Outcomes after intervention for enteral nutrition in patients with amyotrophic lateral sclerosis in multidisciplinary clinics.

INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) are susceptible to malnutrition, with appropriate management of nutritional interventions an active area of investigation. We sought to determine the impact of gastrostomy tube placement in ALS patients, exploring the correlation between forced vital capacity (FVC), malnutrition, and perioperative complications. METHODS: A retrospective review was performed of clinically diagnosed ALS patients treated at two multidisciplinary clinics (University of Kansas, University of Nebraska) from January 2009 to September 2020 who were referred for gastrostomy. Data collected included demographics, disease characteristics, and key gastrostomy related dates/outcomes. RESULTS: Two hundred thirty-nine patients were included with a median age of 65 years and median of 589 days from symptom onset to gastrostomy (interquartile range, 404-943). The population was predominantly Non-Hispanic White with bulbar-onset ALS. 30-day mortality was 4% and 30-day morbidity was 13%. Weight loss, body mass index, and predicted FVC at placement showed no increased 30-day morbidity or mortality association. Bulbar-onset ALS patients exhibited higher overall mortality postplacement than limb onset (odds ratio: 1.85, 95% confidence interval: 1.03-3.33). There was a 5% incidence of symptoms suggestive of refeeding syndrome. DISCUSSION: Rates of major/minor complications and 30-day mortality related to gastrostomy placement in our population were similar compared with prior studies in ALS. The lack of difference in outcomes based on FVC at procedure may suggest this is not predictive of outcome, or perhaps, high-quality perioperative respiratory management. Alternative reasons may account for the increased morbidity and mortality of gastrostomy placement in the ALS population.

Non-dystrophic myotonia: 2-year clinical and patient reported outcomes.

INTRODUCTION/AIMS: Consistency of differences between non-dystrophic myotonias over time measured by standardized clinical/patient-reported outcomes is lacking. Evaluation of longitudinal data could establish clinically relevant endpoints for future research. METHODS: Data from prospective observational study of 95 definite/clinically suspected non-dystrophic myotonia participants (six sites in the United States, United Kingdom, and Canada) between March 2006 and March 2009 were analyzed. Outcomes included: standardized symptom interview/exam, Short Form-36, Individualized Neuromuscular Quality of Life (INQoL), electrophysiological short/prolonged exercise tests, manual muscle testing, quantitative grip strength, modified get-up-and-go test. Patterns were assigned as described by Fournier et al. Comparisons were restricted to confirmed sodium channelopathies (SCN4A, baseline, year 1, year 2: n = 34, 19, 13), chloride channelopathies (CLCN1, n = 32, 26, 18), and myotonic dystrophy type 2 (DM2, n = 9, 6, 2). RESULTS: Muscle stiffness was the most frequent symptom over time (54.7%-64.7%). Eyelid myotonia and paradoxical handgrip/eyelid myotonia were more frequent in SCN4A. Grip strength and combined manual muscle testing remained stable. Modified get-up-and-go showed less warm up in SCN4A but remained stable. Median post short exercise decrement was stable, except for SCN4A (baseline to year 2 decrement difference 16.6% [Q1, Q3: 9.5, 39.2]). Fournier patterns type 2 (CLCN1) and 1 (SCN4A) were most specific; 40.4% of participants had a change in pattern over time. INQoL showed higher impact for SCN4A and DM2 with scores stable over time. DISCUSSION: Symptom frequency and clinical outcome assessments were stable with defined variability in myotonia measures supporting trial designs like cross over or combined n-of-1 as important for rare disorders.

Open-label pilot study of ranolazine for cramps in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Neuronal hyperexcitability (manifested by cramps) plays a pathological role in amyotrophic lateral sclerosis (ALS), and drugs affecting it may help symptomatic management and slow disease progression. We aimed to determine safety and tolerability of two doses of ranolazine in patients with ALS and evaluate for preliminary evidence of drug-target engagement by assessing muscle cramp characteristics. METHODS: We performed an open-label dose-ascending study of ranolazine in 14 individuals with ALS in two sequential cohorts: 500 mg (cohort 1) and 1000 mg (cohort 2) orally twice daily. Each had a 2-week run-in period, 4-week drug administration, and 6-week safety follow-up. Primary outcome was safety and tolerability. Exploratory measures included cramp frequency and severity, fasciculation frequency, cramp potential duration, ALS Functional Rating Scale---Revised score, and forced vital capacity. RESULTS: Six and eight participants were enrolled in cohorts 1 and 2, respectively. There were no serious adverse events. Two subjects in cohort 2 discontinued the drug due to constipation. The most frequent drug-related adverse event was gastrointestinal (40%). Cramp frequency decreased by 54.8% (95% confidence interval [CI], 39%-70.8%) and severity decreased by 46.3% (95% CI, 29.5-63.3%), which appeared to be dose-dependent, with decreased awakening due to cramps. Other outcomes showed no change. DISCUSSION: Ranolazine was well tolerated in ALS up to 2000 mg/day, with gastrointestinal side effects being the most frequent. Ranolazine reduced cramp frequency and severity, supporting its investigation for muscle cramps in a future placebo-controlled trial.

Scoring System to Predict Hospital Outcome After Subarachnoid Hemorrhage-Incorporating Systemic Response: The CRIG Score.

OBJECTIVES: Local and systemic proinflammatory and prothrombotic processes after aneurysmal subarachnoid hemorrhage (aSAH) precipitate delayed cerebral ischemia (DCI) and determine clinical outcome. Recent studies using admission and temporal trends of mean platelet volume to platelet count ratio (MPV:PLT) and neutrophil to lymphocyte ratio (NLR) have identified patients developing DCI. We examine if MPV:PLT and NLR along with admission clinical or radiological features can be used to develop a scoring system to predict DCI and in-hospital clinical outcome. MATERIALS AND METHODS: A 7-year retrospective cohort of aSAH patients admitted to a tertiary care medical center was used to study and identify clinical, radiological and laboratory parameters to predict DCI and clinical outcome (good: discharge to home or rehabilitation facility; poor: all other discharge destinations). Using regression analyses a scoring system (Clinical, Radiological, Inflammatory, dysGlycemia, CRIG) was developed. RESULTS: Of 271 patients, admission clinical grade (World Federation of Neurological Surgeons' scale), radiological grade (modified Fisher score), NLR and glycated hemoglobin were identified as contributors for CRIG score. CRIGDCI score threshold of 112 and CRIGdischarge 109, respectively predicted DCI and adverse clinical outcome in score development cohort. The same threshold predicted DCI and adverse clinical outcome with 78.1 and 100% sensitivity, 44.0 and 52.2% specificity, and 63.2 and 61.4% accuracy, respectively in the score validation cohort. CONCLUSIONS: CRIG is an easily calculable scoring system that incorporates systemic response of aSAH - thus, alluding to its multisystem nature. It can be used at the time of admission to predict DCI and clinical outcome.

Management of Aneurysmal Subarachnoid Hemorrhage: Variation in Clinical Practice and Unmet Need for Follow-up among Survivors-A Single-Center Perspective.

OBJECTIVE: The purpose of the present study is to investigate the existence and/or prevalence of clinical practice variation in management of aneurysmal subarachnoid hemorrhage (aSAH) and to determine the need for long-term follow-up. METHODS: A single-center study was carried out of patients with aSAH over a 5-year period divided into 2 halves (2.5 years each) before and after addition of a dually trained cerebrovascular neurosurgeon. In-hospital clinical practice, clinical outcome (mortality and discharge destination) and long-term outcome (modified Rankin Scale score and Telephone Interview for Cognitive Status [TICS]) were compared using descriptive summaries and nonparametric tests. RESULTS: Among 251 patients admitted with aSAH, 115 (45.8%) were before the index event, whereas 136 (54.2%) were during the later period. The aneurysm-securing procedure changed from coil embolization to clip ligation (12/115 [10.4%] vs. 84/136 [61.8%]; P < 0.0001) during the latter years. Interventional treatment for cerebral vasospasm has decreased (58/115 [50.4%] vs. 49/136 [36.0%]; P = 0.0002). Patients surviving hospitalization had more clinic follow-up after discharge during the latter period (42/85 [49.4%] vs. 76/105 [72.4%]; P = 0.0012) and ventriculoperitoneal shunt placement for delayed hydrocephalus (1/85 [1.2%] vs. 9/105 [8.6%]; P = 0.02). A subcohort of aSAH survivors (n = 46) had lower median TICS score during the earlier study period (31.5 [interquartile range, 22-36] vs. 33 [interquartile range, 27-38]; P = 0.038). Similarly, preictal smoking status and hyperlipidemia were associated with adverse TICS score in a multivariate model (P = 0.007). CONCLUSIONS: Postdischarge clinical follow-up has improved facilitating recognition and treatment of delayed hydrocephalus. Existence of cognitive deficits among survivors calls for establishment of multidisciplinary clinics for long-term management of aSAH.