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BACKGROUND AND OBJECTIVE: CDKL5 deficiency disorder presents as a challenging condition with early-onset refractory seizures, severe developmental delays, and a range of other neurological symptoms. Our study aimed to explore the benefits and side effects of anti-seizure medications (ASMs) in managing seizures among individuals with CDKL5 deficiency disorder, drawing on data from the International CDKL5 Disorder Database. METHODS: Data for this retrospective cohort study were obtained from the International CDKL5 Disorder Database, which contains responses from a baseline questionnaire administered between 2012 and 2022 and a follow-up questionnaire administered between 2018 and 2019. Families of eligible individuals were asked to provide information on ASMs that were previously and currently taken, the dose prescribed, the age at starting the medications, and the age at discontinuation for past medications. The outcome variables of interest were perceived seizure-related benefits for the current and past use of ASMs and caregiver-reported side effects. Rescue medications and infrequently used ASMs were excluded from the analysis. Descriptive statistics were used to summarise the characteristics of the study population. RESULTS: The study included 399 children and adults with CDKL5 deficiency disorder, descriptively analysing the perceived benefits and side effects of 23 unique ASMs based on caregiver reports. The study identified levetiracetam, topiramate, sodium valproate, vigabatrin, phenobarbital and clobazam as the most used ASMs. Notably, cannabidiol showed highly beneficial outcomes with few side effects, whereas levetiracetam and phenobarbital exhibited less favourable benefit-to-side-effect ratios. Dual therapy involving sodium valproate and levetiracetam was only used a small number (n = 5) of times but appeared effective in reducing seizure activity with relatively few side effects. Compared with monotherapy, polytherapy had a relatively higher likelihood of reported side effects than benefits. CONCLUSIONS: The study, leveraging a large sample size that exceeds that of previous research, emphasises the complex nature of seizure management in CDKL5 deficiency disorder. Our findings underscore the necessity of ongoing research to optimise treatment strategies, considering both the efficacy of seizure control and the potential for adverse effects. The study also points to the need for future investigations into the therapeutic potential of emerging treatments such as ganaxolone and the unresolved efficacy of cannabis products in seizure management.

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2-19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3-10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI -2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.

OBJECTIVE: Relapse of epileptic spasms after initial treatment of infantile epileptic spasms syndrome (IESS) is common. However, past studies of small cohorts have inconsistently linked relapse risk to etiology, treatment modality, and EEG features upon response. Using a large single-center IESS cohort, we set out to quantify the risk of epileptic spasms relapse and identify specific risk factors. METHODS: We identified all children with epileptic spasms at our center using a clinical EEG database. Using the electronic medical record, we confirmed IESS syndrome classification and ascertained treatment, response, time to relapse, etiology, EEG features, and other demographic factors. Relapse-free survival analysis was carried out using Cox proportional hazards regression. RESULTS: Among 599 children with IESS, 197 specifically responded to hormonal therapy and/or vigabatrin (as opposed to surgery or other second-line treatments). In this study, 41 (21%) subjects exhibited relapse of epileptic spasms within 12 months of response. Longer duration of IESS prior to response (>3 months) was strongly associated with shorter latency to relapse (hazard ratio = 3.11; 95% CI 1.59-6.10; p = 0.001). Relapse was not associated with etiology, developmental status, or any post-treatment EEG feature. SIGNIFICANCE: This study suggests that long duration of IESS before response is the single largest clinical predictor of relapse risk, and therefore underscores the importance of prompt and successful initial treatment. Further study is needed to evaluate candidate biomarkers of epileptic spasms relapse and identify treatments to mitigate this risk. PLAIN LANGUAGE SUMMARY: Relapse of infantile spasms is common after initially successful treatment. With study of a large group of children with infantile spasms, we determined that relapse is linked to long duration of infantile spasms. In contrast, relapse was not associated with the cause of infantile spasms, developmental measures, or EEG features at the time of initial response. Further study is needed to identify tools to predict impending relapse of infantile spasms.

OBJECTIVE: Infantile epileptic spasms (IS) are epileptic seizures that are associated with increased risk for developmental impairments, adult epilepsies, and mortality. Here, we investigated coherence-based network dynamics in scalp EEG of infants with IS to identify frequency-dependent networks associated with spasms. We hypothesized that there is a network of increased fast ripple connectivity during the electrographic onset of clinical spasms, which is distinct from controls. METHODS: We retrospectively analyzed peri-ictal and interictal EEG recordings of 14 IS patients. The data was compared with 9 age-matched controls. Wavelet phase coherence (WPC) was computed between 0.2 and 400 Hz. Frequency- and time-dependent brain networks were constructed using this coherence as the strength of connection between two EEG channels, based on graph theory principles. Connectivity was evaluated through global efficiency (GE) and channel-based closeness centrality (CC), over frequency and time. RESULTS: GE in the fast ripple band (251-400 Hz) was significantly greater following the onset of spasms in all patients (P  central > anterior, Kruskal-Wallis P

Autoimmune polyendocrine syndromes (APS) is a rare group of disorders caused by impaired function of multiple endocrine glands due to disruption of immune tolerance. Of which, type 2 (APS-2) is the most common. Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA). Anti-GAD antibodies are associated with various neurological disorders, including stiff person syndrome (SPS). SPS is characterized by axial muscle stiffness, rigidity, and intermittent painful muscle spasms, with a prevalence of one to two in a million, making it an extremely rare neurological disorder. The comorbidity of APS-2 with SPS is even rarer. Most practicing neurologists encounter only one or two cases of APS-2 combined with anti-GAD65 antibody-associated SPS in their careers, resulting in underdiagnosis and undertreatment, leading to severe disability and suffering. This case report describes a young male who initially exhibited hair loss, vitiligo, and previously unreported eosinophilia. Before his diagnosis, he was admitted multiple times, with symptoms improving following the addition of intravenous immunoglobulin (IVIG) therapy to a poor treatment regimen. This paper aims to increase physicians' awareness of this condition, enhancing the likelihood of early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Epileptic spasms (ES) are a unique seizure type typically presenting in the form of infantile epileptic spasms syndrome (IESS) with characteristic hypsarrhythmia on scalp EEG and a preponderance with developmental delay or regression. While pharmacotherapy is the mainstay of treatment, surgical options, including disconnective or resective procedures, are increasingly recognized as viable therapeutic options for recurrent or persistent ES. However, limited data on safety, effectiveness, and prognostic factors hinder informed decision-making regarding surgery indications, timing, and intervention type. We performed a systematic review and an individual patient data meta-analysis (IPDMA) in accordance with PRISMA guidelines, focusing on surgical interventions for ES and reporting seizure outcomes using the Engel or ILAE scales. Twenty-six studies encompassing 358 ES patients undergoing resection/callosotomy were included. Participants undergoing other approaches (e.g., multiple subpial transections) or multimodality approaches were excluded from analysis. The median age at spasm onset was 6 months (IQR = 3.0–15.6), with a median age at surgery of 37 months (IQR = 17.2–76.8). Most patients (74.1%) exhibited additional seizure types. A total of 136 patients (35.8%) underwent corpus callosotomy (CC), of whom 125 (91.9%) had a complete callosotomy, while 11 (8.1%) had a partial callosotomy. Resective surgery was performed on 222 patients (58.4%). Among those who underwent resection, 109 (49.1%) had both lesional MRI findings and lateralized EEG abnormalities. Overall, 201 patients (56.1%) remained spasm-free at a median postoperative follow-up of 36 months (interquartile range, IQR = 21–60), including 52 (38.2%) from the callosotomy group and 149 (67.1%) from the resective surgery group. In the resective surgery cohort, patients with MRI-confirmed lesions (p = 0.026; HR = 0.53, 95% CI = 0.31–0.93) and those who underwent hemispherectomy (p = 0.026, HR = 0.46, 95% CI = 0.23–0.91) had better seizure outcomes. Only a minority (24.4%) underwent invasive EEG monitoring prior to ES surgery. Surgical treatment of ES proves effective, with two thirds of patients undergoing resective surgery and a third undergoing CC becoming spasm free. Post-operative developmental improvement was observed in 44 participants (65.7% of those with available data). The presence of lesional MRI and more extensive resection/disconnection (e.g., hemispherectomy) emerged as significant prognostic factors for spasm freedom and can inform clinical decision-making. [ABSTRACT FROM AUTHOR]

Purpose: Currently available grading and classification systems for hemifacial spasm either rely on subjective assessments or are excessively intricate. Here, we make use of facial recognition and facial tracking technologies towards accurately grouping patients according to severity and characteristics of the spasms. Methods: A retrospective review of our prospectively maintained preoperative videos database for hemifacial spasm was done. Videos were analyzed using an Apple AR kit-based App. A facial mesh is automatically allocated to specific biometric facial points. Videos are analyzed using Blender software for measuring the amplitude and frequency of the spasms. Classification of the patients into groups was done using both divisive k-means and agglomerative hierarchical clustering. Correlation-Analysis with preoperative quality of Life (Qol) using SF-36 questionnaire and HFS-8 score was performed. Additionally, correlation with postoperative outcome was calculated. Results: 79 preoperative videos were included. Both up-bottom and bottom-up clustering approaches grouped the patients into 3 different clusters according to 4 variables (eye closure, mouth distance change, rate, and repetition of the spasms). Correlation of the groups with the Qol was done for 46/79 patients (58.2%). Spasms could be classified into mild, moderate clonic and severe tonic spasms. Patients with mild spasms showed better Qol scores. Moderate clonic spasms experienced best outcomes following microvascular decompression. Conclusion: This novel classification using facial-tracking and augmented-reality is easy to use and apply. It quantifies the severity and type of the spasms and relates it to the quality of life of patients, postoperative outcome, and could guide our management strategy. [ABSTRACT FROM AUTHOR]

Paraneoplastic myelopathy (PM) is an enigmatic immune‐mediated disorder rarely associated with breast cancer (BC) and anti‐Ri antibodies. Sometimes diagnosis is difficult due to the heterogeneity of symptoms and the timing of their onset. Herein, we report the case of a woman presenting with cervical myelopathy causing spastic left hemiplegia and painful spasms. Diagnosis of PM was confirmed through the positivity of well‐characterized onconeural antibodies (anti‐Ri) and the discovery of BC after a clinical examination and multiple investigations. We highlight, through this case, the importance of onconeural antibodies in the diagnosis of paraneoplastic neurological syndromes and associated cancer. [ABSTRACT FROM AUTHOR]

In order to provide some references for vein approach selection in adrenal vein sampling (AVS), this retrospective study analyzed 325 cases of primary aldosteronism (PA) patients who underwent AVS via the upper extremity vein approach, comparing the differences in complications and visual analogue scale (VAS) scores through median cubital vein (MCV), basilic vein (BV), and cephalic vein (CV). The results indicated no significant difference in the incidence of venous spasm (right MCV vs. right BV vs. left MCV vs. left BV: 4.2 vs. 5.9 vs. 5.3 vs. 0.0%, p>0.05) and VAS scores between AVS performed using the MCV and the BV. However, the right CV access was associated with a relatively higher incidence of venous spasm (right CV: 20% vs. right MCV: 4.2%, p<0.05) and higher rate of thrombosis formation (right CV: 5.7% vs. right MCV: 0.0%, p<0.05) than right MCV, accompanied by more severe pain. The study suggests that bilateral MCV and BV are both viable options vein access for AVS. When neither the MCV nor the BV on one side is accessible, it may be more prudent to opt for the MCV or BV on the contralateral side rather than the CV. [ABSTRACT FROM AUTHOR]

Background Patients with lissencephaly typically present with severe psychomotor retardation and drug-resistant seizures. The aim of this study was to characterize the epileptic phenotype in a genotypically and radiologically well-defined patient cohort and to evaluate the response to antiseizure medication (ASM). Therefore, we retrospectively evaluated 47 patients of five genetic forms (LIS1/PAFAH1B1 , DCX , DYNC1H1 , TUBA1A , TUBG1) using family questionnaires, standardized neuropediatric assessments, and patients' medical reports. Results All but two patients were diagnosed with epilepsy. Median age at seizure onset was 6 months (range: 2.1–42.0), starting with epileptic spasms in 70%. Standard treatment protocols with hormonal therapy (ACTH or corticosteroids) and/or vigabatrin were the most effective approach for epileptic spasms, leading to seizure control in 47%. Seizures later in the disease course were most effectively treated with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, resulting in seizure freedom in 20%. Regarding psychomotor development, lissencephaly patients presenting without epileptic spasms were significantly more likely to reach various developmental milestones compared to patients with spasms. Conclusion Classic lissencephaly is highly associated with drug-resistant epilepsy starting with epileptic spasms in most patients. The standard treatment protocols for infantile epileptic spasms syndrome lead to freedom from seizures in around half of the patients. Due to the association of epileptic spasms with an unfavorable course of psychomotor development, early and reliable diagnosis and treatment of spasms should be pursued. For epilepsies occurring later in childhood, ASM with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, appears to be most effective. [ABSTRACT FROM AUTHOR]

A small proportion of children with a sudden onset torticollis ("wry neck") presents with an atlantoaxial rotatory subluxation, usually after mild trauma or recent head or neck infection. Torticollis is a clinical diagnosis and imaging is usually not indicated, though often performed in clinical practice. Atlantoaxial rotatory subluxation on imaging is often a physiological phenomenon in torticollis, and concomitant neurological symptoms are therefore rare. Treatment is primarily conservative, with analgesics, a rigid neck collar, and if needed benzodiazepines to counteract muscle spasms and anxiety. In case of treatment failure or chronic subluxation, cervical repositioning and fixation under general anesthesia may be considered. Surgical treatment is only indicated in a small percentage of patients with chronic refractory subluxation, concomitant cervical fractures, or congenital anomalies. Early diagnosis and treatment are important, since this is associated with a more successful conservative outcome than a prolonged approach. [ABSTRACT FROM AUTHOR]

Fenpiverinium is an agent which, from a medical perspective, has anticholinergic and antispasmodic properties, with applications in the treatment of smooth muscle spasm. The crystal and molecular structures of two fenpiverinium-based crystals, namely fenpiverinium bromide and fenpiverinium bromide hemihydrate, were elucidated and explored by single-crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

Reversible cerebral vasoconstriction syndrome is a complex condition characterized by temporary constriction of the brain's arteries. Diagnosis typically involves a retrospective approach, necessitating repeated imaging to confirm the resolution of cerebral arterial spasms. We describe a case of a 22-year-old female with a history of posterior circulation stroke and recurrent thunderclap headaches. On imaging, evidence of stroke, convexity subarachnoid hemorrhage, and multiple areas of stenosis and dilatation in the posterior circulation associated with normal laboratory parameters were found. The resolution of clinical symptoms and angiographic findings were noted in the follow-up. After other diagnoses are excluded, patients can be reassured about favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: Basal cell carcinomas (BCCs) are the most common cancers worldwide. Although most BCCs are amenable to local treatment, there are limited therapeutic options for surgically unresectable locally advanced and metastatic BCCs. Activation of the sonic hedgehog signalling pathway plays a significant role in the development of most BCCs. Hedgehog pathway inhibitors (HPIs) can be used to inhibit this pathway. Efficacy and safety data on HPI use in Australia is scarce. Objectives: This study aims to present the effectiveness and safety of HPI at a tertiary dermatology referral centre. Methods: We conducted a retrospective analysis of the clinical charts of all patients with BCC treated with an HPI at a tertiary Dermatology referral centre in New South Wales, Australia from 1 January 2016 to 1 July 2023. Results: Twenty‐three patients with BCCs were treated with an HPI; 11 locally advanced, 8 multiple, 3 basal cell naevus syndrome and 1 metastatic. All patients were of Caucasian background, with a median age of 56. Across 41 treatment cycles, the median treatment duration was 4 months. The overall response rate (ORR) was 20/23 (87%) and complete response (CR) rate was 9/23 (39%); patients treated with sonidegib achieved an ORR of 11/12 (92%) and CR of 4/12 (33%), and vismodegib‐treated patients achieved an ORR of 9/11 (82%) and CR of 5/11 (45%). Patients who responded to HPI treatment also responded to a subsequent HPI rechallenge. Common treatment emergent adverse events (TEAEs) included muscle spasms, dysgeusia and alopecia. Dysgeusia was more frequent with vismodegib than sonidegib (p = 0.0001). There was no evidence to suggest a difference in other TEAEs between the two HPIs. Four treatment cycles were stopped due to grade 3 muscle spasm. Conclusions: In our cohort of 23 patients being treated with HPI, the ORR was 87% and CR was 39%. All patients who experienced TEAEs and had a drug holiday successfully responded to HPI rechallenge. TEAEs, particularly muscle spasms, are common reasons for treatment cessation. Clinicians should implement strategies to mitigate TEAE to improve drug survivability. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical outcomes beyond pain relief of high-frequency spinal cord stimulation at 10 kHz (10 kHz SCS) in a patient with cervical myelopathy and drug-resistant chronic neuropathic pain with spastic tetraparesis. Methods: A patient with C3-C6 myelomalacia and spastic tetraparesis previously treated with decompressive laminectomy underwent implantation of 10 kHz SCS for pain management through a trial procedure followed by permanent implantation. Due to the presence of epidural fibrotic scar tissue in the area of the previous C3-C6 laminectomy, the leads could not be implanted at the cervical level; therefore, the leads were positioned at the thoracic level. Data were collected during routine follow-up visits up to 15 months after implantation. Results: Since the trialing phase and during all follow-up visits, along with complete pain relief in the lower limbs, a recovery from spasms was observed with an improvement in motor function. The patient recovered from a sensation of stiffness and difficulty in movement, with a significant decrease in muscle tone, regaining confidence in walking, and no longer needing assistance even for long walking distances. Although all disabling and painful symptomatology in the upper limbs instead did not ameliorate, the Oswestry Disability Index (ODI) score decreased from 50% at baseline to 6%. Conclusion: To our knowledge, recovery from spasms and motor improvement in a spastic tetraparesis patient has never been reported before with 10 kHz SCS and possibly this new stimulation paradigm may overcome some performance limitations of traditional low-frequency SCS (LF-SCS). Treatment eliminated spasms at the lower limbs but not at the upper ones, thus suggesting that the location of the epidural leads could affect outcomes. [ABSTRACT FROM AUTHOR]

Lennox-Gastaut syndrome (LGS) is one of the most severe childhood-onset epileptic encephalopathies, primarily characterized by tonic seizures. In clinical practice, we have identified various subtypes of tonic seizures in LGS. This study aimed to analyze the clinical characteristics, electrographic features, treatment responses, and prognosis across different subtypes of LGS. This retrospective cohort study included 46 patients diagnosed with LGS at our center between January 2017 and January 2020. Patients were classified into four groups based on tonic seizure subtypes: Group A (tonic), Group B (spasm-tonic), Group C (myoclonic-tonic), and Group D (combination of spasm-tonic and myoclonic-tonic). Comprehensive clinical data were collected and analyzed. Of the 46 patients, 33 were male. The mean age of onset for Group B (12.38 ± 7.85 months) was significantly less than those of the other three groups (P = 0.02). No significant differences in etiology were found among the groups. Genetic analysis identified mutations in SCN8A , MCCC2 , STXBP1 , GABRB3 , and CACNA1H. After a minimum follow-up of 24 months, the treatment outcomes were more favorable in Groups A and C, whereas psychomotor development was notably poorer in Groups B and D. The findings of this study suggest that LGS may present with distinct subtypes of tonic seizures, with spasm-tonic seizures presenting at an earlier age. Patients with LGS experiencing spasm-tonic seizures, with or without myoclonic-tonic seizures, exhibited poorer treatment responses and psychomotor development than those with other subtypes. [ABSTRACT FROM AUTHOR]

PURPOSE: Understanding the real-world experience of patients with early breast cancer (eBC) is imperative for optimizing outcomes and evolving patient care. However, there is a lack of patient-level data, hindering clinical development. This social listening study was performed to understand patient insights into symptoms and impacts of hormone therapy (HT) for eBC using posts from patient forums on breastcancer.org to inform future clinical research. METHODS: Natural language processing (NLP) and machine learning techniques were used to identify themes related to eBC from a sample of 500,000 posts. After relevant data selection, 362,074 eBC posts were retained for further analysis of symptoms and impacts related to HT, as well as insights into symptom severity, pain locations, and symptom management using exercise and yoga. RESULTS: Overall, 32 symptoms and nine impacts had significant associations with ≥one HT. Hot flush (relative risk [RR], 6.70 [95% CI, 3.36 to 13.36]), arthralgia (RR, 6.67 [95% CI, 3.53 to 12.59]), weight increased (RR, 4.83 [95% CI, 3.20 to 7.28]), mood swings (RR, 7.36 [95% CI, 5.75 to 9.42]), insomnia (RR, 4.76 [95% CI, 3.14 to 7.22]), and depression (RR, 3.05 [95% CI, 1.71 to 5.44]) demonstrated the strongest associations. Severe headache, dizziness, back pain, and muscle spasms showed significant associations with ≥one HT despite their low overall prevalence in eBC posts. CONCLUSION: The social listening approach allowed the identification of real-world insights from posts specific to eBC HT from a large-scale online breast cancer forum that captured experiences from a uniquely diverse group of patients. Using NLP has a potential to scale analysis of patient feedback and reveal actionable insights into patient experiences of treatment that can inform the development of future therapies and improve the care of patients with eBC. [ABSTRACT FROM AUTHOR]

A 4‐year‐old, neutered male domestic short‐haired cat was presented with an abdominal injury, severe extensor rigidity of all limbs and sardonic facial expression. The cat was diagnosed with tetanus and antibiotics, and antiemetics and analgesics were administered. In order to provide myorelaxation, in addition to midazolam, a supraphysiologic dose of magnesium sulphate was infused intravenously at a constant rate of 10 mg/kg/h, after a loading dose of 70 mg/kg; serum magnesium and ionic calcium were measured daily. During hospitalisation, the cat showed hypersensitivity to stimuli, tetanic seizures, hyperthermia and autonomic dysfunction, presenting as severe hypertension, sinus and ventricular tachycardia. An intravenous infusion of dexmedetomidine (1 ± 0.5 µg/kg/h) improved haemodynamic parameters and attenuated muscle spasms, and its administration was continued for 96 h without adverse reactions. The magnesium infusion was maintained for 11 days without toxicity, except for a mild hypocalcaemia. The cat's clinical signs gradually improved and the patient was discharged on day 28. [ABSTRACT FROM AUTHOR]

Objective: There are numerous reports of people substituting medical cannabis (MC) for medications. Our obejctive was to investigate the degree to which this substitution occurs among people with rheumatic conditions. Methods: In a secondary analysis from a cross‐sectional survey conducted with patient advocacy groups in the US and Canada, we investigated MC use and medication substitution among people with rheumatic conditions. We subgrouped by whether participants substituted MC for medications and investigated differences in perceived symptom changes and use patterns, including methods of ingestion, cannabinoid content (cannabidiol vs delta‐9‐tetrahydrocannabinol [THC]), and use frequency. Results: Among 763 participants, 62.5% reported substituting MC products for medications, including nonsteroidal anti‐inflammatory drugs (54.7%), opioids (48.6%), sleep aids (29.6%), and muscle relaxants (25.2%). Following substitution, most participants reported decreases or cessation in medication use. The primary reasons for substitution were fewer adverse effects, better symptom management, and concerns about withdrawal symptoms. Substitution was associated with THC use and significantly higher symptom improvements (including pain, sleep, anxiety, and joint stiffness) than nonsubstitution, and a higher proportion of substitutors used inhalation routes than those who did not. Conclusion: Although the determination of causality is limited by our cross‐sectional design, these findings suggest that an appreciable number of people with rheumatic diseases substitute medications with MC for symptom management. Inhalation of MC products containing some THC was most commonly identified among those substituting, and disease characteristics did not differ by substitution status. Further study is needed to better understand the role of MC for symptom management in rheumatic conditions. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to evaluate the association between QoL, self-assessed physical activity, and the presence and severity of muscle spasms in chronic hemodialysis patients. Patients undergoing regular in-center hemodialysis (HD) have much lower quality of life (QoL) than healthy individuals. However, there is limited knowledge about the impact of specific common complications of hemodialysis, particularly muscle spasms on the overall well-being of patients. Materials and Methods: In this prospective, single-center study, 67 chronic HD patients were surveyed regarding the prevalence of muscle spasms using a validated 9-multiple-choice-question survey, alongside the Physical Activity Questionnaire (IPAQ) and The Short Form (36) Health Survey (SF-36). Based on the muscle spasms survey answers, patients were divided into two subgroups: with (n = 39) and without muscle spasms (n = 28). Results: The findings revealed that patients with muscle spasms had a higher body mass index (BMI) (p = 0.005), a shorter dialysis vintage (p = 0.063), and significantly longer sitting times (p = 0.017). Multivariate analysis identified BMI (p = 0.034), sitting time (p = 0.009), physical functioning scores (p = 0.032), and dialysis vintage (p = 0.040) as significant predictors of muscle spasms. Conclusions: This study concluded that muscle spasms are associated with lower QoL among HD patients. The contributing factors to this dependance are BMI, dialysis vintage, physical functioning, and sitting time. [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the clinical and electrophysiological characteristics of two cases of type I sialidosis in Chinese children with those reported in prior literature. The goal is to elucidate the clinical and genetic features of type I sialidosis. Methods: Clinical investigations and genetic analyses were conducted on an 11-year-old girl, primarily presenting with short stature, who was admitted in June 2020, and a 10-year-old boy, admitted in July 2023, exhibiting rapid weight gain and accompanying visual impairment as primary manifestations. A literature review was performed by summarizing data from 31 published articles encompassing 69 genetically confirmed cases of type I sialidosis up to 2023 for comparative analysis. Results: Patient 1 exhibited short stature, self-reported poor night vision, a history of occasional febrile seizures, mild scoliosis, bilateral cherry-red spots in the fundus, and prolonged P100 latency in both eyes as observed in visual evoked potentials (VEP). Genetic analysis revealed that she carried compound-heterozygous variants c.239 C > T (p.P80L) and c.880 C > T (p.R294C) in the NEU1 gene, inherited from her parents. Patient 2 presented with rapid weight gain and visual impairment, bilateral cherry-red spots in the fundus, abnormal neuroepithelial layer reflexes in both macular areas, approximately normal P100 latency but severely reduced amplitude in VEP after pupillary dilation, and severe bilateral optic nerve conduction block with relatively normal retinal cell function. Compound-heterozygous variants c.239 C > T (p.P80L) and c.803 A > G (p.T268C) were identified in the NEU1 gene of the Patient 2, inherited from his parents. By combining the cases reported in 31 literature articles with the 2 cases in our study, a total of 71 type I sialidosis patients were analyzed. The most common symptoms observed were muscle spasms (91.5%), followed by ataxia (75%) and seizures (63.6%). Intellectual impairment and abnormal electroencephalograms were more prevalent in Caucasian patients. Additionally, abnormal somatosensory evoked potentials, large cortical waves, and prolonged latency of VEP were more frequently observed in both Asian and Caucasian patients, serving as alternative indicators for early diagnosis. Conclusion: NEU1 gene analysis provides essential guidance for genetic counseling and prenatal diagnosis. The exon 2 variant c.239 C > T (p.P80L) in the NEU1 gene may represent a mutation hotspot among Chinese patients. [ABSTRACT FROM AUTHOR]

Hypokalemia is a common condition that has been well studied. In most patients, mild hypokalemia is asymptomatic, while those with moderate-to-severe hypokalemia tend to show more prominent symptoms. In patients with a potassium level of 2.5 milliequivalents/liter (mEq/L) or lower, symptoms such as muscle cramps or weakness, rhabdomyolysis, and myoglobinuria tend to arise. These manifestations can lead to more debilitating consequences, such as renal failure secondary to rhabdomyolysis or respiratory failure secondary to muscle weakness. Other symptoms such as ileus, nausea, and vomiting, as well as cardiac arrhythmia and abnormalities, are also associated. Here we would like to present a patient with a potassium level of 1.4 mEq/L secondary to furosemide who presents to the emergency department with only complaints of muscle spasms for the past few days. [ABSTRACT FROM AUTHOR]

Background: Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study. Methods: NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504). Patients with laBCC are treated with sonidegib 200 mg orally once daily and followed for 3 years. Dose modifications were allowed according to the local prescribing information. Results: Between May 6, 2019, and March 15, 2022, 321 patients with laBCC were enrolled at 46 European sites (data cut-off: June 22, 2023). Treatment was discontinued in 241 (75.1%) patients, with the main reasons being the patient/guardian decision (n = 69, 28.6%), treatment success (n = 40, 16.6%) and the physician decision (n = 35, 14.5%). The median duration of sonidegib exposure was 8.8 months (4.4–13.7 months). Overall, 284 (88.5%) patients had ≥ one treatment-emergent adverse event (TEAE). Most TEAEs were ≤ grade 2 and the most common were muscle spasms (n = 141; 43.9%), dysgeusia (n = 119; 37.1%), and alopecia (n = 97; 30.2%). After 3 months of treatment, the cumulative rates of muscle spasms, dysgeusia, and alopecia were 21.8%, 16.2%, and 3.7%, respectively. TEAEs led to treatment discontinuation in 59 (18.4%) patients, while 149 (46.4%) patients had at least one TEAE leading to dose reduction or interruption. Serious drug-related TEAEs were reported in 13 (4.1%) patients. Conclusions: These results confirm the safety profile previously observed. Most patients experienced the onset of common TEAEs after 3 months of treatment, and the cumulative incidence of most common TEAEs was 10–20% lower compared to the BOLT study, except for dysgeusia and fatigue that had a similar incidence. The percentage of patients experiencing TEAEs requiring interruption or dose reduction was similar to the BOLT study, while the proportion of patients with TEAE leading to discontinuation of sonidegib was lower. This study demonstrates that the tolerability of sonidegib is manageable in routine clinical practice. Trial registration. NCT04066504. [ABSTRACT FROM AUTHOR]

ABSTRACT With the ever‐growing population of patients undergoing cardiac ablation with pulsed electric fields, there is a need to understand secondary effects from the therapy. Coronary artery spasm is one such effect that has recently emerged as the subject of further investigation in electrophysiology literature. This review aims to elucidate the basic anatomy underlying vascular spasm due to pulsed electric fields and the effects of irreversible electroporation on coronary arteries. This review also aims to gather the current preclinical and clinical data regarding the physiology and function of coronary arteries following electroporation. [ABSTRACT FROM AUTHOR]

Background: There are currently no intraoperative neurophysiological tools to assess the effectiveness of trigeminal nerve decompression during microvascular decompression surgery for drug-resistant trigeminal neuralgia. In microvascular decompression surgery for hemifacial spasm, an abnormal electromyographic activation of facial muscles after stimulation of the offending vessel was identified and named 'Z-L response'. Methods: We adapted a neurophysiological protocol to elicit a Z-L response during microvascular decompression surgery for trigeminal neuralgia and applied it to a prospective series of 18 surgical patients. Results: Patients had suffered from trigeminal neuralgia for a median 9-year timeframe, and median preoperative Barrow Neurological Institute pain score was 4.5. Through monopolar stimulation, using rising amplitudes starting from 0.1 mA, we confirmed intraoperatively the true culprit vessel before decompression. In 4/18 cases, multiple offending vessels were identified (22 conflicts overall). After decompression, a significant increase in activation threshold (p < 0.0001) confirmed the effectiveness of the maneuver; in 10 cases, Z-L response was abolished. Using this technique, we obtained excellent or good outcome (Barrow Neurological Institute 1–3) in all patients, with a significant reduction in postoperative Barrow Neurological Institute score as compared with preoperative one (median Barrow Neurological Institute 1; p = 0.0002). Conclusion: we provide the first evidence on the applicability and clinical usefulness of Z-L response during microvascular decompression surgery for trigeminal neuralgia. [ABSTRACT FROM AUTHOR]

Distal esophageal spasm (DES) is a rare motility disorder presenting with dysphagia or chest pain. Although studies suggest a link between DES and gastroesophageal reflux disease (GERD), data supporting a distinct GERD-related phenotype are limited. This study aims to investigate demographic, symptomatic, and physiologic differences between DES subjects with and without GERD. A retrospective cohort analysis of DES patients determined by high resolution manometry (HRM) was conducted between February 2020 and January 2023. Demographics, medications, symptoms, and quantitative reflux testing data were collected. DES subjects with reflux (R-DES) were defined by presence of Los Angeles Grade B/C/D esophagitis, Barrett's metaplasia, or abnormal pH testing. DES subjects without reflux (NR-DES) had normal parameters. Statistical analysis employed two-sided or Wilcoxon Rank-Sum, Chi-squared, or Fisher's exact tests, and multivariate logistic regression. Of 69 DES subjects, 32 (46.3%) had GERD. R-DES and NR-DES patients had similar demographic variables except for higher BMI in R-DES (30.41 vs. 26.88, P  = 0.01). R-DES and NR-DES shared similar symptom profiles (heartburn P  = 0.67, dysphagia P  = 0.448, chest pain P  = 0.32). Proton pump inhibitor use was similar between groups (78.1% vs. 91.9%, P  = 0.202). HRM metrics were comparable except for basal LES tone (20.7 mmHg vs. 32.99 mmHg, P  = 0.03) and median IRP 11.82 mmHg versus 17.20 mmHg, P  = 0.017). This study found no distinguishing clinical or physiologic differences between DES patients with and without GERD, challenging the historical emphasis of GERD in DES pathogenesis. The impact of GERD management on the natural history of DES remains uncertain. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

William Attree (1780–1846) came from a prominent family in Brighton, England. He studied medicine at St Thomas' Hospital, London, and there was unwell for nearly 6 months with severe 'spasms' of the hand/arm/chest (1801–1802). Attree qualified Member of the Royal College of Surgeons in 1803 and served as dresser to Sir Astley Paston Cooper (1768–1841). In 1806 Attree is recorded as 'Surgeon and Apothecary' of Prince's street, Westminster. In 1806 Attree's wife died in childbirth and the following year he underwent emergency amputation of the foot in Brighton following a road traffic accident. Attree served as surgeon in the Royal Horse Artillery at Hastings, presumably in a regimental or garrison hospital. He went onto become surgeon to the Sussex County Hospital, Brighton, and Surgeon Extraordinary to two Kings: George IV and William IV. In 1843 Attree was appointed as one of the original 300 Fellows of the Royal College of Surgeons. He died in Sudbury, near Harrow. His son William Hooper Attree (1817–1875) was surgeon to Don Miguel de Braganza, the former King of Portugal. The medical literature appears to lack a history of nineteenth century doctors (especially military surgeons) with physical disability. Attree's biography goes a small way towards developing this field of enquiry. [ABSTRACT FROM AUTHOR]

Background Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute coronary syndrome (ACS). Various factors predispose individuals to SCAD, including coronary vasospasm, which has been identified in some studies as a related factor. Case summary We present a series of three cases of ACS attributed to SCAD. Two cases involved early de novo recurrence potentially related to coronary spasm, and one case involved iatrogenic coronary artery dissection during a spasm provocation test. Discussion High recurrence rates of SCAD within 30 days of the initial event have been observed, although the effectiveness of pharmacologic therapy has not been conclusively established. While the administration of beta-blockers has been associated with a reduced risk of SCAD recurrence, their use may not be desirable in patients with coronary vasospasm. Detailed evaluations may be beneficial for patients where coronary vasospasm is suspected to tailor appropriate treatment strategies. Moreover, given the higher frequency of iatrogenic coronary artery dissection among patients with SCAD, careful consideration is needed to avoid high-risk periods when scheduling spasm provocation tests. [ABSTRACT FROM AUTHOR]

Background Pulsed field ablation (PFA) is a novel ablation technology. A rare side-effect is the occurrence of mostly subclinical coronary spasms when PF energy is applied in proximity to coronary arteries. However, it has been described that prior application of nitroglycerin attenuates these effects. Case summary A 75-year-old female underwent catheter ablation with a penta-spline PFA catheter. After pulmonary vein isolation, the PFA catheter was positioned on the cavotricuspid isthmus (CTI). Before ablation, 2 mg of nitroglycerin was administered intravenously. After 10 PFA applications, the CTI was successfully blocked. After a timely delay of 95 s, a clinically apparent vasospasm with ST elevations in leads II, III, and aVF on the electrocardiogram was noticed. Shortly thereafter, the clinical course was aggravated by haemodynamically relevant non-sustained ventricular tachycardias (nsVTs) followed by asystole, requiring pacing and additional 4 mg of nitroglycerin. Twelve minutes later, a stable sinus rhythm with normalized ST segments was restored. The spasm resolved without any sequelae. Post-procedural coronary angiogram showed right dominant coronary circulation. Discussion This is the first report of a timely delayed, clinically apparent coronary spasm with a presentation of haemodynamically relevant nsVT and asystole despite the prophylactic application of high-dose intravenous nitroglycerin prior to PFA along the CTI. Subclinical vasospasm during PFA at the CTI has been described before. Severe spasms could be prevented by nitroglycerin. A word of caution needs to be raised as prophylactic nitroglycerin did not prevent the haemodynamically relevant coronary spasm in the here reported patient. Until now, it remains unclear how much later such effects may occur; therefore, patients should be monitored closely. [ABSTRACT FROM AUTHOR]

Chlorzoxazone (CHZ) is a centrally acting muscle relaxant used to treat muscle spasms. It is employed as a first-line medication for treating muscle spasms, offering both musculoskeletal relaxation and mild sedative effects. According to the biopharmaceutics classification system, it belongs to class II drug having poor solubility and high permeability. In order to improve the flow property, water solubility, and dissolution of CHZ, CHZ-nicotinamide (NA) cocrystal was prepared by liquid-assisted grinding cocrystallization (LAG CC) method using methanol as the choice of solvent. CHZ-NA cocrystal was characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry, and scanning electron microscopy (SEM). DSC scan showed a sharp endothermic peak shift, which is caused by the formation of a new crystal form with altered physical properties, which was further confirmed by PXRD. Also, a change in the surface morphology of LAG CC compared to CHZ was observed in SEM. The resultant CHZ-NA cocrystal displayed improved powder flow properties compared to the native form of CHZ. LAG CC demonstrated a 3.1- and 2.6-fold increase in saturated solubility and intrinsic dissolution rate, respectively, compared to CHZ alone. Furthermore, the in vitro dissolution study showed that the cumulative dissolution of CHZ in 2 h was about 53%. Whereas, dissolution of LAG CC reached 99% in 2 h, showing obvious dissolution improvement. Thus, CHZ-NA cocrystal could significantly improve the flow properties, solubility and dissolution of CHZ. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to investigate the prevalence of autism spectrum disorder and its possible correlations with clinical characteristics in patients with infantile epileptic spasms syndrome in a single center in Brazil. METHODS: This retrospective cross-sectional study examined 53 children with the diagnosis of infantile epileptic spasms syndrome prior to an autism spectrum disorder assessment. Participants were divided into two groups based on the presence or absence of autism spectrum disorder. Available variables (sex, medications, median age at onset of infantile epileptic spasms syndrome, and presence of comorbidities) were compared using Mann-Whitney U or chi-square tests. RESULTS: Among the included patients, 12 (23 %) were diagnosed with autism spectrum disorder, corresponding to a relative risk of 0.29 (95 % confidence interval 0.174-0.492). The age at the first seizure ranged from 3 to 15 months, with a mean of 6.65 months. This age significantly differed between participants with autism spectrum disorder (10.58 months) and those without (5.43 months), p

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity. METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended. RESULTS: The CCSA was refined during three rounds of cognitive interviews into two measures: (1) the CDD Developmental Questionnaire - Caregiver (CDQ-Caregiver) focused on developmental skills, and (2) the CDD Clinical Severity Assessment - Caregiver (CCSA-Caregiver) focused on symptom severity. Branching logic was used to ensure questions were age and skill appropriate. Initial pilot data (n = 11) suggested no floor effects. CONCLUSIONS: This study modified the caregiver portion of the initial CCSA and provided evidence for its content and response process validity.

Background: The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS). Methods and findings: In this multicenter dose-escalating open-label Phase 2A study, 54 participants with a diagnosis of ALS received 6 infusions of tegoprubart administered intravenously every 2 weeks. The study was comprised of 4 dose cohorts: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 8 mg/kg. The primary endpoint of the study was safety and tolerability. Exploratory endpoints assessed the pharmacokinetics of tegoprubart as well as anti-drug antibody (ADA) responses, changes in disease progression utilizing the Revised ALS Functional Rating Scale (ALSFRS-R), CD154 target engagement, changes in pro-inflammatory biomarkers, and neurofilament light chain (NFL). Seventy subjects were screened, and 54 subjects were enrolled in the study. Forty-nine of 54 subjects completed the study (90.7%) receiving all 6 infusions of tegoprubart and completing their final follow-up visit. The most common treatment emergent adverse events (TEAEs) overall (>10%) were fatigue (25.9%), falls (22.2%), headaches (20.4%), and muscle spasms (11.1%). Mean tegoprubart plasma concentrations increased proportionally with increasing dose with a half-life of approximately 24 days. ADA titers were low and circulating levels of tegoprubart were as predicted for all cohorts. Tegoprubart demonstrated dose dependent target engagement associated and a reduction in 18 pro-inflammatory biomarkers in circulation. Conclusions: Tegoprubart appeared to be safe and well tolerated in adults with ALS demonstrating dose-dependent reduction in pro-inflammatory chemokines and cytokines associated with ALS. These results warrant further clinical studies with sufficient power and duration to assess clinical outcomes as a potential treatment for adults with ALS. Trial registration: Clintrials.gov ID:NCT04322149. Steven Perrin and colleagues report on the safety and tolerability of different doses of the novel drug tegoprubart in patients with Amyotrophic Lateral Sclerosis. Author summary: Why was this study done?: One of the critical pathways controlling activation of T cells and B cells, cells which are pivotal in inducing inflammation in the body, involves a protein called CD40L and its receptor, CD40. Uncontrolled activation of CD40L/CD40 results in autoimmune disorders and the biological processes associated with organ transplant rejection. The activation of CD40L/CD40 has also been shown to occur in individuals with amyotrophic lateral sclerosis (ALS) as well as in animal models of ALS. Indeed, modulation of CD40L signaling ameliorates disease progression, improves survival, and decreases peripheral and neuroinflammation in rodent models of ALS. This study aimed to assess the safety and impact of an anti CD40L antibody, tegoprubart, on pro-inflammatory biomarkers in patients with ALS. What did the researchers find?: We designed an open label, dose escalating study of tegoprubart in adults with ALS to assess the safety of tegoprubart at multiple doses and to study the effects of increasing doses of tegoprubart on inflammatory biomarkers in the blood. In this dose escalating study, tegoprubart appeared safe and well tolerated in 54 participants with ALS at all 4 doses studied. The amount of tegoprubart in blood increased with increasing dose. The study demonstrated target engagement with a dose-dependent decrease in the levels of CD40L and CXCL13. The study demonstrated a dose-dependent decrease in pro-inflammatory biomarkers after a single infusion of tegoprubart. What do the findings mean?: This is the first clinical study of an anti CD40L antibody in ALS patients. The results suggest the inhibition of CD40L is safe and well tolerated and results in a dose-dependent reduction in a broad spectrum of T cell and myeloid associated pro-inflammatory signaling pathways in adults with ALS. These data support the further exploration of tegoprubart in a randomized, standard of care-controlled trial as a potential treatment for patients with ALS. There are 2 major limitations with the study: it is an open label study with no standard of care arm and the study was not powered to detect changes in clinical outcomes; the study was 12 weeks in duration which is not of sufficient duration to assess changes in clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Hemifacial spasm (HFS) is a neuromuscular disorder characterized by unilateral facial muscle spasms, negatively impacts quality of life due to social embarrassment. Botulinum Neurotoxin (BoNT) injections have emerged as a viable therapeutic approach. This systematic review evaluated the efficacy and safety of BoNT injections for HFS management, along with effects on patients' quality of life and mental health. Materials and methods: A systematic search for studies on BoNT treatment for HFS published between January 1, 2000, and May 1, 2024, was performed across major databases. Study quality was evaluated using Cochrane and Joanna Briggs Institute (JBI) tools, with data management handled by EndNote X9 and statistical analyses conducted via Review Manager (RevMan 5.4) and STATA 14.0. Results: Thirty-five studies met the inclusion criteria: 2 RCTs comprising 83 HFS patients compared the efficacy of perioral injections of botulinum toxin and placebo, while 33 single-arm studies reported outcomes for 2786 patients post-BoNT injection. The selection of 17 single-arm studies focused on the effectiveness rate as the key outcome metric. Pooled estimate signified a remarkably high effectiveness (ES: 0.882, 95% CI: 0.830, 0.926, P < 0.001). Analysis of depression scale (SMD: -0.85, 95% CI: -1.34, -0.35, P < 0.001), anxiety scale (SMD: -1.50, 95% CI: -2.19, -0.80, P < 0.001) and total scale of quality of life (SMD: -0.64, 95% CI: -0.87, -0.41, P = 0.766) showed that BoNT therapy worked well especially in improving mental state and quality of life. Ptosis was considered as the most common adverse reaction during BoNT injections (OR: 0.30, 95% CI: 0.11, 0.81, P = 0.843). Conclusion: BoNT injection showed validity and clinical safety in the treatment of HFS, particular for depression relief. Injections around the mouth were only effective for HFS cases with severe symptoms. A standardized strategy for BoNT injections in managing HFS, detailing parameters such as injection sites, doses, and frequencies, remained elusive. Additional RCTs are necessary to further elucidate the interplay between efficacy and these components. [ABSTRACT FROM AUTHOR]

The efficacy and safety of revision microscopic microvascular decompression (microscopic MVD) for treating residual or recurrent hemifacial spasm (HFS) remain uncertain. We conducted a systematic review and meta-analysis to evaluate the benefits and risks associated with this reoperation, focusing primarily on spasm relief, facial palsy, and hearing impairment. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We performed a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library for eligible articles from their inception through June 2024. A total of 17 studies involving 719 patients were included in this meta-analysis. Among these patients, 668 experienced overall symptom relief following reoperation, resulting in a relief rate of 94% (95% CI: 92–96%). Complete relief was achieved in 603 patients, corresponding to a rate of 87% (95% CI: 80–93%). Transient facial palsy developed in 4% (95% CI: 1–8%) of patients, while persistent facial palsy was observed in 5% (95% CI: 2–8%) of patients following reoperation. Transient hearing impairment occurred in 1% (95% CI: 0–3%) of patients, while persistent hearing impairment was reported in 4% (95% CI: 1–7%) of patients. Patients with recurrent HFS have significantly lower overall and complete relief rates after reoperation compared to those with residual HFS and are at higher risk of long-term hearing loss. Our study suggests that reoperation for residual or recurrent HFS after microscopic MVD could be considered a safe and effective treatment option. Early reoperation may be indicated in specific cases, and the timing should be tailored to each patient's specific circumstances to optimize outcomes. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether people with aquaporin-4 antibody positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) experience a prodrome, although a few cases report AQP4 + serology up to 16 years before the first attack. Objectives: To evaluate whether individuals with AQP4-IgG + NMOSD have prodromal neurologic symptoms preceding the first attack. Methods: We reviewed medical records of participants meeting the 2015 diagnostic criteria for AQP4-IgG + NMOSD from four demyelinating disease centres in the Canadian NMOSD cohort study CANOPTICS. We searched for neurologic symptoms occurring at least 30 days before the first attack. Results: Of 116 participants with NMOSD, 17 (14.7%) had prodromal neurologic symptoms. The median age was 48 years (range 25–83) at first attack; 16 (94.1%) were female. Participants presented with numbness/tingling (n = 9), neuropathic pain (n = 5), visual disturbance (n = 4), tonic spasms (n = 2), Lhermitte sign (n = 2), severe headache (n = 2), incoordination (n = 2), weakness (n = 1), psychosis (n = 1) or seizure (n = 1). Of eight who underwent magnetic resonance imaging (MRI) brain, orbits and/or spinal cord, five had T2 lesions. Within 1.5–245 months (median 14) from the onset of prodromal neurologic symptoms, participants experienced their first NMOSD attack. Conclusions: One in seven people with NMOSD experienced neurologic symptoms before their first attack. Further investigation of a possible NMOSD prodrome is warranted. [ABSTRACT FROM AUTHOR]

Paroxysmal neurological symptoms in patients with multiple sclerosis (MS) have long been acknowledged. However, consideration of whether such symptoms are a clinical attack and sufficient for fulfillment of MS diagnostic criteria has varied as criteria have evolved over time. Previous studies and anecdotal reports indicate that some patients with MS first present with syndromes such as trigeminal neuralgia, Lhermitte's phenomenon, tonic spasm, and seizure years before an attack typical of MS such as optic neuritis or myelitis. We discuss four patients with presumed MS who initially presented with these syndromes with evidence of a corresponding central nervous system (CNS) lesion who, were these symptoms considered an attack, could have been diagnosed with relapsing remitting MS or clinically isolated syndrome. This case series aims to highlight the unmet need for data for such patient presentations and for clinical guidance from future MS diagnostic criteria to optimize care. [ABSTRACT FROM AUTHOR]

Laryngeal dystonia (LD) is an isolated, task‐specific, focal dystonia characterized by intermittent spasms of laryngeal muscles impairing speech production. Although recent studies have demonstrated neural alterations in LD, the consistency of findings across studies is not well‐established, limiting their translational applicability. We conducted a systematic literature search to identify studies reporting stereotactic coordinates of peak structural and functional abnormalities in LD patients compared to healthy controls, followed by a coordinate‐based activation likelihood estimation meta‐analysis. A total of 21 functional and structural neuroimaging studies, including 31 experiments in 521 LD patients and 448 healthy controls, met the study inclusion criteria. The multimodal meta‐analysis of these studies identified abnormalities in the bilateral primary motor cortices, the left inferior parietal lobule and striatum, the right insula, and the supplementary motor area in LD patients compared to healthy controls. The meta‐analytical findings reinforce the current view of dystonia as a neural network disorder and consolidate evidence for future investigations probing these targets with new therapies. [ABSTRACT FROM AUTHOR]

Stiff-person syndrome (SPS) is the prototypical and most common autoimmune neuronal hyperexcitability disorder. It presents with stiffness in the limbs and axial muscles, stiff gait with uncontrolled falls, and episodic painful muscle spasms triggered by anxiety, task-specific phobias and startle responses, collectively leading to disability. Increased awareness of SPS among patients and physicians has created concerns about diagnosis, misdiagnosis and treatment. This Review addresses the evolving diagnostic challenges in SPS and overlapping glutamic acid decarboxylase (GAD) antibody spectrum disorders, highlighting the growing number of overdiagnoses and focusing on the progress made in our understanding of SPS pathophysiology, antibodies against GAD and other inhibitory synaptic antigens, and the fundamentals of neuronal hyperexcitability. It considers the role of impaired GABAergic or glycinergic inhibition in the cortex and at multiple levels in the neuraxis; the underlying autoimmunity and involvement of GAD antibodies; immunopathogenic mechanisms beyond antibodies, including environmental triggers; familial and immunogenetic susceptibility; and potential T cell cytotoxicity. Finally, the mechanistic rationale for target-specific therapeutic interventions is presented along with the available therapeutic approaches, including enhancers of GABA signalling drugs and immunotherapies. Stiff-person syndrome is an autoimmune neuronal hyperexcitability disorder that causes limb stiffness, painful spasms and falls, and increased awareness of the disease is creating diagnostic and management challenges. In this Review, Dalakas provides an overview of the current clinical and mechanistic understanding of stiff-person syndrome and related disorders and discusses current and emerging therapeutic interventions. Key points: Stiff-person syndrome (SPS) is the most common form of glutamic acid decarboxylase (GAD) antibody spectrum disorder; others include cerebellar ataxia, encephalitis and autoimmune epilepsy. SPS is characterized by stiffness, muscle spasms and task-specific phobias; GAD antibody titres are essential for diagnosis and, if titres are low, the presence of GAD antibodies in the cerebrospinal fluid is required. Stiffness and task-specific phobias are explained by impaired reciprocal GABAergic inhibition, reductions in brain levels of GABA, and cortical hyperexcitability. GAD antibodies have some effects on GABAergic neurons and GABA production in vitro and in vivo, but convincing evidence that GAD antibodies are pathogenic is lacking. Intrathecal GAD antibody synthesis occurs in SPS, and circulating GAD-reactive B cells can differentiate into antibody-producing cells in the peripheral blood and bone marrow. Therapeutic approaches to SPS include targeting of GABAergic inhibition with GABA-enhancing antispasmodic drugs, such as baclofen, gabapentin and diazepam, followed by immunotherapy, such as intravenous immunoglobulin or rituximab. Novel immunotherapies are in the offing. [ABSTRACT FROM AUTHOR]

This retrospective study examined the clinical outcomes and complications in 6 cases of compound Meige's syndrome, presenting with blepharospasm and masticatory muscle spasm, following treatment with CT-guided radiofrequency ablation targeting bilateral facial nerves and mandibular branches of the trigeminal nerve. After the operation, the symptoms of eyelid spasm and masticatory muscle spasm resolved, but mild facial paralysis and numbness of mandibular nerve innervation persisted. Follow-up for 4–28 months showed that the symptoms of facial paralysis resolved within 2–5 (3.17 ± 0.94) months after the operation, whereas the numbness in the mandibular region persisted, accompanied by a decrease in masticatory function. During the follow-up period, none of the 6 patients experienced a recurrence of Meige's syndrome. These findings suggest that CT-guided radiofrequency ablation of the bilateral facial nerve and mandibular branches of the trigeminal nerve may offer a promising approach to treating compound Meige's syndrome. [ABSTRACT FROM AUTHOR]

Background: The neurovascular conflict (NVC) causing hemifacial spasm (HFS) can also cause compression of ventrolateral medulla (VLM) which contains the central sympathetic neurons. VLM compression has been associated with hypertension. Whether the VLM compression in HFS patients is associated with hypertension is not clear. Objective: To determine the frequency, severity of VLM compression and its association with hypertension in HFS patients. Methods: A cross-sectional, hospital-based, case control study and recruited 120 study subjects (50 cases of primary HFS, 30 hypertensive and 40 normotensive age-, sex- matched controls). The VLM compression was assessed in magnetic resonance imaging Constructive Interference in Steady State (CISS) 3D sequences. Results: Hypertension was present in 30 cases (60%). Six patients with HFS (20%) were detected to be hypertensive after the onset of HFS. VLM compression was seen in 24 cases (48%), 7 hypertensive controls (23.3%) and 5 normotensive controls (10%) (p = 0.03). Twenty-four patients with hypertension had VLM compression and remaining 6 patients with hypertension did not have VLM compression (80% vs 20%; p = 0.02). Normotensive patients did not have VLM compression. Vertebral artery was the most common artery causing VLM compression (22 patients; 7 hypertensive and 5 normotensive controls). Conclusion: VLM compression is more common in HFS patients as compared to hypertensive and normotensive controls. It is more common in hypertensive HFS patients in comparison with normotensive HFS patients. Microvascular decompression is an option in hypertensive HFS patients with VLM compression if the hypertension is medically refractory. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Educación e Investigación en Emergencias is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: We retrospectively analyzed the usefulness and safety of intracoronary acetylcholine (ACh) 200 μg into the left coronary artery (LCA) as vasoreactivity testing compared with intracoronary ACh 100 μg. Methods: We recruited 1433 patients who had angina‐like chest pain and intracoronary ACh testing in the LCA, including 1234 patients with a maximum ACh 100 μg and 199 patients with a maximum ACh 200 μg. ACh was injected in incremental doses of 20/50/100/200 μg into the LCA. Positive spasm was defined as ≥ 90% stenosis, usual chest pain, and ischemic electrocardiogram (ECG) changes. Results: The incidence of coronary constriction ≥ 90%, usual chest pain, and ischemic ECG changes with a maximum ACh of 100 μg was markedly higher than that with a maximum ACh of 200 μg. The frequency of unusual chest pain in patients with a maximum ACh of 200 μg was higher than that in those with a maximum ACh of 100 μg (13% vs. 3%, p < 0.001). In patients with rest angina, positive spasm of maximum ACh 100 μg was significantly higher than that of maximum ACh 200 μg, whereas there was no difference regarding positive spasm in patients with atypical chest pain between the two ACh doses. Major complications (1.38% vs. 1.51%, p = 0.8565) and the occurrence of paroxysmal atrial fibrillation (1.81% vs. 2.63%, p = 0.6307) during ACh testing in the LCA were not different between the two maximum ACH doses. Conclusions: Intracoronary ACh 200 μg into the LCA is clinically useful and safe for vasoreactivity testing when intracoronary ACh 100 μg dose not provoke spasms. [ABSTRACT FROM AUTHOR]

Background Acute coronary syndrome (ACS) is primarily due to obstructive coronary artery disease (CAD). Nevertheless, in 1–14% of cases, ACS is present without evidence of obstructive CAD. Coronary artery spasm is an uncommon cause of ACS. Diagnostic work-up includes acute invasive coronary angiography and afterwards provocation testing. The optimal patient management is for patients presenting with cardiogenic shock due to ACS caused by coronary artery spasm is unclear. Case summary A 67-year-old Caucasian, who underwent elective revision of hip arthroplasty, presented with ST elevations with circulatory collapse, leading to resuscitation due to anaesthesia induction. Extracorporeal membrane oxygenation (ECMO) implantation led to restoration of spontaneous circulation. Coronary angiography revealed coronary vasospasm, which was successfully treated with nitrates i.c. Later, despite of implanted ECMO, recurring haemodynamic deterioration required continuous administration of nitrates i.v. which finally resulted in the stabilization of circulatory system. Extracorporeal membrane oxygenation removal was possible 48 h after implantation and another 12 h later we extubated the patient. Furthermore, we administered calcium antagonists and an intra-cardiac defibrillator was implanted. Finally, the patient was discharged 12 days after admission with no physical or neurological restrictions after resuscitation. Discussion This unique case highlights that rare causes of severe ACS with cardiogenic shock need to be considered. Administration of vasodilators, which are not part of the standard care in cardiogenic shock, represents the adequate treatment of a patient with spasm of coronary arteries. Furthermore, the recurrence of acute coronary events must be prevented by drug and device therapy in these patients. [ABSTRACT FROM AUTHOR]

Objective To compare the agreement in judging the responsible vessels for hemifacial spasm (HFS) between the preoperative 3D Slicer 3D reconstruction and the actual intraoperative judgment of microvascular decompression (MVD). Methods A total of 62 patients with HFS who underwent MVD in Dong'e County People's Hospital of Shandong Province from July 2018 to January 2024 were included. 3D fast inflow with the steady state precession (3D-FIESTA) and 3D time-of-flight (3D-TOF) MRA were performed before surgery. 3D Slicer software was used to fuse 3D-FIESTA and 3D-TOF MRA images and 3D reconstruction to clarify the responsible vessels. The actual intraoperative judgment was taken as the "gold standard", and the agreement between preoperative 3D reconstruction and actual intraoperative judgment was compared. Results There were 61 cases whose responsible vessels were identified by preoperative 3D reconstruction, including anterior inferior cerebellar artery (AICA) in 47 cases, posterior inferior cerebellar artery (PICA) in 6 cases, vertebral artery (VA) in 5 cases, VA + AICA in 2 cases, and superior cerebellar artery (SCA) in one case. The 59 cases were consistent with actual intraoperative judgment. In one case, the preoperative 3D reconstruction was considered as VA compression, and the intraoperative evidence was VA + AICA compression; in one case, preoperative 3D reconstruction was AICA responsible vessels were found in one case, and the intraoperative evidence was arteriole compression. The accuracy of preoperative 3D reconstruction was 95.16% (59/62). Agreement test showed a high consistency between preoperative 3D reconstruction and actual intraoperative judgment (- = 0.886, P = 0.000). Conclusions It is very accurate to define the responsible vessels by 3D reconstruction before MVD in patients with HFS, which is helpful to make the surgical plan and provide the basis for the judgment of the responsible vessels during the operation. [ABSTRACT FROM AUTHOR]

This document, published in the Neurosurgical Review, provides a detailed description of the surgical technique known as "unilateral biportal endoscopy" (UBE) for the treatment of spinal disorders. The UBE technique involves the use of two small incisions to access the epidural and foraminal areas of the spine, allowing for a magnified view and precise surgical maneuvers. The document outlines the step-by-step process of the surgery, including the use of various instruments and techniques for exposure, laminectomy, flavectomy, hemostasis, and closure. The authors emphasize the benefits of the UBE technique, such as reduced muscle injury, shorter hospital stays, and improved patient recovery. They also provide specific indications and technical variations for different types of spinal hernias and cysts. Overall, this document serves as a comprehensive guide for spine surgeons interested in learning and implementing the UBE technique. [Extracted from the article]