Early initiation of riluzole may improve absolute survival in amyotrophic lateral sclerosis.

Introduction/aims: Riluzole improves survival in amyotrophic lateral sclerosis (ALS), but optimal time and duration of treatment are unknown. The aim of this study was to examine if timing of riluzole initiation and duration of treatment modified its effect on survival.

Methods: Patients from the PRO-ACT dataset with information on ALS Functional Rating Scale, time from onset to enrollment (TFOE), and riluzole use were selected for analysis.

Progressive arm muscle weakness in ALS follows the same sequence regardless of onset site: use of TOMS, a novel analytic method to track limb strength.

: Examine sequence of weakness in arm muscles from longitudinal hand-held dynamometry (HHD) data in ALS for congruence with contiguous spread of neurodegeneration along spinal cord segments. : Longitudinal HHD data from the Ceftriaxone clinical trial were examined using nonlinear mixed models, assuming a logistic trajectory from normal to zero strength. Unobserved baseline normal strength of weak muscles was assumed using strength of the best-preserved muscle.

A Cost-Effectiveness Framework for Amyotrophic Lateral Sclerosis, Applied to Riluzole.

Objectives: Reexamine cost-effectiveness of riluzole in the treatment of amyotrophic lateral sclerosis (ALS) in light of recent advances in disease staging and understanding of stage-specific drug effect.

Methods: ALS was staged according to the "fine'til 9" (FT9) staging method. Stage-specific health utilities (EQ-5D, US valuation) were estimated from an institutional cohort, whereas literature informed costs and transition probabilities.

Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality.

Purpose: Type 2 diabetes-related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P).

Methods: A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016.

Stage-specific riluzole effect in amyotrophic lateral sclerosis: a retrospective study.

: To estimate the effect of riluzole on the stage-specific risk of progression of ALS. : Patients from the PRO-ACT dataset were staged employing two methods (King's and FT9). Hazard ratios associated with riluzole treatment were estimated for forward transition between stages, using unadjusted and adjusted Markov multistate models.

Variation in noninvasive ventilation use in amyotrophic lateral sclerosis.

Objective: We sought to examine prevalence and predictors of noninvasive ventilation (NIV) in a composite cohort of patients with amyotrophic lateral sclerosis (ALS) followed in a clinical trials setting (Pooled Resource Open-Access ALS Clinical Trials database).

Methods: NIV initiation and status were ascertained from response to question 12 of the revised ALS Functional Rating Scale (ALSFRS-R). Factors affecting NIV use in patients with forced vital capacity (FVC) ≤50% of predicted were examined.

Deconstructing progression of amyotrophic lateral sclerosis in stages: a Markov modeling approach.

Objectives: Propose an empirical amyotrophic lateral sclerosis (ALS) staging approach called Fine'til 9 (FT9) based on how many of the patient's ALS functional rating scale (ALSFRS-R) subscores are 9 or less (of normal 12). Gain insights into progression of ALS by applying Markov models to ALS stages by multiple systems (King's, Milan-Torino system (MITOS) and FT9).

Methods: Patients from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) dataset were staged using ALSFRS-R responses.

Trajectories of impairment in amyotrophic lateral sclerosis: Insights from the Pooled Resource Open-Access ALS Clinical Trials cohort.

Introduction: Rate of decline of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score is a common outcome measure and a powerful predictor of mortality in ALS.

Methods: Observed rate of decline (postslope) of ALSFRS-R, its linearity, and its relationship to decline at first visit (preslope) were examined in the Pooled Resource Open-Access ALS Clinical Trials cohort by using longitudinal mixed effects models.

Results: Mean ALSFRS-R postslope in 3,367 patients was -0.

Laughter, crying and sadness in ALS.

Background: Pseudobulbar affect (PBA) is prevalent in amyotrophic lateral sclerosis (ALS), but there is limited information on its associations and course.

Objectives: Explore prevalence, associations, course and manifestations of PBA in outpatient cohort of patients with ALS and examine its relationship to depression.

Methods: Self-reported measures of PBA and depression (Center for Neurologic Study-Lability Scale (CNS-LS) and Patient Health Questionnaire (PHQ-9), respectively) were obtained from consecutive patients with ALS using tablet devices in waiting rooms (Knowledge Program).

Depression in ALS in a large self-reporting cohort.

Objective: To report an observational study of depression in a large cohort of patients with amyotrophic lateral sclerosis (ALS), including its prevalence, associations, longitudinal course, and effect on survival.

Methods: The Patient Health Questionnaire-9 (PHQ-9) (a validated depression instrument) and other self-reported measures were obtained from patients with ALS as part of routine clinical care via tablet devices using a software system (Knowledge Program). Cox proportional hazard models, linear models, mixed effects models, and logistic regression were used for statistical analyses.

A model for idiopathic intracranial hypertension and associated pathological ICP wave-forms.

Idiopathic intracranial hypertension (IIH) is a syndrome of unknown cause characterized by elevated intracranial pressure (ICP). While imaging often reveals a stenosis of the transverse sinuses, the role of this feature in IIH has been in dispute. Many patients with chronic daily headache have been found to actually be suffering from a milder form of IIH without papilledema (IIHWOP).

A modeling study of idiopathic intracranial hypertension: etiology and diagnosis.

Objective: To investigate the relationship between idiopathic intracranial hypertension (IIH) and transverse sinus stenosis through experiments performed on a validated mathematical model.

Methods: A mathematical model of intracranial pressure (ICP) dynamics has been extended to accommodate venous sinus compression through the introduction of a Starling-like resistor between the sagittal and transverse sinuses.

Results: In the absence of this type of resistor, the sinuses are rigid, and the model has only a unique, stable steady state with normal pressures.

Idiopathic intracranial hypertension and transverse sinus stenosis: a modelling study.

Idiopathic intracranial hypertension (IIH) is a syndrome of unknown etiology characterized by elevated intracranial pressure (ICP). Although a stenosis of the transverse sinus has been observed in many IIH patients, the role this feature plays in IIH is in dispute. In this paper, a lumped-parameter model is developed for the purpose of analytically investigating the elevated pressures associated with IIH and a collapsible transverse sinus.

Motor neuronopathy with dropped hands and downbeat nystagmus: a distinctive disorder? A case report.

Background: Eye movements are clinically normal in most patients with motor neuron disorders until late in the disease course. Rare patients are reported to show slow vertical saccades, impaired smooth pursuit, and gaze-evoked nystagmus. We report clinical and oculomotor findings in three patients with motor neuronopathy and downbeat nystagmus, a classic sign of vestibulocerebellar disease.