Somatosensory pathway dysfunction in patients with amyotrophic lateral sclerosis in a completely locked-in state.

OBJECTIVE: To investigate somatosensory pathway function in patients with amyotrophic lateral sclerosis (ALS) dependent on invasive ventilation and in a completely locked-in state (CLIS). METHODS: We examined median nerve somatosensory evoked potentials (SEPs) in 17 ALS patients in a CLIS, including 11 patients with sporadic ALS, one with familial ALS with genes not examined, four with a Cu/Zn superoxide-dismutase-1 (SOD1) gene variant (Val118Leu, Gly93Ser, Cys146Arg), and one with a fused-in-sarcoma gene variant (P525L). We evaluated N9, N13, N20 and P25, and central conduction time (CCT); the data were compared with those of 73 healthy controls. RESULTS: N20 and N13 were abolished in 12 and 10 patients, and their latencies was prolonged in four and three patients, respectively. The CCT was prolonged in five patients with measurable N13 and N20. Two patients with SOD1 gene mutations had absent or slightly visible N9. Compared to the CCT and latencies and amplitudes of N13 and N20 in the controls, those in the patient cohort were significantly abnormal. CONCLUSIONS: The central somatosensory pathway is severely involved in patients with ALS in a CLIS. SIGNIFICANCE: Our findings suggest that median nerve SEP cannot be utilized for communication in patients with ALS in a CLIS.

Clinical relevance of macroglossia to disease progression in ventilation dependent patients with advanced ALS.

BACKGROUND: Macroglossia is one of the clinical signs that emerges in patients with amyotrophic lateral sclerosis (ALS) who are undergoing invasive ventilation. OBJECTIVE: We aimed to investigate the relationship between the progression of macroglossia and the clinical characteristics during the advanced stages of ALS. METHODS: Forty-one patients with ALS using invasive ventilation with tracheostomy were prospectively followed over a 3-year period. We evaluated the prevalence of macroglossia, motor disabilities including oral function, communication ability (communication stage I to V) as a marker of disease progression, and nutritional factors. We analyzed the potential factors affecting the progression of macroglossia using a multivariate logistic analysis. RESULTS: The number of patients with macroglossia was increased during the follow-up (from 24.4 to 53.7%), while the communication stage progressed from 2.6 in average (SD 1.7) to 3.5 (1.4). During the study, body weight increased, while energy intake decreased, suggesting progressive hypometabolism. Eight patients had newly developed macroglossia during the study and showed greater progression of communication impairment than those without macroglossia. Multivariate logistic regression analysis showed that communication impairment was a factor associated with macroglossia. CONCLUSION: Macroglossia in advanced ALS with invasive ventilation is associated with disease progression.

Body Weight Gain Is Associated with the Disease Stage in Advanced Amyotrophic Lateral Sclerosis with Invasive Ventilation.

We investigated the incidence of weight gain and its related factors in patients with amyotrophic lateral sclerosis (ALS) who underwent tracheostomy and invasive ventilation (TIV). Seventy-eight patients with ALS and TIV were enrolled and followed up prospectively. We clarified the clinical profiles of patients with increased weight following TIV and examined chronological variations in their body mass index (BMI), energy intake, and serum albumin levels. Post follow-up, we determined their disease stage according to their communication impairment (stage I to V) and investigated factors associated with BMI increase following TIV. Patients with a post-TIV BMI increase ≥1.86 kg/m2 demonstrated a higher incidence of ophthalmoplegia (76.2%), total quadriplegia (61.9%), severe communication impairment (stage V; 33.3%), and hypoalbuminemia than those with a BMI increase <1.86 kg/m2. Patients with stage V communication impairment exhibited a larger and faster BMI decrease before TIV (mean -4.2 kg/m2 and -2.5 kg/m2/year, respectively); a larger BMI increase (mean +4.6 kg/m2) following TIV, despite lower energy intake; and lower albumin levels post follow-up than those with lower-stage communication impairment. Multilevel linear regression analysis demonstrated an independent association between communication impairment stages (stage V) and a post-TIV BMI increase (p = 0.030). Weight gain and hypoalbuminemia during TIV in patients with ALS were associated with the disease stage and may be attributable to the neurodegenerative processes that are peculiar to ALS.

Body weight variation predicts disease progression after invasive ventilation in amyotrophic lateral sclerosis.

Weight loss is an independent predictor of survival in the early stages of amyotrophic lateral sclerosis (ALS). However, the effects of weight variations on the functional prognosis after tracheostomy and invasive ventilation (TIV) in ALS remain unknown. This prospective cohort study aimed to investigate the relationship between weight loss before TIV and disease progression after TIV in ALS patients. Sixty ALS patients with TIV were enrolled and classified into subgroups based on the rate of decline in body mass index, from onset to TIV utilization (ΔBMI). During follow-up, we assessed the patients for presence of communication impairments, ophthalmoplegia, total quadriplegia, mouth opening disability, and dysuria. We analyzed the relationship between ΔBMI and the communication stage or motor disabilities. The log-rank test showed that patients with a ΔBMI ≥ 1.7 kg/m2/year showed a shorter period of preserved communication ability (p = 0.0001), shorter time to develop ophthalmoplegia (p = 0.0001), total quadriplegia (p < 0.0001), mouth opening disability (p < 0.0001), and dysuria (p = 0.0455). Cox multivariate analyses showed that a larger ΔBMI was an independent prognostic factor for the early development of ophthalmoplegia (p = 0.0400) and total quadriplegia (p = 0.0445). Weight loss in the early stages of ALS predicts disease progression in patients with advanced stages of ALS using TIV.

Prognostic significance of body weight variation after diagnosis in ALS: a single-centre prospective cohort study.

BACKGROUND: Body weight reduction after disease onset is an independent predictor of survival in amyotrophic lateral sclerosis (ALS), but significance of weight variation after diagnosis remains to be established. OBJECTIVE: To investigate weight variation after diagnosis and its prognostic significance in patients with ALS as a prospective cohort study. METHODS: Seventy-nine patients with ALS were enrolled in this study. At the time of diagnosis and about 1 year later, we evaluated the following parameters: age, sex, onset age, onset region, body mass index (BMI) and premorbid BMI, forced vital capacity and the revised ALS functional rating scale. Annual BMI decline rates (∆BMI) from onset to diagnosis and from diagnosis to about 1 year later were calculated. Patients were followed to the endpoints (death or tracheostomy), and the relationships between ∆BMIs and survival were investigated. RESULTS: Patients with post-diagnostic ∆BMI ≥ 2.0 kg/m2/year showed shorter survival length than those with < 2.0 kg/m2/year (log-rank test, p < 0.0001), and multivariate analysis using the Cox model revealed post-diagnostic ∆BMI as an independent prognostic factor. No correlation was identified between pre- and post-diagnostic ∆BMIs. Female patients with post-diagnostic ∆BMI < pre-diagnostic ∆BMI showed longer survival than those with the opposite ∆BMI trend (log-rank test, p = 0.0147). Female patients with post-diagnostic weight increase showed longer survival than those with weight decrease (log-rank test, p = 0.0228). CONCLUSION: Body weight changes after diagnosis strongly predicts survival in ALS, and weight gain after diagnosis may improve survival prognosis, particularly in female ALS patients.

Cough peak flow decline rate predicts survival in patients with amyotrophic lateral sclerosis.

INTRODUCTION: In this study we investigated the prognostic significance of cough peak flow (CPF) decline rate in patients with amyotrophic lateral sclerosis (ALS). METHODS: Thirty-four patients with ALS participated in our investigation. We examined CPF, forced vital capacity (FVC), body mass index, and the revised ALS Functional Rating Scale (ALSFRS-R), and followed patients to death, tracheostomy, or non-invasive ventilator dependency. We analyzed the relationship between the rate of decline of each parameter and survival prognosis. RESULTS: The CPF decline rate significantly correlated with the decline rates of the ALSFRS-R bulbar score (P < 0.0001) and FVC (P < 0.0001). Patients with a CPF decline rate ≥25% had shorter overall survival (P < 0.0001). Cox model multivariate analyses showed that the CPF decline rate was an independent prognostic factor for survival (P = 0.021). DISCUSSION: The CPF decline rate reflects the progression of bulbar and respiratory dysfunction and predicts survival. Muscle Nerve 59:168-173, 2019.

Non-motor manifestations in ALS patients with tracheostomy and invasive ventilation.

INTRODUCTION: This study aimed to investigate non-motor manifestations in amyotrophic lateral sclerosis (ALS) patients with tracheostomy and invasive ventilation (TIV) and their relevance to disease progression. METHODS: Sixty-seven ALS patients with TIV were enrolled, and followed-up prospectively. The patients were classified at the final evaluation into two subgroups according to the duration of TIV use or disease stage measured by communication impairment. We identified non-motor manifestations and investigated their frequencies and differences across the stages. RESULTS: The non-motor manifestations were macroglossia (22.4%), unstable blood pressure (38.8%), hypothermia (26.9%), dysuria (50.7%), and hyperglycemia (12.1%). These manifestations occurred significantly more frequently in patients with TIV ≥5 years than in patients with TIV <5 years, and more in patients with severe communication impairment than in those with preserved communication ability. DISCUSSION: Non-motor manifestations are observed at a high rate in ALS patients with TIV, and are possibly related to disease progression. Muscle Nerve 57: 735-741, 2018.

Analysis of resting salivation rate in patients with amyotrophic lateral sclerosis using tracheostomy invasive ventilation.

Patients with amyotrophic lateral sclerosis (ALS) often suffer from salivation problems such as drooling and dry mouth. We examined resting salivation rate cross-sectionally in 66 advanced ALS patients with tracheostomy invasive ventilation using a cotton roll method, and investigated clinical factors associated with salivation rate. Resting salivation rate in the patients was well preserved (median value 0.6 g/min), and was significantly more increased in patients with impairment of jaw movement (P = 0.007) or mouth opening (P = 0.003) than in patients with less impairment, and in patients with the mouth being constantly open ≥ 10 mm in rostrocaudal length than in patients with < 10 mm. These data indicate that salivation rate was increased with progression of dysfunction of voluntary jaw movement. Appropriate oral care is required in advanced ALS patients to maintain their oral hygiene and to avoid penetration of saliva into the airway.

Macroglossia in advanced amyotrophic lateral sclerosis.

INTRODUCTION: An enlarged tongue (macroglossia) has been reported in advanced-stage patients with amyotrophic lateral sclerosis (ALS). METHODS: In this study we examined the prevalence of macroglossia and analyzed clinical correlations in 65 ALS patients on tracheostomy-invasive ventilation (TIV). RESULTS: Macroglossia was found in 22 patients (33.8%). Compared with those without macroglossia, patients with macroglossia had a younger age of onset, longer duration of disease and TIV use, lower ALS Functional Rating Scale score, higher body mass index, lower energy intake, more severe communication impairment, and lower oral function. Logistic multivariate analysis showed that body mass index (BMI; P = 0.007) and communication impairment (P = 0.029) were significantly correlated with macroglossia. The duration of TIV use was at the cut-off level of significance (P = 0.05). CONCLUSIONS: Macroglossia may be the result of overfeeding and replacement by fat during long-term TIV use in patients with advanced ALS. Muscle Nerve, 2016 Muscle Nerve 54: 386-390, 2016.