Amyotrophic Lateral Sclerosis In Japan Research Articles

Multidisciplinary clinic contributes to the decreasing trend in the number of emergency hospitalizations for amyotrophic lateral sclerosis in Japan

BackgroundMultidisciplinary care is recommended for amyotrophic lateral sclerosis (ALS). We opened the first multidisciplinary care “ALS clinic” in Japan in February 2017. This study aimed to clarify the impact of multidisciplinary care on the number and incidence rate of emergency hospitalizations, as well as the survival rate of patients with ALS. MethodsWe studied the medical charts of patients with ALS who visited our hospital between March 1, 2014, and February 29, 2020, in a retrospective study. All patients were divided into two groups: a General Neurology Clinic group (GNC) and an ALS Clinic group (AC), based on the duration of the first visit to our hospital. ResultsThe survey participants included 90 patients with ALS (32 in the GNC vs 58 in the AC). The mean follow-up duration was 276 ± 257 days in the GNC and 307 ± 267 days in the AC. The number of emergency hospitalizations was 11 in the GNC and nine in the AC. The number of patients with two or more emergency hospitalizations was decreased in the AC (3 in the GNC vs 0 in the AC), which was statistically significantly different (p = 0.04). The survival rate was significantly different between the two groups (p = 0.01). ConclusionsOur results suggest that intervention through ALS multidisciplinary care in the hospital setting effectively controls emergency hospitalizations and improves the survival rate in patients with ALS. Multidisciplinary care is recommended since various medical treatments are required as the condition progresses.

Edaravone, a scavenger for multiple reactive oxygen species, reacts with singlet oxygen to yield 2-oxo-3-(phenylhydrazono)-butanoic acid.

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a synthetic antioxidant used as a drug to treat acute ischemic stroke in Japan and amyotrophic lateral sclerosis in Japan and the USA. Its pharmacological mechanism is thought to be scavenging of reactive oxygen species, which are intimately related with these diseases. Recently, the singlet oxygen (‍1O2) has attracted attention among reactive oxygen species. In this study, we investigated the reactivity of edaravone toward 1O2 and identified its reaction products. Edaravone showed a reactivity toward 1O2 greater than those of uric acid, histidine, and tryptophan, which are believed to be ‍1O2 scavengers in vivo. And we confirmed that 2-oxo-3-(phenylhydrazono)-butanoic acid was formed as an oxidation product. We propose a plausible mechanism for 2-oxo-3-(phenylhydrazono)-butanoic acid production by ‍1O2-induced edaravone oxidation. Since 2-oxo-3-(phenylhydrazono)-butanoic acid has already been identified as a radical-initiated oxidation product, free radical-induced oxidation should be seriously reconsidered. We also found that edaravone can react with not only hypochlorous anions but also ‍1O2 that are formed from myeloperoxidase. This result suggests that edaravone treatment can be beneficial against myeloperoxidase-related injuries such as inflammation.

The ‘way of flowers’ and the care of patients with amyotrophic lateral sclerosis in Japan

Tracheostomy with invasive ventilation (TIV) may be required for the survival of patients at advanced stages of amyotrophic lateral sclerosis (ALS). In Japan it has been shown that a proactive approach toward TIV may prolong the survival of ALS patients by over 10 years by preventing the lethal respiratory failure that generally occurs within 3-5 years of the onset of the disease. Measures to prolong life expectancy without foregoing quality of life have produced better results in Japan than in other developed countries. This ‘Japanese bias’ has been attributed to socio-cultural and religious factors as well as to the availability of material resources in Japan. In this article, we use the concepts of onozukara in kadō (Japanese traditional flower art, also called ikebana) and amae (passive love) to illuminate features of patient care that may contribute to this ‘Japanese bias’.

Current Therapies for Amyotrophic Lateral Sclerosis in Japan

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive muscle wasting and weakness. Riluzole was the sole drug available for treating ALS until 2015, when edaravone was approved as a new anti-ALS drug. Recent discoveries of the disease-causal genes and proteins, as well as the rapid advancement of induced pluripotent stem (iPS) cell manipulations, drug deliveries, and molecular modifications have provided diverse and promising drug candidates. In particular, antisense-oligonucleotide therapy appears to significantly prevent disease progression when introduced early. Moreover, the in vitro modeling of ALS using patients' own iPS cells enables effective screening of approved drugs. Drug repositioning is a robust short-cut to bedside use in patients with ALS, due to the availability of data for safety concerns. Currently, five investigator-initiated drug trials are underway in Japan. These include trials of hepatocyte growth factor, perampanel, ultra-high-dose methylcobalamin, ropinirole, and bosutinib. This is a review of new ALS drugs that are either currently available or in on-going trials. We additionally review the pathogenic pathways that these drugs target.

4-Cl-edaravone and (E)-2-chloro-3-[(E)-phenyldiazenyl]-2-butenoic acid are the specific reaction products of edaravone with hypochlorite.

3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is a synthetic one-electron antioxidant used as a drug for treatment against acute phase cerebral infarction in Japan. This drug also reacts with two-electron oxidants like peroxynitrite to give predominantly 4-nitrosoedaravone but no one-electron oxidation products. It is believed that this plays a significant role in amelioration of amyotrophic lateral sclerosis. The drug was approved for treatment of amyotrophic lateral sclerosis in Japan and USA in 2015 and 2017, respectively. In this study, we examined the reaction of edaravone with another two-electron oxidant, hypochlorite anion (ClO−). Edaravone reacted with ClO− in 50% methanolic phosphate buffer (pH 7.4) solution containing typical two-electron reductants, such as glutathione, cysteine, methionine, and uric acid, as internal references. The concentration of edaravone decreased at a similar rate as each co-existing reference, indicating that it showed comparable reactivity toward ClO− as those references. Furthermore, 4-Cl-edaravone and (E)-2-chloro-3-[(E)-phenyldiazenyl]-2-butenoic acid (CPB) were identified as primary and end products, respectively, and no one-electron oxidation products were detected. These results suggest that edaravone treatment can bring greater benefit against ClO−-related injury such as inflammation, and 4-Cl-edaravone and CPB can be good biomarkers for ClO−-induced oxidative stress.

Bioavailability of Edaravone Sublingual Tablet Versus Intravenous Infusion in Healthy Male Volunteers

PurposeEdaravone is a free-radical scavenger. Edaravone 30 mg IV has been approved for use in the treatment of acute ischemic stroke in Japan and China, and for amyotrophic lateral sclerosis in Japan and the United States. Considering the inconvenience of IV infusion in clinical practice, an oral tablet formulation of edaravone was developed but failed in 2011 due to poor bioavailability. More recently, a sublingual (SL) tablet formulation of edaravone 30 mg was developed by a Good Manufacturing Practices–compliant manufacturer in China. This study explored the bioavailability of the SL tablet of edaravone and aimed to provide evidence to support decision making in future clinical development. MethodsThis 2-way crossover study was conducted in 10 healthy male volunteers. Eligible subjects were randomized, in a 1:1 ratio, to 1 of 2 dosing sequences: (1) SL edaravone 30 mg, followed by edaravone 30 mg IV infusion given over 30 minutes; or (2) edaravone 30 mg IV infusion given over 30 minutes, followed by SL edaravone 30 mg. The washout period between the 2 dosing periods was at least 24 hours. Serial blood samples were collected in each dosing period. The bioavailability of the SL tablet was assessed using bioavailability analysis. Tolerability was evaluated throughout the study. FindingsThe plasma concentration–time profile of the SL tablet was similar to that with the IV infusion. A mean (SD) Cmax of 2030.2 (517.2) ng/mL was reached within a median Tmax of 0.875 hour, which was statistically significantly longer than the median Tmax with IV administration (0.5 hour). The Cmax with SL administration corresponded to 83.92% (90% CI, 73.22%–96.18%) of the Cmax with the start of IV infusion (2354.0 [336.6] ng/mL). The mean AUC0–t with SL dosing was 5420.07 (1429.75) h · ng/mL, which corresponded to 91.94% (90% CI, 86.81%–97.39%) of the AUC0–t with IV administration (5824.42 [1338.48] h · ng/mL). Two cases of adverse events were reported during the study; both were considered by the investigator to have been possibly not related to the study treatment. ImplicationsThe bioavailability of the SL tablet of edaravone was 91.94%. Compared with IV administration, Cmax with SL administration was ∼17% lower and Tmax was statistically significantly longer. The exposure differences can be addressed by modifying the strength of the SL tablet, and then conducting a second study to demonstrate the pharmacokinetic bioavailability of the sublingually administered new strength versus IV infusion of edaravone.

Noncoding repeat expansions for ALS in Japan are associated with the ATXN8OS gene

ObjectiveTo assess the contribution of noncoding repeat expansions in Japanese patients with amyotrophic lateral sclerosis (ALS).MethodsSporadic ALS in Western countries is frequently associated with noncoding repeat expansions in the C9ORF72 gene. Spinocerebellar ataxia type 8 (SCA8) is another noncoding repeat disease caused by expanded CTA/CTG repeats in the ATXN8OS gene. Although the involvement of upper and lower motor neurons in SCA8 has been reported, a positive association between SCA8 and ALS remains unestablished. Spinocerebellar ataxia type 36 is a recently identified disease caused by noncoding repeat expansions in the NOP56 gene and is characterized by motor neuron involvement. We collected blood samples from 102 Japanese patients with sporadic ALS and analyzed the ATXN8OS gene by the PCR–Sanger sequencing method and the C9ORF72 and NOP56 genes by repeat-primed PCR assay.ResultsThree patients with ALS (3%) had mutations in the ATXN8OS gene, whereas no patient had a mutation in the C9ORF72 or NOP56 gene. The mutation-positive patients were clinically characterized by neck weakness or bulbar-predominant symptoms. None of our patients had apparent cerebellar atrophy on MRI, but 2 had nonsymptomatic abnormalities in the white matter or putamen.ConclusionsOur finding reveals the importance of noncoding repeat expansions in Japanese patients with ALS and extends the clinical phenotype of SCA8. Three percent seems small but is still relatively large for Japan, considering that the most commonly mutated genes, including the SOD1 and SQSTM1 genes, only account for 2%–3% of sporadic patients each.

Edaravone: a new hope for deadly amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a fatal motor neuron degenerative disorder leading to paralysis and eventual death. At present, we do not have any specific cure for this deadly disorder. Current drug therapy can only reduce morbidity in ALS patients. In 1995, riluzole was the first drug approved by the U.S. Food and Drug Administration (FDA) for ALS. After a long gap of 22 years, Mitsubishi Tanabe Pharma America got U.S. FDA approval for edaravone (Radicava) in May 2017 for the management of ALS. Edaravone, a novel neuroprotective agent, is indicated to slow down progression of ALS. In 2015, Mitsubishi Tanabe Pharma launched edaravone (Radicut) for the treatment of stroke and ALS in Japan. The U.S. FDA approved edaravone following clinical evidence from three clinical trials conducted in 368 ALS patients in Japan. Edaravone is awaiting approval by the European Medicines Agency (EMA) in Europe. Edaravone (60 mg) is administered by very slow intravenous infusion (60 minutes) in 28-day cycles. It has been shown to slow down the loss of physical function in ALS patients by 33% as compared to placebo. Edaravone is a strong antioxidant that prevents oxidative stress from inducing motor neuron death in ALS patients. Being a potent free radical scavenger, it has been shown to inhibit nitration of tyrosine residues in the cerebrospinal fluid and improve motor functions in mouse models of ALS. The product has been patented and the FDA has not approved any generic version of edaravone. This article discusses the preclinical pharmacology, pharmacokinetics, safety profile, clinical studies and drug interactions of edaravone (Radicava) in ALS.

Novel mutation in the SOD1 gene in a patient with early‐onset, rapidly progressive amyotrophic lateral sclerosis

AbstractGenetic mutations have been found in many familial cases of amyotrophic lateral sclerosis (ALS), and 11% of sporadic cases. The most common causative gene in Japan is the SOD1 gene, encoding Cu, Zn superoxide dismutase, a radical scavenger. We report a 25‐year‐old man who had rapidly progressive sporadic ALS with a novel mutation, Gly147Ala, in this gene. Several missense mutations at this residue have been reported in patients with sporadic and familial ALS, among whom the onset age of the present patient was youngest. He had severe weakness of four limbs, with severe respiratory and bulbar involvements within 8 months. Recently, the radical scavenger, edaravone, has been approved as a medicine to treat ALS in Japan. Accumulation of patients like the present patient might be important for immediate diagnosis and treatment of patients who have sporadic ALS with mutations in causative genes.

A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.

Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione.

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has garnered attention since its approval for amyotrophic lateral sclerosis in Japan (2015) and the United States (2017). Edaravone is administered intravenously, and as such, is distributed in the form of an aqueous solution. However, aqueous solutions of edaravone are very unstable because they present as edaravone anions, which become edaravone radicals when the anion donates an electron to free radicals including oxygen. In this study, glutathione (GSH) stabilized an aqueous edaravone solution during storage at 60°C for 4 weeks, and prevented the formation of potentially carcinogenic phenylhydrazine, while cysteine did not. One possible explanation is that GSH undergoes intermolecular hydrogen bonding with edaravone anions, while cysteine does not, as it favors intramolecular hydrogen boding. The combination of GSH and sodium bisulfite (NaHSO3) stabilized aqueous edaravone at room temperature for more than 1 year even under aerobic conditions. However, the U.S. Food and Drug Administration cautioned that NaHSO3 may cause allergic reactions. Therefore, we developed a stable edaravone aqueous solution without using NaHSO3, namely a combination of GSH with deoxygenation, which resulted in better stabilization of aqueous edaravone than the combination of GSH and NaHSO3.

Prevalence and Incidence of Amyotrophic Lateral Sclerosis in Japan

BackgroundPrevious studies have reported a high incidence of amyotrophic lateral sclerosis (ALS) in endemic foci in the Kii Peninsula, Japan. However, little is known about the ALS frequency in the whole country. Furthermore, the presence of ethnic variation in the incidence of ALS remains unknown.MethodsWe conducted a nationwide survey of ALS frequency in 2013 to estimate its annual prevalence and incidence. ALS was diagnosed based on the El Escorial Criteria. The study period was the 2009 fiscal year, from April 2009 to March 2010. To compare the incidence of ALS among prefectures, standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated under the assumption of Poisson distribution.ResultsThe annual crude prevalence and incidence rates per 100 000 people per year were 9.9 (95% CI 9.7–10.1) and 2.2 (95% CI 2.1–2.3), respectively. The age group with the highest prevalence as well as incidence was 70–79 years, and the male-female ratio was approximately 1.5. The annual incidence rate adjusted for age and sex using the 2000 U.S. standard population was 2.3 (95% CI 2.2–2.4) per 100 000 people. Some prefectures had significantly high SIRs: Okinawa, Nara and Wakayama in the Kii Peninsula, and Niigata for males; Kumamoto for females.ConclusionsThis is the first report on the annual prevalence and incidence of ALS in the representative population of Japan. We identified some prefectures with a high incidence of ALS. However, the incidence of ALS in the Japanese population was much lower than in the Caucasian populations of Europe and North America.

Satoshi Kuwabara: work hard, rock hard

Satoshi Kuwabara: work hard, rock hard

Late-onset Patients with Sporadic Amyotrophic Lateral Sclerosis in Japan have a Higher Progression Rate of ALSFRS-R at the Time of Diagnosis

The population in Japan is aging at a faster rate than in other countries in the world. It is speculated that the number of patients with late-onset amyotrophic lateral sclerosis (ALS) will increase even more in the future. However, few studies have been undertaken on the characteristics of patients with late-onset ALS in Japan. This study sought to investigate the clinical features of patients with late-onset ALS compared with those with early-onset ALS using the progression rate (ΔFS). Forty-five patients with sporadic ALS were divided into 2 groups: 23 patients with early-onset of ALS (<65 years; early onset) and 22 patients with late-onset ALS (≥65 years; late onset). Every patient was followed up from the time of initial diagnosis to the primary endpoint (death or time culminating in death without tracheostomy or ventilation assistance including noninvasive positive pressure ventilation) or for at least 48 months after initial diagnosis. ΔFS in the patient group with late onset was significantly higher than that of the group with early onset (p=0.010). Survival of patients with late onset was significantly decreased compared to that of patients with early onset (p=0.031). Our finding suggested that patients with late-onset ALS showed more rapid disease progression than those with early-onset ALS using ΔFS.

Temporal trends and geographic clusters of mortality from amyotrophic lateral sclerosis in Japan, 1995–2004

The present study examined temporal trends and geographic clustering of amyotrophic lateral sclerosis (ALS) mortality in Japan, during 1995–2004, using vital statistics based on death certificates. ALS was usually diagnosed by neurologists according to clinical guidelines that complied with the El Escorial Criteria. The underlying cause of death for ALS was coded as G12.2A. Regression analysis was used to examine temporal trends. Spatial scan statistic was used to detect any area of elevated risk as a cluster. A total of 12,173 (6864 male and 5309 female) ALS deaths were reported. Annual crude mortality rate per 100,000 population was 1.07 (1.26 for males and 0.89 for females) in 2004. Although the overall temporal trend was stable, the trend increased in the 70+ years age group ( p for trend, < 0.001 in males and < 0.05 in females), while it declined in the under 70 years age group ( p for trend, < 0.01 for both sexes). Male preponderance and M/F ratio remained nearly constant over time. Three clusters were detected: two ( p < 0.005 in males and p < 0.05 in females) in northeast and one ( p < 0.05 in males) in west-central Japan. Further research is needed to clarify contributing factors for the observed trends and clusters in ALS mortality.

TDP-43 M337V Mutation in Familial Amyotrophic Lateral Sclerosis in Japan

The clinical features of a Japanese family with autosomal dominant adult-onset amyotrophic lateral sclerosis (ALS) are reported. Weakness initially affected the bulbar musculature, with later involvement of the extremities. Genetic studies failed to detect any mutations of the Cu/Zn superoxide dismutase-1 (SOD1) and Dynactin1 (DCTN1) genes, but revealed a single base pair change from wild-type adenine to guanine at position 1009 in TAR-DNA-binding protein (TDP-43), resulting in a methionine-to-valine substitution at position 337. The immunohistochemical study on autopsied brain of the proband's aunt showed TDP-43-positive cytoplasmic inclusions in the anterior horn cells of the spinal cord and in the hypoglossal nucleus, as well as glial cytoplasmic inclusions in the precentral gyrus, suggesting that a neuroglial proteinopathy was related to TDP-43. In conclusion, a characteristic clinical phenotype of familial ALS with initial bulbar symptoms occurred in this family with TDP-43 M337V substitution, the pathomechanism of which should be elucidated.

Fruit and Vegetable Intake and Risk of Amyotrophic Lateral Sclerosis in Japan

Background: There has been little interest in the role of nutrition in the prevention of amyotrophic lateral sclerosis (ALS). We investigated the relationship between dietary intake of vegetables, fruit, and antioxidants and the risk of ALS in Japan. Methods: Between 2000 and 2004, we recruited 153 ALS patients aged 18–81 years with disease duration of 3 years within the study period in accordance with El Escorial World Federation of Neurology criteria. Three hundred and six gender- and age-matched controls were randomly selected from the general population. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Results: A higher consumption of all fruits and vegetables and fruit alone in the highest quartiles was associated with a statistically significantly reduced risk of ALS. Although not statistically significant, a beneficial association between intake of all vegetables, green and yellow vegetables and other vegetables and ALS was found. No statistically significant dose-response relationship was observed between intake of β-carotene, vitamin C and vitamin E and the risk of ALS. Conclusion: Our findings suggest that higher intake of food rich in antioxidants such as fruit and vegetables confer protection against the development of ALS.

Illness experiences of invasive mechanical ventilator-dependent amyotrophic lateral sclerosis patients in Japan : A study of trajectories and correlates of psychological well-being

This descriptive retrospective study examines and describes the course of the illness experience over time of invasive mechanical ventilator (IMV)-dependent patients with amyotrophic lateral sclerosis in Japan, with attention to the factors related to psychological well being (PWB). Data from 50 subjects was gathered through written surveys and semi-structured interviews.Three distinct PWB trajectory patterns were observed over time periods beginning onset : “fall-rise,” “fall-rise-fall,” and “fall-remain low.” We found that factors predictive of PWB improvement or deterioration could be grouped into two broad categories : “factors related to illness, survival, and coping,” and “lifestyle-related factors.” The first category included “physical symptoms and disabilities,” “treatment,” “acceptance of the disease,” and second included “daily lifestyle,” “plans for the future,” “personal relationships,” “reasons for living.” The most fundamental reasons for deterioration in PWB were “mental and physical suffering caused by decline of physical function” and “internal conflict about IMV use.” The relief of physical pain related to IMV was the most important factor predictive of an initial improvement in PWB, while the two factors most predictive of ongoing improvements in PWB were “sources of joy” and “family support.” We hope an improved understanding of these factors may aid in informing caregivers and healthcare systems.

Nutritional status and risk of amyotrophic lateral sclerosis in Japan

Only a few human studies have reported the relationship between dietary factors and the risk of amyotrophic lateral sclerosis (ALS). We therefore analyzed the relationship between macronutrients (carbohydrate, protein and fat) and the risk of ALS using a case-control study in Japan. The study comprised 153 ALS patients diagnosed by the El Escorial World Federation of Neurology criteria, and 306 gender- and age- matched controls randomly selected from the general population. A self-administered food frequency questionnaire was used to estimate pre-illness intakes of food groups and nutrients. The strength of association between ALS and a potential risk factor was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). A high intake of carbohydrate was significantly associated with an increased risk of ALS (adjusted OR = 2.14, 95% CI 1.05-4.36; the highest versus the lowest tertile). ORs for the second and third tertile of total fat were 0.57 and 0.41 (95% CI 0.21-0.80), respectively. ORs for the highest tertile of intake versus the lowest were 0.41 (95% CI 0.21-0.80) for total fat, 0.30 (95% CI 0.16-0.5) for saturated fatty acids (SFAs), 0.35 (95% CI 0.18-0.69) for monounsaturated fatty acids (MUFAs) and 0.58 (95%CI 0.40-0.96) for polyunsaturated fatty acids (PUFAs). Our findings suggest that high intakes of carbohydrate and low intakes of fat and some kinds of fatty acids may, when combined, increased the risk of ALS.

Ventilator dependence and expressions of need: A study of patients with amyotrophic lateral sclerosis in Japan

This research examined the experience of Amyotrophic Lateral Sclerosis (ALS) patients who depend on an invasive mechanical ventilator in Japan. We investigated their difficulties in expressing their needs, their desires and wishes, and their sources of support and happiness. We examined the relationship between these factors and patient demographics, and hope as an indicator of successful adaptation to the illness experience (assessed by the Herth Hope Index). Interview results guided the formation of an anonymous questionnaire distributed to patients by mail. We interviewed 27 patients and their families and surveyed 157 respondents with a questionnaire. Most patients experienced multiple categories of difficulties, which correlated with reduced hope. More severe physical symptoms correlated with more emotional and social difficulties. Notable findings included a high prevalence of unalleviated pain, fear or experience of ventilator difficulties, and fear of burdening others. Having more sources of psychosocial support and happiness was associated with greater hope. Living at home was associated with fewer social difficulties. No patients claimed additional sources of support without claiming family or professional caregiver support, suggesting their mediation may be crucial in maintaining other social connections. Users of computer communication reported more sources of support and happiness and less frustration from difficulty expressing themselves. The most common reported desires, following a cure for ALS, related to the happiness of the patients’ families, and a desire not to burden them. We also found that invasive mechanical ventilation (IMV) had been initiated emergently in 30.1% of patients without patient or family consent. Our results provide an insight into the world of this challenged population, elucidating the difficulties they face, and clarifying the role of support and other factors in maintaining hope. We identify concrete areas to which increased attention should be directed in patient care.