Potential roles of gut microbiome and metabolites in modulating ALS in mice.

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder, in which the clinical manifestations may be influenced by genetic and unknown environmental factors. Here we show that ALS-prone Sod1 transgenic (Sod1-Tg) mice have a pre-symptomatic, vivarium-dependent dysbiosis and altered metabolite configuration, coupled with an exacerbated disease under germ-free conditions or after treatment with broad-spectrum antibiotics. We correlate eleven distinct commensal bacteria at our vivarium with the severity of ALS in mice, and by their individual supplementation into antibiotic-treated Sod1-Tg mice we demonstrate that Akkermansia muciniphila (AM) ameliorates whereas Ruminococcus torques and Parabacteroides distasonis exacerbate the symptoms of ALS. Furthermore, Sod1-Tg mice that are administered AM are found to accumulate AM-associated nicotinamide in the central nervous system, and systemic supplementation of nicotinamide improves motor symptoms and gene expression patterns in the spinal cord of Sod1-Tg mice. In humans, we identify distinct microbiome and metabolite configurations-including reduced levels of nicotinamide systemically and in the cerebrospinal fluid-in a small preliminary study that compares patients with ALS with household controls. We suggest that environmentally driven microbiome-brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.

Hypnotic relaxation vs amitriptyline for tension-type headache: let the patient choose.

BACKGROUND: Although both pharmacological and behavioral interventions may relieve tension-type headache, data are lacking regarding treatment preference, long-term patient compliance, and feasibility of behavioral intervention in a standard neurological outpatient clinic setting. OBJECTIVE: To describe patient choice, long-term compliance, and clinical outcome in a neurological clinic setting where patients are given the choice of the approach they wish to pursue. DESIGN: Patients presenting to the headache clinic with a diagnosis of tension-type headache that justified prophylactic therapy (frequent episodic tension-type headache or chronic tension-type headache) were given the choice of amitriptyline (AMT) treatment or hypnotic relaxation (HR), and were treated accordingly. Patients were given the option to cross-over to the other treatment group at each visit. HR was performed during standard length neurology clinic appointments by a neurologist trained to perform hypnosis (Y.E.). Follow-up interviews were performed between 6 and 12 months following treatment initiation to evaluate patient compliance, changes in headache frequency or severity, and quality-of-life parameters. RESULTS: Ninety-eight patients were enrolled, 92 agreed to receive prophylactic therapy of some kind. Fifty-three (57.6%) patients chose HR of which 36 (67.9%) actually initiated this treatment, while 39 (42.4%) chose pharmacological therapy with AMT of which 25 (64.1%) patients actually initiated therapy. Patients with greater analgesic use were more likely to opt for AMT (P= .0002). Eleven of the patients initially choosing AMT and 2 of the patients initially choosing HR crossed over to the other group. Seventy-four percent of the patients in the HR group and 58% of patients in the AMT group had a 50% reduction in the frequency of headaches (P= .16). Long-term adherence to treatment with HR exceeded that of AMT. At the end of the study period, 26 of 47 patients who tried HR compared with 10 of 27 who tried AMT continued receiving their initial treatment. CONCLUSIONS: HR treatment was a more popular choice among patients. Patients choosing HR reported greater symptom relief than those choosing AMT and were found to have greater treatment compliance. Patients receiving HR were less likely to change treatments. HR practiced by a neurologist is feasible in a standard neurological outpatient clinic setting; HR training should be considered for neurologists involved in headache treatment.