Current and emerging treatments for amyotrophic lateral sclerosis Stefano Zoccolella1, Andrea Santamato2, Paolo Lamberti31Azienda Ospedaliero-UniversitariaOspedali Riuniti, Department of Medical and Neurological Sciences, Clinic of Nervous System Diseases, University of Foggia, Italy; 2Department of Physical Medicine and Rehabilitation, University of Foggia, OORR, Italy; 3Department of Neurology and Psychiatry, University of Bari, ItalyBackground: Amyotrophic lateral sclerosis (ALS) is a relatively rare neurodegenerative disorder of both upper and lower motoneurons. Currently, the management of ALS is essentially symptoms-based, and riluzole, an antiglutamatergic agent, is the only drug for the treatment of ALS approved by the food and drug administration.Objective: We reviewed current literature concerning emerging treatments for amyotrophic lateral sclerosis.Methods: A Medline literature search was performed to identify all studies on ALS treatment published from January 1st, 1986 through August 31st, 2009. We selected papers concerning only disease-modifying therapy.Results: Forty-eight compounds were identified and reviewed in this study.Conclusions: Riluzole is the only compound that demonstrated a beneficial effect on ALS patients, but with only modest increase in survival. Although several drugs showed effective results in the animal models for ALS, none of them significantly prolonged survival or improved quality of life of ALS patients. Several factors have been implicated in explaining the predominantly negative results of numerous randomized clinical trials in ALS, including methodological problems in the use of animal-drug screening, the lack of assessment of pharmacokinetic profile of the drugs, and methodological pitfalls of clinical trials in ALS patients.Keywords: amyotrophic lateral sclerosis, therapy, drug, survival

Background: Hyperhomocysteinemia has been associated with cognitive dysfunction and dementia. The incidence of dementia in Parkinsons Disease (PD) patients is higher than in the general population and plasma Homocysteine concentrations are increased in L-dopa treated PD patients. Objective: We evaluated the possible correlations between L-Dopa related hyperhomocysteinemia and cognitive dysfunction in PD. Methods: A Medline literature search was performed to identify all published studies on Homocysteine and cognitive dysfunction and dementia during the course of PD from 1966 to 31/03/2010. Results: Sixteen studies were found for review; ten studies focused on homocysteine and cognitive dysfunction in PD patients, five on homocysteine and PD dementia and two on homocysteine and markers of neurodegeneration in PD. The design of the study was retrospective in 14 studies, while 2 had a prospective design, with a variable follow-up period (from 24-weeks to 2 years). In most of the studies plasma homocysteine levels significantly correlated with cognitive functions, dementia and markers of neurodegeneration in PD patients. However, some studies did not confirm these findings. Several factors may concur to explain these partially conflicting results, including the retrospective design of the studies, their small sample size, their high percentage of excluded patients, and the use of a wide range of neuropsychological tasks in assessment of cognitive dysfunctions across the available studies. Conclusions: Available data seem to indicate a potential role of L-dopa related hyperhomocysteinemia on cognitive impairment and dementia during the course of PD.

INTRODUCTION: Sleep and rest–activity rhythm alterations are common in neurodegenerative diseases. However, their characterization in patients with behavioral variant frontotemporal dementia (bvFTD) has proven elusive. We investigated rest–activity rhythm alterations, sleep disturbances, and their neural correlates in bvFTD.METHODS: Twenty‐seven bvFTD patients and 25 healthy controls completed sleep questionnaires and underwent 7 days of actigraphy while concurrently maintaining a sleep diary. Cortical complexity and thickness were calculated from T1‐weighted magnetic resonance (MR) images.RESULTS: Compared to controls, bvFTD patients showed longer time in bed (95% confidence interval [CI]: 79.31, 321.83) and total sleep time (95% CI: 24.38, 321.88), lower sleep efficiency (95% CI: −12.58, −95.54), and rest–activity rhythm alterations in the morning and early afternoon. Increased sleep duration was associated with reduced cortical thickness in frontal regions.DISCUSSION: Patients with bvFTD showed longer sleep duration, lower sleep quality, and rest–activity rhythm alterations. Actigraphy could serve as a cost‐effective and accessible tool for ecologically monitoring changes in sleep duration in bvFTD patients.Highlights: We assessed sleep and circadian rhythms in behavioral variant frontotemporal dementia (bvFTD) using actigraphy. Patients with bvFTD show increased sleep duration and reduced sleep quality. Patients with bvFTD show rest–activity alterations in the morning and early afternoon. Sleep duration is associated with reduced cortical thickness in frontal regions. These alterations may represent an early sign of neurodegeneration.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and has emerged among the disorders with the largest increasing incidence in Western countries. Although the diagnosis is based on clinical grounds, electromyography (EMG), and nerve conduction studies (NCS) play a crucial role to exclude other potential etiologies of lower motor neuron (LMN) dysfunction. Based on clinical grounds, a peculiar pattern of dissociated atrophy of the intrinsic hand and foot muscles, termed the “split-hand” (SH) and “split-leg” (SL) signs, has been described in a significant proportion of subjects with ALS, even at the early stages of the disease, when symptoms are focal. These signs are rare in neurological and non-neurological diseases other than ALS. In this review, we discussed current evidences concerning SH and SL signs, their pathogenetic hypotheses and neurophysiological findings. We also analyze whether SH and SL signs can be reliable markers in the differential diagnosis and in the prognosis of ALS.