Primary lateral sclerosis (PLS) functional rating scale: PLS-specific clinimetric scale.

INTRODUCTION: Our research aim was to develop a novel clinimetric scale sensitive enough to detect disease progression in primary lateral sclerosis (PLS). METHODS: A prototype of the PLS Functional Rating Scale (PLSFRS) was generated. Seventy-seven participants with PLS were enrolled and evaluated at 21 sites that comprised the PLSFRS study group. Participants were assessed using the PLSFRS, Neuro-Quality of Life (QoL), Schwab-England Activities of Daily Living (ADL), and the Clinical Global Impression of Change scales. Participants completed telephone assessments at 12, 24, and 48 weeks after enrollment. RESULTS: The PLSFRS demonstrated internal consistency as well as intrarater, interrater, telephone test-retest reliability, and construct validity. Significant changes in disease progression were detected at 6 and 12 months; changes measured by the PLSFRS vs the ALSFRS-R were significantly higher. DISCUSSION: The PLSFRS is a valid tool to assess the natural history of PLS in a shorter study period.

Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis.

IMPORTANCE: There is growing interest in the role of nutrition in the pathogenesis and progression of amyotrophic lateral sclerosis (ALS). OBJECTIVE: To evaluate the associations between nutrients, individually and in groups, and ALS function and respiratory function at diagnosis. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional baseline analysis of the Amyotrophic Lateral Sclerosis Multicenter Cohort Study of Oxidative Stress study was conducted from March 14, 2008, to February 27, 2013, at 16 ALS clinics throughout the United States among 302 patients with ALS symptom duration of 18 months or less. EXPOSURES: Nutrient intake, measured using a modified Block Food Frequency Questionnaire (FFQ). MAIN OUTCOMES AND MEASURES: Amyotrophic lateral sclerosis function, measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), and respiratory function, measured using percentage of predicted forced vital capacity (FVC). RESULTS: Baseline data were available on 302 patients with ALS (median age, 63.2 years [interquartile range, 55.5-68.0 years]; 178 men and 124 women). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALSFRS-R scores or percentage FVC. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores (ß [SE], 2.7 [0.69] and 2.9 [0.9], respectively) and percentage FVC (ß [SE], 12.1 [2.8] and 11.5 [3.4], respectively) (all P < .001). Positive and significant associations with ALSFRS-R scores (ß [SE], 1.5 [0.61]; P = .02) and percentage FVC (ß [SE], 5.2 [2.2]; P = .02) for selected vitamins were found in exploratory analyses. CONCLUSIONS AND RELEVANCE: Antioxidants, carotenes, fruits, and vegetables were associated with higher ALS function at baseline by regression of nutrient indices and weighted quantile sum regression analysis. We also demonstrated the usefulness of the weighted quantile sum regression method in the evaluation of diet. Those responsible for nutritional care of the patient with ALS should consider promoting fruit and vegetable intake since they are high in antioxidants and carotenes.

Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort.

OBJECTIVES: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). METHODS: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. RESULTS: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. CONCLUSIONS: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline.

Autonomic evaluation is independent of somatic evaluation for small fiber neuropathy.

BACKGROUND: The relationship between the autonomic reflex screening test (ARS) and measures of sensory function and structure (quantitative sensory testing (QST) and intraepidermal nerve fiber density (IENFD)) remains uncertain in patients with distal small fiber neuropathy (SFN). The aim of this study was to evaluate the correlations among a range of autonomic (quantitative sudomotor axon reflex test (QSART), cardiovagal and cardio adrenergic tests and the composite autonomic severity score (CASS)) and somatic sensory measures (QST of vibration, cooling and heat-pain thresholds and IENFD). METHOD: 122 patients with clinically suspected sensory neuropathy without motor weakness and with normal nerve conduction studies underwent blinded autonomic reflex screening test (ARS), quantitative sensory testing (QST) and skin biopsy (IENFD) for diagnosis of SFN. The relationship between autonomic and somatic sensory measures was assessed. RESULTS: There was no association between autonomic function measures (QSART volume, CASS_QSART, CASS_vagal, CASS_adrenergic or total CASS) and small fiber sensory measures (IENFD, cooling or heat-pain thresholds). Weak correlations were noted among some modalities of QST (vibration and cooling thresholds) and IENFD. DISCUSSION: Autonomic and sensory outcomes are independent (complementary) measures of distal SFN, and should where feasible be used concurrently in the evaluation of SFN.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Contribution of QSART to the diagnosis of small fiber neuropathy.

INTRODUCTION: We evaluated incorporation of the quantitative sudomotor axon reflex test (QSART) into the diagnostic criteria for small fiber neuropathy (SFN) as an addition to quantitative sensory testing (QST) and intraepidermal nerve fiber density (IENFD) testing. METHODS: One hundred one patients with clinically suspected SFN underwent QSART, QST, and skin biopsy. The diagnostic yield of existing SFN criteria in these patients was compared with criteria incorporating QSART. The new combined diagnostic criteria were evaluated. RESULTS: SFN was diagnosed in 38 of the 101 patients (38%) using current criteria. Addition of QSART existing SFN criteria resulted in an increased diagnostic yield to 67 patients (66%). Applying new SFN criteria requiring abnormality in at least 2 assessments among QSART, QST, and IENFD resulted in a diagnosis of SFN in 57 patients (56%). CONCLUSION: Assessment of both somatic and peripheral autonomic small nerve fibers enhances diagnostic criteria for SFN.

Familial ALS with extreme phenotypic variability due to the I113T SOD1 mutation.

We describe a large family with amyotrophic lateral sclerosis (ALS) caused by an I113T mutation in superoxide dismuatse type 1 (SOD1). The proband developed symptoms typical for ALS at age 39 years and is still walking five years later. Marked phenotypic variability is manifested by her mother with onset of gait difficulty and decision-making problems at age 67 years and a five-year course marked by progressive mild upper motor neuron weakness, frontotemporal dementia and chorea. An aunt's initial symptoms included foot numbness and an uncle with the mutation is asymptomatic. Penetrance is only 50% at age 60 years and 88% at age 80 years with an 86-year-old woman harboring the mutation and having a normal neurologic examination. This family highlights the extreme variability in age of onset, clinical manifestations, disease progression and penetrance due to the I113T SOD1 mutation.