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.

Two ischemic stroke events within 48 h: a case report of an unusual presentation of thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) considers a rare cause of ischemic stroke (IS). We reported a case of a newly diagnosed patient with acquired immune-mediated TTP (iTTP), in whom two IS events developed during 48 h. CASE PRESENTATION: A 59-year-old diabetic male was presented to the hospital 24 h after symptoms onset, including left hemiparesis, dysarthria, and decreased consciousness. A brain CT scan was performed with the suspicion of acute IS, indicating infarct lesions in the right middle cerebral artery (MCA) territory. The patient was not eligible for thrombolytic therapy due to admission delay. Over the next 24 h, the patient's neurological condition deteriorated, and the second brain CT scan showed new ischemic lesions in the left MCA territory. Initial laboratory evaluation indicated thrombocytopenia without evidence of anemia. However, in the following days, thrombocytopenia progressed, and microangiopathic hemolytic anemia (MAHA) developed. The ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent plasma exchange activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent and pulse IV methylprednisolone. Rituximab was also added due to the refractory course of the disease. After a prolonged hospital course, he had considerable neurologic recovery and was discharged. CONCLUSIONS: Clinicians should consider two points. First, TTP should be considered in any patient presenting with IS and having thrombocytopenia or anemia without other symptoms of TTP. Second, worsening the patient's condition during hospitalization may indicate a new stroke and should be investigated immediately.

Simultaneous use of sensory stimulation and motor exercise improves the manual skills of educable children with mental retardation at preprimary and primary school levels.

Background: Children with mental retardation have various clinical problems. They mostly have motor delay and sensory deficit. Neurorehabilitation focuses on restoring remaining abilities. Thus, the present study was designed to study the effects of simultaneous use of sensory-motor therapy on manual skills of children with mental retardation. Methods: In this study, 120 educable boys and girls with mental retardation (9-12 years) were selected from 2 preprimary and primary exceptional centers in Tehran using stratified sampling method considering the geographical dispersion. The participants were divided into 2 equal trial and control groups using simple random sampling. Lincoln-Oseretsky Motor Development Scale, Purdue Pegboard test, and Handwriting Legibility Checklist of Persian Language were used. Simultaneous sensory stimulations and motor exercises were used for 3 one-hour weekly sessions for 12 consecutive weeks. Pre and posttests were done for evaluation. Using parametric paired and independent samples t tests, the findings were analyzed in SPSS 23. Results: The manual skills significantly improved following therapeutic use of simultaneous sensory stimulation and motor exercise (p=0.001). In the control group, the pre and post evaluation difference was not significant (p=0.813) Conclusion: Based on the findings of this study, simultaneous use of sensory-motor techniques can have better clinical results in the trial group compared to the control group. Thus, these types of techniques should be used more in clinics. However, further studies are needed for more comparison between separate applications of these techniques.

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.

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.

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.

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.

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.

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.

Impact of multi-arterial revascularization on long-term major adverse cardiovascular events after coronary bypass in 23,798 patients.

BACKGROUND: This study evaluated the association between multiarterial versus single arterial bypass grafting (SAG) and all-cause mortality and major adverse cardiocerebrovascular events (MACCE), overall and across different patient subgroups from a Middle-Eastern nation. METHODS: This single-center retrospective cohort study included 23798 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% male, 65.11±9.94 years), 986 patients (4.1%) underwent MAG. Compared to the SAG group, MAG had lower crude mortality (14.1% vs. 21.6%) and MACCE (28.8% vs. 34.7%) rates during follow-up (9.23 [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% confidence interval[CI]:0.67-1.22]; MACCE: 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 MACCE, in men, younger patients, and those without risk factors. CONCLUSIONS: MAG was not associated with improved post-surgery outcomes among the total CABG 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.

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.

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

Nuclear pore complexes (NPC) 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 7 individuals from 4 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.

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.

The Dialogue Between Neuroinflammation and Adult Neurogenesis: Mechanisms Involved and Alterations in Neurological Diseases.

Adult neurogenesis occurs mainly in the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles. Evidence supports the critical role of adult neurogenesis in various conditions, including cognitive dysfunction, Alzheimer's disease (AD), and Parkinson's disease (PD). Several factors can alter adult neurogenesis, including genetic, epigenetic, age, physical activity, diet, sleep status, sex hormones, and central nervous system (CNS) disorders, exerting either pro-neurogenic or anti-neurogenic effects. Compelling evidence suggests that any insult or injury to the CNS, such as traumatic brain injury (TBI), infectious diseases, or neurodegenerative disorders, can provoke an inflammatory response in the CNS. This inflammation could either promote or inhibit neurogenesis, depending on various factors, such as chronicity and severity of the inflammation and underlying neurological disorders. Notably, neuroinflammation, driven by different immune components such as activated glia, cytokines, chemokines, and reactive oxygen species, can regulate every step of adult neurogenesis, including cell proliferation, differentiation, migration, survival of newborn neurons, maturation, synaptogenesis, and neuritogenesis. Therefore, this review aims to present recent findings regarding the effects of various components of the immune system on adult neurogenesis and to provide a better understanding of the role of neuroinflammation and neurogenesis in the context of neurological disorders, including AD, PD, ischemic stroke (IS), seizure/epilepsy, TBI, sleep deprivation, cognitive impairment, and anxiety- and depressive-like behaviors. For each disorder, some of the most recent therapeutic candidates, such as curcumin, ginseng, astragaloside, boswellic acids, andrographolide, caffeine, royal jelly, estrogen, metformin, and minocycline, have been discussed based on the available preclinical and clinical evidence.

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.

Trail Making Test Could Predict Impairment in Cognitive Domains in Patients with Multiple Sclerosis: A Study of Diagnostic Accuracy.

OBJECTIVE: Cognitive impairment (CI) and executive dysfunction (ED) are prevalent in patients with multiple sclerosis (PwMS). The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is the gold standard neuropsychological battery (NPB) for detecting CI. Delis-Kaplan Executive Function System (DKEFS) NPB evaluates ED. We aimed to find practical test(s) from DKEFS with acceptable diagnostic utility for early detection of impairment in cognitive and executive domains. METHODS: Cognitive and executive tasks, physical disability, and depression scores of 30 PwMS were assessed (17 women, age: 38.1). Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Controlled Oral Word Association Test (COWAT) from MACFIMS and Trail Making Test (TMT), Design Fluency Test (DFT), and Verbal Fluency Test (VFT) from DKEFS were selected. The association between patients' characteristics and performance in tests, and diagnostic accuracy of DKEFS tests in detecting impairment in cognitive tasks were evaluated, using Pearson correlation and receiver operator characteristic curve analyses, respectively. RESULTS: A significant correlation was found between disease duration and SDMT and TMT subtests. Expanded Disability Status Scale was significantly related to SDMT, VFT-switching, and TMT subtests. Beck Depression Inventory was significantly related to DFT. TMT-switching detected abnormalities in SDMT and PASAT with 100% sensitivity, 93.3% (for SDMT), and 85.7% specificity (for PASAT). TMT-letter showed 100% sensitivity and 90% specificity in identifying abnormalities in COWAT. CONCLUSIONS: TMT, particularly the switching condition, is a practical paper-based test that could predict impairment in cognitive tasks. Clinicians may use TMT as a screening tool among PwMS.

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.

Efficacy and safety of adjunctive therapy with fingolimod in patients with schizophrenia: A randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Studies have suggested that fingolimod, a sphingosine-1-phosphate receptor modulator, exerts neuroprotective and anti-inflammatory effects. Although fingolimod is approved for the treatment of relapsing-remitting multiple sclerosis, limited studies have investigated its effects in patients with schizophrenia. This study investigated the efficacy and safety of fingolimod adjuvant to risperidone in schizophrenia treatment. METHODS: This eight-week, randomized, double-blinded, placebo-controlled trial included 80 (clinical trials registry code: IRCT20090117001556N137) patients with chronic schizophrenia. Participants were assigned to two equal arms and received risperidone plus either fingolimod (0.5 mg/day) or a matched placebo. The positive and negative symptom scale (PANSS) was used to measure and compare the effectiveness of treatment strategies at baseline and weeks 2, 4, 6, and 8. Treatment side effects were also compared. RESULTS: Seventy participants completed the trial (35 in each arm). The baseline characteristics of the groups were comparable (P-value > 0.05). There were significant time-treatment interaction effects on negative symptoms (P-value = 0.003), general symptoms (P-value = 0.037), and the PANSS total score (P-value = 0.035), suggesting greater improvement in symptoms following the fingolimod adjuvant therapy. In contrast, the longitudinal changes in positive and depressive symptoms were similar between the groups (P-values > 0.05). Regarding the safety of treatments, there were no differences in extrapyramidal symptoms [assessed by the extrapyramidal symptom rating scale (ESRS)] or frequency of other complications between the fingolimod and the placebo groups (P-values > 0.05). CONCLUSIONS: This study indicated that fingolimod is a safe and effective adjuvant agent for schizophrenia treatment. However, further clinical trials are required to suggest extensive clinical application.

The Effect of Easily Implementable Changes to the "D's of Stroke Care" in Reducing Sex Disparity in Door-to-Needle Time.

BACKGROUND: Door-to-needle (DTN) is the duration between patient's arrival at the hospital and receiving intravenous thrombolysis in ischemic stroke settings, for which studies have reported delays in women. The "D's of stroke care" describes 8 steps (D1 to D8) in patients' time tracker. We implemented simple modifications to the "D's of stroke care" by splitting D4 and D6 steps into these substeps: patients' arrival to the emergency room (D4-A), early assessment by a neurologist (D4-B), neurologist decision on patient's eligibility to receive recombinant tissue plasminogen activator (D6-A), and patient's transfer to the stroke unit (D6-B). We evaluated the effect of these changes on reducing DTN time disparity between men and women. METHODS: This study was conducted from September 2019 to August 2021, at a comprehensive stroke center. Patients were analyzed in 2 groups: group 1, before, and group 2, after using the modifications. Sex as the main variable of interest along with other covariates was regressed toward the DTN time. RESULTS: In groups 1 and 2, 47 and 56 patients received intravenous thrombolysis, respectively. Although there was a significant difference in DTN≤1 hour between women and men in group 1 (36% vs. 52%, P =0.019), it was not significantly different in group 2 ( P =0.97). Regression analysis showed being female was a significant predictor of DTN>1 hour in group 1 (adjusted odds ratio=6.65, P =0.02), whereas after using the modifications, sex was not a significant predictor for delayed DTN. CONCLUSIONS: Implementing these substeps reduced sex disparity in DTN time in our center.

Sleep microstructure and clinical characteristics of patients with restless legs syndrome.

STUDY OBJECTIVES: Restless legs syndrome (RLS) is a sleep-related movement disorder, often accompanied by sleep disruption. Obstructive sleep apnea (OSA) has a controversial prevalence among patients with RLS. We evaluated the clinical and sleep features of patients who attended our sleep clinic considering RLS and OSA. METHODS: In this cross-sectional study, we obtained health records of 1,497 patients during 2015-2019 who underwent polysomnography (PSG). Baseline characteristics, sleep-related and RLS questionnaires, and sleep microstructure were assessed. Descriptive and analytical assessments were performed. RLS was assessed according to the International Restless Legs Syndrome Study Group criteria. RESULTS: RLS was found in 19.4% of patients, with more prevalence among women (26.9% vs 16.4%). RLS affected 19.1% of patients with OSA. Patients with RLS were significantly older with higher insomnia and depression and worse PSG results. As the respiratory disturbance index increased, the odds of RLS slightly decreased (adjusted odds ratio [95% confidence interval]: 0.80 [0.67-0.94]). The odds of OSA (respiratory disturbance index ≥ 5) was not affected by RLS. OSA in patients with RLS was significantly associated with a higher limb movement index. RLS in patients with OSA was significantly associated with higher insomnia, depression, and limb movement index (men and women), higher wake after sleep onset and percentage of N1 sleep (men), and lower sleep efficiency (men). CONCLUSIONS: Patients with RLS had worse PSG results, higher insomnia, and depression. Although men with OSA+/RLS+ had worsened PSG results, PSG parameters in women with OSA+/RLS+ did not differ from the OSA+/RLS- group. Patients with either OSA or RLS should be evaluated for possible comorbidities, including insomnia and depression. Notably, sex-specific characteristics need more consideration in sleep clinics. CITATION: Amirifard H, Jameie M, Akbarpour S, et al. Sleep microstructure and clinical characteristics of patients with restless legs syndrome. J Clin Sleep Med. 2022;18(11):2653-2661.