Androgen receptor post-translational modifications and their implications for pathology.

A major mechanism to modulate the biological activities of the androgen receptor (AR) involves a growing number of post-translational modifications (PTMs). In this review we summarise the current knowledge on the structural and functional impact of PTMs that affect this major transcription factor. Next, we discuss the cross-talk between these different PTMs and the presence of clusters of modified residues in the AR protein. Finally, we discuss the implications of these covalent modifications for the aetiology of diseases such as spinal and bulbar muscular atrophy (Kennedy's disease) and prostate cancer, and the perspectives for pharmacological intervention.

Small intestinal submucosa graft bulbar urethroplasty is a viable technique: results compared to buccal mucosa graft urethroplasty after propensity score matching.

PURPOSE: Small intestinal submucosa (SIS) graft urethroplasty has been employed to decrease buccal mucosa morbidity and facilitate the procedure. The first published series had a short follow-up, inhomogeneous patient selection, and a lack of a control group. Our purpose is to report treatment outcomes at 13 years in a propensity score-matched cohort comparing bulbar urethroplasty with SIS (SISU) or buccal mucosa (BMU). METHODS: From our institutional database of 1132 bulbar urethroplasties, we used propensity score matching with the nearest-neighbor method without replacement to generate a study sample of 25 BMU and 25 SISU. Failure was defined as any treatment after urethroplasty. Survival analyses were used to analyze treatment failure occurrence with data censored at 156mo. RESULTS: Matching resulted in a complete correction of bias between the two samples except for the follow-up duration, which was slightly longer in the SIS group. The cumulative treatment success probability of BMU and SISU at 156mo was 83.4% and 68%, respectively. At multivariable Cox regression, SIS graft, previous urethrotomy, stricture length, and lower postoperative Qmax (within 2mo after catheter removal) were predictors of failure. Stricture length had a more remarkable effect in SISU, with estimated survival probabilities from the Cox model lower than 80% in strictures > = 3 cm. CONCLUSION: SIS has poorer outcomes compared to BM but may still be useful when BM grafting is not possible. The best candidates for SISU, with similar success to BMU, are patients with strictures shorter than 3 cm, preferably without a history of DVIU.

Unexpected frequency of the pathogenic AR CAG repeat expansion in the general population.

CAG repeat expansions in exon 1 of the AR gene on the X chromosome cause spinal and bulbar muscular atrophy, a male-specific progressive neuromuscular disorder associated with a variety of extra-neurological symptoms. The disease has a reported male prevalence of approximately 1:30 000 or less, but the AR repeat expansion frequency is unknown. We established a pipeline, which combines the use of the ExpansionHunter tool and visual validation, to detect AR CAG expansion on whole-genome sequencing data, benchmarked it to fragment PCR sizing, and applied it to 74 277 unrelated individuals from four large cohorts. Our pipeline showed sensitivity of 100% [95% confidence interval (CI) 90.8-100%], specificity of 99% (95% CI 94.2-99.7%), and a positive predictive value of 97.4% (95% CI 84.4-99.6%). We found the mutation frequency to be 1:3182 (95% CI 1:2309-1:4386, n = 117 734) X chromosomes-10 times more frequent than the reported disease prevalence. Modelling using the novel mutation frequency led to estimate disease prevalence of 1:6887 males, more than four times more frequent than the reported disease prevalence. This discrepancy is possibly due to underdiagnosis of this neuromuscular condition, reduced penetrance, and/or pleomorphic clinical manifestations.

Perioperative management of a patient with unexpectedly detected early-stage ovarian mucinous carcinoma combined with progressive bulbar paralysis: a case report and literature review.

BACKGROUND: Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. CASE PRESENTATION: In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. CONCLUSIONS: GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.

Clinical observation of male bulbar urethral strictures resulting from straddle injuries associated with falling from heights and riding activities.

OBJECTIVES: To retrospectively investigate and analyze the characteristics of male bulbar urethral strictures or occlusions resulting from straddle injuries caused by falling from heights and riding activities. METHODS: The study included 56 patients with a history of straddle injury, who were divided into two groups: the falling group (n = 29) and the riding group (n = 27). All patients underwent urethroscopy and X-ray urethrography, followed by urethrotomy and anastomotic procedure. Both urethral and suprapubic catheters were retained for one month postoperatively. Subsequent follow-up assessments were conducted within one month to one year after surgery. RESULTS: The clinical data of two groups were analyzed. The average ages were 40.1 ± 11.2 (falling group, aged 18-59) and 26.8 ± 4.4 (riding group, aged 19-35), P < 0.05. In the falling group, 21 cases (72.4%) had offspring, while in the riding group, only 3 cases (11.1%) had offspring, P < 0.05. The stricture segments in the falling group were predominantly located in the proximal part of the bulbar region (89.7%), whereas in the riding group they mainly found in the distal part (96.3%), P < 0.05. In terms of urethrography results, the average lengths of stricture segments were measured as 17.6 ± 2.8 mm and 15.5 ± 4.6 mm respectively, P < 0.05. During surgery, the average lengths of stricture segments were recorded as 19.0 ± 2.5 mm and 17.4 ± 6.1 mm, P > 0.05. In the falling group, 20 cases (69.0%) involved bulbocavernosus muscle injury, P < 0.05. In the riding group, 5 cases (18.5%) involved corpus cavernosum injury, P < 0.05. After one month of the operation, all cases were able to pass through the 16Fr urethroscope without any apparent urethral strictures or complications observed in urethrography results. The maximum urinary flow rate for all cases exceeded 15 ml/s. Two months and one year after the operation, all cases experienced smooth urinary flow and ejaculation without any disorders reported. 3 cases (10.3%) in the falling group and 7 cases (25.9%) in the riding group complained of urethral stretching pain during erection, P > 0.05. CONCLUSIONS: Male bulbar urethral strictures or occlusions resulting from straddle injuries associated with falling from heights and riding activities exhibit distinct characteristics, necessitating the development of a comprehensive surgical plan tailored to the specific features of each condition and the diverse age groups affected.

Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade.

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs), including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MNDs, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

Exploring Motor Neuron Diseases Using iPSC Platforms.

The degeneration of motor neurons is a pathological hallmark of motor neuron diseases (MNDs), but emerging evidence suggests that neuronal vulnerability extends well beyond this cell subtype. The ability to assess motor function in the clinic is limited to physical examination, electrophysiological measures, and tissue-based or neuroimaging techniques which lack the resolution to accurately assess neuronal dysfunction as the disease progresses. Spinal muscular atrophy (SMA), spinal and bulbar muscular atrophy (SBMA), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS) are all MNDs with devastating clinical outcomes that contribute significantly to disease burden as patients are no longer able to carry out normal activities of daily living. The critical need to accurately assess the cause and progression of motor neuron dysfunction, especially in the early stages of those diseases, has motivated the use of human iPSC-derived motor neurons (hiPSC-MN) to study the neurobiological mechanisms underlying disease pathogenesis and to generate platforms for therapeutic discovery and testing. As our understanding of MNDs has grown, so too has our need to develop more complex in vitro models which include hiPSC-MN co-cultured with relevant non-neuronal cells in 2D as well as in 3D organoid and spheroid systems. These more complex hiPSC-derived culture systems have led to the implementation of new technologies, including microfluidics, multielectrode array, and machine learning which offer novel insights into the functional correlates of these emerging model systems.

Low risk of erectile dysfunction after nontransecting bulbar urethroplasty for urethral stricture: a systematic review and meta-analysis.

BACKGROUND: Sexual function after urethroplasty may be a concern for patients, but there are still some controversies regarding the consequences of nontransecting bulbar urethroplasty (ntBU) in terms of erectile dysfunction (ED). AIM: This meta-analysis aimed to compare the efficacy and safety of ntBU with that of transecting bulbar urethroplasty (tBU). METHODS: The PubMed, Web of Science, Cochrane, and Embase databases were searched and reviewed up to October 31, 2022. Quality evaluation was performed using the Newcastle-Ottawa scale system and Cochrane tools for the nonrandomized and randomized studies, respectively. Baseline characteristics, preoperative information, and postoperative outcomes were collected. OUTCOMES: Outcomes included success rate, ED, overall complication, and maximum urinary flow. RESULTS: Thirteen studies comprising 1683 patients met the inclusion criteria, with 596 and 1087 patients undergoing ntBU and tBU, respectively. The results revealed that compared with the tBU group, the patients who underwent ntBU had a significantly lower incidence of ED, while there were no significant differences in the other perioperative outcomes. In subgroup analysis, the nontransecting anastomotic urethroplasty group had a lower incidence of ED than excision and primary anastomosis, and other perioperative outcomes were similar between the 2 groups. CLINICAL IMPLICATIONS: The results of the study may help clinicians choose procedures that protect sexual function in the treatment of urethral stricture. STRENGTHS AND LIMITATIONS: The strength of this study is that it is, to our knowledge, the first meta-analysis to evaluate the efficacy and safety of ntBU. A limitation is that most of the included studies were retrospective cohort studies. CONCLUSION: ntBU preserves the high efficacy of its transecting counterpart while reducing postoperative ED.

Clinical determinants of sleep quality in patients with amyotrophic lateral sclerosis.

OBJECTIVES: Poor sleep quality is more prevalent in patients with amyotrophic lateral sclerosis (ALS) than in healthy populations. The purpose of this study was to examine whether or not motor dysfunction at various distinct levels correlates with subjective sleep quality. METHODS: Patients with ALS and controls were assessed using the Pittsburgh Sleep Quality Index (PSQI), ALS Functional Rating Scale Revised (ALSFRS-R), Beck Depression Inventory-II (BDI-II), and the Epworth Sleepiness Scale (ESS). The ALSFRS-R was used to obtain information on 12 different aspects of motor function in patients with ALS. We compared these data between the groups with poor and good sleep quality. RESULTS: A total of 92 patients with ALS and 92 age- and sex-matched controls entered the study. The global PSQI score was significantly higher in patients with ALS than in healthy subjects (5.5 ± 4.2 vs. 4.0 ± 2.8) and 44% of the patients with ALS had poor sleep quality (PSQI score > 5). The sleep duration, sleep efficiency, and sleep disturbances components were significantly worse in patients with ALS. Sleep quality (PSQI) score correlated with ALSFRS-R score, BDI-II score, and ESS score. Of the 12 ALSFRS-R functions, swallowing significantly affected sleep quality. Orthopnea, speech, salivation, dyspnea, and walking had a medium effect. In addition, turning in bed, climbing stairs, and dressing and hygiene were found to have a small effect on sleep quality among patients with ALS. CONCLUSIONS: Nearly half of our patients had poor sleep quality related to disease severity, depression, and daytime sleepiness. Bulbar muscle dysfunction may be associated with sleep disturbances in individuals with ALS, particularly when swallowing is impaired. In addition, patients suffering from axial or lower limb muscle disruptions are likely to have trouble sleeping.

Role of echocardiography in the management of ventricular septal rupture after acute myocardial infarction.

Ventricular septal rupture (VSR) is a rare and devastating complication of acute myocardial infarction. Early detection, assessment of the hemodynamic impact, and illustration of the pathophysiological context are crucial functions of echocardiography in decision-making for intensive management and reparative intervention. To evaluate this entity, echocardiography exhibits two strengths: its bedside nature and its multiple modalities. This document reviews the comprehensive use of echocardiography in the study of post-infarction VSR.

Spinal and bulbar muscular atrophy combined with hypertrophic cardiomyopathy and Brugada-pattern electrocardiographic changes: A case report.

Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked recessive neurodegenerative disorder caused by the excessive expansion of cytosine-adenine-guanine repeat sequences in the androgen receptor gene encoded on the Xq11-12 chromosome. SBMA primarily affects adult males and is characterized by weakness and atrophy of the proximal limb muscles, often involving the bulbar muscles. In addition to neuromuscular deficits, nonneuronal symptoms such as hypertension, hyperlipidemia, and liver dysfunction are often observed in patients with SBMA. Previous studies have suggested that SBMA patients have been diagnosed with hypertrophic cardiomyopathy (HCM), while gene detection is lacked. Moreover, according to current reports, SBMA patients can carry Brugada syndrome or HCM respectively, while three kinds of diseases have not been reported to exist in the same patient. Here, we report the first case of a male diagnosed with SBMA combined with HCM and two types of Brugada-pattern electrocardiographic changes, with a heterozygous missense mutation in the TTN gene.

Assessing Prevalence and Characteristics of Oro-bulbar Involvement in Children and Adults with SMA Type 2 and 3 Using a Multimodal Approach.

Bulbar and jaw muscles are impaired in patients with Spinal Muscular Atrophy (SMA) but the assessment of their severity and progression are limited by the lack of age-appropriate and disease-specific measures. We investigated mastication and swallowing in children and adults with SMA, sitters and walkers. In a 2-year multicentre cross-sectional prospective study, lip and tongue strength (Iowa Oral Performance Instrument), chewing and swallowing (Test of Masticating and Swallowing Solids), active mouth opening (aMMO) were compared to age-appropriate normative data. The perceived burden of oro-bulbar involvement (SMA-Health Index) was recorded. 78 patients were included, 45 children (median age 7.4 years),22 adults (median age 26.8 years) on nusinersen and 11 untreated (median age 32.7 years). Forty-three percent children had reduced mouth opening, 50% had prolonged total time to eat. These issues were more prominent in sitters than in walkers (p = 0.019, p = 0.014). Sixty-six percent needed increased swallows for bolus clearance. Nusinersen treated adults had median aMMO, tongue strength and total time at TOMASS values within normal range (z score: -1.40, -1.22, -1.32, respectively) whereas untreated adults had reduced aMMO (z score: -2.68) and tongue strength (z score: -2.20). Only a minority of children (2/17) and treated adults (5/21) reported burden in swallowing or mastication compared to all untreated adults (5/5). After 16 months, mastication and swallowing were stable in treated children and adults, whether sitters or walkers. The reported multimodal approach to assess oro-bulbar functions demonstrate that swallowing and mastication are impaired in SMA despite patients' perception. These results suggest a trend towards stabilization of oro-bulbar function in patients on long-term treatment with nusinersen.

Myofibroblast-dominant proliferation associated with severe fibrosis in bulbar urethral strictures.

OBJECTIVES: Myofibroblast-dominant proliferation (relative to fibroblast proliferation) is the key process in urethral fibrosis, but its association with clinical features is not understood. We conducted a histological analysis of urethral strictures and examined the association between myofibroblast proliferation and stricture characteristics. METHODS: Formalin-fixed, paraffin-embedded urethral sections sliced axially from 175 male patients with bulbar urethral strictures were retrospectively analyzed. All patients underwent excision and primary anastomosis between September 2008 and January 2021 by a surgeon (AH). Masson's trichrome stain was used to estimate the area of fibrosis. Corresponding unstained slides with the largest area of fibrosis were selected and double-immunostained with anti-smooth muscle actin (SMA) and anti-TE-7 mouse monoclonal antibodies for the assessment of myofibroblasts and fibroblasts, respectively. The ratio of the number of SMA-positive cells to the number of TE-7-positive cells (SMA/TE-7 ratio) was calculated. RESULTS: The area of fibrosis in strictures due to perineal trauma (n = 85, median 108.9 mm2 ) was significantly larger than that in non-traumatic strictures (n = 90, median 42.9 mm2 , p < 0.0001). The area of fibrosis positively correlated with SMA expression (r = 0.35, p < 0.0001) and the SMA/TE-7 ratio (r = 0.36, p < 0.0001), but not with TE-7 expression (r = -0.01, p = 0.75). In a multivariate linear regression model, traumatic etiology (standard coefficient 0.37, t value 3.9, p < 0.0001) and increased SMA expression (standard coefficient 0.17, t value 2.1, p = 0.03) were the predictors of wide fibrosis area. CONCLUSIONS: Myofibroblast-dominant proliferation may contribute to the pathogenesis of severe urethral fibrosis.

Good functional outcome following bilateral external capsule hemorrhage mimicking bilateral basal ganglia hemorrhage in a coma patient.

Simultaneous spontaneous bilateral external capsule hemorrhage is a rare clinical entity with extremely poor outcome. However, knowledge on the effective management of this fatal disease is limited. Herein,we described a case of a 42-year-old man with acute coma and quadriplegia as well as respiratory failure related to the disease. The patient underwent minimally invasive surgery plus local thrombolysis. Consequently, he recovered with satisfactory neurological function recovery on the 180th day of follow-up.

Beyond the Epidermal-Melanin-Unit: The Human Scalp Anagen Hair Bulb Is Home to Multiple Melanocyte Subpopulations of Variable Melanogenic Capacity.

The visual appearance of humans is derived significantly from our skin and hair color. While melanin from epidermal melanocytes protects our skin from the damaging effects of ultraviolet radiation, the biological value of pigmentation in the hair follicle, particularly on the scalp, is less clear. In this study, we explore the heterogeneity of pigment cells in the human scalp anagen hair follicle bulb, a site conventionally viewed to be focused solely on pigment production for transfer to the hair shaft. Using c-KIT/CD117 microbeads, we isolated bulbar c-KIT-positive and c-KIT-negative melanocytes. While both subpopulations expressed MITF, only the c-KIT-positive fraction expressed SOX10. We further localized bulbar melanocyte subpopulations (expressing c-KIT, SOX10, MITF, and DCT) that exhibited distinct/variable expression of downstream differentiation-associated melanosome markers (e.g., gp100 and Melan-A). The localization of a second 'immature' SOX10 negative melanocyte population, which was c-KIT/MITF double-positive, was identified outside of the melanogenic zone in the most peripheral/proximal matrix. This study describes an approach to purifying human scalp anagen hair bulb melanocytes, allowing us to identify unexpected levels of melanocyte heterogeneity. The function of the more immature melanocytes in this part of the hair follicle remains to be elucidated. Could they be in-transit migratory cells ultimately destined to synthesize melanin, or could they contribute to the hair follicle in non-melanogenic ways?

MINE-BLAST TRAUMA AS A FACTOR IN THE EARLY DEVELOPMENT OF VASCULAR DISEASES OF THE BRAIN.

OBJECTIVE: The aim of this study is to investigate the state of bulbar conjunctival vessels, rheological properties of blood, catecholamines (adrenaline, norepinephrine), lipid metabolism, alkaline proteins of blood serum in patients with consequences of mild combat traumatic brain injury. PATIENTS AND METHODS: Materials and methods: 76 individuals aged 28 to 41 years were examined. The duration of the injury lasted from 2 to 4 years. The control group consisted of 28 individuals aged 45 to 49 years with primary cerebral atherosclerosis and manifestations of cerebral circulation disorders. The state of the bulbar conjunctiva vessels and blood circulation was studied using a slit lamp SHCHL-2B at 40-fold magnification. Rheological parameters, lipid metabolism, serum alkaline proteins, total catecholamines were studied according to generally accepted methods. RESULTS: Results: Changes in the vessels of the bulbar conjunctiva (stage II-III) were detected in 76% of the subjects, indicating the formation of cerebral vascular pathology, and in 87% of patients with initial cerebral atherosclerosis. The analysis of lipid metabolism showed significantly (p<0.05) increased data on all studied parameters (cholesterol, high-density lipoprotein, ß-lipoprotein, atherogenic index), both in patients with aftereffects of mild combat traumatic brain injury and in patients with initial cerebral atherosclerosis. An increase in alkaline proteins indices we detected in 62% of patients with aftereffects of mild combat cerebral trauma and in 55% of patients with initial cerebral atherosclerosis. At the same time, there was an increase in total catecholamines in the erythrocytes of patients with combat head injury. An increase in fibrinogen was noted in both groups, but in the group with initial cerebral atherosclerosis it was more pronounced. CONCLUSION: Conclusions: Combat traumatic brain injury contributes to the early formation of cerebral atherosclerosis and cerebral circulation disorders in this category of patients. The examination methods we have studied should be included in the survey plan for these patients. They are important not only for diagnosis, but also for improving treatment and preventing vascular disasters.

Advances in urethroplasty.

There has been rapid evolution in management of urethral strictures in the last 3 decades. From the era of dilatation, we have moved to urethral reconstruction. Reinvention of buccal grafts changed the outcomes of urethroplasty. Barbaglis dorsal onlay popularised stricture management across the globe. Kulkarni described a single stage surgery for panurethral stricture. Advances have taken place, and we have moved from transecting to the non-transecting approaches. We describe the various advances in urethral reconstruction in the last decade.

Altered SYNJ2BP-mediated mitochondrial-ER contacts in motor neuron disease.

Synaptojanin 2 binding protein (SYNJ2BP) is an outer mitochondrial membrane protein with a cytosolic PDZ domain that functions as a cellular signaling hub. Few studies have evaluated its role in disease. Here we use induced pluripotent stem cell (iPSC)-derived motor neurons and post-mortem tissue from patients with two hereditary motor neuron diseases, spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis type 4 (ALS4), and show that SYNJ2BP expression is increased in diseased motor neurons. Similarly, we show that SYNJ2BP expression increases in iPSC-derived motor neurons undergoing stress. Using proteomic analysis, we found that elevated SYNJ2BP alters the cellular distribution of mitochondria and increases mitochondrial-ER membrane contact sites. Furthermore, decreasing SYNJ2BP levels improves mitochondrial oxidative function in the diseased motor neurons. Together, our observations offer new insight into the molecular pathology of motor neuron disease and the role of SYNJ2BP in mitochondrial dysfunction.

Laryngospasm in amyotrophic lateral sclerosis.

INTRODUCTION: Laryngospasm is an involuntary, sustained closure of sphincter musculature that leads to an unpleasant subjective experience of dyspnea and choking. It is an underreported symptom in amyotrophic lateral sclerosis (ALS). In this study we aimed to better characterize the prevalence and clinical characteristics of laryngospasm in ALS patients. METHODS: The medical records of 571 patients with ALS followed between 2008 and 2018 were searched for evidence of laryngospasm. A total of 23 patients with laryngospasm were identified and the data related to patient and laryngospasm characteristics were extracted. RESULTS: Laryngospasm was reported in 4% of ALS patients. Females comprised 57% of patients and their mean age was 63.4 years. Laryngospasm frequently manifested in patients with moderate bulbar dysfunction and seemed independent of respiratory function. Among laryngospasm patients, 26% were cigarette smokers and 13% had a history of gastroesophageal reflux. The most common reported trigger was excessive saliva irritating the vocal cords (35%) followed by eating a meal (17%). There was significant variation in laryngospasm frequency (up to 5 per hour) and duration (seconds to minutes). Most patients could not identify an effective coping mechanism, although 13% reported that drinking water was effective. DISCUSSION: Despite its low prevalence in ALS, laryngospasm should be included in the symptom inquiry. The present findings may improve patient care through increased recognition of the clinical features of laryngospasm in ALS patients, identifying a link between laryngospasm and moderate bulbar dysfunction, and highlighting trigger avoidance as a management strategy. Additional research is required to understand the pathophysiology and optimal treatment.

A clinical bulbar assessment scale (CBAS) for amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Comprehensive and valid bulbar assessment scales for use within amyotrophic lateral sclerosis (ALS) clinics are critically needed. The aims of this study are to develop the Clinical Bulbar Assessment Scale (CBAS) and complete preliminary validation. METHODS: The authors selected CBAS items from among the literature and expert opinion, and content validity ratio (CVR) was calculated. Following consent, the CBAS was administered to a pilot sample of English-speaking adults with El Escorial defined ALS (N = 54) from a multidisciplinary clinic, characterizing speech, swallowing, and extrabulbar features. Criterion validity was assessed by correlating CBAS scores with commonly used ALS scales, and internal consistency reliability was obtained. RESULTS: Expert raters reported strong agreement for the CBAS items (CVR = 1.00; 100% agreement). CBAS scores yielded a moderate, significant, negative correlation with ALS Functional Rating Scale-Revised (ALSFRS-R) total scores (r = -0.652, p < .001), and a strong, significant, negative correlation with ALSFRS-R bulbar subscale scores (r = -0.795, p < .001). There was a strong, significant, positive correlation with Center for Neurologic Studies Bulbar Function Scale (CNS-BFS) scores (r = 0.819, p < .001). CBAS scores were significantly higher for bulbar onset (mean = 38.9% of total possible points, SD = 22.6) than spinal onset (mean = 18.7%, SD = 15.8; p = .004). Internal consistency reliability (Cronbach's alpha) values were: (a) total CBAS, α = 0.889; (b) Speech subscale, α = 0.903; and (c) Swallowing subscale, α = 0.801. DISCUSSION: The CBAS represents a novel means of standardized bulbar data collection using measures of speech, swallowing, respiratory, and cognitive-linguistic skills. Preliminary evidence suggests the CBAS is a valid, reliable scale for clinical assessment of bulbar dysfunction.