Bulbar Disease Research Articles

Optimal time for the addition of non-corticosteroid immunosuppressants in myasthenia gravis: a single-center retrospective study in China.

Patients with myasthenia gravis (MG) display strong treatment heterogeneity. Recent studies have indicated that low-dose steroids or immunosuppressants are effective. However, factors affecting the add-on of non-corticosteroid immunosuppressants to corticosteroids remain unknown. Consecutive patients with MG were retrospectively reviewed from May 15, 2015, to December 29, 2020. We included one group of patients with steroid treatment alone and another group who transitioned to non-steroid immunosuppressant therapy. Clinical features of the included patients were analyzed. Univariate and multivariate Cox regression models were used to identify potential influential factors. A total of 107 patients with MG were analyzed, including 66 receiving corticosteroid treatment alone and 41 who subsequently also received non-corticosteroid immunosuppressant therapy. Eight potential factors were primarily selected in univariate analysis (Ps < 0.1). Achieving minimal symptom expression (MSE) within 6 months (HR: 4.424, 95%CI: 2.102-11.865), body mass index (BMI) (HR: 0.385, 95% CI: 0.186-0.797), quantitative MG (QMG) bulbar muscle score (HR: 1.553, 95% CI: 1.140-2.118), disease duration (HR: 0.987, 95% CI: 0.977-0.997) and relapse (HR: 2.638, 95% CI: 1.031-6.750) were finally identified as potential influencing factors. We found multifactorial clinical factors were highly associated with the add-on of non-steroid immunosuppressants after steroid treatment in patients with MG. Achieving MSE within 6 months, BMI, QMG bulbar muscle score at baseline before steroid treatment, disease duration, and disease relapse may represent crucial influencing factors, which should be considered to improve the long-term prognosis for patients with MG in future studies and practice.

Urethroplasty for Bulbar and Penile Stricture Disease in Northern Ireland: A Single Operator Experience with Long Term Follow-up (4–15 Years)

Urethroplasty for Bulbar and Penile Stricture Disease in Northern Ireland: A Single Operator Experience with Long Term Follow-up (4–15 Years)

Case Report: Comprehensive management of Bulbar Motor Neuron disease in an elderly male: A Multidisciplinary case report approaching the treatment

Abstract* Bulbar Motor Neuron Disease (MND), a specific form of amyotrophic lateral sclerosis (ALS) primarily affecting the upper and lower motor neurons in the brainstem’s bulbar region, presents a significant challenge in clinical management. This case report delves into the clinical presentation and management of an 85-year-old male patient with typical symptoms, such as left-sided weakness, dysphagia, and dysarthria, along with a history of aphasia and hypertension, underlining the complexities associated with diagnosing and managing this condition. Methods: The patient underwent a thorough clinical examination, diagnostic investigations, and imaging, leading to a confirmed diagnosis of bulbar MND. Multidisciplinary interventions were employed to addressed the diverse symptoms, including compensation therapy, swallowing function training, physiotherapy, bolus modification, behavioral adjustments, oromotor exercises, postural corrections, and sensory and neurophysiologic stimulation to enhance swallowing safety and comfort. Additionally, interventions for dysarthria and left-sided weakness encompassed speech rate control, strength training, and the use of augmentative communication aids. Results: Over a 30-day follow-up period, the patient showed improvements in dysphagia, dysarthria, and activities of daily living. The treatment strategies effectively addressed the specific challenges associated with bulbar MND, focusing on enhancing the patient’s quality of life and functional abilities. Conclusions: This case report underscores the need for a comprehensive, multidisciplinary approach to manage bulbar MND. It highlights the complexities of diagnosing and addressing the diverse symptoms and difficulties that patients with this condition encounter, emphasizing the importance of a holistic and individualized therapeutic strategy.

Digital markers of motor speech impairments in spontaneous speech of patients with ALS-FTD spectrum disorders

Objective To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD). Methods Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.8 (SD = 1.7)) vs. ALS-nonbulbar (n = 23), behavioral variant frontotemporal dementia (bvFTD, n = 25) without a motor syndrome, and healthy controls (HC, n = 32). Correlations with bulbar motor clinical scales, perceived listener effort, and MRI cortical thickness of the orobuccal primary motor cortex (oral PMC) were examined. We compared vowel measures to speaking rate, a conventional metric for assessing bulbar dysfunction. Results ALS + bulbar had significantly reduced VSA and F2 slope than ALS-nonbulbar (|d|=0.94 and |d|=1.04, respectively), bvFTD (|d|=0.89 and |d|=1.47), and HC (|d|=0.73 and |d|=0.99). These reductions correlated with worse bulbar clinical scores (VSA: R = 0.33, p = 0.043; F2 slope: R = 0.38, p = 0.011), greater listener effort (VSA: R=-0.43, p = 0.041; F2 slope: p > 0.05), and cortical thinning in oral PMC (F2 slope: β = 0.0026, p = 0.017). Vowel measures demonstrated greater sensitivity and specificity for bulbar impairment than speaking rate, while showing independence from cognitive and respiratory impairments. Conclusion Automatic vowel measures are easily derived from a brief spontaneous speech sample, are sensitive to mild-moderate stage of bulbar disease in ALS-FTSD, and may present better sensitivity to bulbar impairment compared to traditional assessments such as speaking rate.

Amyotrophic Lateral Sclerosis-Bulbar Dysfunction Index-Remote: Test-Retest and Interrater Reliability of Candidate Items.

The primary aim of this study was to establish the reliability of candidate items as a step in the development of the Amyotrophic Lateral Sclerosis-Bulbar Dysfunction Index-Remote (ALS-BDI-Remote), a novel tool being developed for the detection and monitoring of bulbar signs and symptoms in remote settings. The set of candidate items included 40 items covering three domains: cranial nerve examination, auditory-perceptual evaluation, and functional assessment. Forty-eight participants diagnosed with ALS and exhibiting a range of bulbar disease severity were included. Data collection for each participant took place on Zoom over three sessions. During Session 1, the participants were instructed to adjust their Zoom settings and to optimize their recording environment (e.g., lighting, background noise). Their cognition and eating were screened to determine their ability to follow instructions and their eligibility to perform the swallowing and chewing tasks. During Session 2, two speech-language pathologists (SLPs) administered the tool consecutively to determine the items' interrater reliability. During Session 3, one of the SLPs readministered the tool within 2 weeks of Session 1 to assess test-retest reliability. The reliability of each item was estimated using weighted kappa and the percentage of agreement. To be considered reliable, the items had to reach a threshold of 0.5 weighted kappa or 80% percentage agreement (if skewed distribution of the scores) for both interrater and test-retest reliability. In total, 33 of the 40 candidate items reached the reliability cutoff for both reliability analyses. All assessment domains included reliable items. Items requiring very good visualization of structures or movements were generally less reliable. This study resulted in the selection of reliable items to be included in the next version of the ALS-BDI-Remote, which will undergo psychometric evaluation (reliability, validity, and responsiveness analyses). Additionally, the results contributed to our understanding of the remote administration of SLP assessments for telehealth applications.

Phenotypical differences of C9ORF72 gene-positive and negative amyotrophic lateral sclerosis: a comparative case series

BackgroundHexanucleotide repeat expansions of C9ORF72 account for a significant proportion of autosomal dominant neurodegenerative diseases in the amyotrophic lateral sclerosis (ALS)–frontotemporal dementia spectrum. In the absence of a family history,...

Ptosis in long standing VKC in young adults

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. Though medically treated, some complications of the disease like ptosis may require surgical intervention, thus identifying the association of ptosis with VKC is of utmost importance. This study was done to see the relation between long-standing VKC and acquired ptosis in young adults.This was a hospital based non-comparative, observational study, conducted in the department of Ophthalmology, SKIMS Medical College Hospital, and Srinagar from March 2020 to May 2022. 60 patients upto the age of 40 years with any form of VKC were included in the study. Ocular examination included visual acuity testing, slit lamp biomicroscopic examination to evaluate corneal and conjunctival involvement, proper history and evaluation of ptosis.Mean age of cases was 16.23± 6.97. Out of 60 patients maximum were in the age group of 10-15 years (31.66%), followed by the age group of 15-20 years (21.66%). Out of total 60 cases 46(76.66%) were male and 14(23.33%) were female. Palpebral form of the disease was seen to be in most of the cases 53.33%, followed by mixed form of the disease in 28.33% and bulbar disease in 18.33% of the cases. Presence of acquired ptosis as a complication due to VKC was seen in 9(15%) patients. Out of these 9 patients 7 patients presented with unilateral ptosis and 2 patients presented with bilateral ptosis. Average duration of symptoms in these patients was 5.0±1.8 years, indicating that ptosis is a complication of long standing VKC. All these patients had palpebral or mixed form of VKC, none had bulbar form of the disease.Our study revealed that prolonged severe VKC may induce a lower position of the upper eyelid and eventually lead to ptosis, which is a non-reversible complication of VKC and requires surgical correction. Thus better primary eye care for the management of VKC in children may prevent this complication.

Predictors of Peak Expiratory Cough Flow in Individuals with Amyotrophic Lateral Sclerosis.

Dystussia is prevalent in individuals with amyotrophic lateral sclerosis (ALS), leading to a diminished physiologic capacity to effectively defend the airway. We aimed to identify predictors of peak expiratory cough flow rate in individuals with ALS. One hundred and thirty-four individuals with a confirmed diagnosis of ALS (El-Escorial criteria revised) completed the ALS Functional Rating Scale-Revised (ALSFRS-R) and underwent pulmonary function and cough spirometry testing. Pearson's correlation coefficients and hierarchical multiple regression modeling were conducted to determine predictors of voluntary cough peak expiratory flow rate (p < 0.05). The full model including age, bulbar disease, cough spirometry metrics, and respiratory parameters had a marginal R2=0.635, F (7, 126) = 30.241, p < 0.0005, adjusted R2 = 0.61. Maximum expiratory pressure, compression phase, and vital capacity did not contribute and were therefore removed (p < 0.05). The most parsimonious predictive model included age, bulbar disease, peak inspiratory flow rate and duration, peak expiratory rise time, and inspiratory pressure generation with a marginal R2 = 0.543. Although expiratory pressure generation has historically served as the therapeutic target to improve dystussia in ALS, the current dataset highlighted that the inability to quickly and forcefully inspire during the inspiratory phase of voluntary cough places patients at a mechanical disadvantage to generate subsequent high-velocity expiratory airflow to clear the airway. Thus, therapeutic training programs that include both inspiratory and expiratory strength targets may optimize airway clearance capacity in this challenging patient population.

Physical activity in patients with amyotrophic lateral sclerosis: Prevalence, patients' perspectives and relation to the motor performance.

There are no recommendations for physical activity in amyotrophic lateral sclerosis (ALS) patients. (i) To describe the prevalence and pattern of physical activity (PA) in ALS patients; (ii) to explore patients' attitude towards PA; and (iii) to investigate the relationship between PA at home environment and the rate of functional decline. 96 ALS patients were followed for 6 months at 3-month intervals and assessed by site of disease onset, disease duration, diagnosis delay, functional status, muscle strength, fatigue and prevalence of PA. Over 70% of patients performed regular exercise and reported a positive effect of PA on functional status and mood. Regularly exercising individuals showed a higher ALSFRS-R bulbar score (11.0 vs 9.0, p = 0.011) and a lower decline of respiratory sub-score of ALSFRS-R compared to non-regularly exercising patients (0 vs 1.0, p = 0.026). Bulbar onset was a negative prognostic factor for regular exercise (odds ratio [OR]: 5.2, p = 0.004). The majority of ALS patients perform regular PA and find it positively influence their motor performance and mood. Bulbar disease onset, but not functional status, is a negative prognostic factor for regular exercise in ALS patients. Regular mild PA may result in a slower deterioration of functional status, especially the respiratory function.

Tensor electrical impedance myography identifies bulbar disease progression in amyotrophic lateral sclerosis

ObjectiveElectrical impedance myography (EIM) is a promising biomarker for amyotrophic lateral sclerosis (ALS). A key issue is how best to utilise the complex high dimensional, multi-frequency data output by EIM to fully characterise the progression of disease. MethodsMuscle volume conduction properties were obtained from EIM recordings of the tongue across three electrode configurations and 14 input frequencies (76 Hz–625 kHz). Analyses of individual frequencies, averaged EIM spectra and non-negative tensor factorisation were undertaken. Longitudinal data were collected from 28 patients and 17 healthy volunteers at 3-monthly intervals for a maximum of 9 months. EIM was evaluated against the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) bulbar sub-score, tongue strength and an overall bulbar disease burden score. ResultsLongitudinal changes to individual patient EIM spectra demonstrated complex shifts in the spectral shape. At a group level, a clear pattern emerged over time, characterised by an increase in centre frequency and general shift to the right of the spectral shape. Tensor factorisation reduced the spectral data from a total of 168 data points per participant per recording to a single value which captured the complexity of the longitudinal data and which we call tensor EIM (T-EIM). The absolute change in tensor EIM significantly increased within 3 months and continued to do so over the 9-month study duration. In a hypothetical clinical trial scenario tensor EIM required fewer participants (n = 64 at 50% treatment effect), than single frequency measures (n range 87–802) or ALSFRS-R bulbar subscore (n = 298). ConclusionsChanges to tongue EIM spectra over time in ALS are complex. Tensor EIM captured and quantified disease progression and was more sensitive to changes than single frequency EIM measures and other biomarkers of bulbar disease. SignificanceObjective biomarkers for the assessment of bulbar disease in ALS are lacking. Tensor EIM enhances the biomarker potential of EIM data and can improve bulbar symptom monitoring in clinical trials.

Psychometric Properties of Rapid Word-Based Rate Measures in the Assessment of Bulbar Amyotrophic Lateral Sclerosis: Comparisons With Syllable-Based Rate Tasks.

Purpose Rapid maximum performance repetition tasks have increasingly demonstrated their utility as clinimetric markers supporting diagnosis and monitoring of bulbar disease in amyotrophic lateral sclerosis (ALS). A recently developed protocol uses novel real-word repetitions instead of traditional nonword/syllable sequences in hopes of improving sensitivity to motor speech impairments by adding a phonological target constraint that would activate a greater expanse of the motor speech neuroanatomy. This study established the psychometric properties of this novel clinimetric protocol in its assessment of bulbar ALS and compared performance to traditional syllable sequence dysdiadochokinetic (DDK) tasks. Specific objectives were to (a) compare rates between controls and speakers with symptomatic versus presymptomatic bulbar disease, (b) characterize their discriminatory ability in detecting presymptomatic bulbar disease compared to healthy speech, (c) determine their articulatory movement underpinnings, and (d) establish within-individual longitudinal changes. Method DDK and novel tongue ("ticker"-TAR) and labial ("pepper"-LAR) articulatory rates were compared between n = 18 speakers with presymptomatic bulbar disease, n = 10 speakers with symptomatic bulbar disease, and n = 13 healthy controls. Bulbar disease groups were determined by a previously validated speaking rate cutoff. Discriminatory ability was determined using receiver operating characteristic analysis. Within-individual change over time was characterized in a subset of 16 participants with available longitudinal data using linear mixed-effects models. Real-time articulatory movements of the tongue front, tongue dorsum, jaw, and lips were captured using 3-D electromagnetic articulography; effects of movement displacement and speed on clinimetric rates were determined using stepwise linear regressions. Results All clinimetric rates (traditional DDK tasks and novel tasks) were reduced in speakers with symptomatic bulbar disease; only TAR was reduced in speakers with presymptomatic bulbar disease and was able to detect this group with an excellent discrimination ability (area under the curve = 0.83). Kinematic analyses revealed associations with expected articulators, greater motor complexity, and differential articulatory patterns for the novel real-word repetitions than their DDK counterparts. Only LAR significantly declined longitudinally over the disease course. Conclusion Novel real-word clinimetric rate tasks evaluating tongue and labial articulatory dysfunction are valid and effective markers for early detection and tracking of bulbar disease in ALS.

Swallowing Safety and Efficiency Impairment Profiles in Individuals with Amyotrophic Lateral Sclerosis.

Dysphagia is common in individuals with amyotrophic lateral sclerosis (ALS) and associated with reductions in quality of life and health-related outcomes. Despite the high prevalence of dysphagia in ALS, functional impairment profiles of swallowing safety and efficiency have not been comprehensively examined. We therefore aimed to determine the relative prevalence of unsafe and inefficient swallowing in a large cohort of individuals with ALS. We further sought to examine the impact of global and bulbar disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised "ALSFRS-R" total and bulbar scores, respectively), disease duration, and onset type on swallowing impairment profiles.One hundred individuals with ALS completed a standardized videofluoroscopic swallowing examinationTwo independent and blinded raters performed validated ratings of safety (Penetration-Aspiration Scale, PAS) and efficiency (Analysis of Swallowing Physiology: Events, Kinematics, and Timing, ASPEKT % residue). Binary classifications of safety (unsafe: PAS ≥ 3), efficiency (inefficient: total residue ≥ 3% of C2-42) and global swallowing status were derived. The ALSFRS-R was completed to derive ALSFRS-R total and bulbar subscale scores.Demographic data (disease duration and onset type) for each participant was also recorded.Descriptives, 2 × 2 contingency tables with Fishers exact test, and independent samples t-tests were performed (α = 0.05). Prevalence of unsafe and inefficient swallowing was 48% and 73%, respectively. Global swallowing profiles were, in rank order: unsafe and inefficient (39%), inefficient but safe (34%), safe and efficient (18%), and unsafe but efficient (9%). There were no differences in global disease progression or disease duration across swallowing impairment profiles. ALSFRS-R bulbar subscale scores were significantly lower in unsafe versus safe swallowers, p<0.05. Spinal onset patients had a greater proportion of safe swallowers as compared to bulbar onset patients (p=0.000, Fisher's exacttest). Both spinal and bulbar onset patients demonstrated a higher prevalence of inefficient swallowers as compared to efficient swallowers (p=0.04, Fisher's exact test).Dysphagia was prevalent in this group of individuals with ALS. Approximately half demonstrated safety impairments and two-thirds had impairments in swallowing efficiency. Inefficient swallowing was approximately four times more likely to be the initial functional impairment in patients with one pathophysiologic functional impairment. A longitudinal study is needed to examine the temporal evolution of dysphagia in ALS.

One-Stage Buccal Mucosal Graft Urethroplasty for Lichen Sclerosus-Related Urethral Stricture Disease: A Systematic Review and Pooled Proportional Meta-Analysis.

Performing 1-stage urethroplasty in patients with urethral strictures caused by lichen sclerosus (LS) is hotly debated among reconstructive urologists due to conflicting reports of success. Therefore, the objective of this study was to determine the pooled incidence of stricture recurrence following 1-stage buccal mucosal graft (BMG) urethroplasty in patients with LS, to determine the impact of surgical technique on recurrence and to compare recurrence risk between patients with and without LS after 1-stage repairs. A systematic review was conducted in accordance with PRISMA criteria. The primary outcome was pooled incidence of recurrence, which was calculated using a Der-Simonian-Laird binary random effects model with a Freeman-Tukey arcsine transformation. A total of 21 studies were included, of which 15 provided data for comparative analyses. Pooled data from 625 LS patients revealed a stricture recurrence rate of 10% (95% CI 6-14). Among studies with longer followup (≥24 months), this increased to 18%. Among patients with penile urethral involvement, studies utilizing a penile skin incision had significantly higher pooled recurrence rates than those utilizing penile invagination (p=0.004). Across all studies, there was no evidence to suggest a difference in pooled recurrence rate between patients with and without LS (p=0.36). However, across only long-term studies, recurrence risk was significantly higher for patients with LS (OR 1.83, p=0.05). One-stage BMG urethroplasty is likely a viable surgical option for patients with LS-related strictures; however, high-quality data are limited. Future multi-institutional, long-term prospective studies are needed to assess durability of 1-stage repair.

Clinical Phenotyping and Biomarkers in Spinal and Bulbar Muscular Atrophy.

Background: Spinal and bulbar muscular atrophy (SBMA) or Kennedy disease [OMIM: 313200] is a rare X-linked neuromuscular disease. Patients commonly present with muscle cramps, tremors, leg weakness, dysarthria and dysphagia.Methods: We deeply phenotyped and evaluated the possible extent of affected systems in all patients with SBMA in Latvia (n = 5). In addition, neurophysiological studies and blood analyses were used to perform a molecular diagnosis and evaluate biochemical values. We analyzed neurofilament light (NfL) as a possible biomarker.Results: Neurological examination revealed typical SBMA clinical manifestations; all patients had small or large nerve fiber neuropathy. Three of five patients had increased neurofilament light levels.Conclusion: The study confirms the systemic involvement in patients suffering from SBMA. Increased NfL concentration was associated with either peripheral neuropathy or decreased body mass index. The complex phenotype of the disease should be kept in mind, as it could help to diagnose patients with SBMA.

Clinical Findings in Isolated Bulbar Amyotrophic Lateral Sclerosis

Background: Isolated bulbar amyotrophic lateral sclerosis (IBALS) is a regional variant of amyotrophic lateral sclerosis (ALS) with weakness restricted to the bulbar muscles for at least 2 years, and slower progression than generalized ALS. Bulbar-onset generalized ALS, by contrast, typically has a more rapid progression than limb-onset ALS.Objective: To characterize patients with IBALS and compare them to patients with isolated bulbar disease at presentation who progress to generalized ALS.Methods: We performed a retrospective chart review of patients seen in our ALS specialty clinic at the University of Kansas Medical Center between 2001-2011. Results: Of 543 patients seen in the ALS clinic, 150 presented with bulbar symptoms at disease onset: 28 (18.7%) had bulbar signs and no evidence of extremity involvement on exam or electrodiagnostic testing at their initial visit; and 14 (9.3%) had weakness restricted to the bulbar muscles after 2 years of follow up (IBALS). IBALS patients were 57.1% male, with a mean age of symptom onset of 60.8 years (range 39-77 years). The mean disease duration was 3.1 years (range of 2-8 years), with 50% mortality at a mean follow up of 3.5 years. Minimal denervation changes were seen in at least one limb in 6 subjects (42.9%). Other clinical features included: 4 subjects (28.6%) had cognitive impairment, 4 (28.6%) had pseudo-bulbar affect, and 5 subjects (35.7%) had impaired eye movements on smooth pursuit.Conclusion: Isolatred bulbar ALS IBALS is an identifiable restricted regional ALS pattern if there is no clinical limb weakness 2 years after symptom onset. It may have a slower progression from typical ALS. The biologic factors that account for the IBALS restricted pattern are unknown.

Comparison of Automated Acoustic Methods for Oral Diadochokinesis Assessment in Amyotrophic Lateral Sclerosis.

Purpose The purpose of this research note is to provide a performance comparison of available algorithms for the automated evaluation of oral diadochokinesis using speech samples from patients with amyotrophic lateral sclerosis (ALS). Method Four different algorithms based on a wide range of signal processing approaches were tested on a sequential motion rate /pa/-/ta/-/ka/ syllable repetition paradigm collected from 18 patients with ALS and 18 age- and gender-matched healthy controls (HCs). Results The best temporal detection of syllable position for a 10-ms tolerance value was achieved for ALS patients using a traditional signal processing approach based on a combination of filtering in the spectrogram, Bayesian detection, and polynomial thresholding with an accuracy rate of 74.4%, and for HCs using a deep learning approach with an accuracy rate of 87.6%. Compared to HCs, a slow diadochokinetic rate (p < .001) and diadochokinetic irregularity (p < .01) were detected in ALS patients. Conclusions The approaches using deep learning or multiple-step combinations of advanced signal processing methods provided a more robust solution to the estimation of oral DDK variables than did simpler approaches based on the rough segmentation of the signal envelope. The automated acoustic assessment of oral diadochokinesis shows excellent potential for monitoring bulbar disease progression in individuals with ALS.

Reflexive Airway Sensorimotor Responses in Individuals with Amyotrophic Lateral Sclerosis.

Progressive motor denervation in amyotrophic lateral sclerosis (ALS) leads to reduced expiratory cough flow and diminished airway clearance physiologic capacity. Although ALS is thought to primarily impact motor systems, preliminary data from our laboratory suggest degradation of afferent pathways that regulate reflexive cough responses to radiographically confirmed aspiration. We, therefore, aimed to delineate both sensory and motor responses to a tussigenic airway irritant in individuals with ALS compared to healthy controls. Thirty-two individuals with ALS and 34 healthy age and gender-matched controls completed reflex cough testing. Capsaicin stimuli (0, 50, 100, 150, 200μM) were presented in a randomized three-block design and motor (cough spirometry metrics) and sensory (patient-rated urge to cough, UtC) ratings collected. ALS patients underwent videofluoroscopy with penetration-aspiration ratings completed. Descriptives, Mann-Whitney U, and mixed models ANOVAs were performed. Sensory: Individuals with ALS demonstrated greater UtC sensitivity slopes (i.e., increased stimulus sensitivity) vs. healthy controls (p = 0.036). Within the ALS group, however, silent aspirators (PAS = 8) demonstrated blunted UtC sensitivity slopes compared to ALS patients who did not (PAS ≤ 7, p = 0.0001). Motor: Compared to healthy controls, ALS individuals demonstrated reduced peak expiratory flow rates (p = 0.004), longer peak expiratory rise time (p = 0.017), and lower cough volume acceleration (p = 0.000). ALS individuals demonstrated increased sensitivity to an upper airway irritant; however, they demonstrated slower and weaker expiratory cough motor output compared to healthy controls. In ALS silent aspirators, blunted sensorimotor responses were observed, suggesting that sensory degradation may occur at the final or most severe stage of bulbar disease progression.

Medical Management of Penile and Urethral Lichen Sclerosus with Topical Clobetasol Improves Long-Term Voiding Symptoms and Quality of Life.

We evaluated the success of minimally invasive management of lichen sclerosus with topical and intraurethral clobetasol, as defined by improvement in patient reported outcome measures and nonprogression to surgery. We conducted a review of our prospective ongoing quality improvement study to determine outcomes of our current standard practice for males with penile and urethral biopsy proven lichen sclerosus. Data were collected between 2011 and 2019, and included patient demographic information, medical and surgical histories, and location and extent of lichen sclerosus related pathology. The primary outcomes for this study were voiding function and voiding related quality of life, and were assessed using the AUASS (American Urological Association Symptom Score) and quality of life bother index, respectively. We identified 42 patients with biopsy proven lichen sclerosus related urethral stricture disease. Of these patients 85.7% were treated with intraurethral steroids alone and did not require surgical intervention. Median AUASS significantly improved from 12 to 8, and median quality of life bother index improved from 4 ("mostly dissatisfied") to 2 ("mostly satisfied"). Average stricture length of those with penile urethral disease and bulbar urethral disease was 4.8 cm (SD 3.0) and 16.2 cm (SD 6.5), respectively. Median followup was 8.4 months (IQR 2.6-26.4). Lichen sclerosus related urethral stricture disease can be effectively managed with intraurethral steroids. This minimally invasive management strategy improves patient reported voiding symptoms and voiding quality of life.

Automated analysis of natural speech in amyotrophic lateral sclerosis spectrum disorders.

We implemented automated methods to analyze speech and evaluate the hypothesis that cognitive and motor factors impair prosody in partially distinct ways in patients with amyotrophic lateral sclerosis (ALS). We recruited 213 participants, including 67 with ALS (44 with motor ALS, 23 with ALS and frontotemporal degeneration [FTD]), 33 healthy controls, and neurodegenerative reference groups with behavioral variant FTD (n = 90) and nonfluent/agrammatic primary progressive aphasia (n = 23). Digitized, semistructured speech samples obtained from picture descriptions were automatically segmented with a Speech Activity Detector; continuous speech segments were pitch-tracked; and duration measures for speech and silent pause segments were extracted. Acoustic measures were calculated, including fundamental frequency (f0) range, mean speech and pause segment durations, total speech duration, and pause rate (pause count per minute of speech). Group comparisons related performance on acoustic measures to clinical scales of cognitive and motor impairments and explored MRI cortical thinning in ALS and ALS-FTD. The f0 range was significantly impaired in ALS spectrum disorders and was related to bulbar motor disease, and regression analyses related this to cortical thickness in primary motor cortex and perisylvian regions. Impaired speech and pause duration measures were related to the degree of cognitive impairment in ALS spectrum disorders, and regressions related duration measures to bilateral frontal opercula and left anterior insula. Automated analyses of acoustic speech properties dissociate motor and cognitive components of speech deficits in ALS spectrum disorders.

Multi-dimensional electrical impedance myography of the tongue as a potential biomarker for amyotrophic lateral sclerosis

ObjectiveIn amyotrophic lateral sclerosis (ALS) bulbar disease biomarkers are lacking. We evaluated a novel tongue electrical impedance myography (EIM) system, utilising both 2D and 3D electrode configurations for detection of tongue pathology. MethodsLongitudinal multi-frequency phase angle spectra were recorded from 41 patients with ALS (baseline, 3 and 6 months) and 30 healthy volunteers (baseline and 6 months). ALS functional rating scale-revised (ALSFRS-R) data and quantitative tongue strength measurements were collected. EIM data were analysed for reliability (intra-class correlation coefficient; ICC) and differences between patients and volunteers ascertained using both univariate (Mann-Whitney U test) and multivariate techniques (feature selection and L2 norm). ResultsThe device produced highly reliable data (pooled ICC: 0.836). Significant EIM differences were apparent between ALS patients and healthy volunteers (P < 0.001). EIM data demonstrated a significant relationship to tongue strength and bulbar ALSFRS-R scores (P < 0.015). The EIM recordings revealed a group level longitudinal change over 6 months and consistently identified patients in whom symptoms or tongue strength changed. ConclusionsThe novel EIM tongue system produces reliable data and can differentiate between healthy muscle and ALS-related disease. SignificanceTongue EIM utilising multiple frequencies and electrode configurations has potential as a bulbar disease biomarker in ALS.