Association between apathy and caregiver burden in patients with amyotrophic lateral sclerosis: a cross-sectional study.

OBJECTIVES: To investigate the relationship among patients' apathy, cognitive impairment, depression, anxiety, and caregiver burden in amyotrophic lateral sclerosis (ALS). DESIGN: A cross-sectional study design was used. SETTING: The study was conducted at a tertiary hospital in Wuhan, Hubei, China. PARTICIPANTS: A total of 109 patients with ALS and their caregivers were included. OUTCOME MEASURES: Patients with ALS were screened using the Edinburgh Cognitive and Behavioural Screen, Beck Depression Inventory-II, Generalised Anxiety Disorder-7 and Apathy Scale to assess their cognition, depression, anxiety and apathy, respectively. The primary caregivers completed the Zarit Burden Interview. The association between apathy, cognitive impairment, depression, anxiety and caregiver burden was analysed using logistic regression. Mediation models were employed to investigate the mediating effect of patients' apathy on the relationship between depression/anxiety and caregiver burden. RESULTS: Patients in the high caregiver burden group exhibited significantly higher levels of depression, anxiety and apathy compared with those in the low caregiver burden group (p<0.05). There was a positive association observed between caregiver burden and disease course (rs=0.198, p<0.05), depression (rs=0.189, p<0.05), anxiety (rs=0.257, p<0.05) and apathy (rs=0.388, p<0.05). There was a negative association between caregiver burden and the Revised ALS Functional Rating Scale (rs=-0.275, p<0.05). Apathy was an independent risk factor for higher caregiver burden (OR 1.121, 95% CI 1.041 to 1.206, p<0.05). Apathy fully mediated the relationship between depression and caregiver burden (ß=0.35, 95% CI 0.16 to 0.54, p<0.05) while partially mediating the relationship between anxiety and caregiver burden (ß=0.34, 95% CI 0.16 to 0.52, p<0.05). CONCLUSIONS: Apathy, depression and anxiety exerted a detrimental impact on caregiver burden in individuals with ALS. Apathy played a mediating role in the relationship between depression and caregiver burden and between anxiety and caregiver burden. These findings underscore the importance of identifying apathy and developing interventions for its management within the context of ALS.

How to break the news in amyotrophic lateral sclerosis/motor neuron disease: practical guidelines from experts.

In amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), it is necessary to communicate difficult news during the initial diagnosis and throughout the disease trajectory as the condition progresses. However, delivering difficult news to people with ALS/MND is an emotionally demanding task for healthcare and allied health professionals-one for which many feel ill-prepared because of limited training in this area. Ineffective communication of difficult news damages the patient-provider relationship and negatively impacts patient quality of life (QoL). To address this issue, we developed the A-L S-PIKES protocol based on available literature and our extensive clinical experience. It provides easy-to-follow, stepwise guidelines to effectively deliver difficult news to people with ALS/MND (PALS) that includes: Advance Preparation (preparing for the discussion logistically and emotionally); Location & Setting (creating a comfortable setting that fosters rapport); Patient's Perceptions (assessing PALS' understanding and perception of their condition); Invitation (seeking PALS' permission to share information); Knowledge (sharing information in a clear, understandable manner); Emotion/Empathy (addressing emotions with empathy and providing emotional support); and Strategy & Summary (summarizing the discussion and collaboratively developing a plan of action). A-L S-PIKES provides practical guidelines on how to prepare for and conduct these challenging conversations. It emphasizes effective communication tailored to the individual needs of PALS and their families, empathy, sensitivity, and support for PALS' emotional well-being and autonomy. The aim of A-L S-PIKES is to both enhance skills and confidence in delivering difficult news and to improve the QoL of PALS and their families. Future studies should systematically evaluate the feasibility and effectiveness of A-L S-PIKES to establish its utility in clinical practice.

Diffusion tensor imaging biomarkers and clinical assessments in amyotrophic lateral sclerosis (ALS) patients: an exploratory study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Biomarkers are needed to improve diagnosis, gauge progression, and evaluate treatment. Diffusion tensor imaging (DTI) is a promising biomarker for detecting microstructural alterations in the white matter tracts. This study aimed to assess DTI metrics as biomarkers and to examine their relationship with clinical assessments in patients with ALS. Eleven patients with ALS and 21 healthy controls (HCs) underwent 3T MRI with DTI. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were compared between key motor and extra-motor tract groups. Group comparisons and correlations between DTI metrics also correlated with clinical scores of disability (ALSFRS-R), muscle strength (dynamometry), and motor unit loss (MUNIX). Widespread differences were found between patients with ALS and HCs in DTI metrics, including decreased FA and increased diffusivity metrics. However, MD and RD are more sensitive metrics for detecting white matter changes in patients with ALS. Significant interhemispheric correlations between the tract DTI metrics were also observed. DTI metrics showed symmetry between the hemispheres and correlated with the clinical assessments. MD, RD, and AD increases significantly correlated with lower ALSFRS-R and MUNIX scores and weaker dynamometry results. DTI reveals microstructural damage along the motor and extra-motor regions in ALS patients. DTI metrics can serve as quantitative neuroimaging biomarkers for diagnosis, prognosis, monitoring of progression, and treatment. Combined analysis of imaging, electrodiagnostic, and functional biomarkers shows potential for characterizing disease pathophysiology and progression.

Predictors of mortality post-gastrostomy in motor neuron disease patients.

INTRODUCTION/AIMS: Motor neuron disease (MND) is a progressive neurodegenerative condition with a limited life expectancy. There is very little data on mortality and its associated factors beyond 30 days following gastrostomy. We explored the demographic, clinical, and nutritional predictors for early mortality at 30, 90, and 180 days following gastrostomy in these patients. METHODS: This was a retrospective study involving 94 MND patients in Western Australia who underwent gastrostomy between 2015 and 2021. Patients were divided into two groups based on mortality at 30, 90, and 180 days post-gastrostomy. T-test (or Mann-Whitney), chi-square test and Fisher's exact test were used for detecting between-group differences in various factors. Multivariable logistic regression was used to identify factors associated with post-gastrostomy mortality at 90 and 180 days. RESULTS: No mortality was attributable to gastrostomy-related complications. Lower forced vital capacity (FVC) (p = .039) and greater weight loss (%) (p = .022) from diagnosis to gastrostomy were observed in those who died within 30 days post-gastrostomy. Older age (p = .022), male sex (p = .041), lower FVC (p = .04), requiring but not tolerating noninvasive ventilation (p = .035), and greater weight loss (%) (p = .012) were independent predictors of 90-day post-gastrostomy mortality. However, only older age (p = .01) and greater weight loss (p = .009) were predictors of mortality at 180 days post-gastrostomy. DISCUSSION: Our data indicated that mortality at 90 and 180 days was influenced by the weight loss (%) from diagnosis to gastrostomy, highlighting the importance of nutritional care in the MND population. Gastrostomy placement prior to substantial weight loss may reduce the risk of weight loss-associated mortality and warrants further investigation.

Combination AAV therapy with galectin-1 and SOD1 downregulation demonstrates superior therapeutic effect in a severe ALS mouse model.

Neuroinflammation is a miscreant in accelerating progression of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, treatments targeting neuroinflammation alone have led to disappointing results in clinical trials. Both neuronal and non-neuronal cell types have been implicated in the pathogenesis of ALS, and multiple studies have shown correction of each cell type has beneficial effects on disease outcome. Previously, we shown that AAV9-mediated superoxide dismutase 1 (SOD1) suppression in motor neurons and astrocytes significantly improves motor function and extends survival in ALS mouse models. Despite neuron and astrocyte correction, ALS mice still succumb to death with microgliosis observed in endpoint tissue. Therefore, we hypothesized that the optimal therapeutic approach will target and simultaneously correct motor neurons, astrocytes, and microglia. Here, we developed a novel approach to indirectly target microglia with galectin-1 (Gal1) and combined this with our previously established AAV9.SOD1.short hairpin RNA treatment. We show Gal1 conditioning of SOD1 G93A microglia decreases inflammatory markers and rescues motor neuron death in vitro. When paired with SOD1 downregulation, we found a synergistic effect of combination treatment in vivo and show a significant extension of survival of SOD1 G93A mice over SOD1 suppression alone. These results highlight the importance of targeting inflammatory microglia as a critical component in future therapeutic development.

The cross-sectional area of the median nerve: An independent prognostic biomarker in amyotrophic lateral sclerosis.

INTRODUCTION: Ultrasound changes in the cross-sectional area of the median nerve (CSAmn) could be of interest as biomarkers in patients with amyotrophic lateral sclerosis (ALS). METHODS: Eighty-four ALS patients (51 men [60.7%]; mean 62.0 [SD 11.46] years old) and forty-six controls (27 men [58.7%]; mean 59.9 [SD 8.08] years old) of two different cohorts were recruited between September 2013 and February 2018. The CSAmn was measured bilaterally in each cohort, by two different examiners with two different ultrasound machines (one in each cohort). Its association with clinical variables (disease duration, muscle strength, disability, progression rate and tracheostomy-free survival) was assessed. RESULTS: The CSAmn was smaller in patients than in controls, and the study cohort did not influence its values. A mild correlation between the strength of the wrist flexor and the CSAmn was found. In the multivariable analysis, the probability of this association being true was 90%. In the cox regression, both a faster progression rate and a larger CSAmn independently predicted poor survival (HR=4.29, [Cr.I95%: 2.71-6.80], p<0.001; and HR=1.14, [Cr.I95%: 1.03-1.25], p=0.01), after adjusting by age, body mass index, bulbar onset, and diagnostic delay. CONCLUSIONS: The CSAmn is an easy to assess biomarker that seems reliable and reproducible. Our data also suggest that it could act as a progression and prognostic biomarker in ALS patients. Longitudinal studies with repeated measures are warranted to confirm its usefulness in the clinical practice.

[Electrodiagnostic support in an atypical form of amyotrophic lateral sclerosis (Vulpian-Bernhardt syndrome)]. / Apoyo del electrodiagnóstico en una forma atípica de esclerosis lateral amiotrófica (síndrome de Vulpian-Bernhardt).

Background: Vulpian-Bernhardt syndrome is an atypical form of the motor neuron disease described since the 19th century. The importance of a timely diagnosis lies in the increased survival present in this variant. Due to the clinical rarity and complex diagnosis we report a clinical case of this disease, which is why we describe the typical clinical presentation, the diagnostic approach, and we make a bibliographic review of this neurodegenerative disorder as well. Clinical case: Latin American man whose clinical case onset was characterized by thoracic asymmetric and increasing limb weakness, showing affection from distal to proximal upper limbs area. Subsequently, symptoms worsened to the point of limiting day-to-day activities and conditioning patient's physical independence. Physical examination was consistent with motor neuron disease. Nerve conduction studies were performed and confirmed findings compatible with motor neuron involvement limited to thoracic limbs. Conclusion: Vulpian-Bernhardt syndrome is an uncommon form of motor neuron disease. Due to the rarity of its presentation, it is frequent to confuse clinical profile even for trained physicians. The importance of electrodiagnosis relies in identifying the neurogenic origin of the disease, as well as the active denervation and reinnervation data. Considering that with this syndrome patients have a longer survival than with the classic form of amyotrophic lateral sclerosis, it is important to have a clear diagnosis approach in order to provide a better quality of life and supportive treatment.

Introducción: el síndrome de Vulpian-Bernhardt es una forma atípica de la enfermedad de la motoneurona descrita desde el siglo XIX. La importancia de un diagnóstico oportuno radica en la mayor supervivencia que presenta esta variante. Debido a la rareza clínica y al diagnóstico complejo presentamos un caso clínico de esta enfermedad, por lo que describimos el cuadro clínico típico, el abordaje diagnóstico y hacemos una revisión bibliográfica de este trastorno neurodegenerativo. Caso clínico: hombre de origen latinoamericano que comenzó su padecimiento con debilidad de miembros torácicos, asimétrica y progresiva de distal a proximal. Los síntomas progresaron hasta limitar sus actividades de la vida diaria y su independencia física. La exploración física fue compatible con enfermedad de motoneurona. Se hicieron estudios de extensión y neuroconducción que confirmaron hallazgos compatibles con afectación en motoneurona limitada a miembros torácicos. Conclusión: el síndrome Vulpian-Bernhardt es una forma clínica poco común. Debido a su rareza, es fácil confundir el cuadro clínico, incluso por parte de experimentados. La importancia del electrodiagnóstico radica en identificar el origen neurogénico de la enfermedad, los datos de denervación activa y reinervación. Al ser una forma en la que se presenta una supervivencia mayor que en la forma clásica, es importante el diagnóstico claro para dar una mejor calidad de vida y tratamiento de soporte.

[Amyotrophic lateral sclerosis associated with a new pathogenic variant of the ERBB4 gene]. / Sluchai bokovogo amiotroficheskogo skleroza, svyazannogo s novoi mutatsiei v gene ERBB4.

Amyotrophic lateral sclerosis (ALS) is a sporadic disease in most of the cases; in 10-15% of cases genetic forms are recorded. A genetic form of ALS associated with the mutation in the ERBB4 gene (ALS19) has been reported in 2013. A protein encoded by the ERBB4 is probably involved in ubiquitous component of the pathogenesis of ALS. We present a case of ALS associated with a new pathogenic variant of the ERBB4 gene, with early bulbar onset and slow progression of the disease within 10 years.

Plasma, brain and spinal cord concentrations of caffeine are reduced in the SOD1G93A mouse model of amyotrophic lateral sclerosis following oral administration.

Modifications to the small intestine and liver are known to occur during the symptomatic disease period of amyotrophic lateral sclerosis (ALS), a member of the motor neuron disease (MND) family of neurodegenerative disorders. How these modifications impact on oral absorption and pharmacokinetics of drugs remains unknown. In this study, model drugs representing different mechanisms of intestinal transport (caffeine for passive diffusion, digoxin for P-glycoprotein efflux, and sulfasalazine for breast cancer resistance protein efflux) were administered via oral gavage to postnatal day 114-120 male and female SOD1G93A mice (model of familial ALS) and wild-type (WT) littermates. Samples of blood, brain and spinal cord were taken at either 15, 30, 60 or 180 min after administration. In addition, the in vivo gastric emptying of fluorescein isothiocyanate-dextran (FITC-dextran) and the ex vivo intestinal permeability of caffeine were assessed. The area under the plasma concentration-time curves (AUCplasma) of digoxin and sulfasalazine were not significantly different between SOD1G93A and WT mice for both sexes. However, the AUCplasma of caffeine was significantly lower (female: 0.79-fold, male: 0.76-fold) in SOD1G93A compared to WT mice, which was associated with lower AUCbrain (female: 0.76-fold, male: 0.80-fold) and AUCspinal cord (female: 0.81-fold, male: 0.82-fold). The AUCstomach of caffeine was significantly higher (female: 1.5-fold, male: 1.9-fold) in SOD1G93A compared to WT mice, suggesting reduced gastric emptying in SOD1G93A mice. In addition, there was a significant reduction in gastric emptying of FITC-dextran (0.66-fold) and ex vivo intestinal permeability of caffeine (0.52-fold) in male SOD1G93A compared to WT mice. Reduced systemic and brain/spinal cord exposure of caffeine in SOD1G93A mice may therefore result from alterations to gastric emptying and small intestinal permeability. Specific dosing requirements may therefore be required for certain medicines in ALS to ensure that they remain in a safe and effective concentration range.

Cortical inexcitability in ALS: correlating a clinical phenotype.

BACKGROUND: Cortical inexcitability, a less studied feature of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS), was identified in a large cross-sectional cohort of ALS patients and their demographic and clinical characteristics were contrasted with normal or hyperexcitable ALS cohorts to assess the impact of cortical inexcitability on ALS phenotype and survival. METHODS: Threshold-tracking transcranial magnetic stimulation (TMS) technique with measurement of mean short interval intracortical inhibition (SICI) differentiated ALS patients into three groups (1) inexcitable (no TMS response at maximal stimulator output in the setting of preserved lower motor neuron (LMN) function), (2) hyperexcitable (SICI≤5.5%) and (3) normal cortical excitability (SICI>5.5%). Clinical phenotyping and neurophysiological assessment of LMN function were undertaken, and survival was recorded in the entire cohort. RESULTS: 417 ALS patients were recruited, of whom 26.4% exhibited cortical inexcitability. Cortical inexcitability was associated with a younger age of disease onset (p<0.05), advanced Awaji criteria (p<0.01) and Kings stage (p<0.01) scores. Additionally, patients with cortical inexcitability had higher UMN score (p<0.01), lower revised ALS Functional Rating Scale score (p<0.01) and reduced upper limb strength score (MRC UL, p<0.01). Patient survival (p=0.398) was comparable across the groups, despite lower riluzole use in the cortical inexcitability patient group (p<0.05). CONCLUSION: The present study established that cortical inexcitability was associated with a phenotype characterised by prominent UMN signs, greater motor and functional decline, and a younger age of onset. The present findings inform patient management and could improve patient stratification in clinical trials.

Clinical characterization of common pathogenic variants of SOD1-ALS in Germany.

Pathogenic variants in the Cu/Zn superoxide dismutase (SOD1) gene can be detected in approximately 2% of sporadic and 11% of familial amyotrophic lateral sclerosis (ALS) patients in Europe. We analyzed the clinical phenotypes of 83 SOD1-ALS patients focusing on patients carrying the most frequent (likely) pathogenic variants (R116G, D91A, L145F) in Germany. Moreover, we describe the effect of tofersen treatment on ten patients carrying these variants. R116G patients showed the most aggressive course of disease with a median survival of 22.0 months compared to 198.0 months in D91A and 87.0 months in L145F patients (HR 7.71, 95% CI 2.89-20.58 vs. D91A; p < 0.001 and HR 4.25, 95% CI 1.55-11.67 vs. L145F; p = 0.02). Moreover, R116G patients had the fastest median ALSFRS-R progression rate with 0.12 (IQR 0.07-0.20) points lost per month. Median diagnostic delay was 10.0 months (IQR 5.5-11.5) and therefore shorter compared to 57.5 months (IQR 14.0-83.0) in D91A (p < 0.001) and 21.5 months (IQR 5.8-38.8) in L145F (p = 0.21) carriers. As opposed to D91A carriers (50.0%), 96.2% of R116G (p < 0.001) and 100.0% of L145F (p = 0.04) patients reported a positive family history. During tofersen treatment, all patients showed a reduction of neurofilament light chain (NfL) serum levels, independent of the SOD1 variant. Patients with SOD1-ALS carrying R116G, D91A, or L145F variants show commonalities, but also differences in their clinical phenotype, including a faster progression rate with shorter survival in R116G, and a comparatively benign disease course in D91A carriers.

Physiological Biomarkers of Upper Motor Neuron Dysfunction in ALS.

Upper motor neuron (UMN) dysfunction is an important feature of amyotrophic lateral sclerosis (ALS) for the diagnosis and understanding of pathogenesis. The identification of UMN signs forms the basis of ALS diagnosis, although may be difficult to discern, especially in the setting of severe muscle weakness. Transcranial magnetic stimulation (TMS) techniques have yielded objective physiological biomarkers of UMN dysfunction in ALS, enabling the interrogation of cortical and subcortical neuronal networks with diagnostic, pathophysiological, and prognostic implications. Transcranial magnetic stimulation techniques have provided pertinent pathogenic insights and yielded novel diagnostic and prognostic biomarkers. Cortical hyperexcitability, as heralded by a reduction in short interval intracortical inhibition (SICI) and an increase in short interval intracortical facilitation (SICF), has been associated with lower motor neuron degeneration, patterns of disease evolution, as well as the development of specific ALS clinical features including the split hand phenomenon. Reduction in SICI has also emerged as a potential diagnostic aid in ALS. More recently, physiological distinct inhibitory and facilitatory cortical interneuronal circuits have been identified, which have been shown to contribute to ALS pathogenesis. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction. Resting-state EEG is a novel neurophysiological technique developed for directly interrogating cortical neuronal networks in ALS, that have yielded potentially useful physiological biomarkers of UMN dysfunction. The present review discusses physiological biomarkers of UMN dysfunction in ALS, encompassing conventional and novel TMS techniques developed to interrogate the functional integrity of the corticomotoneuronal system, focusing on pathogenic, diagnostic, and prognostic utility.

Development of a novel patient reported outcome measure for health-related quality of life in amyotrophic lateral sclerosis (PROQuALS): study protocol.

BACKGROUND: Patient reported outcome measures (PROMs) can be used to assess the impact of health conditions upon an individual's health-related quality of life (HRQoL). Whilst PROMs have been used to quantify the HRQoL impact of amyotrophic lateral sclerosis (ALS), existing instruments may not fully capture what matters to people living with ALS (plwALS) or be appropriate to be used directly to inform the cost-effectiveness of new treatments. This highlights a need for a new condition-specific PROM that can both capture what's important to plwALS and be used in economic evaluation. This study has two key aims: 1) to produce a novel PROM for measuring HRQoL in plwALS (PROQuALS). 2) to value a set of items from the novel PROM to generate an associated preference-weighted measure (PWM) that will enable utility values to be generated. METHODS: A mixed-methods study design will be conducted across three stages. Stage 1 involves concept elicitation and the generation of draft PROM content from a robust and comprehensive systematic review of HRQoL in ALS, with input from plwALS. Stage 2 consists of cognitive debriefing of the draft PROM content to ascertain its content validity (Stage 2a), followed by a psychometric survey (Stage 2b) to assess statistical performance. Evidence from Stage 2 will be used to make decisions on the final content and format of the novel PROM. Stage 3 will involve valuation and econometric modeling using health economics methods to generate preference weights, so a PWM derived from the novel PROM can be used in the cost-effectiveness analyses of treatments. Patient and clinical advisory groups will have critical, collaborative input throughout the project. DISCUSSION: The novel PROM will be designed to comprehensively assess important aspects of HRQoL to plwALS and to quantify HRQoL in terms of subjective impact. The PROQuALS measure will be available for use in research and healthcare settings. The associated PWM component will extend and enable the use of PROQuALS in cost-effective analyses of new treatments for ALS. TRIAL REGISTRATION: Not applicable.

Narrative review of diagnosis, management and treatment of dysphagia and sialorrhea in amyotrophic lateral sclerosis.

The degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) frequently leads bulbar symptoms like dysarthria, dysphagia, and sialorrhea, in approximately one-third of cases being the initial symptom. Throughout the disease, more than two-thirds of ALS patients experience dysphagia, regardless of the region of onset. In this review, we aimed to offer an updated overview of dysphagia and sialorrhea in ALS, covering its diagnosis, monitoring, and treatment in clinical practice. Regular assessment of dysphagia and sialorrhea during each patient visit is essential and should be a standard aspect of ALS care. Early discussion of potential treatments such as high-calorie diets or percutaneous endoscopic gastrostomy (PEG) is crucial. Furthermore, this review highlights and discusses potential areas for improvement in both clinical practice and research.

Pattern of pareses in 5q-spinal muscular atrophy.

Background: This prospective study investigates the pattern of pareses in 5q-associated spinal muscular atrophy (SMA) to identify disease-specific characteristics and potential differences from amyotrophic lateral sclerosis (ALS) and spinobulbar muscular atrophy (SBMA). Detailed knowledge about pareses patterns in SMA facilitates differential diagnosis and supports therapeutic monitoring. Methods: Between January 2021, and June 2021, 66 SMA patients (59.1% male, aged 33.6 ± 15.2 years) were included in the study. Most patients had SMA type II (n = 28) or SMA type III (n = 28), seven patients had SMA type I, and three patients had SMA type IV. We analyzed the pattern of pareses using the UK Medical Research Council (MRC) scoring system. Results: In both, upper and lower limbs muscle weakness was less pronounced in distal (upper limbs: MRC median 3.0 (interquartile range 1.5-3.5); lower limbs: 1.5 (0.5-3.0)) compared to proximal muscle groups (upper limbs: 2.0 (1.5-2.6); p < 0.001; lower limbs: 0.5 (0.5-1.5); p < 0.001). Thenar muscles were stronger than other small hand muscles (3.0 (2.0-3.5) vs 3.0 (1.5-3.5); p = 0.004). Muscles had more strength in upper (2.3 (1.5-3.1)) compared to lower limbs (1.1 (0.5-2.3); p < 0.001) and in flexors compared to extensors. Conclusion: We identified a specific pattern of muscle paresis in SMA which is different from the pattern of paresis in ALS and SBMA. As a rule of thumb, the pattern of pareses is similar, but not identical to ALS in distal, but different in proximal muscle groups.

Amyotrophic lateral sclerosis associated with Sjögren's syndrome: a case report.

BACKGROUND: Motor neuron disease (MND) is a chronic and progressive neurodegenerative disorder with an unknown cause. The development of amyotrophic lateral sclerosis (ALS) is believed to be linked to an immune response. Monocytes/macrophages and T cells are key players in the disease's advancement. Monitoring levels of cytokines in the blood can help forecast patient outcomes, while immunotherapy shows promise in alleviating symptoms for certain individuals. CASE PRESENTATION: A 56-year-old male patient was admitted to the hospital due to progressive limb weakness persisting for eight months. The neurological examination revealed impairments in both upper and lower motor neurons, as well as sensory anomalies, without corresponding signs. Electrophysiological examination results indicated extensive neuronal damage and multiple peripheral nerve impairments, thereby the diagnosis was ALS. One month ago, the patient began experiencing symptoms of dry mouth and a bitter taste. Following tests for rheumatic immune-related antibodies and a lip gland biopsy, a diagnosis of Sjögren's syndrome (SS) was proposed. Despite treatment with medications such as hormones (methylprednisolone), immunosuppressants (hydroxychloroquine sulfate), and riluzole, the symptoms did not significantly improve, but also did not worsen. CONCLUSION: It is recommended to include screening for SS in the standard assessment of ALS. Furthermore, research should focus on understanding the immune mechanisms involved in ALS, providing new insights for the diagnosis and treatment of ALS in conjunction with SS.

User expectations and experiences of an assistive robotic arm in amyotrophic lateral sclerosis: a multicenter observational study.

OBJECTIVE: Robotic arms are innovative assistive devices for ALS patients with progressive motor deficits of arms and hands. The objective was to explore the patients´ expectations towards a robotic arm system and to assess the actual experiences after the provision of the device. METHODS: A prospective observational study was conducted at 9 ALS centers in Germany. ALS-related functional deficits were assessed using the ALS-Functional Rating Scale-revised (ALSFRS-R). Motor deficit of the upper limbs was determined using a subscore of three arm-related items of the ALSFRS-R (items 4-6; range 0-12 points). User expectations before provision (expectation group, n = 85) and user experiences after provision (experience group, n = 14) with the device (JACO Assistive Robotic Device, Kinova, Boisbriand, QC, Canada) were assessed. RESULTS: In the total cohort, mean ALSFRS-R subscore for arm function was 1.7 (SD: 2.0, 0-9) demonstrating a severe functional deficit of the upper limbs. In the expectation group (n = 85), the following use cases of the robotic arm have been prioritized: handling objects (89%), close-body movements (88%), pressing buttons (87%), serving drinks (86%), and opening cabinets and doors (85%). In the experience group (n = 14), handling objects (79%), serving drinks (79%), near-body movements (71%), pushing buttons (71%), serving food (64%), and opening doors (64%) were the most frequent used cases. Most patients used the device daily (71.4%, n = 10), and 28.6% (n = 4) several times a week. All patients of the experience group found the device helpful, felt safe while using the device, and were satisfied with its reliability. NPS of the assistive robotic arm revealed 64% "promoters" (strong recommendation), 29% "indifferents" (uncertain recommendation) and 7% "detractors" (no recommendation). Total NPS was + 57 demonstrating strong patient satisfaction. CONCLUSIONS: Initiation of procurement with a robotic assistive arm was confined to patients with severe functional deficit of the upper limbs. User experience underlined the wide spectrum of use cases of assistive robotic arms in ALS. The positive user experience together with high satisfaction underscore that robotic arm systems serve as a valuable treatment option in ALS patients with severe motor deficits of the arms.