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A 21-year-old female patient presented to the Ophthalmology Department of Yunnan University Affiliated Hospital with complaints of "bilateral blurred vision accompanied by diplopia for 3 weeks". The patient's main symptoms included intermittent visual blurring, diplopia, headaches, and ocular discomfort. Ocular examination revealed intermittent exotropia, sometimes accompanied by esotropia or orthotropia, along with signs of pupillary constriction and pseudomyopia. Based on the clinical presentation, a diagnosis of intermittent exotropia complicated by spasm of the near reflex (SNR) was made. The patient underwent bilateral exotropia surgery, which corrected the ocular alignment and resolved the symptoms and signs of SNR postoperatively.

Transradial access has become the most commonly used method for cardiac catheterization. Many medical and technical applications have been proposed to reduce TRA complications. The aim of this study is to examine the effect of hand dominance on radial artery spasm and radial artery occlusionin subjects undergoing CC via TRA. Between April 2020 and August 2022, 1713 subjects who underwent CC via TRA were included in the study. Patient data were obtained in terms of hand dominance of the catheterized side and RAS and RAO during a 1-month follow-up period. RAS was seen in 9.6% of the subjects. The RAS in patients catheterized by the dominant hand was significantly higher than that performed by the non-dominant hand (12 vs 7.8%; P = .004). RAO was seen in 1% of the subjects. RAO was significantly higher in the spasm side than in the no-spasm side (3 vs .8%; P = .009). Hand dominance was determined as an independent predictor of radial artery spasm (P = .006). In our study, RAS and RAO were more common on the dominant hand side than on the non-dominant side. Choosing the non-dominant hand for TRA for CC may reduce the incidence of RAS and RAO., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A 74-year-old woman taking dulvalumab for lung adenocarcinoma developed muscle tonicity in the extremities and trunk. Painful paroxysmal muscle spasms with profuse sweating were frequently observed, and surface electromyography showed simultaneous contraction of the active and antagonist muscles. Blood tests were strongly positive for anti-amphiphysin antibodies, and stiff-person syndrome (SPS) was diagnosed. Intravenous immunoglobulin therapy and clonazepam were initiated, and the paroxysmal painful muscle spasms disappeared. As the primary tumor was under control, and the onset occurred approximately six weeks after the resumption of immune checkpoint inhibitors, we considered SPS to be an immune-related adverse event. Although extremely rare, it should be considered a neuromuscular disease that can occur in association with immune checkpoint inhibitors.

Objectives: To describe a patient with mild GAD-positive stiff-leg syndrome (SLS) who developed severely disabling stiff-person syndrome (SPS) 1 week after mild COVID-19 and discuss the impact of viral implications., Methods: Video-documented serial clinical observations at baseline, after acute COVID-19, and after IVIG treatments., Results: A 39-year-old man with left-SLS was stable during a 2-year follow-up with low-dose antispasmodics, working fully and functioning normally, even able to run. One week after mild COVID-19, he started to experience generalized SPS symptomatology that steadily worsened the following 2-3 weeks, becoming unable to walk, requiring a walker, with significant thoracolumbar and bilateral leg stiffness and spasms. GAD ab were very high. After 3 monthly IVIg infusions he showed improvements, but his gait remains significantly stiff. All clinical changes, from baseline to post-Covid, and then post- IVIg have been video-documented., Discussion: This is the first, clearly documented, severe GAD-positive SPS after COVID-19. Although viral or postviral causation can be incidental, the temporal connection with acute COVID-19, the severe disease worsening after symptom-onset, and the subsequent steady improvement after IVIg, suggest viral-triggered autoimmunity. Because COVID-19 reportedly can trigger or worsen GAD-associated diabetes type 1 through proinflammatory mediators, and SPS has been reportedly triggered by West Nile Virus, possibly through molecular mimicry, this case of acutely converting GAD-SLS to GAD-SPS suggest the need to explore viral etiologies in patients with GAD-SPS experiencing acute, long-lasting episodic exacerbations of stiffness and spasms.

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1 , TSC2 , CDKL5 , ARX , KCNQ2 , STXBP1 and SCN2A . Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities., (© 2023. Fondazione Società Italiana di Neurologia.)

Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.

Background: This study aimed to investigate and analyze the risk factors for non-etiology-specific infantile spasms (IS) and unrelieved clinical symptoms after treatment., Methods: Eighty-eight children with IS who were treated at our hospital from March 2018 to December 2021 were included in the study. The children were divided into etiology-specific (n = 46) and nonetiology-specific (n = 42) groups, based on the diagnostic results, and remission (n = 45) and nonremission (n = 43) groups, based on clinical outcomes after treatment. The clinical data from patients in the etiology-specific and nonetiology-specific groups and the remission and nonremission groups were compared. Risk factors for non-etiology-specific IS were identified using logistic regression analysis., Results: Gender, family history, birth status, and metabolic abnormalities were significantly different between the etiology-specific and non-etiology-specific groups. Gender and metabolic abnormalities were risk factors for nonetiology-specific IS. Family history, birth status, metabolic abnormalities, and brain magnetic resonance imaging were significantly different between the remission and nonremission groups, and different etiologies were risk factors for unrelieved symptoms after treatment., Conclusion: The occurrence of nonetiology-specific IS is associated with gender and metabolic abnormalities in children. After medication, unrelieved IS symptoms are associated with etiologies., (© 2023. The Author(s).)

To describe a new phenotype and the diagnostic workup of a vitamin-B 6 -dependent epilepsy due to pyridoxal 5'-phosphate-binding protein (PLPBP) deficiency in an infant with early-onset epilepsy at the age of 5 years 6 months. Following immediate and impressive clinical response to treatment with pyridoxine, metabolic screening for vitamin-B 6 -dependent epilepsies and targeted next-generation sequencing (NGS)-based gene panel analysis were performed. Potentially pathogenic variants were confirmed by Sanger sequencing in the patient, and variants were analyzed in both parents to confirm biallelic inheritance. The clinical phenotype and course of disease were compared to the 44 cases reported in the literature, harboring variants in pyridoxal phosphate homeostasis protein ( PLPHP ) and with cases of vitamin-B 6 -dependent epilepsy due to other known causative genes. Levels of alpha-aminoadipic semialdehyde in urine and amino acids were normal. Two inherited pathogenic variations in PLPHP were found in compound heterozygosity, including one novel deletion. We here describe a previously unreported individual harboring biallelic pathogenic PLPHP variants presenting with paroxysmal eye-head movements followed by epileptic spasms and an almost normal interictal electroencephalogram, thus expanding the clinical spectrum of PLPBP deficiency. This warrants consideration of vitamin-B 6 -dependent epilepsies in patients with early-onset epilepsy, including epileptic spasms, and eye movement disorders also beyond the neonatal period even when metabolic screening for vitamin-B 6 -dependent epilepsies is negative. PLPHP should be included systematically in NGS epilepsy gene panels., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH., Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled., Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed., Conclusion: These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens., Competing Interests: Jin Seok Kim has received honoraria and consulting fees from Handok Inc. Jun Ho Jang has received research support from Alexion, AstraZeneca Rare Disease. Sung-Soo Yoon has received research funding from Chong Kun Dang Pharm, JW Pharmaceutical, Kyowa Kirin, Roche-Genentech, and Yuhan Pharmaceutical; has served on the advisory board for Amgen, Antengene, Astellas, Celgene, Janssen, Merck, Novartis, and Takeda; and has received consulting fees from Ticaros Therapeutics. BokJin Hyun, HyunSun Nam, and Eunhye Kim are employees of Handok Inc. Min Joo Kwak and Yong Kyun Won were an employee of Handok Inc. at the time of study. Jong Wook Lee has served on advisory boards and has received honoraria and research grants from Alexion, AstraZeneca Rare Disease. Deog-Yeon Jo, Seo-Yeon Ahn, Je-Hwan Lee, Sung-Hyun Kim, Chul Won Choi, Ho-Jin Shin, Min-Kyoung Kim, Jae Hoon Lee, Yeung-Chul Mun, and Jee Hyun Kong have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Purpose: Information is scarce regarding the comprehensive profile of patients with essential blepharospasm and hemifacial spasm in Brazil. The present study aimed to assess the clinical features of patients with these conditions, followed up in two reference centers in Brazil., Methods: The study included patients with essential blepharospasm and hemifacial spasm, followed up at the Departments of Ophthalmology at Universidade Federal de São Paulo and Universidade de São Paulo. Apart from demographic and clinical features, past stressful events related to the first symptoms (triggering event), aggravating factors, sensory tricks, and other ameliorating factors for the eyelid spasms were assessed., Results: A total of 102 patients were included in this study. Most patients were female (67.7%). Essential blepharospasm was the most frequent movement disorder [51/102 patients (50%)], followed by hemifacial spasm (45%) and Meige's syndrome (5%). In 63.5% of the patients, the onset of the disorder was associated with a past stressful event. Ameliorating factors were reported by 76.5% of patients; 47% of patients reported sensory tricks. In addition, 87% of the patients reported the presence of an aggravating factor for the spasms; stress (51%) was the most frequent., Conclusion: Our study provides information regarding the clinical features of patients treated in the two largest ophthalmology reference centers in Brazil.

Purpose: The purpose of this study was to assess blepharospasm patients regarding the effect of botulinum toxin in ocular surface parameters., Methods: A prospective study was performed in blepharospasm patients treated with onabotulinumtoxinA. A smartphone (iPhone 6S, Apple) and custom-made software were used to record the eyelid movements for 3 minutes in a standardized manner. Optical coherence tomography of the tear meniscus was used to assess the tear meniscus area. Tear break-up time and the Ocular Surface Disease Index questionnaire were also evaluated. Patients were assessed before and 15 days after botulinum toxin injections., Results: Forty eyes of 20 patients were evaluated. The frequency of the spontaneous eyelid movements was significantly reduced after treatment (23.18 ± 12.85 movements/min vs. 9.29 ± 6.87 movements/min; p < 0.0001). Significant increases in the tear meniscus area (0.020 ± 0.015 mm 2 vs. 0.057 ± 0.104 mm 2 ; p = 0.01) and in break-up time (4.2 ± 1.2 seconds vs. 5.1 ± 1.3 seconds; p = 0.03) were observed 15 days after treatment. A significant reduction in the Ocular Surface Disease Index (59.05 ± 19.04 vs. 21.2 ± 19.5; p < 0.0001) was also observed., Conclusion: Significant changes in the tear meniscus area, break-up time, and Ocular Surface Disease Index after treatment reflect the effect of botulinum toxin on the lacrimal pump and in the improvement of dry eye symptoms. Reduction of eyelid spasms after treatment in blepharospasm patients was demonstrated using a smartphone and custom-made software. Thus, beyond relieving eyelid spasms, botulinum toxin injections were associated with subjective and objective improvement of dry eye parameters in patients with blepharospasm., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Transradial access (TRA) and transulnar access (TUA) are in close vicinity, but TRA is the preferred intervention route. The cardiovascular outcomes and access site complications of TUA and TRA are understudied. Databases, including MEDLINE and Cochrane Central registry, were queried to find studies comparing safety outcomes of both procedures. The outcome of interest was in-hospital mortality and access site bleeding. Secondary outcomes were all-cause major adverse cardiovascular events, crossover rate, artery spasm, access site large hematoma, and access site complications between TUA and TRA. A random-effect model was used with regression to report unadjusted odds ratios (ORs) by limiting confounders and effect modifiers, using software STATA V.17. A total of 4,796 patients in 8 studies were included in our analysis (TUA = 2,420 [50.4%] and TRA = 2,376 [49.6%]). The average age was 61.3 and 60.1 years and the patients predominantly male (69.2% vs 68.4%) for TUA and TRA, respectively. TUA had lower rates of local access site bleeding (OR 0.58, 95% confidence interval 0.34 to 0.97, I 2  = 1.89%, p = 0.04) but higher crossover rate (OR 1.80, 95% confidence interval 1.04 to 3.11, I 2  = 75.37%, p = 0.04) than did TRA. There was no difference in in-hospital mortality, all-cause major adverse cardiovascular events, arterial spasm, and large hematoma between both cohorts. Furthermore, there was no difference in procedural time, fluoroscopy time, and contrast volume used between TUA and TRA. TUA is a safer approach, associated with lower access site bleeding but higher crossover rates, than TRA. Further prospective studies are needed to evaluate the safety and long-term outcomes of both procedures., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Satoyoshi syndrome is a rare multisystem disease of presumed autoimmune aetiology. We carried out a systematic review to evaluate the available evidence to support that autoimmune hypothesis., Methods: We searched for Satoyoshi syndrome cases in PubMed, the Web of Science and Scopus up to January 2022, using keywords 'Satoyoshi syndrome' or 'Komuragaeri disease'. Data on symptoms, associated autoimmune diseases, presence of autoantibodies and response to treatment were collected., Results: A total of 77 patients from 57 articles published between 1967 and 2021 were included; 59 patients were women. The mean age at diagnosis was 21.2 years. All cases had painful muscular spasms and alopecia. Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. Satoyoshi syndrome was associated with other autoimmune diseases: myasthenia gravis, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, atopic dermatitis, bronchial and lupus erythematosus. Autoantibody determinations were performed in 39 patients, of which 27 had positive results. The most frequently detected autoantibodies were ANAs. Other less frequently found autoantibodies were: anti-acetylcholine receptor antibodies, anti-DNA antibodies, antithyroid antibodies, anti-glutamic acid decarboxylase (anti-GAD) and anti-gliadin antibodies. Pharmacological treatment was reported in 50 patients. Most of them improved with CS, immunosuppressants and immunoglobulins, or a combination of these medications., Conclusion: Satoyoshi syndrome is associated with other autoimmune diseases and a variety of autoantibodies. Improvement after CS or other immunosuppressant treatment was observed in 90% of cases. These data support an autoimmune aetiology for Satoyoshi syndrome. More studies including systematic determination of autoantibodies in all patients with Satoyoshi syndrome will help us advance in our understanding of this disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess whether access to smartphone video capture of infantile spasms at initial presentation is associated with improved time to diagnosis and treatment., Methods: We conducted a collaborative retrospective cohort study of 80 consecutive infants with confirmed infantile epileptic spasms syndrome initially presenting from 2015 to 2021 at 2 US pediatric centers. Statistical methods used included Mann-Whitney U test to assess the difference in lead times to electroencephalogram (EEG), diagnosis, and treatment between groups with and without video capture. A χ 2 analysis was used to assess differences in demographics, clinical characteristics, and treatment outcomes between groups. Multivariate regression analysis was used to account for etiology types and infantile spasms capture on EEG., Results: Patients with smartphone video infantile spasms capture initially presented a median of 9 days earlier (P = .02), had their first EEG 16 days earlier (P = .007), and were diagnosed and started treatment 17 days earlier (P = .006 and P = .008, respectively) compared with the nonvideo group. The video group had a 25% greater response to initial standard treatment (P = .02) and a 21% greater freedom from infantile spasms at long-term follow-up (P = .03), although this long-term outcome lost statistical significance after adjustment for etiology type (P = .07) and EEG capture of infantile spasms (P = .059)., Conclusion: Our findings suggest a benefit of smartphone video capture of infantile spasms in reduced time to diagnosis and initial standard treatment, which are associated with improved treatment response rates. Substantial differences in lead times and treatment response highlight the clinical importance of pediatricians recommending caregivers to obtain smartphone video of events concerning for infantile spasms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We aimed to analyze the efficiency of corpus callosotomy (CC) and subsequent disconnection surgeries in patients with late-onset epileptic spasms (LOES) by comparing post-encephalitis/encephalopathy (PE) and non-encephalitis/encephalopathy (NE). We hypothesized these surgeries can control potential focal onset epileptic spasms (ES) in the NE group but not in the PE group., Methods: We retrospectively included 23 patients (12 with PE and 11 with NE) who initially underwent CC and subsequent disconnection surgeries (five NE). We compared the clinical courses, seizure types, MRI, video-EEG, epilepsy surgery, and seizure outcomes between the two groups., Results: The median age of LOES onset in the PE group was 2.8 (range 1.0-10.1 years) and 2.9 years (range 1.1-12.6) in the NE group. Bilateral MRI abnormalities were observed in both groups (PE, n = 12; NE, n = 3; P < 0.05). The PE group presented ES alone (n = 2), ES + focal seizures (FS) (n = 3), ES + generalized seizures (GS) (n = 3), and ES + FS + GS (n = 4) in addition to stimulus-induced startle seizures (SS) (n = 8) (mean 3.1 seizure types/patient). The NE group presented ES alone (n = 1), ES + FS (n = 2), and ES + FS + GS (n = 8) (mean 2.7 seizure types/patient). In the PE group, CC stopped ES (n = 1) and SS (n = 1) and achieved <50% SS (n = 3). In the NE group, CC achieved immediate ES-free status (n = 2) and < 50% ES (n = 1), and additional disconnection surgeries subsided all seizure types (n = 3) based on lateralized interictal/ictal EEG findings. LOES was significantly remitted by surgery in the NE group (6/11 [55%]) compared with the PE group (1/12 [8%]) (P < 0.05)., Significance: LOES is a drug-resistant, focal/generalized/unknown onset ES. Lateralization of ES in NE could be achieved after CC and eliminated by further disconnection surgeries because of potential focal onset ES. LOES in PE had little benefit from CC for generalized onset ES. However, CC might reduce SS in patients in the PE group with multiple seizure types., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

This systematic review and meta-analysis aimed to evaluate the efficacy of vigabatrin (VGB) in treating infantile epileptic spasms syndrome (IESS). Databases of PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library were systematically searched. All the relevant randomized controlled trials (RCTs) and observational studies (OSs) of VGB for IESS were included and analyzed separately. The primary outcome was the cessation of epileptic spasms (ES). Five RCTs and nine OSs compared the efficacy of VGB vs hormonal monotherapy for IESS. Meta-analysis of the five RCTs showed that hormonal monotherapy was significantly better than VGB monotherapy (OR = 0.37, 95% CI = 0.20-0.67) for patients with new-onset IESS. Meta-analysis of the nine OSs agrees with the result from RCTs (OR = 0.61, 95% CI = 0.43-0.85). VGB was more effective in patients with TSC than in those with other etiologies (five OSs, OR = 5.59, 95% CI = 2.17-14.41). There was no significant difference in the efficiency of VGB combined with hormonal therapy vs hormonal monotherapy for IESS (two RCTs, OR = 0.75, 95% CI = 0.09-6.45). Hormonal monotherapy is better than VGB monotherapy for non-TSC-associated IESS. But for patients with IESS due to TSC, VGB is the first choice. VGB combined with hormone therapy does not definitely increase ES control rates compared with that of hormonal monotherapy., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Aim: To better understand the aetiologies of epileptic spasms in infants, as well as the safety and efficacy of high dose corticosteroids in tuberculosis and human immunodeficiency virus (HIV) endemic resource-limited settings., Method: This was a retrospective analysis of infants with epileptic spasms managed at the tertiary referral centres in the Western Cape, South Africa., Results: Of 175 children with epileptic spasms, the median age at onset was 6 months (interquartile range 4-8 months). Structural aetiologies were most common (115 out of 175 [66%]), with two-thirds related to perinatal insults. A lead time to treatment (LTTT) of less than 1 month was more likely in the epileptic encephalopathy/developmental and epileptic encephalopathy (DEE) group: 58 out of 92 (63%), compared to 28 out of 76 (37%) of those with developmental encephalopathy (p = 0.001). Failure to recognize preceding developmental delay was common. Ninety-nine children (57%) received first line hormonal therapy such as adrenocorticotropic hormone. A total of 111 out of 172 children (65%) from the developmental encephalopathy and epileptic encephalopathy/DEE groups had clinical and/or electroencephalogram resolution of spasms within 14 days. In our population, children in whom an aetiology could not be identified were statistically more likely to have moderate to profound developmental delay at 1 year of age: 33 out of 44 (p = 0.001). Based on reported incidence of epileptic spasms, 23 to 58 cases per annum would be expected but a far smaller proportion presented to our centres., Interpretation: Whilst this is the largest cohort of infants with epileptic spasms from sub-Saharan Africa, the study size is less than expected; this may reflect misdiagnosis and failure of referral pathways. Despite a reported shorter LTTT, infants with DEE had worse developmental outcomes compared to international studies. Hormonal therapy was safe and effective in our setting, despite exposure to high levels of tuberculosis and HIV., What This Paper Adds: The number of unreferred cases of epileptic spasms in South Africa remains high. Caregivers and health care workers in primary care facilities often fail to recognize developmental delay. The burden of disease from hypoxic-ischaemic encephalopathy remains high in our resource-limited setting. Hormonal treatment (e.g. adrenocorticotropic hormone) was safe and effective despite the high prevalence of human immunodeficiency virus and tuberculosis., (© 2022 Mac Keith Press.)

Background and Purpose: Randomized controlled trials and observational studies of nabiximols oromucosal spray in patients with multiple sclerosis (MS) spasticity have shown improvement in a range of associated symptoms (pain, spasms, fatigue, bladder dysfunction, and sleep disturbances). This study evaluated the effectiveness and tolerability of add-on nabiximols in the routine management of patients with MS spasticity in Austria, with a focus on spasticity-associated symptoms., Methods: This was an open, prospective, multicenter, observational, non-interventional study of patients with MS spasticity receiving add-on treatment with nabiximols oromucosal spray. Main endpoints were patient-reported changes from baseline in the frequency (counts) or severity (mean Numerical Rating Scale [NRS] scores) of spasticity-associated symptoms, and patient-reported changes from baseline in impairment of daily activities due to spasticity, after 1 and 3 months of nabiximols treatment. No analyses were conducted for statistical significance., Results: There were 55 patients in the effectiveness population, and 62 in the safety population. Patients reported clinically relevant reductions from baseline to month 3 in the average number of spasms/day (-68.2%) and number of urinary incontinence episodes (-69.3%) in the week prior to the clinic visit, and reductions in mean 0-10 NRS scores for sleep impairment (-47.2%), fatigue (-26.4%), pain (40.4%), and spasticity severity (39.0%). There was no change from baseline in daily activity impairment due to spasticity. The majority of patients were at least partly satisfied with add-on nabiximols for spasticity-associated symptoms. There were 31 adverse events (27 treatment related) reported in 19 patients, with no new safety signals., Conclusions: Add-on nabiximols improved the severity of MS spasticity and a range of spasticity-associated symptoms during real-world use in Austria. Nabiximols is an option for patients with MS spasticity who fail first-line oral antispasticity treatment., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: The purpose of this study was to find the most and least commonly prescribed medications for treating secondary health complications associated with spinal cord injury (SCI); and determine overall polypharmacy rates and risk factors associated with it., Design: Observational design, cross-sectional analysis., Setting: Community; Canada., Participants: Individuals with spinal cord injury ( n  = 108)., Results: A total of 515 prescriptions were issued to the sample comprising 213 different medications to treat 10 SCI-related complications. Forty-five (45%) participants were prescribed >5 medications concurrently. No associations were found between the number of drugs taken and age, sex, level of injury, completeness of injury, time since injury, or cause of injury. The most commonly treated complications included pain (56.5%), muscle spasms (54%) and urinary tract infections (43%). Anti-convulsants (pregabalin, gabapentin), anti-spasmodics (baclofen, diazepam) and nitrofurantoins (Macrobid) were the most commonly prescribed medications to treat each of the three conditions, respectively. Thirty five percent of the total sample received a combination of two or more analgesics including fourth-line agents in the opiate class (hydromorphone, hydrocodone and morphine). Similarly, some participants were prescribed general muscle relaxants and cephalosporins for treatment of muscle spasms and urinary tract infections, respectively, that are generally not recommended in SCI patients. We compare these prescribing patterns with the available clinical practice guidelines and highlight areas where the prescriptions fall outside the recommended clinical practice while considering the complexity of medication management in SCI., Conclusion: Medication management in SCI is complex. Tools are required that enable prescribers to choose evidence-based medical regimens and deprescribe potentially inappropriate medications for their patients with SCI.

Background: Infantile epileptic spasms syndrome is an epileptic encephalopathy, characterized by spasms, hypsarrhythmia, and developmental regression. Appropriately selected patients with infantile epileptic spasms syndrome may be candidates for epilepsy surgery. Methods: This is a single-center retrospective case series of children 0-18 years with a current or previous diagnosis of infantile epileptic spasms syndrome with a lesion on magnetic resonance imaging (MRI) and/or positron emission tomography scan who underwent epilepsy surgery at The Hospital for Sick Children (HSC) in Toronto, Canada. The records of 223 patients seen in the infantile epileptic spasms syndrome clinic were reviewed. Results: Nineteen patients met inclusion criteria. The etiology of infantile epileptic spasms syndrome was encephalomalacia in 6 patients (32%), malformations of cortical development in 12 patients (63%), and atypical hypoglycemic injury in 1 patient (5%). Nine patients (47%) underwent hemispherectomy, and 10 patients (53%) underwent lobectomy/lesionectomy. Three patients (16%) underwent a second epilepsy surgery. Fifteen patients (79%) were considered ILAE seizure outcome class 1 (completely seizure free; no auras) at their most recent follow-up visit. The percentage of patients who were ILAE class 1 at most recent follow-up decreased with increasing duration of epilepsy prior to surgery. Developmental outcome after surgery was improved in 14 of 19 (74%) and stable in 5 of 19 (26%) patients. Conclusions: Our study found excellent seizure freedom rates and improved developmental outcomes following epilepsy surgery in patients with a history of infantile epileptic spasms syndrome with a structural lesion detected on MRI brain. Patients who undergo surgery earlier have improved seizure freedom rates and improved developmental outcomes.

Background: Haemorrhoidectomy is often complicated by significant post-operative pain, to which spasm of the internal anal sphincter is thought to be a contributing factor. This study appraises the evidence behind interventions aimed at lowering sphincter spasm to relieve post-haemorrhoidectomy pain., Methods: A Preferred Reporting Items for Systematic Reviews and Meta-analyses compliant systematic review was conducted. Medline, EMBASE, and CENTRAL databases were systematically searched. All RCTs which compared interventions targeting the internal anal sphincter to relieve pain post excisional haemorrhoidectomy were included. The primary outcome measure was pain on the visual analogue scale., Results: Of the initial 10,221 search results, 39 articles were included in a qualitative synthesis, and 33 studies were included in a meta-analysis. Topical glyceryl trinitrate (GTN) reduced pain on day 7 (7 studies, 485 participants), with a mean difference and 95% confidence interval (MD, 95% CI) of -1.34 (-2.31; -0.37), I 2  = 91%. Diltiazem reduced pain on day 3 on the VAS, and the MD was -2.75 (-398; -1.51) shown in five studies (n = 227). Botulinum toxin reduced pain on day 7, in four studies with 178 participants, MD -1.43 (-2.50; -0.35) I 2  = 62%. The addition of Lateral Internal Sphincterotomy to haemorrhoidectomy reduced pain on day 2 in three studies with 275 participants, MD of -2.13 (-3.49; -0.77) I 2  = 92%. The results were limited by high heterogeneity and risk of bias., Conclusion: Evidence suggests that lateral sphincterotomy, administration of botulinum toxin and the application of topical diltiazem or GTN can reduce post-operative pain after haemorrhoidectomy. Lateral sphincterotomy should not be routinely used due to the risk of incontinence., (© 2022. The Author(s).)

The molecular mechanisms leading to infantile epileptic spasm syndrome (IESS) remain obscure. The only common factor seems to be that the spasms are restricted to a limited period of infancy, during a certain maturational state. Here the current literature regarding the biochemical mechanisms of brain maturation in IESS is reviewed, and various hypotheses of the pathophysiology are put together. They include: (1) imbalance of inhibitory (NGF, IGF-1, ACTH, GABA) and excitatory factors (glutamate, nitrites) which distinguishes the different etiological subgroups, (2) abnormality of the hypothalamic pituitary adrenal (HPA) axis linking insults and early life stress, (3) inflammation (4) yet poorly known genetic and epigenetic factors, and (5) glucocorticoid and vigabatrin action on brain development, pinpointing at molecular targets of the pathophysiology from another angle. An altered maturational process may explain why so many, seemingly independent etiological factors lead to the same clinical syndrome and frequently to developmental delay. Understanding these factors can provide ideas for novel therapies., Competing Interests: Declaration of Competing Interest I have no conflict of interest to disclose., (Copyright © 2023 The Author. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis., Methods: The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis., Results: ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures ( P <0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia ( P <0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease ( P <0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control ( P <0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology ( P <0.05)., Conclusions: Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.

Objective: To examine the efficacy, dosing, and safety profiles of intrathecal and oral baclofen in treating spasticity after spinal cord injury (SCI)., Data Sources: PubMed and Cochrane Databases were searched from 1970-2018 with keywords baclofen, spinal cord injury, and efficacy., Study Selection: The database search yielded 588 sources and 10 additional relevant publications. After removal of duplicates, 398 publications were screened., Data Extraction: Data were extracted using the following population, intervention, comparator, outcomes, and study designs criteria: studies including adult patients with SCI with spasticity; the intervention could be oral or intrathecal administration of baclofen; selection was inclusive for control groups, surgical management, rehabilitation, and alternative pharmaceutical agents; outcomes were efficacy, dosing, and adverse events. Randomized controlled trials, observational studies, and case reports were included. Meta-analyses and systematic reviews were excluded., Data Synthesis: A total of 98 studies were included with 1943 patients. Only 4 randomized, double-blinded, and placebo-controlled trials were reported. Thirty-nine studies examined changes in the Modified Ashworth Scale (MAS; 34 studies) and Penn Spasm scores (Penn Spasm Frequency; 19 studies), with average reductions of 1.7±1.3 and 1.6±1.4 in individuals with SCI, respectively. Of these data, a total of 6 of the 34 studies (MAS) and 2 of the 19 studies (Penn Spasm Frequency) analyzed oral baclofen. Forty-three studies addressed adverse events with muscle weakness and fatigue frequently reported., Conclusions: Baclofen is the most commonly-prescribed antispasmodic after SCI. Surprisingly, there remains a significant lack of large, placebo-controlled, double-blinded clinical trials, with most efficacy data arising from small studies examining treatment across different etiologies. In the studies reviewed, baclofen effectively improved spasticity outcome measures, with increased efficacy through intrathecal administration. Few studies assessed how reduced neural excitability affected residual motor function and activities of daily living. A host of adverse events were reported that may negatively affect quality of life. Comparative randomized controlled trials of baclofen and alternative treatments are warranted because these have demonstrated promise in relieving spasticity with reduced adverse events and without negatively affecting residual motor function., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

The article describes a 45-year-old female patient with recurrent transient ischemic attacks and ischemic stroke due to spontaneous spasm of the middle cerebral artery, the anterior cerebral artery and distal part of the internal cerebral artery on the left, verified by MR angiography and CT angiography. It is assumed that the spasm caused damage to the vascular wall, an increase in its permeability, the development of edema, inflammation and subsequent fibrosis, therefore a complete restoration of the arterial lumen did not occur.

Aim: To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence., Methods: In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days., Results: Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P < 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non-responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment., Conclusion: We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non-use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non-responders., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Radial artery spasm (RAS) is the most common cause of transradial access site crossover and is a common intra-procedural complication. RAS incidence can lead to radial artery occlusion (RAO) postprocedure, preventing the radial artery as a future access site. We evaluated the efficacy of nitroglycerin preventing RAS and RAO during transradial catheterization discussing the different routes of administration, including topical, subcutaneous, and intra-arterial. A systematic review and meta-analysis included all relevant articles until April 23, 2022. We searched six databases Google Scholar, Web of Science, SCOPUS, EMBASE, PubMed (MEDLINE), and CENTRAL. We registered our review protocol in PROSPERO with ID: CRD42022330356. We included 11 trials with 5814 patients. Compared to placebo, the pooled analysis favored subcutaneous nitroglycerin in preventing RAS (risk ratio [RR]: 0.57 with 95% confidence interval [CI] [0.43-0.77], p = .0003) and RAO (RR: 0.39 with 95% CI [0.16-0.98], p = .05). In contrast to the intra-arterial nitroglycerin that showed nonstatistically significant results in preventing RAS and RAO (RR: 0.8 with 95% CI [0.63-1.02], p = .07)- (RR: 0.78 with 95% CI [0.6-1.01], p = .06)), respectively. Also, topical nitroglycerin did not prevent RAS (RR: 0.73 with 95% CI [0.42-1.24], p = .24). Compared with placebo, subcutaneous nitroglycerin during transradial catheterization reduced the incidence of RAS and RAO. Meanwhile, Intra-arterial and topical nitroglycerin did not show statistically significant outcomes. Subcutaneous nitroglycerin may be a practical and cost-effective technique to facilitate transradial catheterization; however, more RCTs are needed to evaluate the subcutaneous versus intra-arterial nitroglycerin administration., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Gene variants that dysregulate signaling through the RAS-MAPK pathway cause cardiofaciocutaneous syndrome (CFCS), a rare multi-system disorder. Infantile epileptic spasms syndrome (IESS) and other forms of epilepsy are among the most serious complications. To investigate clinical presentation, treatment outcomes, and genotype-phenotype associations in CFCS patients with IESS, molecular genetics and clinical neurological history were reviewed across two large clinical research cohorts (n = 180). IESS presented in 18/180 (10%) cases, including 16 patients with BRAF variants and 2 with MAP2K1 variants. Among IESS patients with BRAF variants, 16/16 (100%) had sequence changes affecting the protein kinase domain (exons 11-16), although only 57% of total BRAF variants occurred in this domain. Clinical onset of spasms occurred at a median age of 5.4 months (range: 1-24 months). Among 13/18 patients whose IESS resolved with anti-seizure medications, 10 were treated with ACTH and/or vigabatrin. A substantial majority of CFCS patients with IESS subsequently developed other epilepsy types (16/18; 89%). In terms of neurodevelopmental outcomes, gross motor function and verbal communication were more limited in patients with a history of IESS compared to those without IESS. These findings can inform clinical neurological care guidelines for CFCS and development of relevant pre-clinical models for severe epilepsy phenotypes., (© 2022 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)

Background: Coronary vasomotor abnormalities are important causes of myocardial ischemia in patients with nonobstructive coronary artery disease (NOCAD). However, the role of air pollution in determining coronary vasomotor disorders has never been investigated., Objectives: We aimed to evaluate the association between long-term exposure to particulate matter 2.5 (PM2.5) and 10 (PM10), and coronary vasomotor disorders in NOCAD patients., Methods: Patients with myocardial ischemia and NOCAD undergoing coronary angiography and intracoronary provocation test with acetylcholine were prospectively studied. Both patients with chronic myocardial ischemia and nonobstructive coronary arteries and myocardial infarction with nonobstructive coronary arteries (MINOCA) were enrolled. Based on each case's home address, exposure to PM2.5 and PM10 was assessed., Results: We included 287 patients (median age, 62.0 years [IQR: 52.0-70.0 years], 149 [51.9%] males); there were 161 (56.1%) myocardial ischemia and nonobstructive coronary arteries and 126 (43.9%) MINOCA cases. One hundred seventy-six patients (61.3%) had positive provocation test. Exposure to PM2.5 and PM10 was higher in patients with a positive provocation test (P < 0.001). At multivariate logistic regression analysis, PM2.5 and PM10 were independent predictors of a positive provocation test (P = 0.001 and P = 0.029, respectively). Interestingly, among these patients, PM2.5 and PM10 were both independent predictors of MINOCA (P < 0.001 and P = 0.001, respectively) as clinical presentation, whereas PM2.5 was independently associated with the occurrence of epicardial spasm as opposed to microvascular spasm (P = 0.001)., Conclusions: Higher exposure to PM2.5 and PM10 in patients with myocardial ischemia and NOCAD is associated with coronary vasomotor abnormalities. In particular, PM2.5 is an independent risk factor for the occurrence of epicardial spasm and MINOCA as clinical presentation., Competing Interests: Funding Support And Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Computed tomography (CT)-guided percutaneous stylomastoid foramen puncture radiofrequency ablation for the treatment of hemifacial spasm has a significant clinical effect; however, related risk factors for recurrence have not been studied., Objective: To investigate the risk factors for the recurrence of hemifacial spasm after radiofrequency ablation and construct a model for predicting recurrence., Study Design: This is a single-center retrospective observational study., Setting: The study was conducted at the Pain Department of the Affiliated Hospital of Jiaxing College in Jiaxing, China., Methods: A retrospective analysis was performed on 99 patients diagnosed with primary hemifacial spasm (HFS) admitted to the Affiliated Hospital of Jiaxing University between August 2018 and December 2021. All patients underwent CT-guided percutaneous stylomastoid foramen radiofrequency ablation. Kaplan-Meier survival analysis, log-rank test, and Cox proportional risk regression model were used to analyze the clinical factors that affect the recurrence of patients with HFS after radiofrequency ablation, and a recurrence prediction model was established., Results: Follow-up was 3-12 months; recurrence rates were 20.2%, 36.4%, and 71.9% at 3, 6, and 12 months postoperatively, respectively. Univariate analysis showed that puncture approach, operation time, and facial paralysis level were factors influencing recurrence in patients with HFS after radiofrequency ablation (P < 0.05). The multivariate Cox proportional risk regression model showed that the operative time and facial paralysis grade were independent factors for recurrence after radiofrequency ablation in patients with facial spasms. The recurrence risk function model of patients with facial spasms after radiofrequency ablation was expressed as h(t) = h0exp(-0.619X1-2.589X2), where X1 and X2 represent the operation time and facial paralysis grade, respectively. The likelihood ratio of the model was statistically significant (chi squared = 55.769, P < 0.001)., Limitations: We look forward to increasing the sample size in follow-up studies and exploring relevant conclusions in randomized controlled trials., Conclusion: Long operation times and high-grade facial paralysis can reduce the risk of recurrence in patients with facial spasms. The constructed recurrence prediction model could serve as a reference for clinical diagnosis and treatment.

Summary: The infantile spasms (IS) syndrome is a catastrophic developmental epileptic encephalopathy syndrome characterized by an age-specific expression of epileptic spasms that are associated with extremely abnormal, oftentimes described as chaotic, interictal EEG pattern known as hypsarrhythmia. Patients with IS generally have poor neurodevelopmental outcomes, in large part because of the frequent epileptic spasms and interictal EEG abnormalities. Current first-line treatments such as adrenocorticotropic hormone or vigabatrin are often ineffective and are associated with major toxic side effects. There is therefore a need for better and safer treatments for patients with IS, especially for the intractable population. Hope is on the horizon as, over the past 10 years, there has been robust progress in the development of etiology-specific animal models of IS. These models have been used to identify potential new treatments for IS and are beginning to provide some important insights into the pathophysiological substrates for this disease. In this review, we will highlight strengths and weaknesses of the currently available animal models of IS in addition to new insights into the pathophysiology and treatment options derived from these models., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Summary: Electroclinical features in surgical candidates with epileptic spasms differ significantly from the other focal epilepsy phenotypes. EEG findings tend to be more diffuse and less localizing in children with epileptic spasms. These are illustrated with five case studies to highlight three different categories of findings on interictal and ictal EEG: lateralizing , nonlateralizing , and false lateralizing . Hemihypsarrhythmia on interictal EEG is the most striking lateralizing abnormality that occurs in a minority of surgical candidates. Persistent focal epileptiform discharges in one region or asymmetric physiologic rhythms decreased over the abnormal hemisphere may provide localization clues. Ictal EEG patterns are diffuse and nonlocalizing in over half of the patients. Ictal patterns are best expressed in the posterior head regions even in patients with epileptogenic zone in anterior regions. Semiologically, epileptic spasms tend to be symmetrical in majority of surgical candidates. Asymmetric spasms and coexisting focal seizures (concurrent or remote), when present, may provide localization findings. False lateralizing interictal or ictal EEG abnormalities, paradoxically higher over the healthier hemisphere, occur in the setting of large encephaloclastic/volume loss lesions. In these patients, the diffuse discharges are less expressed over the abnormal hemisphere with less cerebral tissue. Recognition of such false lateralizing findings is important to avoid excluding appropriate surgical candidates based on the EEG findings alone. Epileptogenic lesions are visible on brain MRI in majority of surgical candidates with epileptic spasms. Electroclinical findings are often concordant with the lesion, but discordant findings are not uncommon in children with epileptic spasms., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Programmed cell death protein 1 (PD-1) inhibitors open a new era of cancer immunotherapy, but they are associated with immune-related adverse events (irAEs) involving multiple endocrine organs of which thyroid dysfunction is the most common An uncommon condition of coronary artery spasm and ventricular tachycardia associated with thyrotoxicosis, induced by a PD-1 inhibitor, is discussed in this case. A 60-year-old male patient with a 1-week history of chest tightness and palpitation at rest was referred to us in July 2021. No obvious abnormalities were noted on physical examination and electrocardiography. He was being treated with a PD-1 inhibitor (camrelizumab, 200 mg) for lung metastasis of liver cancer; treatment stopped because he was found to have hyperthyroidism. Holter recorded intermittent STsegment arch back raised 0.5-14 mm upward lasting for 1-5 min, accompanied by ventricular tachycardia. He was treated with antivasospasm drugs (isosorbide mononitrate and diltiazem). Thyroid function was reexamined and revealed elevated FT3 and FT4 levels, decreased TSH levels, and negative thyroid-associated antibodies. After antivasospasm treatment and iodine taboo diet, his symptoms were relieved, and ST-segment elevation and ventricular tachycardia were disappeared. This case adds to our knowledge of the association between coronary artery spasms and thyrotoxicosis, which is an irAE induced by a PD-1 inhibitor. Patients treated with PD-1 inhibitors need regular follow-ups for cardiac complications, especially those with a history of heart disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Infantile epileptic spasms syndrome (IESS) is the most common type of severe epilepsy in infants. However, etiological frequency and optimized therapy, particularly corticosteroid regimen and dose, remain unknown., Methods: An ambispective study of an IESS-diagnosed cohort was conducted. Etiologies were evaluated based on the 2017 International League Against Epilepsy classification system. Patients received intravenous dexamethasone or methylprednisolone for 3-5 consecutive days, followed by usual-dose (2 mg/kg/d) oral prednisone for 60-90 days with tapering doses for 1-2 months or high-dose (4 mg/kg/d) oral prednisone for 9-11 days with tapering doses for 2-4 weeks. Treatment responses were compared between the usual and high-dose prednisone groups after propensity score matching. Correlation analysis between treatment responses and underlying etiology was performed., Results: Of the 441 included participants, 218 (49.4%) cases had proven etiologies. The most common etiology of IESS was acquired-structural (23.6%), followed by genetic (15.4%) and congenital-structural (7.0%). Hypoxic-ischemic encephalopathy (55, 52.8%) was the most common acquired-structural etiology. Among the 242 patients administered corticosteroids, 95 received usual-dose oral prednisone and 147 received high-dose oral prednisone. After propensity score matching, 54 patients were included in the usual-dose and high-dose groups, respectively, and treatment effectiveness was compared. There were no significant differences in seizure freedom at days 13-14 (55.6% vs. 51.9%, p = 0.700) and continued seizure freedom between days 14-42 (29.6% vs. 38.9%, p = 0.311) post corticosteroid administration between the usual- and high-dose prednisone groups. The proportion of children achieving seizure cessation at days 13-14 (χ 2  = 1.470, p = 0.698) and days 14-42 (χ 2  = 0.928, p = 0.836) was similar in the different etiological subgroups. Unknown etiological group showed significantly higher resolution of hypsarrhythmia than other etiological groups (χ 2  = 10.761, p = 0.009). Both usual-dose and high-dose group showed tolerance to full-dose corticosteroids and similar adverse events over the observation period., Conclusion: IESS etiology was primarily related to structural causes. Clinical response in short-term follow-up was independent of prednisone dosage and underlying etiology. Better EEG responses may occur in patients with unknown etiology., Competing Interests: Conflicts of interest The authors declare that they have no potential conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Ephedrine, metaraminol, epinephrine and maneuvers like carotid sinus stimulation used during intraoperative period have been postulated to cause temporary spasm of the coronary vessels leading to decrease supply to the myocardium and precipitating myocardial infraction in non-obstructive coronary arteries (MINOCA). As an anaesthesiologists, we should be aware that even a dose as small as 25 mcg epinephrine infiltrated along with local anaesthetic in the subcutaneous plane may be responsible for coronary vessel spasm and thus myocardial infraction in nonobstructive coronary arteries. We report a case of 45 years old female with papillary carcinoma of thyroid who developed features of non-ST elevation myocardial infarction 5 minutes after the subcutaneous infiltration of 5 ml of 2% Xylocaine with 1:200000 Epinephrine. Patient was managed for acute Myocardial Infarction. Coronary angiogram done the next day revealed normal coronary arteries, hence the diagnosis Myocardial infraction in non-obstructive coronary arteries was made.

Competing Interests: Declaration of Competing Interest KAM is a site principal investigator for studies sponsored by LivaNova, GeneTx, and Ionis. HP reports no relevant conflicts of interest.

Background: Multiple sclerosis (MS) is a chronic neurological autoimmune disease, affecting the psychological and physical health of patients. Manual therapies have been proven to relieve pain, strengthen muscles, and improve bladder and bowel problems with a high safety and low adverse event profile. Previous studies have reported the results of manual therapy in alleviating symptoms associated with MS, but the conclusions were controversial. Objective: The purpose of this meta-analysis is to comprehensively analyze and determine the efficacy and safety of manual therapy in relieving symptoms associated with MS. Methods: Eight electronic databases were searched from inception of the database to April 30, 2021. Randomized controlled trials (RCTs) using manual therapy in patients to relieve symptoms associated with MS were considered eligible for this study. Two reviewers independently extracted data using pre-established standards. Results: Finally, 10 eligible RCTs with 631 subjects were included in this meta-analysis. These data establish that massage therapy can significantly ameliorate fatigue, pain, and spasms, while reflexology was only effective in relieving pain in MS patients. No adverse events were reported in eligible RCTs. Conclusions: The present study provides strong evidence that massage therapy could alleviate fatigue, pain, and spasms in MS patients, while reflexology plays a positive role in relieving pain. Physicians could consider massage therapy or reflexology as a safe and effective complementary and alternative treatment. Larger RCTs with higher methodological quality are needed in the future, which aim to provide more meaningful evidence for further proof of efficacy.

Background and Purpose: Nabiximols is a therapeutic option for patients with multiple sclerosis (MS) spasticity whose symptoms are poorly controlled by conventional oral first-line medications. This study aimed to assess the relationship between changes in spasticity severity (measured on the 0-10 numeric rating scale [NRS]) and the presence of associated symptoms in patients treated with nabiximols, and to investigate the presence of the newly described 'spasticity-plus syndrome'., Methods: We analyzed real-world data from the Italian Medicines Agency e-Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation time points were baseline, 4 weeks, and 3, 6, 12 and 18 months after treatment start., Results: Common symptoms associated with MS spasticity in this cohort were pain (38.4% at baseline), sleep disturbances (32.7%), and spasms/cramps (28.5%). Pain was frequently clustered with sleep disturbances (57.2% of pain cases) and spasms/cramps (43.9%). Approximately one-third of patients with data at all evaluation time points maintained treatment at 18 months. Nabiximols reduced the baseline mean spasticity 0-10 NRS score by 24.6% at Week 4, and by 33.9% at 18 months in treatment continuers. Nabiximols resolved a range of MS spasticity-associated symptoms at Week 4, and after 18 months in treatment continuers., Conclusion: This real-world analysis supports the concept of a spasticity-plus syndrome and suggests that nabiximols can favorably impact a range of spasticity-associated symptoms., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

This is a case report of an 81-year-old woman who underwent tracheostomy, bilateral cervical dissection, partial tongue resection, radial forearm free flap reconstruction, and split-thickness skin grafting under general anesthesia. After successful surgery, she was moderately sedated postoperatively with intravenous dexmedetomidine (DEX) and fentanyl. The fentanyl was discontinued 5 hours postoperatively. Eight hours after the operation, an atrioventricular junctional rhythm, a 2-mm elevation of the ST segment, and biphasic T waves were detected in lead II that lasted approximately 3 minutes. Hypotension and bradycardia were observed simultaneously with the abnormal electrocardiogram. The next day, a cardiologist examined the patient and suggested that coronary spasm had occurred based on those findings. The transient coronary spasm was likely caused by a combination of various factors including surgical stress and altered autonomic function. However, it is possible that stimulation of α-2 adrenergic receptors induced by DEX may also be linked to the coronary vasospasm that occurred., (© 2022 by the American Dental Society of Anesthesiology.)

Purpose: Psychogenic ptosis is a rare ophthalmic manifestation of conversion disorder. The aim of this study was to describe the clinical parameters, etiology, psychological, and clinical aspects of psychogenic ptosis., Methods: A retrospective case series was conducted of patients with psychogenic ptosis seen between 1990 to 2020. Medical records were reviewed for patient demographics, including psychiatric history, clinical findings, diagnostic studies, treatment, and resolution rates. A literature review was performed to identify cases of psychogenic ptosis previously published between 1990 and 2020., Results: Six female patients (aged 14-60 years) were diagnosed with unilateral psychogenic ptosis. Physical trauma preceded the onset of ptosis in all cases. Imaging studies had been previously obtained in all patients, none of who were correctly diagnosed at time of referral. Associated signs included concurrent brow ptosis, orbicularis oculi spasm, squint on upgaze, and variable levator function and eyelid margin measurements. Four patients had preexisting psychological conditions. Patients were primarily managed with reassurance., Conclusions: Psychogenic ptosis is an often delayed or misdiagnosed condition, resulting in unnecessary referrals and imaging. Psychogenic ptosis should be considered in patients with atypical findings of ptosis including ipsilateral brow depression, orbicularis oculi spasm, squint on upgaze, and variable eyelid measurements. A prior history of minor trauma and female sex were common in this series. Our experience suggests that psychogenic ptosis can often be treated with reassurance, leading to partial or complete resolution. Given the number of patients with comorbid psychiatric conditions, the authors recommend a low threshold for psychiatric or psychological evaluation., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Objective: To determine epilepsy and neurodevelopmental outcomes beyond 2 y of age and their putative prognostic factors in children with West syndrome (WS)., Methods: This cross-sectional study was initiated after approval from Institutional Ethics Committee. A follow-up cohort of 114 children (aged ≥ 2 y) diagnosed and treated for WS at the authors' center were assessed in-person for epilepsy and neurodevelopmental outcomes using Vineland Social Maturity Scale - Malin's adaptation for Indian children. Subsequently, age at onset, lead-time-to-treatment, etiology, and response to any of the standard therapies were analyzed as possible predictors of these outcomes., Results: Of 114 children (mean age: 55 ± 32 mo, 91 boys), structural etiology was the predominant underlying etiology (79.8%) for WS. At 2 y of age, 64% had ongoing seizures. At the last follow-up, 76% had social quotient < 55, and 39% had cerebral palsy (spastic quadriparesis in 21%). An underlying structural etiology was associated with ongoing seizures [OR (95% CI) 3.5 (1.4-9); p = 0.008] at 2 y of age and poor developmental outcomes [OR (95% CI): 3.3 (1.3-8.9); p = 0.016]. Complete cessation of spasms with the standard therapy was significantly associated with better seizure control [OR (95% CI): 5.4 (2.3-13); p < 0.001] and neurodevelopmental outcome [OR (95% CI): 5.2 (1.8-14.9); p < 0.001]., Conclusion: The majority of children with WS have a poor neurodevelopmental outcome and epilepsy control on follow-up. The underlying etiology and response to initial standard therapy for epileptic spasms have a prognostic role in predicting the neurological outcome in these patients on follow-up., (© 2021. Dr. K C Chaudhuri Foundation.)

Background: Coronary spasm has been suggested to be the underlying mechanism of chest pain in patients with myocarditis and unobstructed coronary arteries. Here we sought to investigate a potential association between virus type and coronary spasm endotype in patients with biopsy-proven viral myocarditis., Methods: A total of 618 consecutive patients with unobstructed coronary arteries who underwent endomyocardial biopsy between 2008 and 2018 were screened. Viral myocarditis defined as (immuno-)histological evidence of myocardial inflammation and proof of viral genome by PCR was confirmed in 114 patients. Of these, 34 patients had undergone additional intracoronary acetylcholine (ACh) testing and served as the final study cohort., Results: Patients in this study were 51 ± 27 years old, 41% were female and mean left ventricular ejection fraction was 58 ± 23%. Most frequently, virus DNA was detected by PCR from parvovirus B19 (PVB19, 59%) and human herpesvirus 6 (HHV6, 26%). ACh testing revealed epicardial spasm in 10 patients (29%) and microvascular spasm in 11 patients (32%). The rate of coronary spasm was higher in patients with PVB19-associated myocarditis compared to those with HHV6-associated myocarditis (80% vs. 33%, p = 0.031). In particular, there was a higher prevalence of microvascular spasm in patients with PVB19 compared to HHV6 infection (45% vs. 0%, p = 0.018)., Conclusion: Coronary spasm is a frequent finding in patients with biopsy-proven viral myocarditis supporting the hypothesis that coronary spasm may contribute to chest pain in these patients. We observed a particular association of microvascular spasm with PVB19 infection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Stiff person syndrome (SPS) is a rare, debilitating neurological illness characterised by rigidity and spasms of the axial muscles, causing severe restrictions to mobility. SPS can be classic, partial or paraneoplastic. We report a case of a young woman who presented with seizures and painful spasms of the thoracolumbar muscles who was subsequently diagnosed with SPS. Serological work revealed glutamic acid decarboxylase (GAD) antibodies and imaging showed a large mediastinal mass. The patient underwent surgical resection of the mediastinal mass and final pathology revealed well-differentiated mediastinal liposarcoma. She received five sessions of plasma exchange and her neurological symptoms gradually improved after surgery. This case highlights a rare case of GAD antibody-positive paraneoplastic SPS associated with mediastinal liposarcoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: As an upper oesophageal sphincter (UES) dysfunction disorder, cricopharyngeal achalasia (CPA) is a common cause of dysphagia and is associated with an increased risk of pulmonary complications. The aim of this study was to investigate the effectiveness and safety of BTX-A injection using ultrasound combined with balloon guidance for the treatment of CPA caused by stroke., Methods: A total of 21 patients diagnosed with CPA were treated with BTX-A injection into the cricopharyngeal muscle using ultrasound combined with balloon guidance. Primary outcome measures, including the functional oral intake scale (FOIS), videofluoroscopic dysphagia scale (VDS) and penetration aspiration scale (PAS), which are quantitative measures for a video fluoroscopic swallowing study (VFSS), and scores of the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were assessed from baseline to 12 weeks after treatment. Repeated measures analysis of variance was used to compare the scores between time points., Results: BTX-A injection led to improved dysphagia symptoms and scores in 19 patients (90.48%). Among them, 5 cases were cured (23.81%), 11 cases showed significant improvement (52.38%), and 3 cases showed improvement (14.29%). Two cases were absolutely ineffective (9.52%). Compared with the scores prior to treatment, the scores on the FOIS, VDS, PAS, SAS and SDS significantly improved beginning at 3 days ( p  < .05) and lasting for at least 12 weeks after injection., Conclusions: Ultrasound with balloon-guided BTX-A injection is probably a relatively safe, easy, and effective technique for the treatment of CPA caused by stroke, with better visualization of the injection procedure. A well-designed controlled trial with a larger sample size is needed for more convincing conclusions.