Isaacs' syndrome: Clinical and paraclinical perspectives in a series of cases.

Background: Isaacs' syndrome is a form of generalized peripheral nerve hyperexcitability (PNH) causing increased and continuous muscle activity characterized by muscle twitching, stiffness, cramps, myokymia, and pseudomyotonia. Herein, we aimed to review the clinical and paraclinical aspects of Isaacs' syndrome in a number of cases. Methods: We reported a series of 12 patients with Isaacs' syndrome, including their clinical features, electrophysiological findings, laboratory parameters, malignancy work-up, and therapeutic management. Results: In all cases, clinical and electrodiagnostic assessment was suggestive of Isaacs' syndrome. Of the 12 studied cases, 5 patients were positive for both leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies, 5 patients were CASPR2 positive and LGI1 negative, and 1 had borderline positive titers for CASPR2 with negative LGI1 antibody. The search for underlying malignancies was inconclusive in all subjects. After symptomatic treatment, mostly with carbamazepine or gabapentin, immunotherapies with double filtration plasmapheresis or Intravenous immunoglobulin (IVIG) provided favorable outcomes. Ultimately, all subjects fully recovered after 3-6 months of follow-up and all signs and symptoms resolved. Conclusion: Despite the rarity of the disease, our results provide valuable information for understanding the epidemiological, clinical, and paraclinical features of Isaacs' syndrome.

Anticoagulation in the management of septic cavernous sinus thrombosis secondary to rhino-orbito-cerebral mucormycosis: A retrospective real-world experience.

Background: COVID-19 was associated with an increased number of patients with mucormycosis (MCR), followed by septic cavernous sinus thrombosis (SCST). We evaluated the association between anticoagulation (AC) and mortality/morbidity of COVID-19-associated MCR (CAM)-induced SCST. Methods: In this retrospective study, neurological sequelae, functional outcomes, and in-hospital mortality were compared between AC receivers and non-receivers. In addition, the association between AC and survivability was examined. Results: Twenty-nine patients (17 male; mean age: 51.27 years) with CAM-induced SCST were included in the study. The median intervals between COVID-19 and MCR, and COVID-19 and SCST were 19 and 27 days, respectively. Among AC recipients, the interval between SCST and AC initiation was 18 days, with an AC duration of 37 days. Baseline and management-related characteristics were comparable between AC recipients and non-recipients (P > 0.050). AC receivers (n = 15) and non-receivers (n = 14) did not significantly differ in terms of the proportion of sequelae (6/15 vs. 5/14; P = 1.000), complete recovery (2/15 vs. 4/14; P = 0.687), and in-hospital mortality (3/15 vs. 3/14; P > 0.999). Nevertheless, AC recipients had a longer hospital stay (72.0 vs. 35.5; P = 0.016). AC-related characteristics (AC receiving, type, early initiation, and duration) were not significantly different between survivors and non-survivors, or between recovered and disabled patients. Conclusion: In our study, CAM-induced SCST in-hospital mortality/morbidity did not differ between AC receivers and non-receivers. AC characteristics were not different between survivors and non-survivors, or recovered and disabled patients. However, the small sample size may have limited the ability to detect significant differences, leading to inconclusive results.

New diagnosis of multiple sclerosis in the setting of recent Sinopharm COVID-19 vaccine (BBIBP-CorV) exposure: A series of clinical cases and updated review of the literature.

Background: Multiple sclerosis (MS) is the most common cause of non-traumatic disability in young individuals. There are limited reports of developing demyelinating events following the coronavirus disease 2019 (COVID-19) vaccination. Methods: We reported all individuals (n = 8) with new MS diagnoses with recent exposure (≤ 6 weeks) to the Sinopharm (BBIBP-CorV) vaccine between September 2021 and June 2022. We also reviewed the related literature published as of September 2023. Results: Of 338 newly diagnosed patients with MS who attended our tertiary referral MS center during the study period, 8 (2.36%) had their first demyelinating attack with a median interval of 2 [2.0, 4.0] weeks following the Sinopharm vaccine (sex ratio 1:1, median age: 20.5 [18.0, 27.0] years). No personal or family history of autoimmune/neurological disorders was documented, except for one patient's history of a previous potential demyelinating event and another's family history of immune thrombocytopenic purpura (ITP). All patients had demyelinating brain MRI lesions, and 4 had cervical spinal cord involvement. The brain areas most commonly affected were the periventricular and subcortical regions. Positive oligoclonal bands (OCBs) in all patients supported the MS diagnosis. All patients were diagnosed with relapsing-remitting MS and received intravenous methylprednisolone (IVMP) alone or in combination with plasma exchange (3/8). Rituximab was the most frequently used disease-modifying treatment (3/8). Conclusion: This study provides preliminary evidence of a potential association between the Sinopharm vaccine and the initial manifestations of MS. However, further larger-scale studies with control groups and long-term follow-ups are needed to confirm this association and determine the underlying mechanisms.

Incidence trends, histological subtypes, and topographical distribution of bladder cancer in Iran: a study based on the Iranian National Cancer Registry during 2006-2015.

Background: Bladder cancer (BCa) is a significant public health concern. This study aimed to analyze the incidence trends, histological subtypes, and topographical distribution of BCa in Iran over a decade. Methods: This retrospective registry-based study analyzed data on BCa patients diagnosed between March 20, 2006, and March 20, 2015. Following data quality control, age-standardized incidence rates (ASIRs) were calculated for BCa overall, by sex and histological subtype using the new World Health Organization (WHO) standard population. Results: We identified 51,379 BCa cases (81.97% male) with a mean age of 65.10 ± 14.89 years. The overall ASIR was 8.92 per 100,000 (95% CI: 8.84-9.00). While a modest increase in ASIR was observed overall (8.77 in 2006 to 9.64 in 2015) and among males (14.13 in 2006 to 15.95 in 2015) during the study period, males consistently had a significantly higher ASIR compared to females (approximately 4.5:1 ratio). BCa incidence showed a progressive increase across older age groups, particularly those aged 40-44 to 80-84 years. Urothelial cell carcinoma (UCC) was the most prevalent histological type (ASIR: 8.19 to 7.93), followed by adenocarcinoma (AC; ASIR: 0.13 to 0.11). Squamous cell carcinoma (SCC) displayed a decreasing trend (ASIR: 0.11 to 0.06). Both UCC and AC were more frequent in males (approximately 5 and 3 times higher than females, respectively). Malignant neoplasm of the bladder, unspecified, constituted over 95% of BCa topography classifications. Conclusion: This study identified a modest rise in BCa incidence, with male predominance and a higher burden in older adults. Further investigation into potential risk factors contributing to this increase is warranted.

Optical coherence tomography angiography measurements in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease: A systematic review and meta-analysis.

PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are immune-mediated disorders that can often manifest with optic neuritis (ON) among other symptoms. Optical coherence tomography angiography (OCTA) is an emerging diagnostic method that can quantify retinal capillary blood flow and vessel density (VD), which have been shown to be affected in NMOSD and MOGAD. Hence, we aimed to systematically review the studies addressing retinal microvasculature using OCTA in these diseases. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, and Web of Sciences were systematically searched to identify articles addressing OCTA measurements in patients with NMOSD or MOGAD. Following the data extraction, a meta-analysis was performed on the study population and OCTA types amongst at least two homogenous studies. RESULTS: Twenty-two studies on NMOSD, MOGAD, or both were included. Parafoveal superficial retinal capillary plexus (SRCP) VD and radial peripapillary capillary (RPC) VD were diminished in NMOSD ON+ and NMOSD ON- groups compared to healthy controls (HCs). In addition, both the SRCP VD and RPC VD were significantly reduced in NMOSD ON+ compared to NMOSD ON-. However, meta-analysis for deep retinal capillary plexus (DRCP) did not show a significant difference between NMOSD patients and HCs, or among ON+ and ON- patients. Furthermore, there was no significant difference in foveal avascular zone (FAZ) area size between NMOSD patients and HCs. Regarding MOGAD, the meta-analysis showed decreased parafoveal SRCP VD and RPC VD in MOGAD ON+ patients compared to HCs. Comparing NMOSD ON+ and MOGAD ON+, a meta-analysis was conducted for RPC VD, which showed no significant difference between the two groups. CONCLUSIONS: This systematic review and meta-analysis confirmed reduced VD in the macular and peripapillary areas in NMOSD and MOGAD eyes, particularly in the parafoveal SRCP and RPC, which is further impacted by prior ON.

Immunogenicity, clinical efficacy, and safety of the sinopharm (BBIBP-CorV) SARS-CoV-2 vaccine among people with multiple sclerosis receiving disease-modifying therapies: a prospective cohort study.

BACKGROUND: To investigate the safety (adverse events [AEs] and post-vaccination multiple sclerosis [MS] activity within 6 weeks), clinical efficacy (protection against coronavirus disease 2019 [COVID-19]), and vaccine-induced humoral immunogenicity (SARS-CoV-2 neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG) of the Sinopharm (BBIBP-CorV) vaccine among people with MS (PwMS) receiving different disease-modifying therapies (DMTs). METHODS: This prospective cohort study was conducted between November 2021 and May 2022. PwMS were followed for six months after the 2nd dose of vaccination. Antibody responses were measured 2-16 weeks after the 2nd dose injection. Multivariate logistic regression was employed to assess the impact of each DMT on dichotomous antibody responses, adjusting for age, sex, MS phenotype, expanded disability status scale, disease duration, and vaccination-antibody titration interval. RESULTS: Among the 261 screened PwMS, 209 (aged 38.23 ± 9.73 years, female: 70.8%; relapsing-remitting MS: 80.4%) were included. The frequencies of experiencing non-serious AEs and post-vaccination MS activity were 66.0% and 4.8%, respectively. Breakthrough COVID-19 infection was observed in 14.8% of the PwMS. A subcohort of 125 PwMS was assessed for antibody responses. Positive neutralizing antibodies, anti-nucleocapsid IgG, and anti-spike IgG were detected in 36.8%, 35.2%, and 52.0% of the PwMS, respectively. Multivariate regression indicated a 96% (OR: 0.04 [95% CI: 0.00, 0.51], P = 0.013), 93% (OR: 0.07 [0.01, 0.64], P = 0.019), and 89% (OR: 0.11 [0.01, 0.96], P = 0.045) reduced odds of positive neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG, respectively, among fingolimod-receivers. Additionally, anti-CD20s-receivers had 88% (OR: 0.12 [0.02, 0.85], P = 0.034) lower odds of being positive for anti-nucleocapsid IgG. CONCLUSIONS: BBIBP-CorV appeared to be well tolerated in PwMS, with promising clinical efficacy. However, a suboptimal humoral response was observed in PwMS receiving fingolimod and anti-CD20s. Future research should investigate the relationship between humoral responses and the frequency and severity of COVID-19 infection across various DMTs.

Association of new onset seizure and COVID-19 vaccines and long-term follow-up: A systematic review and meta-analysis.

OBJECTIVE: Seizures have been reported as an adverse event of the COVID-19 vaccine. However, there is no solid evidence of increased seizure occurrence compared to the general population. This study was undertaken to investigate seizure occurrence among COVID-19 vaccine recipients compared to unvaccinated controls. METHODS: A systematic search was made of PubMed, Web of Science, Scopus, and Cochrane Library up to April 9, 2024. Studies reporting seizure occurrence following COVID-19 vaccination were included. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and was conducted using random- and common-effect models. The risk of bias in the studies was evaluated by the Newcastle-Ottawa Scale. The outcome of interest was new onset seizure incidence proportion compared among (1) COVID-19 vaccine recipients, (2) unvaccinated cohorts, and (3) various types of COVID-19 vaccines. RESULTS: Forty studies were included, of which seven entered the meta-analysis. Results of the pooled analysis of the new onset seizure incidence (21- or 28-day period after vaccination) in 13 016 024 vaccine recipients and 13 013 262 unvaccinated individuals by pooling the cohort studies did not show any statistically significant difference between the two groups (odds ratio [OR] = .48, 95% confidence interval [CI] = .19-1.20, p = .12, I2 = 95%, τ2 = .7145). Pooling four studies accounting for 19 769 004 mRNA versus 47 494 631 viral vector vaccine doses demonstrated no significant difference in terms of new onset seizure incidence between the groups (OR = 1.18, 95% CI = .78-1.78, p = .44, I2 = 0%, τ2 = .004). SIGNIFICANCE: This systematic review and meta-analysis shows no statistically significant difference in the risk of new onset seizure incidence between COVID-19 vaccinated individuals and unvaccinated individuals.

Impact of Multiarterial Revascularization on Long-term Major Adverse Cardiovascular Events After Coronary Bypass in 23,798 Patients.

BACKGROUND: This study evaluated the association between bypass grafting with multiarterial grafts (MAG) and single arterial grafts (SAG) and all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE), overall and across different patient subgroups from a Middle Eastern nation. METHODS: This single-center retrospective cohort study included 23,798 patients. MAG and SAG groups were balanced using inverse probability weighting (IPW). Associations between MAG and outcomes were assessed using Cox regression. A series of covariate-adjusted Cox models were conducted to evaluate the effect of MAG on outcomes at different levels of independent variables, including age, sex, and cardiovascular risk factors. RESULTS: In the study population (73.9% were men, 65.11 ± 9.94 years), 986 patients (4.1%) underwent MAG. Compared with the SAG group, MAG had lower crude mortality (14.1% vs 21.6%) and MACCE (28.8% vs 34.7%) rates during a median follow-up of 9.23 years (quartile 1-quartile 3, 9.13-9.33 years). Although MAG was significantly associated with reduced risk of study outcomes at the univariate level, these associations disappeared after matching (all-cause mortality (IPW hazard ratio, 0.90; 95% CI, 0.67-1.22) and MACCEs (IPW hazard ratio, 0.94; 95% CI, 0.76-1.15). However, covariate-adjusted models indicated that MAG was associated with a significantly reduced risk of adverse events, particularly MACCEs, in men, younger patients, and those without risk factors. CONCLUSIONS: MAG was not associated with improved postsurgery outcomes among the total coronary artery bypass graft population. Our findings, however, should be interpreted in the context of a relatively low total institutional MAG burden. Choosing a second arterial conduit over saphenous vein grafts in specific patient subgroups might be reasonable. This hypothesis-generating finding should be investigated in future clinical trials in these patients.

The hidden link: How oral and respiratory microbiomes affect multiple sclerosis.

BACKGROUND: Extensive research has explored the role of gut microbiota in multiple sclerosis (MS). However, the impact of microbial communities in the oral cavity and respiratory tract on MS is an emerging area of investigation. PURPOSE: We aimed to review the current literature related to the nasal, oral, and lung microbiota in people with MS (PwMS). METHODS: We conducted a narrative review of clinical and preclinical original studies on PubMed that explored the relationship between the bacterial or viral composition of the nasal, lung, and oral microbiota and MS. Additionally, to find relevant studies not retrieved initially, we also searched for references in related review papers, as well as the references cited within the included studies. RESULTS AND CONCLUSIONS: Thirteen studies were meticulously reviewed in three sections; oral microbiota (n = 8), nasal microbiota (n = 3), and lung microbiota (n = 2), highlighting considerable alterations in the oral and respiratory microbiome of PwMS compared to healthy controls (HCs). Genera like Aggregatibacter and Streptococcus were less abundant in the oral microbiota of PwMS compared to HCs, while Staphylococcus, Leptotrichia, Fusobacterium, and Bacteroides showed increased abundance in PwMS. Additionally, the presence of specific bacteria, including Streptococcus sanguinis, within the oral microbiota was suggested to influence Epstein-Barr virus reactivation, a well-established risk factor for MS. Studies related to the nasal microbiome indicated elevated levels of specific Staphylococcus aureus toxins, as well as nasal glial cell infection with human herpes virus (HHV)-6 in PwMS. Emerging research on lung microbiome in animal models demonstrated that manipulating the lung microbiome towards lipopolysaccharide-producing bacteria might suppress MS symptoms. These findings open avenues for potential therapeutic strategies. However, further research is crucial to fully understand the complex interactions between the microbiome and MS. This will help identify the most effective timing, bacterial strains, and modulation techniques.

Biallelic NDC1 variants that interfere with ALADIN binding are associated with neuropathy and triple A-like syndrome.

Nuclear pore complexes (NPCs) regulate nucleocytoplasmic transport and are anchored in the nuclear envelope by the transmembrane nucleoporin NDC1. NDC1 is essential for post-mitotic NPC assembly and the recruitment of ALADIN to the nuclear envelope. While no human disorder has been associated to one of the three transmembrane nucleoporins, biallelic variants in AAAS, encoding ALADIN, cause triple A syndrome (Allgrove syndrome). Triple A syndrome, characterized by alacrima, achalasia, and adrenal insufficiency, often includes progressive demyelinating polyneuropathy and other neurological complaints. In this report, diagnostic exome and/or RNA sequencing was performed in seven individuals from four unrelated consanguineous families with AAAS-negative triple A syndrome. Molecular and clinical studies followed to elucidate the pathogenic mechanism. The affected individuals presented with intellectual disability, motor impairment, severe demyelinating with secondary axonal polyneuropathy, alacrima, and achalasia. None of the affected individuals has adrenal insufficiency. All individuals presented with biallelic NDC1 in-frame deletions or missense variants that affect amino acids and protein domains required for ALADIN binding. No other significant variants associated with the phenotypic features were reported. Skin fibroblasts derived from affected individuals show decreased recruitment of ALADIN to the NE and decreased post-mitotic NPC insertion, confirming pathogenicity of the variants. Taken together, our results implicate biallelic NDC1 variants in the pathogenesis of polyneuropathy and a triple A-like disorder without adrenal insufficiency, by interfering with physiological NDC1 functions, including the recruitment of ALADIN to the NPC.

An unusual presentation of severe obstructive sleep apnea with nocturnal seizure-like movements: A case report.

Key Clinical Message: This study suggests that severe obstructive sleep apnea can present as sleep-related epileptic or non-epileptic seizures. A detailed history and physical examination, along with polysomnography and video electroencephalography findings can lead to the correct diagnosis. Abstract: Obstructive sleep apnea (OSA) is defined by recurrent episodes of the upper airway complete or partial collapse while sleeping. The obstructive episodes result in gradual suffocation that increases breathing attempts till the person is awakened. The main manifestations are excessive daytime sleepiness, snoring, observed episodes of stopped breathing, and abrupt awakenings accompanied by gasping or choking. Nevertheless, there are very few reports of patients with OSA, manifesting other symptoms such as seizure-like movements. Differentiating OSA with nocturnal seizures could be challenging due to their overlapping features. A 53-year-old man presented to the clinic, experiencing seizure-like involuntary movements during nocturnal sleep for the past 2 years with a frequency of 2-3 times per night. Neurologic examinations were normal. Further evaluation with polysomnography revealed impaired arousal followed by seizure-like movements during sleep. Video electroencephalography (EEG) did not show any epileptiform discharges, ruling out the nocturnal seizure diagnosis. The patient was diagnosed with OSA. Subsequently, continuous positive airway pressure (CPAP) treatment resolved all symptoms.

Machine learning applied to the prediction of relapse, hospitalization, and suicide in bipolar disorder using neuroimaging and clinical data: A systematic review.

BACKGROUND: Bipolar disorder (BD) is associated with increased morbidity/mortality. Adverse outcome prediction might help with the management of patients with BD. METHODS: We systematically reviewed the performance of machine learning (ML) studies in predicting adverse outcomes (relapse or recurrence, hospital admission, and suicide-related events) in patients with BD. Demographic, clinical, and neuroimaging-related poor outcome predictors were also reviewed. Three databases (PubMed, Scopus, and Web of Science) were explored from inception to July 2023. RESULTS: Eighteen studies, accounting for >30,000 patients, were included. Support vector machine, decision trees, random forest, and logistic regression were the most frequently used ML algorithms. ML models' area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity ranged from 0.71 to 0.98, 72.7-92.8 %, and 59.0-95.2 % for relapse/recurrence prediction (4 studies (3 on relapses and 1 on recurrences). The corresponding values were 0.78-0.88, 21.4-100 %, and 77.0-99.7 % for hospital admissions (3 studies, 21,266 patients), and 0.71-0.99, 44.4-97.9 %, and 38.9-95.0 % for suicide-related events (10 studies, 5558 patients). Also, one study addressed a combination of the interest outcomes. Adverse outcome predictors included early onset BD, BD type I, comorbid psychiatric or substance use disorder, circadian rhythm disruption, hospitalization characteristics, and neuroimaging parameters, including increased dynamic amplitude of low-frequency fluctuation, decreased frontolimbic functional connectivity and aberrant dynamic functional connectivity in corticostriatal circuitry. CONCLUSIONS: ML models can predict adverse outcomes of BD with relatively acceptable performance measures. Future studies with larger samples and nested cross-validation validation should be conducted to reach more reliable results.

Coexistence of myasthenia gravis and lichen planus: A case report and systematic review of related case reports from 1971 to 2024.

Key Clinical Message: The co-occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases. Abstract: Myasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co-occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co-occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67-year-old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti-AchR-Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late-onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x-ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co-occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases.

Association of New-Onset Seizures With SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Importance: Seizures have been reported as an adverse effect of the SARS-CoV-2 vaccine. However, no study has answered the question of whether there is any association between seizures in the general population and COVID-19 vaccination. Objective: To evaluate the seizure incidence among SARS-CoV-2 vaccine recipients compared with those who received a placebo. Data Sources: A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, Google Scholar, review publications, editorials, letters to editors, and conference papers, along with the references of the included studies from December 2019 to July 7, 2023. Study Selection: Randomized clinical trials (RCTs) reporting seizure incidence with SARS-CoV-2 vaccination were included. Data Extraction and Synthesis: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and used the Mantel-Haenszel method with random- and common-effect models. The risk of bias of the studies was assessed using the Cochrane assessment tool for RCTs. Main Outcomes and Measures: The outcome of interest was new-onset seizure incidence proportion compared among (1) SARS-CoV-2 vaccine recipients and (2) placebo recipients. Results: Six RCTs were included in the study. Results of the pooled analysis comparing the incidence of new-onset seizure between the 63 521 vaccine and 54 919 placebo recipients in the 28-day follow-up after vaccine/placebo injection showed no statistically significant difference between the 2 groups (9 events [0.014%] in vaccine and 1 event [0.002%] in placebo recipients; odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12; I2 = 0%, τ2 = 0, Cochran Q P = .74). Likewise, in the entire blinded-phase period after injection, with a median of more than 43 days, no significant difference was identified between the vaccine and placebo groups regarding incident new-onset seizure (13/43 724 events [0.03%] in vaccine and 5/40 612 [0.012%] in placebo recipients; OR, 2.31; 95% CI, 0.86-6.23, P = .10, I2 = 0%, τ2 = 0, Cochran Q P = .95). Conclusions and Relevance: According to this systematic review and meta-analysis, there was no statistically significant difference in the risk of new-onset seizure incidence between vaccinated individuals and placebo recipients.

Potential efficacy of caffeine ingestion on balance and mobility in patients with multiple sclerosis: Preliminary evidence from a single-arm pilot clinical trial.

OBJECTIVES: Caffeine's potential benefits on multiple sclerosis (MS), as well as on the ambulatory performance of non-MS populations, prompted us to evaluate its potential effects on balance, mobility, and health-related quality of life (HR-QoL) of persons with MS (PwMS). METHODS: This single-arm pilot clinical trial consisted of a 2-week placebo run-in and a 12-week caffeine treatment (200 mg/day) stage. The changes in outcome measures during the study period (weeks 0, 2, 4, 8, and 12) were evaluated using the Generalized Estimation Equation (GEE). The outcome measures were the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for self-reported ambulatory disability, Berg Balance Scale (BBS) for static and dynamic balance, Timed Up and Go (TUG) for dynamic balance and functional mobility, Multiple Sclerosis Impact Scale (MSIS-29) for patient's perspective on MS-related QoL (MS-QoL), and Patients' Global Impression of Change (PGIC) for subjective assessment of treatment efficacy. GEE was also used to evaluate age and sex effect on the outcome measures over time. (Iranian Registry of Clinical Trials, IRCT2017012332142N1). RESULTS: Thirty PwMS were included (age: 38.89 ± 9.85, female: 76.7%). Daily caffeine consumption significantly improved the objective measures of balance and functional mobility (BBS; P-value<0.001, and TUG; P-value = 0.002) at each study time point, and the subjective measure of MS-related QoL (MSIS-29; P-value = 0.005) two weeks after the intervention. Subjective measures of ambulatory disability (MSWS-12) and treatment efficacy (PGIC) did not significantly change. The effect of age and sex on the outcome measures were also assessed; significant sex-time interaction effects were found for MSWS-12 (P-value = 0.001) and PGIC (P-value<0.001). The impact of age on BBS scores increased as time progressed (P-value = 0.006). CONCLUSIONS: Caffeine may enhance balance, functional mobility, and QoL in PwMS. Being male was associated with a sharper increase in self-reported ambulatory disability over time. The effects of aging on balance get more pronounced over time. TRIAL REGISTRATION: This study was registered with the Iranian Registry of Clinical Trials (Registration number: IRCT2017012332142N1), a Primary Registry in the WHO Registry Network.

Effects of non-pharmacological interventions on gait and balance of persons with Multiple Sclerosis: A narrative review.

BACKGROUND: Multiple Sclerosis (MS) is among the most common reasons for disability in young adults. Mobility impairment, primarily related to gait and balance, is ranked as the preeminent concern among persons with MS (PwMS). Gait and balance dysfunction can directly affect the quality of life and activities of daily life in PwMS, hence the importance of effective treatment strategies. Previous studies have demonstrated the positive effect of various non-pharmacological rehabilitation methods, including physiotherapy and electrical stimulation, on gait and mobility in PwMS. Non-pharmacological methods can be tailored to the individual needs and abilities of each patient, allowing healthcare providers to create personalized training programs. Furthermore, these methods typically result in minimal or no side effects. PURPOSE: This review provides a comprehensive overview of an array of non-pharmacological treatment approaches aimed at enhancing ambulatory performance in PwMS. METHODS: We performed a narrative review of the original papers available in PubMed, investigating the effects of different nonmedical approaches on the gait and balance performance of the PwMS. Reviewed treatment approaches include "exercise, physical rehabilitation, dual-task (DT) rehabilitation, robot-assisted rehabilitation, virtual reality-assisted rehabilitation, game training, electrical stimulation devices, auditory stimulation, visual feedback, and shoe insoles". RESULTS AND CONCLUSIONS: Eighty articles were meticulously reviewed. Our study highlights the positive effects of non-pharmacological interventions on patients' quality of life, reducing disability, fatigue, and muscle spasticity. While some methods, including exercise and physiotherapy, showed substantial promise, further research is needed to evaluate whether visual biofeedback and auditory stimulation are preferable over conventional approaches. Additionally, approaches such as functional electrical stimulation, non-invasive brain stimulation, and shoe insoles demonstrate substantial short-term benefits, prompting further investigation into their long-term effects. Non-pharmacological interventions can serve as a valuable complement to medication-based approaches.

Good response to rectal diazepam in refractory cases of cyclic vomiting: A case-series and review of the literature.

Key Clinical Message: Although increasing in number, cases of CVS are being frequently misdiagnosed and many are refractory to the available treatments. This paper draws attention to a timely consideration of this disorder upon suspicion and proposes rectal diazepam and cinnarizine as highly effective treatments in refractory cases of CVS. Abstract: Cyclic vomiting syndrome (CVS) is a set of recurrent episodic attacks of nausea and vomiting. This is a migraine-related disorder that mostly affects children. Several medications have been recommended for abortive and prophylactic treatment. Unfortunately, in some cases, the treatment is not completely effective and affects the quality of life of the sufferer. In this paper, we report on two cases of children experiencing refractory CVS attacks who were not responsive to recommended medications for acute phase and prophylaxis. This account highlights the efficacy of rectal diazepam for the acute phase of CVS and cinnarizine, an anti-migraine and anti-histamine agent, for prophylaxis of further attacks.

Association of seizure with COVID-19 vaccines in persons with epilepsy: A systematic review and meta-analysis.

Seizure aggravation following coronavirus disease 2019 (COVID-19) vaccines is a major cause behind vaccine hesitancy among persons with epilepsy (PwE), resulting in lower immunization rates. We systematically reviewed seizure-activity-related events in PwE following COVID-19 vaccination. We systematically searched PubMed, Web of Science, Scopus, and Cochrane Library, until January 31, 2023, and included articles reporting seizure activity-related events in PwE receiving COVID-19 vaccination. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. The protocol was registered with PROSPERO (CRD42022312475). Outcomes included pooled incidence proportions of (a) increased seizure frequency, (b) status epilepticus (SE), and (c) change in seizure type. Of the 2207 studies, 16 entered the meta-analysis. The pooled incidence proportion of increased seizure frequency (16 studies-3245 PwE) was 5% (95% CI: 3%-7%, I2 = 52%). Regarding increased seizure frequency, no significant difference was observed between mRNA and viral vector (OR: 1.11, 95% CI: 0.49-2.52, I2 = 0%), and between mRNA and inactivated virus (OR: 1.60, 95% CI: 0.27-9.37; I2 = 0%). The pooled incidence proportion of SE (15 studies-2387 PwE) was 0.08% (95% CI: 0.02%-0.33%, I2 = 0%). Ultimately, the pooled incidence proportion of change in seizure type (7 studies-1172 PwE) was 1% (95% CI: 1%-2%, I2 = 0%). The meta-analysis revealed post-COVID-19-vaccination increased seizure frequency in 5% of PwE, with no difference between mRNA and viral vector or inactivated virus vaccines. Furthermore, we found 0.08% and 1% incidence proportions for postvaccination SE and change in seizure type, respectively. While noteworthy, these values are far less than reports for COVID-19 infection, emphasizing vaccination importance in preventing COVID-19 consequences in PwE.

Characteristics of headaches attributed to SARS-CoV-2 vaccination and factors associated with its frequency and prolongation: a cross-sectional cohort study.

Background: Headache is the most frequent neurological adverse event following SARS-CoV-2 vaccines. We investigated the frequency, characteristics, and factors associated with post-vaccination headaches, including their occurrence and prolongation (≥ 48 h). Methods: In this observational cross-sectional cohort study, retrospective data collected between April 2021-March 2022 were analyzed. Univariate and multivariate logistic regressions were used to evaluate the effect of clinicodemographic factors on the odds of post-vaccination headache occurrence and prolongation. Results: Of 2,500 people who were randomly sent the questionnaire, 1822 (mean age: 34.49 ± 11.09, female: 71.5%) were included. Headache prevalence following the first (V1), second (V2), and third (V3) dose was 36.5, 23.3, and 21.7%, respectively (p < 0.001). Post-vaccination headaches were mainly tension-type (46.5%), followed by migraine-like (36.1%). Headaches were mainly bilateral (69.7%), pressing (54.3%), moderate (51.0%), and analgesic-responsive (63.0%). They mainly initiated 10 h [4.0, 24.0] after vaccination and lasted 24 h [4.0, 48.0]. After adjusting for age and sex, primary headaches (V1: aOR: 1.32 [95%CI: 1.08, 1.62], V2: 1.64 [1.15, 2.35]), post-COVID-19 headaches (V2: 2.02 [1.26, 3.31], V3: 2.83 [1.17, 7.47]), headaches following the previous dose (V1 for V2: 30.52 [19.29, 50.15], V1 for V3: 3.78 [1.80, 7.96], V2 for V3: 12.41 [4.73, 35.88]), vector vaccines (V1: 3.88 [3.07, 4.92], V2: 2.44 [1.70, 3.52], V3: 4.34 [1.78, 12.29]), and post-vaccination fever (V1: 4.72 [3.79, 5.90], V2: 6.85 [4.68, 10.10], V3: 9.74 [4.56, 22.10]) increased the odds of post-vaccination headaches. Furthermore, while primary headaches (V1: 0.63 [0.44, 0.90]) and post-COVID-19 headaches (V1: 0.01 [0.00, 0.05]) reduced the odds of prolonged post-vaccination headaches, psychiatric disorders (V1: 2.58 [1.05, 6.45]), headaches lasting ≥48 h following the previous dose (V1 for V2: 3.10 [1.08, 10.31]), and migraine-like headaches at the same dose (V3: 5.39 [1.15, 32.47]) increased this odds. Conclusion: Patients with primary headaches, post-COVID-19 headaches, or headaches following the previous dose, as well as vector-vaccine receivers and those with post-vaccination fever, were at increased risk of post-SARS-CoV-2-vaccination headaches. Primary headaches and post-COVID-19 headaches reduced the odds of prolonged post-vaccination headaches. However, longer-lasting headaches following the previous dose, migraine-like headaches at the same dose, and psychiatric disorders increased this odd.

Association of SARS-CoV-2 Vaccination or Infection With Bell Palsy: A Systematic Review and Meta-analysis.

Importance: Bell palsy (BP) has been reported as an adverse event following the SARS-CoV-2 vaccination, but neither a causative relationship nor a higher prevalence than in the general population has been established. Objective: To compare the incidence of BP in SARS-CoV-2 vaccine recipients vs unvaccinated individuals or placebo recipients. Data Sources: A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, and Google Scholar from the inception of the COVID-19 report (December 2019) to August 15, 2022. Study Selection: Articles reporting BP incidence with SARS-CoV-2 vaccination were included. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted with the random- and fixed-effect models using the Mantel-Haenszel method. The quality of the studies was evaluated by the Newcastle-Ottawa Scale. Main Outcomes and Measures: The outcomes of interest were to compare BP incidence among (1) SARS-CoV-2 vaccine recipients, (2) nonrecipients in the placebo or unvaccinated cohorts, (3) different types of SARS-CoV-2 vaccines, and (4) SARS-CoV-2-infected vs SARS-CoV-2-vaccinated individuals. Results: Fifty studies were included, of which 17 entered the quantitative synthesis. Pooling 4 phase 3 randomized clinical trials showed significantly higher BP in recipients of SARS-CoV-2 vaccines (77 525 vaccine recipients vs 66 682 placebo recipients; odds ratio [OR], 3.00; 95% CI, 1.10-8.18; I2 = 0%). There was, however, no significant increase in BP after administration of the messenger RNA SARS-CoV-2 vaccine in pooling 8 observational studies (13 518 026 doses vs 13 510 701 unvaccinated; OR, 0.70; 95% CI, 0.42-1.16; I2 = 94%). No significant difference was found in BP among 22 978 880 first-dose recipients of the Pfizer/BioNTech vaccine compared with 22 978 880 first-dose recipients of the Oxford/AstraZeneca vaccine (OR, 0.97; 95% CI, 0.82-1.15; I2 = 0%). Bell palsy was significantly more common after SARS-CoV-2 infection (n = 2 822 072) than after SARS-CoV-2 vaccinations (n = 37 912 410) (relative risk, 3.23; 95% CI, 1.57-6.62; I2 = 95%). Conclusions and Relevance: This systematic review and meta-analysis suggests a higher incidence of BP among SARS-CoV-2-vaccinated vs placebo groups. The occurrence of BP did not differ significantly between recipients of the Pfizer/BioNTech vs Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccination.