed by UV analysis. The assays, dissolutions and disintegration values predicated stable formula under long term stability study conditions. These results had shown non significant changes (p>0.05) for assay and disintegration over 3 years. This formula provided successful distribution of Miconazole in mucoadhesive tablet for mass production. This formula could be achieved for oral disease with high efficiency

Objective: The aim of this study is to evaluate the effects and outcomes of the hybrid education model, which became widespread during the pandemic period, on medical students with attention-deficit/hyperactivity disorder (ADHD) symptoms. Methods: A thorough sociodemographic data form and the Adult ADHD Self-Report Scale (ASRS) were distributed to 531 medical students for this cross-sectional study. The students were contacted via online platforms and offered to complete the form using a Google Forms survey application. Results: It was shown that the individuals in the group with probable ADHD were less motivated outside of the university (P=.002), experienced greater difficulty focusing and paying attention (P < .001), and spent more time in front of screens outside of the classroom (P=.001). Similarly, negative affect scores related to eating habits were higher in the group with probable ADHD (P=.005). Moreover, physical complaints were found to be more frequent in the probable ADHD group (P=

Objective:In diabetes mellitus (DM) patients, in the development of neuropathy and pain, uric acid (UA), C-reactive protein (CRP), γ-glutamyltransferase (GGT), erythrocyte sedimentation rate (ESR), and fibrinogen increased levels may affect the being of neuropathy by increasing oxidative stress through mechanisms related to inflammation and vascular impairment. In the study, we intended to compare serum UA, GGT, CRP, ESR, and fibrinogen levels in type 2 DM patients, with and without polyneuropathy.Method:Ninety-six type 2 DM patients and 24 participants were included in the study. Physical examinations, neuropathic pain scales, laboratory tests (UA, GGT, CRP, ESR, and fibrinogen levels), and electroneuromyography were evaluated.Results:Ninety-six type 2 DM patients and 24 healthy persons were included in the study as the study and control groups. Diabetic polyneuropathy (DPN) patients with neuropathic pain showed that CRP and low-density lipoprotein cholesterol levels were statistically significantly higher. No statistically significant difference was found between the groups in terms of UA, GGT, CRP, and fibrinogen levels.Conclusion:Increased CRP levels in DPN patients with neuropathic pain may reflect the inflammatory mechanisms involved in the pathogenesis of pain associated with DPN.

Plain language summary Child migration is increasingly becoming a common feature of many African countries as children migrate within and away from their countries of origin in search of better livelihoods due to widespread poverty, instability and rapid urbanisation. Many of the migrating children have little or no education and limited employable skills, thereby exposing themselves to sexual and reproductive health (SRH) risks. This paper is a scoping review of existing literature from 2000 to 2019 to document relevant findings on SRH of African migrant and refugee children. The review identified migrant children within refugee camps to experience overcrowding and sexual exploitation amidst limited and underutilized reproductive health services. Language barriers are also key obstacles against young migrants’ access to SRH information and services as these services are delivered in local languages unfamiliar to them. Child migrants continue to suffer from cultural practices including genital cutting with serious reproductive health implications. SRH risk factors of unaccompanied migrant minors remain as a gap in the review and, therefore, more SRH studies on unaccompanied child migrants are needed. Attention should also be paid to the different dimensions of SRH challenges among child migrants to reflect gender differences, whether documented or undocumented, within or across national borders, and within or outside refugee camps for better understanding. In conclusion, child migration in Africa will continue to be economic-driven and will expose the actors to diverse sexual and reproductive health risks. Further in-depth quantitative and qualitative research is required to inform relevant policies on child migrants’ SRH.

Introduction: This study aimed to investigate the possible excitability changes in the trigeminovascular system based on blink reflex (BR) in patients experiencing migraine and to compare migraine aura attacks and attack-free period. Materials and Methods: A total of 56 patients diagnosed with migraine headache with aura and 20 healthy individuals without migraine were evaluated electrophysiologically using the BR test. The BR test was repeated twice in patients with migraines during attacks with aura and attack-free period. Results: During the migraine attack with aura, R1 latencies were shorter, and R2 latencies were longer than in the interictal period. Likewise, R1 latencies were shorter, and R2 latencies were longer, in the interictal period compared to normal values obtained in the control group. Conclusion: The detected BR abnormalities have been thought to be able to reflect migraine-related dysfunction in the brainstem and trigeminovascular connections. Significance: It has been concluded that the detected BR abnormalities might reflect migraine-related dysfunction in the brainstem and trigeminovascular connections, indicating increased neuronal excitability in migraine.

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Amaç: Yakın zamanda yayınlanan karotis arter darlığı tedavisindeki çalışmalar eski sonuçlarla çelişmektedir. Bazı uzmanlar, bu bulguların asemptomatik hastalarda karotis revaskülarizasyona (karotis endarterektomi veya karotis stentleme) konservatif yaklaşımı desteklediğini ifade etmektedir. Bu çalışmanın amacı karotis endarterektomi sonuçlarının preoperatif semptom durumuna dayalı olarak incelenmesidir.Gereç ve Yöntemler: Bu retrospektif çalışmaya Ağustos 2008 ve Ağustos 2015 tarihleri arasında internal karotis arter darlığına karotis endarterektomi uygulanan hastalar dahil edilmiştir. Hastalar preoperative semptomlarına göre iki gruba ayrıldı. Asemptomatik grup preoperatif nörolojik semptomu bulunmayan 41 hasta içermekte ve semptomatik grup preoperatif nörolojik semptomu (vertigo, amorozis fugax, geçici iskemik atak ve iskemik inme) olan 62 hasta içermekte idi. Postoperatif dönemde tüm hastalara kılavuzların önerisine uygun olarak standart tedavi uygulandı.Bulgular: Bu çalışmaya 103 hasta dahil edildi. Hastaların ortalama yaşı 68,20±9,79 (aralık, 41-86) yıl ve 27 (%26,2)’si kadın idi. Gruplar arasında, risk grubu dışında demografik özellikler açısından istatiksel anlamlı farklılık yoktu; asemptomatik grupta yüksek riskli olarak gruplanan hasta daha fazlaydı (p=0,001). Asemptomatik grupta, semptomatik grup ile karşılaştırıldığında postoperatif mortalite istatistiksel olarak anlamlı şekilde daha fazla görüldü (p=0,028). Preoperatif değişkenlerinin hiç biri postoperatif inme ile ilişkili değildi. Semptomatik grupta, postoperatif inme preoperatif geçici iskemik atak ve majör inme olan hastalarda görüldü.Sonuç: Asemptomatik karotis arter hastalığında cerrahi tedavinin zamanlaması hastanın kardiak risk faktörlerine göre yapılmalıdır.

Oral carcinogenesis is a multi-step process, affecting predominantly elderly males with a long history of smoking and alcohol drinking while the role of infectious agents in its progression has not been fully identified. Human cytomegalovirus (HCMV) has been hypothesized in the oral pathogenesis and carcinogenesis. Usually, p16 protein is absent in oral squamous cell carcinoma (OSCC), either for p16 gene being mutated or deleted or its expression being abrogated while p16 expression is associated with favorable prognosis. Is to analyze the concordant impact of p16 expression and HCMV infection on tissues from a group of patients with Oral squamous cell carcinoma (OSCC) in mid-Euphrates-Iraq. One-hundred formalin-fixed, paraffin- embedded Oral tissues enrolled in this study; 40 oral tissue-biopsies from Oral squamous cell carcinoma (OSCC); 40 tissues obtained from patients with benign oral tumors and 20 apparently healthy oral tissues were used as control group. Detection of HCMV was done by chromogenic in situ hybridization (CISH) technique while the protein expression of p16 gene by using immunohistochemistry (IHC) detection system. In OSCC group, the hCMV-positive CISH and the p16-positive IHC reactions were detected in 42.5% and.52.5% of tissues, respectively. The correlation between HCMV and P16 was highly significant (P= 0.003). The significant co-expression of P16 and HCMV genes in OSCC tissues could point for their possible role in either oral pathogenesis or carcinogenesis.

Objectives:Maintaining a balance between controlling epileptic seizures and potential teratogenic effects of anti-epileptic drugs (AEDs) is fundamental in epileptic pregnancies. We aimed to present demographic and clinical data of pregnant women with epilepsy, and determine the potential complications that could occur with the use of AEDs.Methods:A total of 101 pregnancies of 55 epileptic women were retrospectively evaluated. Demographic characteristics, duration of epilepsy, seizure frequency, type and doses of AEDs, delivery mode, birth weight of infants, malformations, abortions, early deliveries, and still-births were registered.Results:Out of 190 patients 55 (28.9%) had experienced pregnancy, and a total number of pregnancies was 101. Mean age of patients was 30.7±9.7 years and mean duration of epilepsy was 14.5±10.8 years. 50 (61.7%) had experienced at least one seizure during pregnancy, while no epileptic seizures were observed in 31 (38.3%). 19.8% resulted in spontaneous abortion, 72.3% with term live birth, 4.9% in preterm delivery, 2% in still-birth, and 1% in premature still-birth. Mean birth weight of infants whose mothers had no AED treatment, those under monotherapy, and those under polytherapy during pregnancy was 3065.4 g, 2941.3 g, and 2696.6 g, respectively. Congenital malformations, namely dextrocardia, hypospadias, and horseshoe kidney were observed in newborns.Conclusion:Epileptic pregnancies frequently result with the delivery of a healthy infant. Planning of antiepileptic therapy in the pre-conceptional period, using the appropriate AED for woman’s seizure disorder as monotherapy in the lowest effective dose throughout pregnancy is important.

Background Internally displaced children are those who have been forced to flee their homes due to severe unfavourable conditions (war, violence or disasters) but have not crossed international borders. Emerging research shows these children face multiple health challenges. However, we found no review focused solely on the health of such internally displaced children. Thus, this review sought to examine what is known about their health and their health concerns.Methods A scoping review of the literature was conducted. A total of 10 databases were searched in January 2019, yielding 6602 articles after duplicates were eliminated. Two research assistants independently selected articles that met inclusion criteria. A numerical summary and thematic analysis were conducted to facilitate data extraction and data analysis.Results A total of 25 articles met the inclusion criteria, including 16 quantitative, 6 qualitative and 3 mixed methods studies. The findings reveal elevated mental health problems and infectious diseases in this population. Findings on the nutritional status of internally displaced children as a broad group are mixed, with some studies showing poorer nutritional status among the children in this group and others showing poorer nutritional health status among host society children. Internally displaced children also experience challenges with access to health services. Premigration factors (trauma) and postmigration factors (humanitarian assistance on displacement) all contribute to the health of internally displaced children.Conclusion Findings provide insight into the complex array of factors influencing the health of internally displaced children. More intervention studies are required to address the needs of this population.

Piyoderma gangrenozum, tahmini insidansı yılda milyon kişi başına 3 ila 10 vaka olan, etiyolojisi açıklanamamış çok nadir görülen bir durumdur. Alt ekstremitenin akut iskemisi ile tetiklenen, daha önce öyküsü olmayan bir pyoderma gangrenozum vakası bildiriyoruz. Yetmiş yedi yaşında kadın hasta acil servise sol alt ekstremite anteriyor yüzde nekrotik yara ile başvurdu. Digital subtraction arteriography ile total tıkalı olduğu saptanan sol ana femoral artere lokal anestezi altında başarılı bir şekilde thrombektomi uygulandı. Nekrotik alan debride edildi ve biyopsiler alındı. Patolojik incelemede pyoderma gangrenozum saptandı ve steroid tedavisi başlandı. Hasta postoperative 10. günde 30 gün boyunca günlük 48 mg prednisone tedavisi ile taburcu edildi. Sebat eden cilt lezyonlu iskemik perifer arter hastalığı olan hastaların tedavisi sırasında, piyoderma gangrenozum ayırıcı tanılar listesinde bulunmalıdır.

Background: Intramedullary neurosarcoidosis may be the first manifestation of the disease and may mimic a tumor clinically and radiographically. Two patients who presented with cervical intramedullary lesions on magnetic resonance imaging (MRI) scans were found to have neurosarcoidosis.Clinical Presentation: Two patients with negative past medical history presented with progressive myelopathic features, and intramedullary cervical lesions were detected on MRI scan; the diagnosis was made on biopsy of the lesions. Early therapeutic intervention led to a favorable outcome.Conclusion: Intra-medullary neurosarcoidosis, especially in the cervical cord, can be the initial presentation of the disease, mimicking a tumor. MRI scan, biopsy, and, in fewer cases, angiotensin-converting enzyme levels can help with the diagnosis and may lead to a favorable outcome. [ABSTRACT FROM AUTHOR]

Introduction: Chronic post-traumatic arteriovenous fistula (AVF) is a late complication of vascular injury and can be presented with symptoms of congestive heart failure, venous hypertension and distal ischaemia. We present an unusual case of chronic leg swelling in adult caused by post-traumatic AVF. Case presentation: A 52 year old white-male patient complained of palpitation, pain and swollen right leg. Arterial pulses distally from the groin were present. His medical history revealed him to have sustained gunshot injury of the left thigh 5 years before. Angiography showed a large AVF between superficial femoral artery and femoral vein. The patient underwent surgical repair of AVF with ligation of AVF between superficial femoral artery under spinal anaesthesia. Completion angiography confirmed AVF exclusion. Leg swelling healed within a month. Conclusion: Post-traumatic fistula should be obliterated as soon as possible. Untreated fistula results in complications including renin-mediated hypertension and high-output heart failure, venous and/or arterial insufficiency. Keywords: Cardiovascular disease, Trauma, Arteriovenous fistula, Lower extremity

The prevalence of Trichomonas vaginalis (TV) and Candida albicans (CA) has been determined in 182 symptomatic married women (70 pregnant and 112 non pregnant) randomly selected from private gynecology clinics in Baghdad city. The relationship between infection and some risk factors was assessed. Data were collected by questionnaire and vaginal swabs were examined microscopically. Of the 182 women the pregnant 4 infected with TV and19 with CA while non-pregnant 2 infected with TV and 14 with CA. The age group between (20-29years) represents the highest frequency of infection with the two microorganisms. Abortion number and monthly family income were statistically non significant with high infection rates.

Factors related with hyperhomocysteinemia (HHcy) and the impact of HHcy in Parkinson’s disease (PD) are not well understood. We investigated the factors associated with increased levels of homocysteine (Hcy) and the relationship between HHcy and motor symptoms, cognitive status, and vascular risk in patients with Parkinson’s disease. Among 60 patients (29 males, 48.3%) with PD, the stage of the disease, the severity of clinical symptoms, and the patients’ cognitive status were measured using a modified Hoehn and Yahr Staging Scale (mHY), Unified Parkinson’s Disease Rating Scale (UPDRS) II and III, and Mini-Mental State Examination (MMSE), respectively. Patients were also noted for having dyskinesia and hallucinations. Serum vitamin B12, folic acid, and plasma Hcy ​​levels were measured. Furthermore, the presence of vascular risk factors was recorded. Finally, we investigated carotid artery intima-media thickening and stenosis using colour Doppler ultrasonography as well as the presence of ischemic lesions using brain imaging techniques. Plasma Hcy ​​levels were higher with advanced age and in males. In addition, there was an inverse relationship between Hcy ​​and vitamin B12 levels. There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions. Plasma Hcy levels may rise due to several factors in PD. However, the resulting HHcy has no significant effect on the clinical picture in terms of motor features, cognitive status, and vascular diseases.

Scientific BACKGROUND: Neuroacanthocytosis consist of a group of rare neurodegenerative disorders associated with acanthocytosis on peripheral blood smear. Chorea-acanthocytosis, a variety of neuroacanthocytosis, is an autosomal recessive condition with clinical and radiologic features similar to Huntington disease. CASE: Forty-eight year old male patient who had the symptoms of involuntary movements, speech disorders, forgetfulness referred to our institution. Neurological examination revealed dysarthria, orofacial dyskinesias, choreoathetosis on arms and legs. The patient’s orofacial dyskinesias and acanthocytes had seen his peripheral blood smear led to the confirm the diagnosis of chorea-acanthocytosis. CONCLUSION: Significant clinical and radiologic similitaries between chorea-acantocytosis and Huntington disease may lead to an initial misdiagnosis. Clinical clues suggestive of chorea-acanthocytosis include orofacial dyskinesias and acanthocytosis on peripheral blood smear can confirm the diagnosis

Background: Immune checkpoint inhibitors are a relatively new advancement in the world of cancer therapy. As such, their adverse effects have yet to be fully understood, with only recent literature documenting autoimmune phenomena secondary to their utilization. Specific immune checkpoint inhibitors have recently been linked with the development of myasthenia gravis, which is classically known to manifest spontaneously in patients. Given the relative rarity of this presentation, the risk of misdiagnosis and subsequent mortality and morbidity is concerning., Case Presentation: We discuss the case of a 73-year-old male who presented with clinical symptoms of myasthenia gravis and myositis shortly after beginning treatment with Pembrolizumab. The diagnosis of myasthenia gravis was initially missed at an outside hospital, which delayed initiation of proper treatment., Conclusion: While the incidence of "de-novo" diseases secondary to immune checkpoint inhibitors might be increasing, guidelines regarding best treatment options do not yet exist, leaving many providers at a loss when faced with making clinical decisions surrounding patients with De novo myasthenia gravis. Thus, our goal is to underscore the importance of early recognition of this disease, and emphasize the need for a standard of care as immune checkpoint inhibitors usage becomes more prevalent., (© 2024. The Author(s).)

Introduction/Aims . Primary lateral sclerosis (PLS) is exceedingly rare and has been an enigmatic disease. Recent progress has drastically changed this perception, with early biomarkers being investigated and potential medications for PLS emerging at the preclinical stage. The aim of this paper is to describe a study of PLS natural history and discuss the limitations and proposed solutions to the study of a rare and slowly progressive disease. Methods . The PLS Natural History Study is a 30-site, 24-month, prospective study that is supported by multiple funding sources. The study aims to enroll 50 early PLS (disease duration ≤4 years) and 50 definite PLS (disease duration 4 to 15 years) participants using modified PLS Diagnostic Criteria. Smartphone-based assessments including semi-quantitative and quantitative measures and patient-reported outcomes are utilized. In-person quantitative measures are also completed during site visits. The change in the PLS Functional Rating Scale score is the primary outcome. The study utilizes the NeuroBANK ® patient-centric data capture and management platform. The biostatistical analysis plan has been developed. Results . In one year, 28 participants have been recruited. Enrollment has been much slower than anticipated due to the COVID-19 pandemic, the rarity of PLS, and potential study competition for internal resources from ALS clinical trials. Discussion . We discuss the need for more innovative methods to enroll and study individuals with such rare diseases and propose a number of mechanisms by which more efficient enrollment could be facilitated.

Background: Amyotrophic lateral sclerosis (ALS) is a rare disease with urgent need for improved treatment. Despite the acceleration of research in recent years, there is a need to understand the full natural history of the disease. As only 40% of people living with ALS are eligible for typical clinical trials, clinical trial datasets may not generalize to the full ALS population. While biomarker and cohort studies have more generous inclusion criteria, these too may not represent the full range of phenotypes, particularly if the burden for participation is high. To permit a complete understanding of the heterogeneity of ALS, comprehensive data on the full range of people with ALS is needed., Methods: The ALS Natural History Consortium (ALS NHC) consists of nine ALS clinics and was created to build a comprehensive dataset reflective of the ALS population. At each clinic, most patients are asked to participate and about 95% do. After obtaining consent, a minimum dataset is abstracted from each participant's electronic health record. Participant burden is therefore minimal., Results: Data on 1925 ALS patients were submitted as of 9 December 2022. ALS NHC participants were more heterogeneous relative to anonymized clinical trial data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. The ALS NHC includes ALS patients of older age of onset and a broader distribution of El Escorial categories, than the PRO-ACT database., Conclusions: ALS NHC participants had a higher diversity of diagnostic and demographic data compared to ALS clinical trial participants.Key Messages What is already known on this topic: Current knowledge of the natural history of ALS derives largely from regional and national registries that have broad representation of the population of people living with ALS but do not always collect covariates and clinical outcomes. Clinical studies with rich datasets of participant characteristics and validated clinical outcomes have stricter inclusion and exclusion criteria that may not be generalizable to the full ALS population. What this study adds: To bridge this gap, we collected baseline characteristics for a sample of the population of people living with ALS seen at a consortium of ALS clinics that collect extensive, pre-specified participant-level data, including validated outcome measures.How this study might affect research , practice, or policy: A clinic-based longitudinal dataset can improve our understanding of the natural history of ALS and can be used to inform the design and analysis of clinical trials and health economics studies, to help the prediction of clinical course, to find matched controls for open label extension trials and expanded access protocols, and to document real-world evidence of the impact of novel treatments and changes in care practice.

Aim: Parkinson's disease (PD) is a progressive neurological disorder that predominately affects dopaminergic neurons. We believe that this pooling of data will help to better understand the prodromal nature of depression in PD. Materials & methods: We conducted this study in accordance with PRISMA guidelines 2020. Fifteen eligible articles were shortlisted for final analysis. Risk of bias assessment was also conducted Results: The random-effect model revealed that the risk of subsequent PD in patients with prodromal depression was twice as likely (odds ratio, 2.04; 95% CI, 1.02-4.08) as compared with a healthy population. Conclusion: Our meta-analysis concluded that the subsequent risk of PD is significantly higher in patients with depression as compared with healthy individuals.

Carpal tunnel syndrome, ulnar neuropathy at the elbow, and peroneal neuropathy are the most common mononeuropathies; however, other individual nerves may also be injured by various processes. These uncommon mononeuropathies may be less readily diagnosed owing to unfamiliarity with the presentations and vague symptoms. Electrodiagnostic studies are essential in the evaluation of uncommon mononeuropathies and can assist in localization and prognostication. However, they can also be challenging; stimulation at the proximal sites is difficult and well-validated reference values are not available. This article reviews the electrodiagnostic assessment of several uncommon upper and lower extremities mononeuropathies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to reldesemtiv 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Results: Patients ( N  = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance ( p  = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R, p  = 0.09; muscle strength mega-score, p  = 0.31). Post hoc analyses pooling all active reldesemtiv -treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). Reldesemtiv was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Conclusions: Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring reldesemtiv for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of reldesemtiv on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898).

Importance: Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers. There are no comparative studies that identify the most effective medication for pain reduction in CSPN., Objective: To determine which medication (pregabalin, duloxetine, nortriptyline, or mexiletine) is most effective for reducing neuropathic pain and best tolerated in patients with CSPN., Design, Setting, and Participants: From December 1, 2014, through October 20, 2017, a bayesian adaptive, open-label randomized clinical comparative effectiveness study of pain in 402 participants with CSPN was conducted at 40 neurology care clinics. The trial included response adaptive randomization. Participants were patients with CSPN who were 30 years or older, with a pain score of 4 or greater on a numerical rating scale (range, 0-10, with higher scores indicating a higher level of pain). Participant allocation to 1 of 4 drug groups used the utility function and treatment's sample size for response adaptation randomization. At each interim analysis, a decision was made to continue enrolling (up to 400 participants) or stop the whole trial for success (80% power). Patient engagement was maintained throughout the trial, which helped guide the study and identify ways to communicate and disseminate information. Analysis was performed from December 11, 2015, to January 19, 2018., Interventions: Participants were randomized to receive nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69)., Main Outcomes and Measures: The primary outcome was a utility function that was a composite of the efficacy (participant reported pain reduction of ≥50% from baseline to week 12) and quit (participants who discontinued medication) rates., Results: Among the 402 participants (213 men [53.0%]; mean [SD] age, 60.1 [13.4] years; 343 White [85.3%]), the utility function of nortriptyline was 0.81 (95% bayesian credible interval [CrI], 0.69-0.93; 34 of 134 [25.4%] efficacious; and 51 of 134 [38.1%] quit), of duloxetine was 0.80 (95% CrI, 0.68-0.92; 29 of 126 [23.0%] efficacious; and 47 of 126 [37.3%] quit), pregabalin was 0.69 (95% CrI, 0.55-0.84; 11 of 73 [15.1%] efficacious; and 31 of 73 [42.5%] quit), and mexiletine was 0.58 (95% CrI, 0.42-0.75; 14 of 69 [20.3%] efficacious; and 40 of 69 [58.0%] quit). The probability each medication yielded the highest utility was 0.52 for nortriptyline, 0.43 for duloxetine, 0.05 for pregabalin, and 0.00 for mexiletine., Conclusions and Relevance: This study found that, although there was no clearly superior medication, nortriptyline and duloxetine outperformed pregabalin and mexiletine when pain reduction and undesirable adverse effects are combined to a single end point., Trial Registration: ClinicalTrials.gov Identifier: NCT02260388.

Introduction: Our research aim was to develop a novel clinimetric scale sensitive enough to detect disease progression in primary lateral sclerosis (PLS)., Methods: A prototype of the PLS Functional Rating Scale (PLSFRS) was generated. Seventy-seven participants with PLS were enrolled and evaluated at 21 sites that comprised the PLSFRS study group. Participants were assessed using the PLSFRS, Neuro-Quality of Life (QoL), Schwab-England Activities of Daily Living (ADL), and the Clinical Global Impression of Change scales. Participants completed telephone assessments at 12, 24, and 48 weeks after enrollment., Results: The PLSFRS demonstrated internal consistency as well as intrarater, interrater, telephone test-retest reliability, and construct validity. Significant changes in disease progression were detected at 6 and 12 months; changes measured by the PLSFRS vs the ALSFRS-R were significantly higher., Discussion: The PLSFRS is a valid tool to assess the natural history of PLS in a shorter study period., (© 2019 Wiley Periodicals, Inc.)

Objective: To assess the intraepidermal nerve fiber density in patients diagnosed with fibromyalgia (FM) and to evaluate the role of IgM binding to trisulfated heparin disaccharide (TS-HDS) in these patients., Methods: FM is a poorly understood pain disorder with several proposed pathophysiologic mechanisms. It is characterized by widespread pain, fatigue, and sleep abnormalities. Small fiber neuropathy (SFN) has been proposed as an underlying mechanism, and patients with FM have been shown to have a reduction in the intraepidermal nerve fiber density. An underlying inflammatory process that could be a result of autoimmune phenomena has also been suggested. Non-length-dependent SFN (NLDSFN) has been shown to have a higher incidence of autoimmune disease. Twenty-two patients with established diagnosis of FM underwent skin biopsy at 2 sites; 10 cm above the lateral malleolus and 10 cm above the patella. Serum IgM binding to TS-HDS was assayed using an ELISA method., Results: A total of 5/22 patients had positive TS-HDS antibodies; of these, 4 had NLDSFN (P = 0.0393). Comparison with a control group at Washington University showed no significant difference in percentage with TS-HDS antibodies (P = 0.41). When compared with Washington University database of skin biopsy, there was a trend for an increased percentage of NLDSFN in patients with FM (P = 0.06)., Conclusions: This study further supports the hypothesis that a subgroup of patients with FM has SFN. We suggest a correlation between the presence of NLDSFN and TS-HDS antibodies.

Introduction: Rasagiline is a monoamine oxidase B (MAO-B) inhibitor with possible neuroprotective effects in patients with amyotrophic lateral sclerosis (ALS)., Methods: We performed a randomized, double-blind, placebo-controlled trial of 80 ALS participants with enrichment of the placebo group with historical controls (n = 177) at 10 centers in the United States. Participants were randomized in a 3:1 ratio to 2 mg/day rasagiline or placebo. The primary outcome was average slope of decline on the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary measures included slow vital capacity, survival, mitochondrial and molecular biomarkers, and adverse-event reporting., Results: There was no difference in the average 12-month ALSFRS-R slope between rasagiline and the mixed placebo and historical control cohorts. Rasagiline did not show signs of drug-target engagement in urine and blood biomarkers. Rasagiline was well tolerated with no serious adverse events., Discussion: Rasagiline did not alter disease progression compared with controls over 12 months of treatment. Muscle Nerve 59:201-207, 2019., (© 2018 Wiley Periodicals, Inc.)

Idiopathic inflammatory myopathies (IIM) are a group of chronic, autoimmune conditions affecting primarily the proximal muscles. The most common types are dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myopathy (NAM), and sporadic inclusion body myositis (sIBM). Patients typically present with sub-acute to chronic onset of proximal weakness manifested by difficulty with rising from a chair, climbing stairs, lifting objects, and combing hair. They are uniquely identified by their clinical presentation consisting of muscular and extramuscular manifestations. Laboratory investigations, including increased serum creatine kinase (CK) and myositis specific antibodies (MSA) may help in differentiating clinical phenotype and to confirm the diagnosis. However, muscle biopsy remains the gold standard for diagnosis. These disorders are potentially treatable with proper diagnosis and initiation of therapy. Goals of treatment are to eliminate inflammation, restore muscle performance, reduce morbidity, and improve quality of life. This review aims to provide a basic diagnostic approach to patients with suspected IIM, summarize current therapeutic strategies, and provide an insight into future prospective therapies.

Background: Chronic herpes simplex virus type-1 encephalitis (HSE-1) is uncommon. Past reports focused on its association with prior documented acute infection. Here, we describe a patient with increasingly intractable epilepsy from chronic HSE-1 reactivation without history of acute central nervous system infection., Case Presentation: A 49-year-old liver transplant patient with 4-year history of epilepsy after initiation of cyclosporine developed increasingly frequent seizures over 3 months. Serial brain magnetic resonance imaging showed left temporoparietal cortical edema that gradually improved despite clinical decline. Herpes simplex virus type-1 (HSV-1) DNA was detected in cerebrospinal fluid by polymerase chain reaction. Cerebrospinal fluid HSV-1&2 IgM was negative. Seizures were controlled after acyclovir treatment, and the patient remained seizure free at 1-year follow-up., Conclusion: Chronic HSE is a cause of intractable epilepsy, can occur without a recognized preceding acute phase, and the clinical course of infection may not directly correlate with neuroimaging changes.