Amyotrophic Lateral Sclerosis Symptoms Research Articles

Fiberoptic laryngoscopic neurological examination of amyotrophic lateral sclerosis patients with bulbar symptoms

ObjectiveBulbar symptoms in amyotrophic lateral sclerosis (ALS) are variable, reflecting bulbar and pseudobulbar palsy. The current study sought to characterize the pharyngeal findings in ALS using a fiberoptic laryngoscope and compare them with the findings of general neurological examination. MethodsWe enrolled ALS patients with bulbar symptoms who were admitted between 2014 and 2020. All participants were evaluated on salivary status, velopharyngeal movement during speech and swallowing, pharyngeal constriction, and vocal cord movement using fiberoptic laryngoscopy. The laryngoscopic findings were compared with general neurological examination results. ResultsA total of 50 patients (31 men; median age: 69 years) were enrolled. Salivary residue in the hypopharynx was the most common abnormal finding on laryngoscopy (40 patients; 80%). Twenty-three patients (46%) exhibited velopharyngeal insufficiency, 18 of which exhibited good velopharyngeal closure in swallowing and poor velopharyngeal closure in speech. Thus, these patients presented speech-swallow dissociation (SSD) in velopharyngeal closure. Five patients (10%) exhibited unilateral weakness of the pharyngeal constrictor muscles in phonation. Compared with general neurological examinations, emotional incontinence was more frequent in patients who presented with SSD in velopharyngeal movement, compared with those who did not. None of the five patients with unilateral weakness of pharyngeal constriction showed curtain movement on examination via the mouth. ConclusionThe specific findings of laryngoscopy in ALS patients, such as SSD in velopharyngeal closure and laterality in pharyngeal constriction, could not be evaluated by general neurological examination via the mouth.

Pain in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition characterized by loss of motor neurons, resulting in motor weakness of the limbs and/or bulbar muscles. Pain is a prevalent but neglected symptom of ALS, and it has a significant negative impact on the quality of life of patients and their caregivers. This review outlines the epidemiology, clinical characteristics, underlying mechanisms, and management strategies of pain in ALS to improve clinical practice and patient outcomes related to pain. Pain is a prevalent symptom among patients with ALS, with a variable reported prevalence. It may occur at any stage of the disease and can involve any part of the body without a specific pattern. Primary pain includes neuropathic pain and pain from spasticity or cramps, while secondary pain is mainly nociceptive, occurring with the progression of muscle weakness and atrophy, prolonged immobility causing degenerative changes in joints and connective tissue, and long-term home mechanical ventilation. Prior to treatment, the exact patterns and causes of pain must first be identified, and the treatment should be tailored to each patient. Treatment options can be classified into pharmacological treatments, including nonsteroidal anti-inflammatory drugs, antiepileptic drugs, drugs for cramps or spasticity, and opioid; and nonpharmacological treatments, including positioning, splints, joint injections, and physical therapy. The development of standardized and specific assessment tools for pain-specific to ALS is required, as are further studies on treatments to reduce pain, diminish suffering, and improve the quality of life of patients with ALS.

Lessons to Learn from the Gut Microbiota: A Focus on Amyotrophic Lateral Sclerosis

The gut microbiota is able to modulate the development and homeostasis of the central nervous system (CNS) through the immune, circulatory, and neuronal systems. In turn, the CNS influences the gut microbiota through stress responses and at the level of the endocrine system. This bidirectional communication forms the “gut microbiota–brain axis” and has been postulated to play a role in the etiopathology of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Numerous studies in animal models of ALS and in patients have highlighted the close communication between the immune system and the gut microbiota and, therefore, it is possible that alterations in the gut microbiota may have a direct impact on neuronal function and survival in ALS patients. Consequently, if the gut dysbiosis does indeed play a role in ALS-related neurodegeneration, nutritional immunomodulatory interventions based on probiotics, prebiotics, and/or postbiotics could emerge as innovative therapeutic strategies. This review aimed to shed light on the impact of the gut microbiota in ALS disease and on the use of potential nutritional interventions based on different types of biotics to ameliorate ALS symptoms.

Role of Superoxide Dismutase in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig's disease, is an adult‐onset neurodegenerative disorder that has been linked to over 200 mutations from the SOD1 gene. The protein created from this gene is superoxide dismutase (SOD1), an enzyme responsible for breaking down toxic superoxide radicals by facilitating the binding to zinc and copper. Superoxide dismutase is a homodimer, composed of two identical subunits, and is located in the cytoplasm of the cell, Each subunit has 154 amino acid residues with a β‐barrel core, formed by 8 beta‐sheets, and three outer loops which are linked together by a disulfide bond, a hydrogen bond network, and a metal‐binding site for both zinc and copper. This metal‐binding site is responsible for the catalyzation of superoxide radicals to hydrogen peroxide and dioxygen. The redox reactions that SOD1 allows to occur are the oxidation of superoxide to dioxygen and the reduction of superoxide to hydrogen peroxide while alternating the oxidation states of Copper. The zinc molecule acts as a structural element for the reaction. The catalyzation of superoxide radicals to safer components occurs because the accumulation of superoxide radicals is toxic to the cell, and can lead to cell death. Another role of SOD1 is its responsibility in preventing oxidative stress. Oxidative stress is the result of the imbalance between reactive oxygen species such as superoxide, and the activity of superoxide dismutase to detoxify the affected areas. In cases of ALS, mutations cause this accumulation, which leads to motor neuron death. The most common mutation of SOD1 in the United States, as well as the one that causes the fastest onset for ALS to occur, is A5V, which is the replacement of the alanine residue with valine at position 5. This mutation can result in not only the accumulation of superoxide radicals but also the production of more neurotoxic radicals and fibrillar aggregates of misfolded SOD1, which can occur due to the absence of the disulfide bond or bound zinc ions. These effects lead to motor neuron death, which manifests as the symptoms of ALS. The symptoms of ALS are progressive muscle weakness, loss of voluntary muscle control, the decline of the ability to initiate movement, and paralysis. ALS, especially as a result of the A5V mutation, often leads to a shorter life expectancy. Amyotrophic Lateral Sclerosis currently has no cure, but there are many evolving therapies for the disease. Patients with ALS are encouraged to participate in gentle, low‐impact physical therapies and use special equipment to support communication, nutrition, and breathing. The drugs approved by the FDA to help treat ALS include Riluzole (Rilutek), which reduces damage to cells by blocking the release of glutamate, and Edaravone (Radicava) which removes free radicals. In addition, small‐molecule therapies are being developed to stabilize the native form of SOD1 in the absence of zinc or in the presence of protein mutations, which may reduce the effects of the manifestation of the disease. Further research is needed to determine specifically how mutations of SOD1 lead to motor neuron death, and the resulting symptoms of Amyotrophic Lateral Sclerosis.

Methylome analysis of ALS patients and presymptomatic mutation carriers in blood cells

Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron disease with a monogenic cause in approximately 10% of cases. However, familial clustering of disease without inheritance in a Mendelian manner and the broad range of phenotypes suggest the presence of epigenetic mechanisms. Hence, we performed an epigenome-wide association study on sporadic, symptomatic and presymptomatic familial ALS cases with mutations in C9ORF72 and FUS and healthy controls studying DNA methylation in blood cells. We found differentially methylated DNA positions (DMPs) and regions embedding DMPs associated with either disease status, C9ORF72 or FUS mutation status. One DMP reached methylome-wide significance and is attributed to a region encoding a long non-coding RNA (LOC389247). Furthermore, we could demonstrate co-localization of DMPs with an ALS-associated GWAS region near the SCN7A/SCN9A and XIRP2 genes. Finally, a classifier model that predicts disease status (ALS, healthy) classified all but one presymptomatic mutation carrier as healthy, suggesting that the presence of ALS symptoms rather than the presence of ALS-associated genetic mutations is associated with blood cell DNA methylation.

Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatments (ALS-SSIT) for Evaluating Therapeutic Effect of Traditional Chinese Medicine: A Prospective Study.

Objective To evaluate the reliability, validity, sensitivity, and clinical applicability of a new scale—the amyotrophic lateral sclerosis symptom score in integrative treatments (ALS-SSIT)—for measuring the effect of traditional Chinese medicine (TCM) in patients with amyotrophic lateral sclerosis (ALS). Methods A total of 160 patients with ALS were enrolled and followed up for 6 months. All patients received TCM. Patients were evaluated at enrollment and at the end of 6 months with a new scale, the ALS-SSIT, developed after extensive consultations with TCM experts with several years of experience in the treatment of ALS. The 36-item Medical Outcomes Study Short Form (SF-36) scale and the amyotrophic lateral sclerosis functional rating scale (ALSFRS) were used as the reference standards. Results The acceptance rate and completion rate of the ALS-SSIT scale were high, and the content validity was confirmed by experts. Test-retest performed at enrollment and at 6 months showed good reliability of the ALS-SSIT scale (Cronbach α, 0.9172 and 0.9181, respectively). The ALS-SSIT scale score showed significant change at 6 months, indicating the ability to reflect the change in disease severity. Conclusion The ALS-SSIT appears to be a feasible, reliable, and sensitive tool for the evaluation of the effect of TCM in patients with ALS.

Management of Depression in ALS with the use of Methylphenidate and Sertraline

<h3>Introduction</h3> Amyotrophic lateral sclerosis (ALS) is now a well-known disease that was first described by Charcot in the 19th century. It is a relentlessly progressive neurodegenerative disorder, with voluntary muscle action progressively affected, people may experience muscle weakness, disability, and eventually death. The loss of motor neurons results in the primary clinical symptoms and produces impairment affecting limb, bulbar, axial, and respiratory function. The focus of research and treatment has been on the loss of motor neurons, but equally debilitating and associated problems with ALS include mood alterations such as depression and anxiety. Initial depression has been associated with shorter survival time. Quality of life appears to be more dependent on psychological factors such as depression and hopelessness being common in ALS patients. <h3>Methods</h3> Quality of life can be improved with treatment of depression in ALS patients, however, there are no controlled trials supporting certain pharmacological treatments. One patient we describe here has been diagnosed with ALS without prior depressive symptoms until diagnosis. Patient was tried on citalopram and wellbutrin combintation without much clinical resonse. At this time, referral was made to the psychiatric clinic and patient had already been started on methylphenidate treatment alone without additional SSRI. We describe our algoritihm into finding the patient and his family the treatment that was most responsive for him. <h3>Results</h3> Combination treatments with SSRI and methylphenidate has demonstrated enhanced clinical response in mood, well-being, higher rate of remission, and enhancement in cognitive functioning in the geriatric population. Here, we used combintation treatment of methylphenidate with sertraline and observed benefical response including improvements in mood, anxiety, motivation, apathy, energy, and concentration. <h3>Conclusions</h3> To the best of our knowledge, there are no case reports that have reported methylphenidate or stimulants in general as treatment adjunct to antidepressants for depressive symptoms in ALS. This patient responded to sertraline and methylphenidate combination at relatively low doses. The use of stimulants was tried in a single patient, so more studies will be needed to confirm the utility of this class of medications and combination in the ALS population with depressive mood symptoms. Further literature on treatment of depression in ALS is needed including different pharmacological measures and treatment modalities. We suggest that in addition to an antidepressant, stimulants can be considered to help specific symptoms including motivation, energy, and concentration.

Fatigue in Chinese Patients With Amyotrophic Lateral Sclerosis: Associated Factors and Impact on Quality of Life.

ObjectivesFatigue was considered as a common symptom in amyotrophic lateral sclerosis (ALS). Previous studies about the impact of fatigue on Quality of Life (QoL) in patients with ALS were limited and inconsistent. Besides, a systematic investigation of fatigue in Chinese patients with ALS was lacking. Therefore, this study aimed to comprehensively evaluate the frequency and associated factors of fatigue and impact on QoL in Chinese patients with ALS.Participants and MethodsProbable and definitive patients with ALS and age- and gender-matched healthy controls (HCs) were consecutively recruited. The frequency of fatigue between both the groups was determined by the Fatigue Severity Scale (FSS). Disease severity, sleep quality, sleepiness, anxiety, depression, and QoL were evaluated in patients with ALS by the ALS Functional Rating Scale-revised (ALSFRS-R) and the ALS Severity Scale (ALSSS), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the McGill Quality of Life Questionnaire (MQOL). Then, clinical characteristics of patients with ALS with fatigue were compared with those without fatigue. Lastly, associated factors of fatigue and impact on QoL in Chinese patients with ALS were assessed.ResultsA total of 175 patients with ALS and 175 HCs were included. Fatigue was significantly more frequent in patients with ALS than in controls (32.6 vs. 17.7%, p = 0.001). Patients with ALS with fatigue scored lower on the ALSFRS-R, the ALSSS [lower extremity (LE) + upper extremity (UE)], the total ALSSS, higher in the HARS, HDRS, PSQI, ESS scores, and a poorer QoL. Daytime dysfunction and the ALSSS (LE + UE) score were associated with a higher risk of fatigue. The ALSSS (LE + UE), the FSS, age, the HARS, and the HDRS score were significantly associated with various aspects of QoL.ConclusionThis study has described fatigue in Chinese patients with ALS and finding daytime dysfunction and the lower ALSSS (LE + UE) were associated with a higher risk of fatigue. Also, we identified an inverse relationship of fatigue intensity with the psychological domain of QoL.

Cortical and subcortical changes in resting-state neuronal activity and connectivity in early symptomatic ALS and advanced frontotemporal dementia

The objective of this study was to examine if patterns of resting-state brain activity and functional connectivity in cortical and subcortical regions in patients with early symptomatic amyotrophic lateral sclerosis (ALS) resemble those of behavioural variant frontotemporal dementia (bvFTD). In a cross-sectional design, eyes-closed resting-state magnetoencephalography (MEG) data of 34 ALS patients, 18 bvFTD patients and 18 age- and gender-matched healthy controls (HCs) were projected to source-space using an atlas-based beamformer. Group differences in peak frequency, band-specific oscillatory activity and functional connectivity (corrected amplitude envelope correlation) in 78 cortical regions and 12 subcortical regions were determined. False discovery rate was used to correct for multiple comparisons. BvFTD patients, as compared to ALS and HCs, showed lower relative beta power in parietal, occipital, temporal and nearly all subcortical regions. Compared to HCs, patients with ALS and patients with bvFTD had a higher delta (0.5–4 Hz) and gamma (30–48 Hz) band resting-state functional connectivity in a high number of overlapping regions in the frontal lobe and in limbic and subcortical regions. Higher delta band connectivity was widespread in the bvFTD patients compared to HCs. ALS showed a more widespread higher gamma band functional connectivity compared to bvFTD. In conclusion, MEG in early symptomatic ALS patients shows resting-state functional connectivity changes in frontal, limbic and subcortical regions that overlap considerably with bvFTD. The findings show the potential of MEG to detect brain changes in early symptomatic phases of ALS and contribute to our understanding of the disease spectrum, with ALS and bvFTD at the two extreme ends.

Laryngospasm in amyotrophic lateral sclerosis.

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

Motor neuron disease as an outcome of neurodegeneration, neuroinflammation or mercury poisoning?

Amyotrophic lateral sclerosis (ALS) is the main disease in the group of motor neuron diseases. It is fatal disease that affects lateral columns of spinal cord, leads to generalized muscular atrophy. Most severe damage to respiratory muscles resulting from degeneration of motor neurons ultimately leads to certain death approximately 5 months after first symptoms onset. Mercury intoxication (MI) in some cases makes significant contribution to neurodegenerative processes or aggravates existing symptoms of ALS and simultaneously immune deficiency.

Illness Cognitions in ALS: New Insights Into Clinical Management of Behavioural Symptoms.

Timely management of frontotemporal dysfunction associated with amyotrophic lateral sclerosis (ALS) has important prognostic and therapeutic implications. However, there remains a paucity of research on best practise recommendations to guide the development of interventions for cognitive and behavioural symptoms as part of ALS care. Accordingly, a focus on illness perceptions may provide a preliminary framework for managing cognitive and behavioural symptoms. The aim of the present study was to explore the nature of illness perceptions among ALS patients with cognitive and behavioural symptoms. A total of 39 patients were recruited from a specialised ALS clinic. Factor analysis showed three independent and clinically interpretable factors corresponding to “cognitive and emotion related ALS perceptions,” “cognitive- specific ALS perceptions” and “ALS coherence”. Of these factors, greater perceived cognitive and emotional impacts of ALS were associated with an approximate 4-fold increased risk of behavioural changes (p < 0.05). Greater perceived cognitive and emotional impacts of ALS was also associated with more rapid disease progression (p < 0.001). As such, timely provision of intervention addressing perceptions about the impact of ALS on functioning as well as associated emotional distress may optimise clinical management of cognitive and behavioural symptoms of ALS.

Nonmotor Symptoms in Amyotrophic Lateral Sclerosis and Their Correlation With Disease Progression.

Motor neuron disease is a progressive neurodegenerative disease involving upper and lower motor neurons. Nonmotor symptoms (NMS) are part of disease manifestation. We aim to report the prevalence and severity of NMS in patients with motor neuron disease (MND) in Lebanon. . Fifty-eight patients diagnosed with MND at the American University of Beirut Medical Center were interviewed using the NMS Scale. The prevalence of these symptoms was assessed and correlated with disease progression. All our patients had at least 2 NMS with an average total score of 15.8. Symptoms reported in more than half of the patients were fatigue, depression, dysphagia, lack of motivation, pain, change in weight, anxiety, constipation, and lack of pleasure. A significant correlation was found between the total NMS score and Amyotrophic Lateral Sclerosis Functional Rating Scale score (P = 0.002) and between the NMS score corresponding to mental health and Amyotrophic Lateral Sclerosis Functional Rating Scale score (P = 0.012). Patients with bulbar symptoms had a significantly higher NMS score corresponding to gastrointestinal symptoms (P < 0.0001). It is important to note that NMS such as dysphagia could be related to motor neuron involvement. NMS are commonly reported in patients with MND and seem to positively correlate with disease progression. Treating NMS is a critical aspect of the clinical care delivered to patients with MND to maintain a good quality of life.

Impact of Percutaneous Endoscopic Gastrostomy (PEG) on the Evolution of Disease in Patients with Amyotrophic Lateral Sclerosis (ALS).

Dysphagia is a highly prevalent symptom in Amyotrophic Lateral Sclerosis (ALS), and the implantation of a percutaneous endoscopic gastrostomy (PEG) is a very frequent event. The aim of this study was to evaluate the influence of PEG implantation on survival and complications in ALS. An interhospital registry of patients with ALS of six hospitals in the Castilla-León region (Spain) was created between January 2015 and December 2017. The data were compared for those in whom a PEG was implanted and those who it was not. A total of 93 patients were analyzed. The mean age of the patients was 64.63 (17.67) years. A total of 38 patients (38.8%) had a PEG implantation. An improvement in the anthropometric parameters was observed among patients who had a PEG from the beginning of nutritional follow-up compared to those who did not, both in BMI (kg/m2) (PEG: 0 months, 22.06; 6 months, 23.04; p < 0.01; NoPEG: 0 months, 24.59–23.87; p > 0.05). Among the deceased patients, 38 (40.4%) those who had an implanted PEG (20 patients (52.6%) had a longer survival time (PEG: 23 (15–35.5) months; NoPEG 11 (4.75–18.5) months; p = 0.01). A PEG showed a survival benefit among ALS patients. Early implantation of a PEG produced a reduction in admissions associated with complications derived from it.

The Evaluation of Pain with Nociceptive and Neuropathic Characteristics from Three Different Perspectives in Amyotrophic Lateral Sclerosis Patients: A Case Controlled Observational Study in Southwestern China.

Background Pain was considered a common and neglected symptom in amyotrophic lateral sclerosis (ALS) and had a substantial impact on the quality of life of ALS patients and their caregivers. However, pain in ALS was mainly evaluated from the perspective of nociceptive pain; only three studies referred to neuropathic pain in ALS, and there has been yet no study considering the neuropathic pain characteristics in ALS patients from China. Therefore, the purpose of our study was to determine characteristics of pain (nociceptive pain and neuropathic pain) by three different types of questionnaires. The correlation between pain and clinical parameters in ALS patients was also evaluated. Methods Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Healthy normal controls, matched to ALS patients by age and gender, were recruited. Pain was evaluated by numerical pain rating scale (NRS), Brief Pain Inventory (BPI), and Douleur Neuropathique-4 (DN4) in ALS patients and controls. Physical status of ALS patients was evaluated with ALS Functional Rating Scale-revised (ALSFRS-R). Results 65 patients with sporadic ALS and 100 healthy normal controls in Southwestern China were included. Pain in the preceding week was more frequently reported by patients with ALS (30, 46.2%) than controls (36, 36%) (p = 0.193). DN4 score⩾4 was found in three ALS patients and one control (p = 0.480). Ten ALS patients (33.3%) and twenty-eight controls (77.8%) (p < 0.001) received therapy for pain. ALS patients with a DN4 score ≥ 4 had a longer disease duration and a higher PSI and PII score than ALS cases reporting nociceptive pain (p = 0.041, 0.048, and 0.027, respectively). Pain mainly interfered with ALS patients' mood, enjoyment of life, and the Pain Interference Index (PII) score. Conclusions Our findings indicated that pain in our ALS cohorts was insufficiently treated and interfered with patients' mood and enjoyment of life. Most notably, we found that ALS patients with a DN4 score⩾4 may have a longer disease duration and a higher PSI and PII score than ALS patients reporting nociceptive pain, which has never been reported, strongly deserving further validation.

Progression of Oropharyngeal Dysphagia in Amyotrophic Lateral Sclerosis: A Retrospective Cohort Study

Little is known regarding the optimal timing of dysphagia assessment and PEG indication in amyotrophic lateral sclerosis (ALS). The study aims to investigate the progression of dysphagia in a cohort of ALS patients and to analyse whether there are variables linked to a faster progression of dysphagia and faster indication of PEG placement. A retrospective cohort study in 108 individuals with ALS. Fiberoptic endoscopic evaluation of swallowing was performed 6 monthly until PEG indication or death. Dysphagia severity and PEG indication were assessed using Penetration Aspiration Scale. Progression Index (PI) analysed the risk of disease progression (fast/slow) in relation to dysphagia onset and PEG indication. Patients were grouped based on ALS onset and PI. Person-time incidence rates were computed considering dysphagia onset and PEG indication from ALS symptoms during the entire observation period and have been reported as monthly and 6-month rates. Cox regression survival analysis assessed dysphagia and PEG risk factors depending on onset. Person-time incidence rates of dysphagia progression and PEG risk were increased based on type of ALS onset and PI. Patients with a fast progressing disease and with bulbar onset (BO) show statistically significant increased risk of dysphagia (BO 178.10% hazard ratio (HR) = 2.781 P < 0.01; fast 181.10% HR 2.811 P < 0.01). Regarding PEG risk, fast patients and patients with BO had a statistically significant increased risk (fast 147.40% HR 2.474 P < 0.01, BO 165.40% HR 2.654 P < 0.01). Fast PI predicts the likelihood of faster progression of dysphagia and PEG indication and should be included in multidisciplinary assessments and considered in the design of future guidelines regarding dysphagia management in ALS patients.Level of Evidence Level IV.

Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations

ObjectiveCerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition.MethodsA prospective...

Syndrome amyotrophic lateral sclerosis — Alz heimer's dementia

Recently, there is more and more evidence of the presence of a cognitive defect of varying severity in the clinical picture of ALS. A rare form of the disease is the amyotrophic lateral sclerosis (ALS) — dementia complex, characterized by a combination of dementia (usually frontotemporal) with ALS symptoms. The profile of cognitive deficit in ALS includes impairment of executive functions, memory, speech and visual-spatial disorders. A literature review on this problem is presented with a description of the clinical observation of ALS–dementia syndrome (frontal variant of possible Alzheimer’s disease). A patient with a reliable diagnosis of ALS showed rapidly progressive cognitive impairments in the form of hippocampal memory impairments, speech, visual-spatial impairments, and defective executive functions, accompanied by behavioral changes (apathy, decreased criticism). Magnetic resonance imaging of the brain revealed significant atrophy of the hippocampus, frontal lobe cortex, and left temporal lobe. In the literature, there are practically no descriptions of patients with a clinical picture of a combination of AD and ALS. Difficulties in diagnosing this condition are discussed. The relationship between these neurodegenerative diseases is discussed. The presented literature data and the presented clinical observation confi rm the expediency of studying cognitive functions in patients with suspected or signifi cant ALS, on the one hand, and analysis of the state of the central and peripheral neurons in patients with neuropsychiatric disorders of the frontotemporal type, on the other hand, which can be useful for diagnostics and treatment and rehabilitation measures.

The diagnostic, therapeutic and assistance pathway for amyotrophic lateral sclerosis in a north-eastern Italian region: satisfaction of patients and their caregivers.

In order to evaluate the users' satisfaction degree for the diagnostic, therapeutic and assistance services for amyotrophic lateral sclerosis (ALS) in the Italian region Friuli-Venezia Giulia (FVG), a self-compiled anonymous multiple-choice questionnaire was administered to ALS patients and their caregivers. The questionnaire explored 41 different issues covering the following areas: (a) access to diagnostic pathway and communication among patients, families and health professionals; (b) quality of disease monitoring and effectiveness of interventions aimed at mitigating ALS symptoms; (c) easiness of access to assistive devices (e.g. wheelchair, ankle-foot-orthosis) and home assistance; (d) patient' choices sharing and health professionals empathy. The same issues were proposed both to patients and carers, appropriately adapting the questions, during the period between June and December 2019. The answers were categorised according to criticality level. Median with interquartile range of the numeric variables and percentages of the categorical variables and of the answers to questions were calculated. The mean percentage of satisfied users was 72.8%, considering all the areas. Pain treatment and easiness of access to ambulance transport were the most positive aspects (95.7% and 92.5% of satisfied respondents, respectively), while information about possible enrolment in clinical trials and about possible registration to the regional ALS association were the most critical issues (30.9% and 43.4% of satisfied users). Although the satisfaction level of ALS patients and their caregivers for the services provided resulted generally good, there were some areas that have to be improved. For this purpose, enhancement of multidisciplinary collaboration, sharing of points of view from users and different practitioners and rising awareness among healthcare professionals through clinical audits could be useful. Further research is needed to identify a wider range of users' unexplored unmet needs.

Retinal Damage in Amyotrophic Lateral Sclerosis: Underlying Mechanisms.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting in a gradual loss of motor neuron function. Although ophthalmic complaints are not presently considered a classic symptom of ALS, retinal changes such as thinning, axonal degeneration and inclusion bodies have been found in many patients. Retinal abnormalities observed in postmortem human tissues and animal models are similar to spinal cord changes in ALS. These findings are not dramatically unexpected because retina shares an ontogenetic relationship with the brain, and many genes are associated both with neurodegeneration and retinal diseases. Experimental studies have demonstrated that ALS affects many “vulnerable points” of the retina. Aggregate deposition, impaired nuclear protein import, endoplasmic reticulum stress, glutamate excitotoxicity, vascular regression, and mitochondrial dysfunction are factors suspected as being the main cause of motor neuron damage in ALS. Herein, we show that all of these pathways can affect retinal cells in the same way as motor neurons. Furthermore, we suppose that understanding the patterns of neuro-ophthalmic interaction in ALS can help in the diagnosis and treatment of this disease.