Real-time ultrasound-guided sacral plexus block combined with mild sedation for hemorrhoidectomy and hemorrhoidal artery ligation in a patient with amyotrophic lateral sclerosis: a case report.

BACKGROUND: Patients with amyotrophic lateral sclerosis present perioperative challenges for clinical anesthesiologists for anesthesia-associated complications. CASE PRESENTATION: A 54-year-old Han woman with a 2-year history of amyotrophic lateral sclerosis was scheduled for hemorrhoidectomy and hemorrhoidal artery ligation. We performed real-time ultrasound-guided sacral plexus block with dexmedetomidine under standard monitoring. The anesthesia method met the surgical demands and avoided respiratory complications during the procedures. There was no neurological deterioration after the surgery and 3 months after, the patient was discharged. CONCLUSIONS: Real-time ultrasound-guided sacral plexus block combined with mild sedation may be an effective and safe technique in patients with amyotrophic lateral sclerosis undergoing hemorrhoidectomy and hemorrhoidal artery ligation.

Anterior insula is more vulnerable than posterior insula to TDP-43 pathology in common dementias and ALS.

Based on the anatomic proximity, connectivity, and functional similarities between the anterior insula and amygdala, we tested the hypothesis that the anterior insula is an important focus in the progression of TDP-43 pathology in LATE-NC. Blinded to clinical and neuropathologic data, phospho-TDP (pTDP) inclusion pathology was assessed in paired anterior and posterior insula samples in 105 autopsied patients with Alzheimer disease, Lewy body disease, LATE-NC and hippocampal sclerosis (HS), amyotrophic lateral sclerosis (ALS), and other conditions. Insular pTDP pathology was present in 34.3% of the study cohort, most commonly as neuronal inclusions and/or short neurites in lamina II, and less commonly as subpial processes resembling those described in the amygdala region. Among positive samples, pTDP pathology was limited to the anterior insula (41.7%), or occurred in both anterior and posterior insula (58.3%); inclusion density was greater in anterior insula across all diseases (p < .001). pTDP pathology occurred in 46.7% of ALS samples, typically without a widespread TDP-43 proteinopathy. In LATE-NC, it was seen in 30.4% of samples (mostly LATE-NC stages 2 and 3), often co-occurring with basal forebrain pathology and comorbid HS, suggesting this is an important step in the evolution of this pathology beyond the medial temporal lobe.

Optimizing breathlessness management in amyotrophic lateral sclerosis: insights from a comprehensive systematic review.

BACKGROUND: Breathlessness is a prevalent symptom affecting the quality of life (QOL) of Amyotrophic Lateral Sclerosis (ALS) patients. This systematic review explored the interventions for controlling breathlessness in ALS patients, emphasizing palliative care (PALC), non-invasive ventilation (NIV), opioids, and non-pharmacological strategies. METHODS: A comprehensive search of PubMed, Cochrane Library, and Web of Science databases was conducted. Eligibility criteria encompassed adults with ALS or motor neuron disease experiencing breathlessness. Outcomes included QOL and symptom control. Study designs comprised qualitative studies, cohort studies, and randomized controlled trials. RESULTS: Eight studies were included, most exhibiting low bias risk, comprising one randomized controlled trial, three cohort studies, two comparative retrospective studies, and two qualitative studies (interviews). Most studies originated from Europe, with one from the United States of America. The participants totaled 3423, with ALS patients constituting 95.6%. PALC consultations significantly improved symptom assessment, advance care planning, and discussions about goals of care. NIV demonstrated efficacy in managing breathlessness, with considerations for device limitations. Opioids were effective, though predominantly studied in non-ALS patients. Non-pharmacological strategies varied in efficacy among patients. CONCLUSION: The findings underscore the need for individualized approaches in managing breathlessness in ALS. PALC, NIV, opioids, and non-pharmacological strategies each play a role, with unique considerations. Further research, especially ALS-specific self-management studies, is warranted.

Differing patterns of cortical grey matter pathology identified by multifractal analysis in UMN-predominant ALS patients with and without corticospinal tract hyperintensity.

The pathological hallmarks of amyotrophic lateral sclerosis (ALS) are degeneration of the primary motor cortex grey matter (GM) and corticospinal tract (CST) resulting in upper motor neuron (UMN) dysfunction. Conventional brain magnetic resonance imaging (MRI) shows abnormal CST hyperintensity in some UMN-predominant ALS patients (ALS-CST+) but not in others (ALS-CST-). In addition to the CST differences, we aimed to determine whether GM degeneration differs between ALS-CST+ and ALS-CST- patients by cortical thickness (CT), voxel-based morphometry (VBM) and fractal dimension analyses. We hypothesized that MRI multifractal (MF) measures could differentiate between neurologic controls (n = 14) and UMN-predominant ALS patients as well as between patient subgroups (ALS-CST+, n = 21 vs ALS-CST-, n = 27). No significant differences were observed in CT or GM VBM in any brain regions between patients and controls or between ALS subgroups. MF analyses were performed separately on GM of the whole brain, of frontal, parietal, occipital, and temporal lobes as well as of cerebellum. Estimating MF measures D (Q = 0), D (Q = 1), D (Q = 2), Δf, Δα of frontal lobe GM classified neurologic controls, ALS-CST+ and ALS-CST- groups with 98% accuracy and > 95% in F1, recall, precision and specificity scores. Classification accuracy was only 74% when using whole brain MF measures and < 70% for other brain lobes. We demonstrate that MF analysis can distinguish UMN-predominant ALS subgroups based on GM changes, which the more commonly used quantitative approaches of CT and VBM cannot.

Emotion recognition in amyotrophic lateral sclerosis in a dynamic environment.

OBJECTIVE: The aim of our study was to measure the ability of ALS patients to process dynamic facial expressions as compared to a control group of healthy subjects and to correlate this ability in ALS patients with neuropsychological, clinical and neurological measures of the disease. METHODS: Sixty-three ALS patients and 47 healthy controls were recruited. All the ALS patients also underwent i) the Geneva Emotion Recognition Test (GERT) in which ten actors express 14 types of dynamic emotions in brief video clips with audio, ii) the Edimburgh Cognitive and Behavioral ALS Screen (ECAS) test; iii) the ALS Functional Rating Scale Revised (ALSFRS-R) and iv) the Medical Research Council (MRC) for the evaluation of muscle strength. All the healthy subjects enrolled in the study underwent the GERT. RESULTS: The recognition of irritation and pleasure was significantly different between ALS patients and the control group. The amusement, despair, irritation, joy, sadness and surprise had been falsely recognized differently between the two groups. Specific ALS cognitive impairment was associated with bulbar-onset phenotype (OR = 14,3889; 95%CI = 3,96-52,16). No association was observed between false emotion recognition and cognitive impairment (F(1,60)=,56,971, p=,45,333). The number of categorical errors was significantly higher in the ALS patients than in the control group (27,66 ± 7,28 vs 17,72 ± 5,29; t = 8723; p = 0.001). CONCLUSIONS: ALS patients show deficits in the dynamic processing of a wide range of emotions. These deficits are not necessarily associated with a decline in higher cognitive functions: this could therefore lead to an underestimation of the phenomenon.

Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.

Prognostic value of geriatric nutritional risk index in patients with amyotrophic lateral sclerosis.

BACKGROUND: The geriatric nutritional risk index (GNRI) is a prognostic indicator for several diseases, meanwhile, nutrition and inflammation play important roles in the disease progression of amyotrophic lateral sclerosis (ALS). However, the association between the GNRI and ALS remains unknown. METHODS: 443 patients diagnosed with ALS were divided into two groups based on the GNRI levels. Associations between GNRI and survival time were analyzed using Kaplan-Meier curves and compared by the log-rank test. Univariate and multivariate analyses were used to assess their prognostic values for survival time. Spearman correlation analysis was used to evaluate the correlation coefficients between GNRI and other clinical variables. RESULTS: No significant differences were found in diagnostic delay between the two groups. The onset age and disease progression rate (DPR) were significantly lower in high GNRI group while forced vital capacity (FVC), revised version of the ALS functional rating scale (ALSFRS-R), serum albumin and body mass index (BMI) were significantly lower in low GNRI group. Lower GNRI levels were linked with shorter ALS patients' survival time by Kaplan-Meier curves. The univariate and multivariate analysis identified the onset age, gender, onset site, diagnostic delay, DRP and GNRI as predictors of survival time in patients with ALS. CONCLUSION: Nutritional status was closely corelated with ALS progression. The GNRI may be used as a potential prognostic indictor for ALS patients.

Rhythmic Jaw Movements in Amyotrophic Lateral Sclerosis: Is It Clonus or Tremor?

Background: Jaw clonus refers to involuntary, rhythmic jaw contractions induced by a hyperactive trigeminal nerve stretch reflex; however, the movements, when triggered without a stretch, can be confused with a tremor. Phenomenology Shown: This video demonstrates a patient with amyotrophic lateral sclerosis presenting with rapid rhythmic jaw movements seen at rest, alongside a power spectrum analysis revealing a narrow high-frequency peak of 10 Hz. Educational Value: Rhythmic jaw movements are seen in many disorders such as Parkinson's disease, essential tremor, tardive syndromes, and cranial myorhythmias; however, a high-frequency movement, regardless of clonus or tremor, can indicate amyotrophic lateral sclerosis when accompanied by typical upper and lower motor neuron signs. Highlights: The presented video abstract shows a patient with amyotrophic lateral sclerosis with rhythmic jaw movements seen at rest. A power spectrum analysis of the rhythmic movements revealed a 10 Hz peak, a frequency higher than those seen in patients with Parkinson's disease, essential tremor, myorhythmia, and tardive syndromes.

Cervical and thoracic spinal cord gray matter atrophy is associated with disability in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator-independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA-derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS. METHODS: A total of 36 patients with ALS (mean [SD] age 61.7 [12.6] years, 14 women) and 36 healthy, age- and sex-matched controls (HCs; mean [SD] age 63.1 [12.1] years, 14 women) underwent two-dimensional axial rAMIRA imaging at the inter-vertebral disc levels C2/3-C5/C6 and the lumbar enlargement level Tmax. ALS Functional Rating Scale-revised (ALSFRS-R) score, muscle strength, and sniff nasal inspiratory pressure (SNIP) were assessed. RESULTS: Compared to HCs, GM and WM areas were reduced in patients at all cervical levels (p < 0.0001). GM area (p = 0.0001), but not WM area, was reduced at Tmax. Patients with King's Stage 3 showed significant GM atrophy at all levels, while patients with King's Stage 1 showed significant GM atrophy selectively at Tmax. SC GM area was significantly associated with muscle force at corresponding myotomes. GM area at C3/C4 was associated with ALSFRS-R (p < 0.001) and SNIP (p = 0.0016). CONCLUSION: Patients with ALS assessed by rAMIRA imaging show significant cervical and thoracic SC GM and SC WM atrophy. SC GM area correlates with muscle strength and clinical disability. GM area reduction at Tmax may be an early disease sign. Longitudinal studies are warranted.

Clinical prognostic factors predicting survival of motor neuron disease patients with gastrostomy: A retrospective analysis.

INTRODUCTION/AIMS: Enteral feeding via gastrostomy is a key intervention to prevent significant weight loss in Motor Neuron Disease (MND). The aim of this study was to explore demographic, clinical, and nutritional factors associated with survival time in MND patients with gastrostomy. METHODS: The retrospective study analyzed 94 MND patients (n = 58 bulbar-onset and n = 36 limb-onset) who underwent gastrostomy between 2015 and 2021. The primary outcome was the survival time from gastrostomy insertion to death. Independent variables of interest explored were: age at gastrostomy insertion, disease onset type, known genetic cause, use of riluzole, non-invasive ventilation (NIV) use, forced vital capacity prior to gastrostomy, weight loss from diagnosis to gastrostomy insertion, and body mass index (BMI) at the time of gastrostomy insertion. RESULTS: The median survival time from gastrostomy to death was 357 days (± 29.3, 95%CI: 299.5, 414.5). Kaplan-Meier method and log-rank test revealed patients with lower body mass index <18.5 kg/m2 at the time of gastrostomy insertion (p = .023) had shorter survival. Cox proportional hazards model with multivariable adjustment revealed that older age (p = .008), and greater weight loss from diagnosis to gastrostomy (p = .003) were associated with shorter survival time post gastrostomy. Limb onset (p = .023), NIV use not being required (p = .008) and daily NIV use when required and tolerated (p = .033) were associated with longer survival. DISCUSSION: Preventing or minimizing weight loss from MND diagnosis and encouraging NIV use when clinically indicated are modifiable factors that may prolong the survival of MND patients with gastrostomy.

Health-related quality of life across disease stages in patients with amyotrophic lateral sclerosis: results from a real-world survey.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by a rapid disease course, with disease severity being associated with declining health-related quality of life (HRQoL) in persons living with ALS (pALS). The main objective of this study was to assess the impact of disease progression on HRQoL across King's, Milano-Torino Staging (MiToS), and physician-judgement clinical staging. Additionally, we evaluated the impact of the disease on the HRQoL of care partners (cALS). METHODS: Data were sourced from the Adelphi ALS Disease Specific Programme (DSP)™, a cross-sectional survey of neurologists, pALS and cALS presenting in a real-world clinical setting between July 2020 and March 2021 in Europe and the United States. RESULTS: Neurologists (n = 142) provided data for 880 pALS. There were significant negative correlations between all three clinical staging systems and EuroQol (European Quality of Life) Five Dimension Five Level Scale (EQ-5D-5L) utility scores and visual analogue scale (VAS) ratings. Although not all differences were significant, 5-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) scores showed a stepwise increase in HRQoL impairment at each stage of the disease regardless of the staging system. At later stages, high levels of fatigue and substantial activity impairment were reported. As pALS disease states progressed, cALS also experienced a decline in HRQoL and increased burden. CONCLUSIONS: Across outcomes, pALS and cALS generally reported worse outcomes at later stages of the disease, highlighting an unmet need in this population for strategies to maximise QoL despite disease progression. Recognition and treatment of symptoms such as pain and fatigue may lead to improved outcomes for pALS and cALS.

In-depth analysis of data from the RAS-ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add-on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. METHODS: We performed further exploratory in-depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. RESULTS: Placebo-treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65-0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS-R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. CONCLUSIONS: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12-18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future.

Diaphragmatic pacing for respiratory failure in children.

Diaphragm pacing is a ventilation strategy in respiratory failure. Most of the literature on pacing involves adults with common indications being spinal cord injury and amyotrophic lateral sclerosis (ALS). Previous reports in pediatric patients consist of case reports or small series; most describe direct phrenic nerve stimulation for central hypoventilation syndrome. This differs from adult reports that focus most commonly on spinal cord injuries and the rehabilitative nature of diaphragm pacing. This review describes the current state of diaphragm pacing in pediatric patients. Indications, current available technologies, surgical techniques, advantages, and pitfalls/problems are discussed.

A case of Mills' syndrome: initially characterized by one cerebral hemisphere atrophy and decreased brain metabolism then evolving into amyotrophic lateral sclerosis.

This article reports a case of Mills' syndrome that initially manifested as atrophy of one cerebral hemisphere and decreased brain metabolism, which developed into amyotrophic lateral sclerosis in the fourth year of the disease. Mills' syndrome is a rare type of motor neuron disease, with only over 20 cases reported since 1990, but most lack imaging such as PET and DTI. This article provides a complete report of the 18F-FDG-PET and DTI images consistent with the characteristics of Mills' syndrome. In addition, we have discovered some new phenomena, which have certain clinical and teaching values. Firstly, the frontal, parietal and temporal lobes on the side of the lesion in the pyramidal tract of this patient were significantly atrophic, indicating that unilateral brain lobe atrophy may be a new feature of Mills' syndrome. Secondly, although there were no abnormalities in three EMG tests taken during the 4 years prior to the onset of the disease, amyotrophy and ALS-like EMG features appeared in the fourth year, suggesting that some Mills' syndrome may progress more rapidly to ALS. This highlights the importance of regular follow-up electromyography in Mills' syndrome patients.

A Fine-Grained Temporal Analysis of Multimodal Oral Diadochokinetic Performance to Assess Speech Impairment in Amyotrophic Lateral Sclerosis.

PURPOSE: This study used a semiautomated fine-grained temporal analysis to extract features of temporal oral diadochokinetic (DDK) performance across multiple modalities and tasks, from neurologically healthy and impaired individuals secondary to amyotrophic lateral sclerosis (ALS). The aims were to (a) delineate temporal oral DDK deficits relating to the neuromotor pathology of ALS and (b) identify the optimal task-feature combinations to detect speech impairment in ALS. METHOD: Mandibular myoelectric, kinematic, and acoustic data were acquired from 13 individuals with ALS and 10 healthy controls producing three alternating motion rate tasks and one sequential motion rate task. Twenty-seven features were extracted from the multimodal data, characterizing three temporal constructs: duration/rate, variability, and coordination. The disease impacts on these features were assessed across tasks, and the task eliciting the greatest disease-related change was identified for each feature. Such "optimal" task-feature combinations were fed into logistic regression to differentiate individuals with ALS from healthy controls. RESULTS: Temporal deficits in ALS were characterized by (a) increased duration and variability and reduced coordination of jaw muscle activities, (b) increased duration and variability and altered temporal symmetry of jaw velocity profile, (c) increased muscle-burst-to-peak-velocity duration, and (d) increased motion-to-voice onset duration. These temporal features were differentially affected across tasks. The optimal task-feature combinations, which were further clustered into three composite factors reflecting temporal variability, coarser-grained duration, and finer-grained duration, differentiated ALS from controls with an F1 score of 0.86 (precision = 1.00, recall = 0.75). CONCLUSIONS: Temporal oral DDK deficits are likely attributed to a hierarchy of interrelated neurophysiological and biomechanical factors associated with the neuromotor pathology of ALS. These deficits, as assessed crossmodally, provide previously unavailable insights into the multifaceted timing impairment of oromotor performance in ALS. The optimal task-feature combinations targeting these deficits show promise as quantitative markers for (early) detection of speech impairment in ALS.

Airway Clearance Strategies and Secretion Management in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative motor neuron disease that affects voluntary muscle movement. Often, difficulty in coughing, breathing, and swallowing are sequela associated with the condition, and the presence of bulbar muscle predominant weakness results in deleterious effects on airway clearance and secretion management. This narrative review will provide practical guidance for clinicians treating this population. Cough insufficiency in this population typically manifests as a prolonged, slow, weak cough effort that impedes the clearability of secretions and airway protection. Dystussia and dysphagia frequently occur simultaneously in bulbar dysfunction, subsequently impacting respiratory health. Measures of respiratory strength should be obtained and monitored every 3-6 months, preferably in a multidisciplinary clinic setting. Cough augmentation, whether manual or mechanical techniques, should be sought as early in the disease progression as possible to adequately control secretions in the proximal airways. This airway clearance strategy can aid in the prevention and treatment of respiratory tract infections (RTIs), which can pose a significant clinical hurdle to those with ALS. The use of mechanical insufflation-exsufflation may be complicated by severe bulbar dysfunction rendering this technique ineffective. Though peripheral airway clearance strategies, such as high-frequency chest-wall compression, have the advantage of being less impacted by bulbar dysfunction, it is only recommended this modality be used in conjunction with, versus in lieu of, proximal strategies. Salivary secretion management includes the use of anticholinergics, botulinum toxin, and radiation therapy depending on severity and desire for relief.