Peer victimization and developmental psychopathology in childhood and adolescence Italian psychiatric emergency unit. A single center retrospective observational study.

Peer victimization is a public health concern that affects a significant proportion of children and adolescents. The study evaluated the prevalence of peer victimization among 440 subjects referred to Emergency Department for a psychiatric consultation and analyzed the association with psychopathological symptoms. Sample was divided into two categories (6-13 and 14-18 years old). Logistics regression analysis was performed. Peer victimized were reported in 16.3% of subjects; 27.7% were younger than13 years old and 72.3% were between 14-18 years old, representing the main targets for peer victimization.A significant association was found between being peer victimized and depressive disorder (OR=4.57) in subjects younger than 13 years old and, with post-traumatic stress disorder (PTSD)(OR=6.52) in subjects older than 13 years old. Furthermore, linkage between being peer victimized and obsessive-compulsive disorder (OCD)(OR=4.45) was noted. Increased frequency of repeated hospitalizations was also documented.This is the first Italian study about children and adolescent peer victimization in psychiatric setting, showing a significant higher risk for depressive disorder in subjects younger than 13 years old and PTSD and OCD in subjects older than 13 years old. Investigating experiences of peer victimization provides an early diagnosis and a more efficient treatment plans, guaranteeing an improved clinical outcome.

Epidemiological and Psychopharmacological Study About Off-Label Treatment in Child and Adolescent Psychiatric Emergencies: A Tertiary/Single Center Experience.

OBJECTIVE: The study used an epidemiological and pharmacological description of child and adolescent psychiatric emergencies (CAPEs), during which psychotropic medications are frequently administered as off-label therapies. METHODS: We retrospectively describe CAPE in 190 patients (mean age, 14.7 years) referring in the emergency department of a single tertiary center, from June 2016 to June 2018, focusing on off-label administration rate, most of all in emergency setting. RESULTS: An intrinsic fragility was observed in this population, where 28.4% of patients present a history of self-harm, 24.7% a concomitant neurodevelopmental disorder, and 17.3% a history of substance abuse. Psychomotor agitation was the most frequent referral reason, and it represents an unspecified clinical presentation of several conditions, while self-harm showed a stronger association with depressive disorders (55.2%).Globally, 811 medications were administered both as baseline therapy (67.8% of off-label rate) and/or in the emergency setting, where the off-label rate raised to 78.3%. Benzodiazepines had the highest rate of off-label use (98.2% as baseline therapy, 92.9% in acute context). Nevertheless, in 83.5% cases of acute administrations, a singular oral benzodiazepine (mostly lorazepam) guaranteed psychomotor agitation resolution, with a lower rate of adverse effects in contrast with atypical antipsychotics. CONCLUSIONS: Off-label drug use in CAPEs is a recurrent clinical practice. An international agreement about off-label drugs is crucial to obtain standard long-term pharmacoepidemiological, safety, and efficacy data. Pharmacological pediatric trials and international guidelines are also required to regulate pharmacological treatments of CAPEs, most of all in emergency settings.

Excessive daytime sleepiness and fatigue in neurological disorders.

Excessive daytime sleepiness (EDS) and fatigue are some of the most frequent symptoms in neurological diseases and could impact on quality of life by increasing the risk of accidents and generally affecting daily life activities. In this review, we will examine the variety of causes responsible for EDS in neurological diseases, including nocturnal sleep alterations, CNS pathological abnormalities with alterations in arousal and/or REM regulation systems, circadian rhythms disorders, drugs, and comorbid psychiatric or primary sleep disorders. Among neurological diseases, epilepsy, dementia, Parkinson disease, multiple sclerosis, and myotonic dystrophies represented a model for these interactions between EDS and neurological diseases. A complete diagnostic workup in neurological patients with EDS should be undertaken since EDS can worsen many different aspects such as psychiatric symptoms, cognitive deficit, and in some cases, the severity of the neurological disease per se. Moreover, quality of life and risk of accidents are dependent on EDS. An individualized approach to this symptom in neurological patients should be considered with a focus on modifiable causes such as SDB, psychiatric comorbidities, and drugs. When considering EDS and fatigue in neurological diseases, close attention to lifestyle and sleep hygiene is advisable. A critical review of ongoing pharmacological therapy should not be overlooked. Possible diagnosis and treatment of SDB should be always considered.

Fatigue, sleep-wake pattern, depressive and anxiety symptoms and body-mass index: analysis in a sample of episodic and chronic migraine patients.

Migraine clinical presentation and life-time course can be highly heterogeneous, with a subgroup of patients developing chronic migraine; moreover, migraine clinical spectrum is expanded by the association with different coexisting conditions and interictal dysfunctions. The aim of this study was to systematically evaluate migraine clinical features, daily functioning parameters, sleep pattern, presence of depressive-anxiety symptoms and body mass index (BMI) in a sample of 75 episodic and 75 chronic migraine without aura patients. Migraine-related disability, fatigue, daily sleepiness, subjective sleep quality, anxiety and depressive symptoms were, respectively, evaluated using the following questionnaires: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire 9-item Scale (PHQ-9). Mean FSS score (p < 0.001), PSQI score (p = 0.015), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.012) were significantly higher in chronic compared to episodic migraineurs. Additionally, a correlation analysis carried out in the total sample of 150 migraine patients documented a statistically significant, positive correlation between monthly frequency of migraine attacks and FSS score (p < 0.001), PSQI score (p = 0.006), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.049). Data from the present report seem to expand the concept of migraine as a continuum or spectrum, with greater occurrence of fatigue, poor sleep quality, anxiety-depressive symptoms and higher BMI score in chronic compared to episodic migraine patients; further investigation is certainly necessary to better define the biological basis and mechanisms associated with migraine transformation from episodic to chronic pattern.

Evidences of Reduced Antioxidant Activity in Patients With Chronic Migraine and Medication-Overuse Headache.

BACKGROUND: Migraine is a complex multifactorial, neurobiological disorder, whose pathogenesis is not fully understood, nor are the mechanisms associated with migraine transformation from episodic to chronic pattern. A possible role of impaired oxidative mitochondrial metabolism in migraine pathogenesis has been hypothesized, and increased levels of peripheral markers of oxidative stress have been reported in migraine patients, although the literature data are limited and heterogeneous. OBJECTIVES: The aim of this cross-sectional study was to determine plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power and total plasmatic thiol groups, all plasmatic markers related to oxidative stress, in a sample of chronic migraine patients and medication-overuse headache, compared to a control group of healthy subjects. METHODS: Thirty-three patients with a diagnosis of both chronic migraine and medication-overuse headache (International Classification of Headache Disorders,3rd edition, beta version) and 33 healthy, headache-free subjects were enrolled. Patients with comorbid/coexisting conditions were excluded, as well as patients in treatment with migraine preventive drugs. Plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power, and total thiol groups were determined in migraine patients and controls; moreover, oxidative stress biomarkers were compared in migraine patients with triptan compared to non-steroidal anti-inflammatory drug overuse. RESULTS: The statistical analysis showed significantly lower levels of ferric-reducing antioxidant power and total plasmatic thiol groups, both expression of antioxidant power, in patients with chronic migraine and medication-overuse headache compared to controls (respectively, ferric antioxidant power median [interquartile range] 0.53 [0.22] vs 0.82 [0.11] mmol/L, P < .001; total thiol groups 0.25 [0.08] vs 0.51 [0.11] µmol/L, P < .001). Moreover, no statistically significant differences in oxidative stress biomarkers were detected between patients with triptan and nonsteroidal anti-inflammatory drug overuse. CONCLUSIONS: The data from the present study suggest that antioxidant capacity is lower in chronic migraine patients and medication-overuse headache compared to healthy headache-free subjects, with no differences between patients with triptan or nonsteroidal anti-inflammatory drug overuse. Further investigation is certainly necessary in order to define the causal or consequential role of an imbalance between pro-oxidants and antioxidant defenses in migraine pathogenesis and "chronification" and the possible therapeutic implications in clinical practice.

Clinical features associated with ictal osmophobia in migraine.

Olfactory hypersensitivity may occur during migraine attacks and has been found to be very specific for this form of headache. Aim of this study was to investigate if migraineurs with ictal osmophobia have particular clinical features comparing to patients without ictal osmophobia. We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, depression and anxiety symptoms. Migraine triggers both spontaneously and selecting from a specific list. Allodynia during the migraine attack was measured using the Allodynia symptoms check-list 12 (ASC-12). Eighty four (42 %) patients are non-osmophobic vs. 116 patients (58 %) who are osmophobic. After a logistic regression analysis, pain intensity (OR 1.391; p = 0.008) and anxiety (OR 1.099; p = 0.047) were significantly higher while aura (OR 0.421; p = 0.028) is less frequent in osmophobic migraineurs. We found significant differences in clinical features of osmophobic patients in respect to non-osmophobic ones. Ictal osmophobia seems being related to a broader sensorial hypersensitivity that could lead to a more florid clinical presentation.

Beyond Pain Relief: Unveiling the Multifaceted Impact of Anti-CGRP/R mAbs on Comorbid Symptoms in Resistant Migraine Patients.

The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study is pivotal to unveiling the role of this neurotransmitter beyond pain processing. We conducted an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis. All patients were treated with anti-CGRP/R mAbs for 3 months. Seventy-seven patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44%, respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥50% of headache frequency. The two groups were highly homogeneous for the investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms was reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. We found that anti-CGRP/R antibodies improved pain together with affection, fatigue, and sensory sensitization in a cohort of migraine patients resistant to traditional prophylaxis. Our results offer novel perspectives on the early efficacy of anti-CGRP/R mAbs in difficult-to-treat patients focusing on clinical features other than pain relief.

Brainstem activation in cluster headache: an adaptive behavioural response?

INTRODUCTION: The functional neuroimaging of headache patients has revolutionized our understanding of the pathophysiology of primary headaches, providing unique insights into these syndromes. Indeed, functional neuroimaging studies have shown the activation of specific brain structures, the brainstem in migraine and posterior hypothalamus in cluster headache (CH), as well as in other trigeminal autonomic cephalalgias. We describe the functional neuroimaging findings in a patient suffering from CH headache, investigated with functional magnetic resonance imaging (fMRI) during typical pain attacks. MATERIAL AND METHODS: Two typical, consecutive CH attacks were investigated by two fMRI imaging sessions on the same day. Both fMRI scans were performed at rest, during the CH attacks and the pain-free state induced by subcutaneous administration of sumatriptan. RESULTS: Significant activation of the bilateral red nucleus, ventral pons and trigeminal root entry zone ipsilaterally to the pain side was detected during the pain state, in addition to the hypothalamic region ipsilaterally to the pain side. CONCLUSION: Being that such structures are mainly involved in motor function and reactive behaviour, their activation, in our hypothesis, may be linked to pain avoidance and may well represent a defence reaction in cluster headache, which is characterised by a "fight-or-flight" type behavioural pattern during pain attacks.

Evidence of increased restless legs syndrome occurrence in chronic and highly disabling migraine.

The existence of an association between migraine and restless legs syndrome (RLS) has recently been reported, although the possible implications of this for migraine clinical presentation remain poorly understood. The objectives of this study were to determine RLS frequency in a population of migraineurs compared with healthy subjects and to assess RLS occurrence in episodic versus chronic migraine patients; the relationship between migraine-related disability and RLS comorbidity was also evaluated. Two hundred and seventy-seven consecutive migraineurs (ICHD-II, 2004) were enrolled and compared with 200 controls; migraine was episodic in 175 and chronic in 102 patients. RLS (IRLSSG criteria, 2003) was present in 22.7% of the total sample of migraineurs and in 7.5% of the controls (p<0.0001). RLS occurred significantly more frequently in chronic compared with episodic migraineurs (34.3% vs 16%, respectively, p=0.0006); a significant association between RLS diagnosis and moderate-severe migraine-related disability was also documented (p=0.0003). In conclusion, the results of the present study not only confirm the higher occurrence of RLS in migraine patients compared with the general population, but also suggest that RLS (the condition itself, or the disruption of sleep patterns often found in patients affected by RLS) might affect migraine clinical presentation, being associated with chronic and highly disabling migraine. These findings could have important therapeutic and prognostic implications in clinical practice.

Inflammatory myopathy in a patient with postural and kinetik tremor.

Essential tremor (ET) is a common neurological disease of unknown etiopathogenesis, possibly neurodegenerative, characterized by kinetic tremor at the arms. Here we reported the case of an HCV-positive patient with inflammatory myopathy, who did not develop typical neuromuscular signs or symptoms during at least 7 years of hyperCKemia, in whom kinetic tremor of the arms was the prominent clinical feature, suggesting a possible diagnosis of ET. After 3 months of treatment with corticosteroids/methotrexate, creatine kinase (CK) levels were nearly normal and the tremor was remarkably improved. To our knowledge, similar cases have not been previously reported. Postural tremor can be present in muscular diseases, but only very rarely tremor has been reported as a major clinical feature. Because inflammatory myopathies are potentially treatable conditions it is very important to consider this diagnosis. Our case suggests that in patients with isolated postural and kinetic tremor routine laboratory assays should include CK blood screening.

Victimization among children and adolescents accessing the Meyer pediatric hospital: A retrospective study.

PROBLEM: The consistent prevalence and occasionally severe consequences of bullying and victimization suggest the need to include a more accurate assessment of these episodes within the Emergency Departments (ED). However, the literature on mental health related symptoms of bullying/victimization treated in the ED is still scarce. The aim of this study is to assess the prevalence of peer victimization amongst children and adolescents referred to an Italian Pediatric Emergency Department. Differences between Hospital Departments, type of victimization and ages are tested. METHODS: A retrospective observational study was conducted with 705 subjects. The age range was from 6 to 18 years old (M = 13.09; SD = 3.048). FINDINGS: 15.3% of the sample reported to be victimized (8.2% occasionally; 7.1% systematically). For the Child and Adolescent Psychiatry Unit, we found a significant association between peer victimization and being adolescent (Fisher's p = 0.003). In addition, a significant association was found between verbal victimization and Child and Adolescent Psychiatry Unit (Fisher's p = 0.02) and physical victimization and Child Abuse Department (Fisher's p < 0.001). CONCLUSION: Findings suggest the importance of an accurate assessment of victimization experiences of children and adolescents with access to ED, to prevent future re-victimization and crystallization of symptoms across time.

CGRP Inhibitors and Oxidative Stress Biomarkers in Resistant Migraine: A Real-Life Study with Erenumab, Fremanezumab, and Galcanezumab.

Patients with high-frequency resistant migraine and medication-overuse headache are still the main clinical challenge in tertiary headache centers. The approval of targeted antibodies against the calcitonin gene-related peptide (CGRP) and its receptor represents a powerful instrument. In this study, we observed how biological and clinical features of resistant migraineurs responded to erenumab, fremanezumab, or galcanezumab. We found a reduction in advanced oxidation protein products (AOPP) as a biomarker of improved redox state after six months of treatment. We also found that treatment efficacy was precocious and maintained with high individual responder rates. In particular, seven out of ten patients achieved a reduction of 50% from the baseline at three months, which was maintained at six months, while about one out of our patients experienced a 75% reduction in headache frequency from the first month of treatment. The migraine disability assessment (MIDAS) and the associated fatigue, anxiety, and sleep quality also significantly improved. The allodynia symptom dropped from moderate/severe to mild/absent as a sign of central sensitization reduction. Our study confirmed the safety and efficacy of CGRP inhibition in real-life, high-challenging patients. Additional evidence is needed to understand the role of oxidative stress as a migraine biomarker.

Supersaturation of VEP in Migraine without Aura Patients Treated with Topiramate: An Anatomo-Functional Biomarker of the Disease.

Migraine is a primary headache with high prevalence among the general population, characterized by functional hypersensitivity to both exogenous and endogenous stimuli particularly affecting the nociceptive system. The hyperresponsivity of cortical neurons could be due to a disequilibrium in the excitatory/inhibitory signaling. This study aimed to investigate the anatomo-functional pathway from the retina to the primary visual cortex using visual evoked potentials (VEP). Contrast gain protocol was used in 15 patients diagnosed with migraine without aura (at baseline and after 3 months of topiramate therapy) and 13 controls. A saturation (S) index was assessed to monitor the response of VEP's amplitude to contrast gain. Non-linear nor monotone growth of VEP (S < 0.95) was defined as supersaturation. A greater percentage of migraine patients (53%) relative to controls (7%) showed this characteristic. A strong inverse correlation was found between the S index and the number of days separating the registration of VEP from the next migraine attack. Moreover, allodynia measured through the Allodynia Symptoms Check-list (ASC-12) correlates with the S index both at baseline and after 3 months of topiramate treatment. Other clinical characteristics were not related to supersaturation. Topiramate therapy, although effective, did not influence electrophysiological parameters suggesting a non-intracortical nor retinal origin of the supersaturation (with possible involvement of relay cells from the lateral geniculate nucleus). In conclusion, the elaboration of visual stimuli and visual cortex activity is different in migraine patients compared to controls. More data are necessary to confirm the potential use of the S index as a biomarker for the migraine cycle (association with the pain-phase) and cortical sensitization (allodynia).

Epilepsy after neuroimaging normalization in a woman with tacrolimus-related posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is known to occur after solid organ transplantation, and is caused by immunosuppressive agents such as tacrolimus. PRES onset usually occurs within the first 2months after liver transplantation. Clinical findings include seizures, headache, focal neurological deficits, visual disturbances, and altered mental status. These are associated with characteristic imaging features of subcortical white matter lesions on brain MRI. Atypical localizations of this posterior leukoencephalopathy have been reported. Expeditious recognition of the syndrome may lead to a complete recovery. Abnormalities of EEG during follow-up might be associated with unfavorable seizure outcome, even when neuroimaging changes resolve. We report a case of late-onset PRES with atypical localization following liver transplantation. The patient developed epilepsy despite resolution of MRI lesions at 8 months of follow-up. EEG was a prognostic factor of seizure persistence, suggesting an incomplete recovery of brain lesions in contrast to neuroimaging findings.

Functional magnetic resonance imaging in episodic cluster headache.

We have investigated the cerebral activation centre in four patients with episodic cluster headache (CH) with functional magnetic resonance imaging (f-MRI). The patients underwent MRI scans for anatomical and functional data acquisition in the asymptomatic state, during a headache attack and after subcutaneous administration of sumatriptan. Anatomical images were acquired by means of 3D-MPRAGE sequences and f-MRI images were obtained by means of echo-planar imaging. Data was analysed using the BrainVoyager QX version 1.7.81 software package. In all patients, the data showed significant hypothalamic activation of the hypothalamus ipsilateral to the pain side, attributable to a headache attack. Overall, we have demonstrated the anatomical location of central nervous system activation by means the first f-MRI study in CH patients. f-MRI offers a good balance of spatial and temporal resolution, and this method of study appears appropriate for investigating the pathogenetic aspects of primary headaches. Positron emission tomography and f-MRI may be regarded as little or no importance in a clinical context, they do, however, offer great potential for the exploration of headache physiopathology and the effects of pharmacological treatment.