Increased orexin A concentrations in cerebrospinal fluid of patients with behavioural variant frontotemporal dementia

Orexins are hypothalamic neuropeptides that regulate several physiological functions, such as appetite, arousal, cognition, stress, sleep and metabolism. Emerging pieces of evidence suggest an orexinergic dysfunction in several neuropsychiatric disorders, including depression, anxiety and addiction. A syndromic overlap between behavioural variant frontotemporal dementia (bvFTD) and several psychiatric disorders was recently demonstrated. Therefore, we analysed cerebrospinal fluid (CSF) orexin A concentrations of 40 bvFTD and 32 non-demented patients, correlating neuropeptide concentrations with several clinical characteristics. A significant increase of orexin A concentrations was found in bvFTD patients when compared to controls (p<0.001). CSF orexin A concentration showed a correlation with Mini-Mental State Examination scores, drug assumption, history of compulsive behaviour and extrapyramidal signs. Moreover, we found a relationship between CSF markers of neurodegeneration, total tau and Aβ(1–42) and CSF orexin A concentrations. Our study provides evidence of an orexinergic dysfunction in bvFTD, correlating with several clinical symptoms. Further larger studies are needed to confirm our data. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-021-05250-x

The effectiveness of metal on metal hip resurfacing: a systematic review of the available evidence published before 2002

BACKGROUND: Conventional total hip replacement (THR) may be felt to carry too high a risk of failure over a patient's lifetime, especially in young people. There is increasing interest in metal on metal hip resurfacing arthroplasty (MoM) as this offers a bone-conserving option for treating those patients who are not considered eligible for THR. We aim to evaluate the effectiveness of MoM for treatment of hip disease, and compare it with alternative treatments for hip disease offered within the UK. METHODS: A systematic review was carried out to identify the relevant literature on MoM published before 2002. As watchful waiting and total hip replacement are alternative methods commonly used to alleviate the symptoms of degenerative joint disease of the hip, we compared MoM with these. RESULTS: The data on the effectiveness of MoM are scarce, as it is a relatively new technique and at present only short-term results are available. CONCLUSION: It is not possible to make any firm conclusions about the effectiveness of MoM based on these early results. While the short-term results are promising, it is unclear if such results would be replicated in more rigorous studies, and what the long-term performance might be. Further research is needed which ideally should involve long-term randomised comparisons of MoM with alternative approaches to the clinical management of hip disease

Sleep quality, circadian rhythms and melatonin in headache; facts and perspectives

Several pieces of evidence indicate that headache and sleep are strictly related. Melatonin nocturnal secretory patterns were reportedly blunted in various forms of headache during and out of the attacks. The hypothalamic dysfunction underppining headache attacks in migraine as well as in cluster headache, headacherelated life style changes and pharmachological treatments, all may account for altered melatonin secretion in headache sufferers. The altered melatonin secretory patterns may in turn play a role in the genesis of the headache attacks and of sleep disorders which are frequently comorbid wih headache. The potential benefit of melatonin and melatoninergic agonists in migraine and cluster headache pave the way to new, interesting therapeutic options in these forms of headache

Pain, cancer, fibromyalgia and gastrointestinal disorders

Daytime sleepiness is very frequent in chronic pain sufferers and it is underpinned by disrupted nocturnal sleep patterns as well as by pain medications. There is emerging evidence that sleep disorders and daytime sleepiness are clinically relevant with respect to the quality of life in cancer patients. To distinguish daytime sleepiness from fatigue may be challenging in these conditions so that a comprehensive approach is advisable. Disrupted nocturnal sleep and daytime sleepiness are reportedly frequent in gastrointestinal disorders such as irritable bowel syndrome (IBS) and in cirrhosis. Daytime sleepiness has recently been reported to be associated with hepatic encephalopathy in cirrhotics. As far as the management of daytime sleepiness in chronic pain, cancer and gastrointestinal disorders is concerned, both pharmacological and behavioural treatments should be taken into account with the main goal being to improve nocturnal sleep quality. The Z-drugs and short half-life benzodiazepines proved to be effective in improving sleep continuity and stability in these patients. Activating drugs were also reportedly of use and appropriate to increase daytime alertness. Finally, specific treatments for the basic pathology and for comorbid sleep disorders such as sleep disordered breathing and Restless Legs Syndrome should be done

Chronotype in patients with epilepsy: A controlled study in 60 subjects with late-onset focal epilepsy

Studies based on self-administered questionnaires indicate that most patients with epilepsy are morning-oriented. We aimed to investigate chronotype in patients with epilepsy with late-onset focal epilepsy by combining subjective data with dim light melatonin onset (DLMO) as an objective marker of the circadian phase. Sixty adult patients (mean age 46.5 ± 13.8; 27 males) with late-onset focal epilepsy under pharmacological treatment were prospectively studied. Subjective chronotype was determined using the Morningness-Eveningness Questionnaire (MEQ) and circadian phase through analysis of salivary melatonin secretion, considering 3. pg/ml as the dim light melatonin onset (DLMO) threshold. The mean MEQ score was significantly higher in the patients with epilepsy than in the controls, and significantly, more patients had a MEQ score indicative of the morning type (50.0% vs 30.0%, p = 0.02). However, no significant differences were found in mean time of DLMO (21:38. ± 01:21 vs 21:26 ± 01:03; p = ns), and DLMO time was in the range indicative of an intermediate chronotype in both patients and controls. Sleep onset and sleep offset phase angles were significantly shorter in the patients. Patients whose global MEQ score identified them as morning types were significantly older than those with an intermediate or evening chronotype, and they had less social jet lag. No difference in epilepsy features and treatments was found between morning-oriented and nonmorning-oriented patients. Our analyses showed that the patients with epilepsy tended to be morning-oriented and to perceive themselves as morning types, even though this was not reflected in their DLMO values which did not differ significantly from those of controls and mostly fell within the intermediate chronotype range. Several factors may considerably influence subjective chronotype. We speculate that, in patients with epilepsy, the disease itself, prompting certain lifestyle choices, including a regular sleep schedule and early bedtime, may induce morning orientation and a morning-type self-perception