Phenotype of carnitine palmitoyltransferase II (CPT II) deficiency: A questionnaire-based survey.

Wide spectrums of symptoms besides muscle weakness, different triggering factors and varied muscles involvement are associated with CPT II deficiency. However, systematic clinical characterization of CPT II deficiency is not known. A Questionnaire-based retrospective study on 13 biochemically and genetically confirmed CPT II deficient patients was performed to analyze these aspects. Attacks of myalgia (13/13 patients), weakness (13/13) and rhabdomyolysis (10/13 patients) were most frequently reported. The number of attacks ranged from 1 to 85/year. Common triggers were exercise (13/13), fasting (13/13), cold (12/13) and infections (12/13). Exercise lasting from 15 to 60 min was sufficient for attacks in 9/13 patients, 1-4 h in 3/13 patients and more than 4 h in 1/13 patient. 2/13 patients required dialysis. Limb muscles were affected slightly more often than other muscles. Mean intensity of pain in visual analogue scale (VAS) during regular attack was 4.77 (±1.36). Frequency and severity of attacks did not increase during the course of disease in 10/13 patients. 7/13 patients quit sports after the symptoms emerged. 3/13 patients changed their profession permanently. Increased number of attacks were positively correlated with higher BMI (P = 0.05). Body rest, carbohydrate-rich nutrients and fluid-supplement mitigated the pain. After the first attack [Mean: 9.7 (±4.46) years], diagnosis took an average of 26.7 (± 13.06) years. In myopathic CPT II deficiency, frequencies of attacks are highly variable. Generally, the myopathic form is a mild form. However, severe patients requiring dialysis due to kidney failure could be present. Individuals with higher BMI are at risk of developing more frequent attacks.

Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic lateral sclerosis mouse models based on TDP-43 (Tardbp) and FUS mutations. Finally, we demonstrate that the melanocortin defect is primarily caused by serotonin loss in mutant SOD1(G86R) mice. Altogether, the current study combined clinical evidence and experimental studies in rodents to provide a mechanistic explanation for abnormalities in food intake and weight control observed in patients with amyotrophic lateral sclerosis. Importantly, these results also show that amyotrophic lateral sclerosis progression impairs responsiveness to classical drugs leading to weight gain. This has important implications for pharmacological management of weight loss in amyotrophic lateral sclerosis.

Attitudes towards complementary and alternative medicine in chronic pain syndromes: a questionnaire-based comparison between primary headache and low back pain.

BACKGROUND: Complementary and Alternative Medicine (CAM) is widely used and popular among patients with primary headache or low back pain (LBP). Aim of the study was to analyze attitudes of headache and LBP patients towards the use of CAM. METHODS: Two questionnaire-based surveys were applied comparing 432 primary headache and 194 LBP patients. RESULTS: In total, 84.75% of all patients reported use of CAM; with significantly more LBP patients. The most frequently-used CAM therapies in headache were acupuncture (71.4%), massages (56.4%), and thermotherapy (29.2%), in LBP thermotherapy (77.4%), massages (62.7%), and acupuncture (51.4%). The most frequent attitudes towards CAM use in headache vs. LBP: "leave nothing undone" (62.5% vs. 52.1%; p = 0.006), "take action against the disease" (56.8% vs. 43.2%; p = 0.006). Nearly all patients with previous experience with CAM currently use CAM in both conditions (93.6% in headache; 100% in LBP). However, the majority of the patients had no previous experience. CONCLUSION: Understanding motivations for CAM treatment is important, because attitudes derive from wishes for non-pharmacological treatment, to be more involved in treatment and avoid side effects. Despite higher age and more permanent pain in LBP, both groups show high use of CAM with only little specific difference in preferred methods and attitudes towards CAM use. This may reflect deficits and unfulfilled goals in conventional treatment. Maybe CAM can decrease the gap between patients' expectations about pain therapy and treatment reality, considering that both conditions are often chronic diseases, causing high burdens for daily life.