The neurology of itch.

Research over the past 15 years has helped to clarify the anatomy and physiology of itch, the clinical features of neuropathic itch syndromes and the scientific underpinning of effective treatments. Two itch-sensitive pathways exist: a histamine-stimulated pathway that uses mechanically insensitive C-fibres, and a cowhage-stimulated pathway primarily involving polymodal C-fibres. Interactions with pain continue to be central to explaining various aspects of itch. Certain spinal interneurons (Bhlhb5) inhibit itch pathways within the dorsal horn; they may represent mediators between noxious and pruritic pathways, and allow scratch to inhibit itch. In the brain, functional imaging studies reveal diffuse activation maps for itch that overlap, but not identically, with pain maps. Neuropathic itch syndromes are chronic itch states due to dysfunction of peripheral or central nervous system structures. The most recognized are postherpetic itch, brachioradial pruritus, trigeminal trophic syndrome, and ischaemic stroke-related itch. These disorders affect a patient's quality of life to a similar extent as neuropathic pain. Treatment of neuropathic itch focuses on behavioural interventions (e.g., skin protection) followed by stepwise trials of topical agents (e.g., capsaicin), antiepileptic drugs (e.g., gabapentin), injection of other agents (e.g., botulinum A toxin), and neurostimulation techniques (e.g., cutaneous field stimulation). The involved mechanisms of action include desensitization of nerve fibres (in the case of capsaicin) and postsynaptic blockade of calcium channels (for gabapentin). In the future, particular histamine receptors, protease pathway molecules, and vanilloids may serve as targets for novel antipruritic agents.

Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS: The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE: Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449865.

Therapies for dopaminergic-induced dyskinesias in Parkinson disease.

Existing and emerging strategies for managing L-dopa-induced dyskinesias (LIDs) in patients with Parkinson disease have involved either delaying the introduction of L-dopa therapy, treatment with an antidyskinetic agent, using a therapy or delivery system that can provide continuous dopaminergic stimulation, or using novel agents that target receptors implicated in the mechanisms underlying LIDs. Treatment with dopamine agonists such as pramipexole or ropinirole allows levodopa to be delayed, but once levodopa is added to the drug regimen the usual course of onset of dyskinesias is observed. Amantadine, an N-methyl-D-aspartate antagonist, is so far the only approved compound with evidence of providing a sustained antidyskinetic benefit in the absence of unacceptable side effects. These findings support the hypothesis of glutamate overactivity in the development of dyskinesias. More continuous delivery of dopaminergic medication, such as through intraintestinal or subcutaneous routes, is promising but invasive and associated with injection site reactions. As a result of molecular research and elucidation of the role of a variety of neurotransmitters in the mechanism of LIDs, new compounds have been identified, including those that modulate the direct and indirect striatal output pathways; some of these new agents are in the early stages of development or undergoing proof-of-concept evaluation as antidyskinetic agents.

Seizures in corticobasal degeneration: a case report.

Seizures are relatively common in Alzheimer disease (AD) and other neurodegenerative disorders. To our knowledge, however, there have been no reports of seizures associated with corticobasal degeneration (CBD). We describe a patient with brain biopsy features suggestive of CBD whose course was complicated by complex partial seizures with secondary generalization. Thus, the occurrence of seizures in a patient with dementia should not exclude the diagnosis of CBD.