Aggressiveness in the dreams of drug-naïve and clonazepam-treated patients with isolated REM sleep behavior disorder.

BACKGROUND: Although aggressive dream content is considered a distinctive feature of REM Sleep Behavior Disorder (RBD) and patients often report violent dreams during medical interviews, nonviolent behaviors (eating, drinking, urinating) and pleasant actions (e.g laughing, singing, dancing) or simply elemental, jerky limb movements are frequently observed during video-polysomnography. As a first-line pharmacological treatment, clonazepam has been shown to reduce motor symptoms during REM sleep, but its effect on dream content remains unclear. Here, we aimed to prospectively assess the dream content of individuals with drug-naïve isolated RBD (iRBD) and iRBD patients treated with clonazepam. METHODS: Thirteen (12 Male, 1 Female; age 65.38 ± 10.95) iRBD patients treated with clonazepam (iRBD-T), eleven (9 M, 2 F; age 68.90 ± 6.8) drug-naïve patients (iRBD-NT) and twelve (8 M, 1 F; age 63.33 ± 12.88) healthy control subjects of comparable age kept a dream diary over a 3-week period. Dream content analysis was conducted according to the Hall and Van de Castle method (HVdC). The Threat Simulation Scale (TSS) was employed to assess the frequency of threatening contents. RESULTS: A total of 214 dream reports were collected. No significant differences were found in the frequency of threatening dream contents between the iRBD subsamples and healthy control subjects (p = 0.732). The HVdC analysis detected higher levels of Friendliness in iRBD patients compared to the control group (p = 0.036). Increased levels of Aggressiveness were only observed when differentiating dreams in which dream enactment behaviors (DEB) were present compared to dreams without DEBs, both in the iRBD-T group (p = 0.007) and the iRBD-NT group (p = 0.012). CONCLUSION: Our study shows no difference in the frequency of violent or threatening dreams in drug-naïve iRBD patients, clonazepam-treated iRBD patients and healthy control individuals. Aggressiveness is more frequent when DEBs are reported, suggesting motor disinhibition could require sufficiently dramatic and emotionally intense dreams, independent of clonazepam treatment.

Morphological analysis of the brain subcortical gray structures in restless legs syndrome.

BACKGROUND: Although several studies have shown the involvement of specific structures of the central nervous system, the dopaminergic system, and iron metabolism in restless legs syndrome (RLS), the exact location and extent of its anatomical substrate is not yet known. The scope of this new study was to investigate the brain subcortical gray structures, by means of structural magnetic resonance imaging (MRI) studies, in RLS patients in order to assess the presence of any volume or shape abnormalities involving these structures. METHODS: Thirty-three normal controls (24 females and nine males) and 45 RLS patients (34 females and 11 males) were retrospectively recruited and underwent a 1.5 Tesla MRI study with two-dimensional T1 sequences in the sagittal plane. Post-processing was performed by means of the Functional Magnetic Resonance Imaging of the Brain Analysis Group Integrated Registration and Segmentation Tool (FIRST) software, and both volumetric and morphological analyses of the thalamus, caudate, putamen, globus pallidus, brainstem, hippocampus, and amygdala, bilaterally, were carried out. RESULTS: A statistically significant volumetric reduction in the left amygdala and left globus pallidus was found in subjects with RLS, as well as large surface morphological alterations affecting the amygdala bilaterally and other less widespread surface changes in both hippocampi, the right caudate, the left globus pallidus, and the left putamen. CONCLUSIONS: These findings seem to indicate that the basic mechanisms of RLS might include a pathway involving not only the hypothalamus-spinal dopaminergic circuit (nucleus A11), but also pathways including the basal ganglia and structures that are part of the limbic system; moreover, structural alterations in RLS seem to concern the morphology as well as the volume of the above structures. The role of basal ganglia in the complex neurophysiological and neurochemical mechanism of RLS needs to carefully reconsidered.

Excessive sleepiness in shift work disorder: a narrative review of the last 5 years.

INTRODUCTION: Shift work sleep disorder (SWSD), also known as shift work disorder (SWD), is a circadian rhythm sleep disorder characterized by insomnia and/or excessive sleepiness, associated with a recurring work schedule that overlaps the usual time designated for sleeping. PURPOSE: This article aims to provide a narrative review of the pharmacological trials conducted on SWD in the last 5 years, to better address safety and health issues inherent to this disorder. METHODS: An electronic literature search was conducted using PubMed. All eligible randomized controlled trials (RCTs) and cross-over RCTs with employees undertaking shift work (including night shifts) were considered, yielding three articles. RESULTS: All three studies showed the efficacy of armodafinil in improving subjective and objective sleepiness, clinical conditions, and global functioning regardless of shift duration. Both performance and driving simulator performance tests administered during the night shift bore better results following armodafinil administration than after placebo. However, armodafinil only reduced subjective disability in individuals working more than 9 h; furthermore, even after armodafinil, alertness was reduced but not normalized. CONCLUSION: These studies underscore the importance of preventing and/or minimizing disturbances due to shift work. This may be achieved through various strategies, such as the employer's commitment to adopt ergonomic criteria in shift design and to implement work-environment interventions like controlled bright light. Health personnel is of pivotal importance to detect potential factors of intolerance to shift work or early symptoms of SWD. Additional and improved studies are needed to further evaluate the effectiveness and safety of both pharmacological and non-pharmacological interventions.

Convexal subarachnoid hemorrhage and acute ischemic stroke: a border zone matter?

BACKGROUND: Convexal subarachnoid hemorrhage (c-SAH) is an infrequent condition with variable causes. c-SAH concomitant to acute ischemic stroke (AIS) is even less frequent, and the relationship between the two conditions remains unclear. METHODS: Between January 2016 and January 2018, we treated four patients who were referred to our stroke unit with ischemic stroke and concomitant nontraumatic c-SAH. The patients underwent an extensive diagnostic workup, including digital subtraction angiography (DSA). RESULTS: All four patients developed acute focal neurological symptoms with restricted MRI diffusion in congruent areas. In three of the patients, infarcts were in a border zone between the main cerebral arteries and c-SAH was nearby. The fourth patient showed a small cortical infarct, and c-SAH was in a border zone territory of the contralateral hemisphere. An embolic source was discovered or strongly suspected in all cases. One patient was treated with intravenous thrombolysis, but this treatment was not related to c-SAH. None of the four patients showed microbleeds or further cortical siderosis, thus excluding cerebral amyloid angiopathy. In addition, DSA did not show signs of vasculitis, reversible cerebral vasoconstriction syndrome, or intracranial arterial dissection. CONCLUSIONS: We proposed the embolism or hemodynamic changes of the border zone arterioles as a unifying pathogenetic hypothesis of coexisting c-SAH and AIS.

Subjective hypnotic efficacy of Trazodone and Mirtazapine in patients with chronic insomnia: a retrospective, comparative study.

OBJECTIVE: To compare the efficacy of two sedating antidepressants, trazodone and mirtazapine, for the treatment of chronic insomnia. DESIGN: Retrospective cross-sectional study. Patients received trazodone or mirtazapine for at least three months at the dosage that was effective in the titration period. MATERIAL AND METHODS: 150 patients with chronic insomnia, referred to the Sleep Disorder Center of Bari, diagnosed as chronic insomniacs according to ICSD-3 diagnostic criteria, with or without dysthymic disorder according to DSM V diagnostic criteria, and treated with trazodone or mirtazapine were retrospectively chart-reviewed. 79 patients satisfying inclusion criteria were enrolled: 33 had been treated with trazodone (12 males and 21 females aged 36 to 77 years, mean age 63.57+10.38 years; 18 with psychophysiological insomnia and 15 with insomnia associated with dysthymic disorder) and 46 with mirtazapine (26 males and 20 females aged 25 to 86 years, mean age 60.04+16.67 years; 25 with psychophysiological insomnia and 21 with insomnia comorbid with dysthymic disorder). The patients were considered responsive to the treatment when they no longer met the criteria for insomnia at the end of the maintenance period. RESULTS: Both drugs were efficacious in more than 60% without any difference in the proportion of responders between the two medication groups (87.87% in the trazodone group versus 86.95% in the mirtazapine group; p=0.26 and regardless of sex, age and possible association of insomnia with depression). The minimum dosages used for both drugs (25 mg for trazodone and 7.5 mg for mirtazapine) corresponded to the highest percentage of responders in the groups treated successfully with either trazodone (37.93%) or mirtazapine (52.5%). For each medication group, subgroup analysis revealed higher statistically significant rates of responders in patients with lower final dosage (25 to 75 mg for trazodone and 7.5 to 15 mg for mirtazapine) than in those with higher final dosage (100 to 150 mg for trazodone and 15 to 30 mg for mirtazapine) (100% versus 42.85%; p<0.001 in the trazodone group and 100% versus 53.84%; p<0.001 in mirtazapine group) Conclusion. On a long term basis trazodone administration appeared as effective and well tolerated as mirtazapine in the treatment of chronic insomnia regardless of its association with dysthymia. Both medications resulted efficacious at very low doses and had a sustained efficacy, likely without problems of tolerance.

Sleep disorders and the natural history of Parkinson's disease: the contribution of epidemiological studies.

BACKGROUND: Sleep disorders (SD) are one of the most frequent non-motor manifestations of Parkinson's disease (PD). Recent studies showed that SD may precede the onset of PD. OBJECTIVES: We reviewed current literature concerning 1) the incidence of PD among subjects with SD; and 2) the occurrence and possible clinical correlations of SD during the course of PD. METHODS: A Medline search found 17 longitudinal studies. RESULTS: The incidence of PD among patients with rapid eye-movement sleep behavioural disorders ranged from 20% to 65% of cases, within a wide interval of time (range: 2.2-13.3). The incidence of SD during PD progressively increased with disease duration in population-based studies but presented marked fluctuations in clinical based studies. Older age, male gender, dopaminergic treatment with higher dosage, cognitive impairment and hallucinations were associated with the onset of SD during PD. In the only population-based study among Japanese men excessive daytime sleepiness was associated with a threefold increased risk of developing PD. CONCLUSIONS: Available data suggest that SD could be the heralding clinical manifestation or a risk factor for PD onset. The prevalence of SD increases during the course of the PD and may be related to specific phenotype and rapid progression of PD. However, the current data are limited because of limited sample size and poor study design; prospective studies with larger sample size are warranted.

Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study.

STUDY OBJECTIVES: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. DESIGN: Prospective, multicenter, case-control epidemiologic survey. SETTINGS: Twenty sleep centers certified by the Italian Association of Sleep Medicine. PATIENTS: Eight hundred and sixty-one patients affected by MS and 649 control subjects. INTERVENTIONS: N/A. MEASURES AND RESULTS: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. CONCLUSIONS: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.

Tertiary treatment for psychiatric comorbidity in headache patients.

The presence of significant and confounding psychiatric comorbidity is greater in patients attending headache clinics than in headache patients from the general population. The frequent comorbidity of headache with generalized anxiety disorder can take advantage of the administration of benzodiazepines. With regard to depression-related headache, it's wellknown that the antidepressive drugs can improve migraine as well as tension-type headache. Antiepileptic drugs give one more good opportunity. The recognition of a psychiatric comorbidity is mandatory for an accurate management of the patient because prevents the clinicians from using any drug that might be dangerous for a mysdiagnosed psychiatric disturbance and often permits to administer medications that can efficaciously control both headache and psychiatric disorders.

Insomnia in general practice : a consensus report produced by sleep specialists and primary-care physicians in Italy.

Insomnia is an extremely common condition with major social and economic consequences worldwide. Two large epidemiological studies (Morfeo 1 and Morfeo 2) recently performed in Italy provided much-needed novel data on the impact of insomnia in patients whose primary healthcare is provided by general practitioners (GPs). These studies found that insomnia is managed relatively well by GPs in Italy, although diagnosis and treatment can be compromised because of the lack of standardised criteria. Although a number of consensus reports on insomnia have been published, these are mainly highly specific documents that are difficult to implement in general practice. To address this, a consensus group involving 695 GPs and over 60 specialists from the Italian Association of Sleep Medicine was established. The major objectives of the consensus study were to establish basic knowledge for the diagnosis and treatment of insomnia, and to produce guidelines for the management of insomnia by GPs. This is the first time that GPs have been directly involved in producing insomnia guidelines of this type, and this approach reflects their pivotal role in the diagnosis and management of this condition. Participants were carefully selected to ensure adequate representation of sleep specialists and GPs, with the group being headed by a steering committee and an advisory board. Guideline statements were selected following careful literature review and were voted on using formalised consensus procedures. This review describes current views on the diagnosis and management of insomnia from the perspective of the GP. In addition, the results of the consensus study are presented. They include recognition of the following principles: (i) insomnia is a genuine pathology that must be appropriately diagnosed and treated; (ii) when concomitant pathologies are present, additional significance should be given to treatment of insomnia since it can influence prognosis of coexistent disorders; (iii) appropriate treatment should consider the cause of insomnia as well as the characteristics of available pharmacological agents; (iv) with regard to hypnotic drugs, preference should be given to medications with a short half-life in order to limit residual effects; (v) non-benzodiazepine hypnotics are preferred to classic benzodiazepines as they have higher selectivity and present a lower risk of undesirable effects; (vi) tablets are preferable to liquid preparations as they are less likely to lead to dependence and to overdosing by the patient; and (vi) once treatment has been initiated, insomnia patients should be carefully followed up. These statements provide much needed criteria for better management of insomnia by GPs in Italy.