Generation of a human induced pluripotent stem cell line from a patient with GM3 synthase deficiency using self-replicating RNA vector.

GM3 synthase deficiency (GM3SD) is caused by biallelic variants in the ST3GAL5 gene. Early clinical features of GM3SD include infantile onset of severe irritability and feeding difficulties, early intractable seizures, growth failure, hypotonia, sensorineural hearing impairment. We describe the generation and characterization the human induced pluripotent stem cell (hiPSC) line derived from fibroblasts of a 13-year-old girl with GM3 synthase deficiency resulted compound heterozygous for two new variants in the ST3GAL5 gene, c.1166A > G (p.His389Arg) and the c.1024G > A (p.Gly342Ser). The generated hiPSC line shows a normal karyotype, expresses pluripotency markers, and is able to differentiate into the three germ layers.

Childhood primary stabbing headache: A double center study.

BACKGROUND: Primary stabbing headache (PSH) is an idiopathic headache disorder characterized by head pain occurring as a transient and localized single stab or a series of stabs. The present study aimed to examine the characteristics of childhood PSH and whether they fit the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria. We also investigated the association with migraine and episodic syndromes. METHODS: In this retrospective study, we included 60 patients seen at two headache clinics (Rome and Bari) between 2016 and 2022. A headache-focused history was obtained. All patients had normal neurological examination. PSH was defined according to ICHD-3 criteria. RESULTS: Twenty-three patients were male (38%) and median (range) age at disease onset was 8 (3-17) years. Stabs recurred with irregular frequency and their duration varied from a few seconds up to 30 minutes. Stabs were located in different head regions. Twenty-five patients (42%) underwent neuroimaging exams. Five children reported a limitation of daily activities and none had a chronic pattern. Forty-seven patients (78%) reported a family history of primary headache, especially migraine, and forty-three had episodic syndromes (i.e. infantile colic, benign paroxysmal vertigo, motion sickness, recurrent abdominal pain, cyclic vomiting). Twenty patients had an associated primary headache: 16 suffered from migraine and four suffered from tension type-headache. According to ICHD-3 criteria, thirty-one patients had a diagnosis of probable PSH as a result of a duration of stabs longer than a few seconds (>3 seconds). CONCLUSIONS: Features of childhood PSH can vary widely. As seen in previous studies, several patients reported a stab duration longer than a few seconds and this might suggest that current ICHD-3 criteria may need adjustments to be suitable for children. High frequency of associated migraine and episodic syndromes could suggest a common pathophysiological mechanism between PSH and migraine. We can hypothesize that PSH and migraine attacks may be part of a spectrum of the same disease, although further evidence is needed. Larger studies with long-term follow-up are needed to improve understanding of this condition.

A Narrative Review of Visual Hallucinations in Migraine and Epilepsy: Similarities and Differences in Children and Adolescents.

Since the earliest descriptions of the simple visual hallucinations in migraine patients and in subjects suffering from occipital lobe epilepsy, several important issues have arisen in recognizing epileptic seizures of the occipital lobe, which often present with symptoms mimicking migraine. A detailed quantitative and qualitative clinical scrutiny of timing and characteristics of visual impairment can contribute to avoiding mistakes. Differential diagnosis, in children, might be challenging because of the partial clinical, therapeutic, and pathophysiological overlaps between the two diseases that often coexist. Ictal elementary visual hallucinations are defined by color, shape, size, location, movement, speed of appearance and duration, frequency, and associated symptoms and their progression. The evaluation of the distinctive clinical features of visual aura in migraine and visual hallucinations in occipital epilepsy could contribute to understanding the pathogenetic mechanisms of these two conditions. This paper aims to critically review the available scientific evidence on the main clinical criteria that address diagnosis, as well as similarities and differences in the pathophysiological mechanisms underlying the visual impairment in epilepsy and migraine.

Clinical Correlates of Osmophobia in Primary Headaches: An Observational Study in Child Cohorts.

Primary headaches, especially migraines, have a significant impact on physical and mental health, as well as on the scholarly performance and quality of life of children and adolescents. Osmophobia could be a potential diagnostic marker of migraine diagnosis and disability. This multicenter observational cross-sectional study included 645 children, aged 8-15, with a diagnosis of primary headaches. We took into consideration the duration, intensity and frequency of headaches, pericranial tenderness, allodynia and osmophobia. In a subgroup of migraine children, we evaluated the migraine-related disability, Psychiatric Self-Administration Scales for Youths and Adolescents, and the Child Version of the Pain Catastrophizing Scale. Osmophobia was found to be present in 28.8% of individuals with primary headaches, with children suffering from migraines having the highest prevalence (35%). Migraine patients with osmophobia also showed a more severe clinical picture, with enhanced disability, anxiety, depression, pain catastrophizing, and allodynia symptoms (F Roy square 10.47 p < 0.001). The presence of osmophobia could help in identifying a clinical migraine phenotype coherent with an abnormal bio-behavioral allostatic model that is worthy of prospective observations and careful therapeutic management.

Idiopathic Non-Dental Facial Pain Syndromes in Italian Children: A Clinical Case Series.

BACKGROUND: The orofacial pain syndromes (OFPs) are a heterogeneous group of syndromes characterized by painful attacks involving the orofacial structures. They may be summarily subdivided into two great categories: (1) orofacial pain mainly attributed to dental disorders such as dentoalveolar and myofascial orofacial pain or temporomandibular joint (TM) pain; (2) orofacial pain mainly attributed to non-dental pain as neuralgias, facial localization of primary headaches or idiopathic orofacial pain. The second group is uncommon, often described by single case reports, can often show overlapping symptoms with the first group, and represents a clinical challenge, carrying the risk of undervaluation and possibly invasive odontoiatric treatment. We aimed to describe a clinical pediatric series of non-dental orofacial pain and better to underline some topographic and clinical features associated with them. We retrospectively collected the data of children admitted to our headache centers (Bari, Palermo, Torino) from 2017 to 2021. Our inclusion criterion was the presence of non-dental orofacial pain following the topographic criteria of 3° International Classification of Headache Disorders (ICHD-3), and exclusion criteria included the pain syndromes attributed to the dental disorders and pain syndromes due to the secondary etiologies Results. Our sample comprised 43 subjects (23/20 M/F, in the range of ages 5-17). We classified them int: 23 primary headaches involving the facial territory during attacks, 2 facial trigeminal autonomic cephalalgias, 1 facial primary stabbing headache, 1 facial linear headache, 6 trochlear migraines, 1 orbital migraine 3 red ear syndrome and 6 atypical facial pain. All patients described debilitating pain for intensity (moderate/severe), 31 children had episodic attacks, and 12 had continuous pain. Almost all received drugs for acute treatment (less than 50% were satisfied), and some received non-pharmacological treatment associated with drug therapy Conclusion. Although rare OFP can occur in pediatric age, it can be debilitating if unrecognized and untreated, affecting the psychophysical well-being of young patients. We highlight the specific characteristics of the disorder for a more correct and earlier identification during the diagnostic process, already difficult in pediatric age, and to define the approach and possible treatment to prevent negative outcomes in adulthood.

Evolution of Pediatric Migraine Patients Admitted at an Emergency Department after a 10-Year Follow-Up.

BACKGROUND: Despite its high prevalence, the clinical course of pediatric migraine has not been fully understood, and previous studies present conflicting results. We present here the findings of a 10-year follow-up study involving children with severe migraine pain admitted to our emergency department. Furthermore, all studies were carried out on selected outpatient clinical case studies. Our aim was to evaluate a population of migraine children admitted to an emergency department because of increased severity or frequency of pain or even because of very anxious parents concerning their child's headache in order to describe their long-term outcomes, whether it differed from that of outpatient populations and to identify possible predictors of prognosis. METHODS: We recruited 80 subjects with migraine headaches (mean age 8 years with a range of 4-14 years, 50% females), attending the baseline examination of a population admitted for a headache to the Emergency Department in the first half year of 2012. Of the 80 subjects, 48 (60%) were eligible for follow-up in 2022. We included in our study only patients diagnosed with migraine, according to the diagnostic criteria of the International Classification of Headache Disorders. All were contacted by telephone, and a semi-structured questionnaire was provided to them by email. The association between several possible prognostic factors (gender, familiar neurologic disorders, prenatal and perinatal disorders, social activities, sleep disorders, etc.) and the long-term persistence of migraine headaches were explored using logistic regression analysis. RESULTS: Of 48 subjects with migraine headaches at baseline, 31 (65%) had persistent migraine, and 17 (35%) experienced remission. The preliminary results showed that the presence of neurologic disorders in parents (p < 0.01-odds ratio 9.34 (2.53-41.64) and sleep disorders (p < 0.01-odds ratio 13.18 (2.25-252.74) significantly predicted the 10-year persistence of migraine headaches, while the other considered predictors were found not to influence prognosis. CONCLUSIONS: To our knowledge, this was the first study conducted on a selected pediatric population upon admission to the emergency room. Our study suggests that a population of pediatric migraine selected for admission to the emergency department also shows a favorable long-term prognosis, like the studies conducted in the outpatient sample. Familial neurological comorbidity and sleep disorders were unfavorable factors for predicting good outcomes.

A registry for Dravet syndrome: The Italian experience.

OBJECTIVES: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. METHODS: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. RESULTS: At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0-9) while at last follow-up was 11 years (IQR 5-18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). SIGNIFICANCE: The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes.

Pediatric Migraine: Diagnosis and Management.

The WHO recognizes migraine as one of the most disabling diseases [...].

The Pediatric Trochlear Migraine: Diagnostic and Therapeutic Implications.

Trochlear Migraine has been recently described as the concurrence of strictly unilateral migraine and ipsilateral trochleodynia with relief of migraine after successful treatment of trochleodynia. This disorder has been interpreted as "cluster-tic syndrome" or "seizure-triggered migraine". Trochlear Migraine is unrecognized and rarely described in childhood. The aim of this study is to review the few cases of Trochlear Migraine reported in the literature in addition to the cases observed in our clinical experience. In particular, our cases showed recurrent attacks of severe and pulsating headache associated with nausea, vomiting, phonophobia, photophobia, and strict trochlear localization of pain. They often presented with alternating side attacks. Therefore, we suggest that the term "Trochlear Migraine" should be reserved for clinical migraine attacks strictly localized in the trochlear region, and we assume that the excessive increase in descriptions of new primary headache syndromes, according to the International Classification of Headache Disorders, can be probably be ascribed to the common physiopathological mechanisms characterizing these forms of migraine.

Lower Prevalence of Chronic Pain in Manifest Huntington's Disease: A Pilot Observational Study.

Pain is a minor problem compared with other Huntington Disease (HD) symptoms. Nevertheless, in HD it is poorly recognized and underestimated. So far, no study evaluated the presence of chronic pain in HD. The aim of this pilot study was to evaluate the presence and features of chronic pain in a cohort of HD gene carriers. An observational cross-sectional study was conducted in a cohort of HD gene carriers compared to not gene carriers (n.134 HD subjects, n.74 not gene mutation carriers). A specific pain interview, alongside a neurological, cognitive and behavioural examination, was performed in order to classify the type of pain, subjective intensity. A significant prevalence of "no Pain" in HD was found, which tended to increase with HD progression and a reduced frequency of pain in the last 3 months. A clear difference was found between manifest and premanifest HD in terms of intensity of pain, which did not change significantly with HD progression; however, a tendency emerges to a progressive reduction. No significant group difference was present in analgesic use, type and the site of pain. These findings could support a lower prevalence of chronic pain in manifest HD. Prevalence and intensity of chronic pain seem directly influenced by the process of neurodegeneration rather than by an incorrect cognitive and emotional functioning.

The association between gastro-oesophageal reflux and migraine in the paediatric population: a multicentre case-control study.

Infantile regurgitation is one of the most common discomforts in the first months of life. Infantile colic and, in older children, functional dyspepsia have been linked to migraine. To date, this is the first study to investigate a possible association between infantile regurgitation and primary headaches in children. This is a case-control study of 195 children aged 6-17 years, with primary headache (migraine, or tension type headache) in 5 European paediatric hospitals. The control group is composed of 240 same-aged children attending with minor injuries during the same period - February 1st 2020 to December 1st 2020. A structured questionnaire identified a history of infantile regurgitation and other functional gastrointestinal disorders for case and control participants. The outcome was the difference in the prevalence of infantile regurgitation among children with or without a diagnosis of primary headache. The analysis showed a significant association between infantile regurgitation and migraine (OR = 1.88, CI 95 = 1.01-3.4, p = 0.04). No association was found between infantile regurgitation and tension type headache (p = 0.33). Subgroup analysis confirmed that the association was only significant for migraine without aura (OR = 2.3, CI 95 = 1.2-4.4, p = 0.01). In a further subgroup analysis, the presence of functional dyspepsia, irritable bowel syndrome and abdominal migraine was associated with migraine without aura. CONCLUSION: The presence of migraine among children aged 6-17 was associated with a history of infantile regurgitation. Additional longitudinal studies are required to confirm whether infantile regurgitation could be considered as a precursor of migraine. WHAT IS KNOWN: • Children suffering from functional gastrointestinal disorders are more likely to be suffering from migraine and tension-type headache as well. • Children suffering from primary headache are more likely to have had infantile colic in their first six month of life. WHAT IS NEW: • It is the first study to find an association between migraine and infantile regurgitation in children. • These findings could have an impact on the diagnosis and therapeutics of both migraine and infantile regurgitation.

Case report: LAMC3-associated cortical malformations: Case report of a novel stop-gain variant and literature review.

Background: Malformations of cortical development (MCDs) can lead to peculiar neuroradiological patterns and clinical presentations (i.e., seizures, cerebral palsy, and intellectual disability) according to the specific genetic pathway of the brain development involved; and yet a certain degree of phenotypic heterogeneity exists even when the same gene is affected. Here we report a man with an malformations of cortical development extending beyond occipital lobes associated with a novel stop-gain variant in LAMC3. Case presentation: The patient is a 28-year-old man suffering from drug-resistant epilepsy and moderate intellectual disability. He underwent a brain magnetic resonance imaging showing polymicrogyria involving occipital and temporal lobes bilaterally. After performing exome sequencing, a novel stop-gain variant in LAMC3 (c.3871C>T; p. Arg1291*) was identified. According to the cortical alteration of the temporal regions, temporal seizures were detected; instead, the patient did not report occipital seizures. Different pharmacological and non-pharmacological interventions (i.e., vagus nerve stimulation) were unsuccessful, even though a partial seizure reduction was obtained after cenobamate administration. Conclusion: Our case report confirms that variants of a gene known to be related to specific clinical and neuroradiological pictures can unexpectedly lead to new phenotypes involving different areas of the brain.

I stay at home with headache. A survey to investigate how the lockdown for COVID-19 impacted on headache in Italian children.

OBJECTIVE: The present Italian multicenter study aimed at investigating whether the course of primary headache disorders in children and adolescents was changed during the lockdown necessary to contain the COVID-19 emergency in Italy. METHODS: During the lockdown, we submitted an online questionnaire to patients already diagnosed with primary headache disorders. Questions explored the course of headache, daily habits, psychological factors related to COVID-19, general mood and school stress. Answers were transformed into data for statistical analysis. Through a bivariate analysis, the main variables affecting the subjective trend of headache, and intensity and frequency of the attacks were selected. The significant variables were then used for the multivariate analysis. RESULTS: We collected the answers of 707 patients. In the multivariate analysis, we found that reduction of school effort and anxiety was the main factor explaining the improvement in the subjective trend of headache and the intensity and frequency of the attacks (p < 0.001). The greater the severity of headache, the larger was the clinical improvement (p < 0.001). Disease duration was negatively associated with the improvement (p < 0.001). It is noteworthy that clinical improvement was independent of prophylaxis (p > 0.05), presence of chronic headache disorders (p > 0.05) and geographical area (p > 0.05). CONCLUSIONS: Our study showed that lifestyle modification represents the main factor impacting the course of primary headache disorders in children and adolescents. In particular, reduction in school-related stress during the lockdown was the main factor explaining the general headache improvement in our population.

Juvenile Fibromyalgia and Headache Comorbidity in Children and Adolescents: A Literature Review.

Juvenile fibromyalgia (JFM) is a chronic pain syndrome with onset in developmental age, characterized by widespread musculoskeletal pain associated with other neurological or nonneurological symptoms. Headache is one of the most frequent comorbid conditions with JFM, but this association is still poorly studied in the juvenile population. The literature review was conducted searching through PubMed, Scopus, and Web of Science with a combination of the following free-text terms: "fibromyalgia," "juvenile fibromyalgia," "headache," "primary headache," "migraine," "children," "adolescents," and "comorbidity." The research resulted only in two specific studies regarding comorbidity JFM + Juvenile Headache (JH). From each study, we extracted data about sample features, clinical characteristics of both JFM and PH, and assessment tools. The clinical approach to JFM and JH should include a complete examination of the main causes of comorbid diseases, thus improving the therapeutic approach to the patient in developmental age.

Pain Catastrophizing in Childhood Migraine: An Observational Study in a Tertiary Headache Center.

Background: Migraine is the most common cause of primary headache in children leading to a decrease in the quality of life. During the last decade, pain catastrophizing construct became a major focus of interest in the study and treatment of pain. Aim of the study: To evaluate pain catastrophizing in episodic and chronic migraine children and adolescents selected in a tertiary headache Center.To test whether the children's pain catastrophizing might be associated (a) with the frequency of attacks and disability (b) with psychopathological aspects (c) with allodynia and total tenderness score as symptom of central sensitization.To test the best discriminating clinical variables and scores between episodic and chronic migraine, including pain catastrophizing. Methods: We conducted a cross sectional observational study on consecutive pediatric patients affected by migraine. We selected 190 headache patients who met the diagnostic criteria for Migraine without aura, Migraine with aura and Chronic migraine. We submitted all children to the Child version of the Pain Catastrophizing Scale (PCS-C), and to the disability scale for migraine (PedMIDAS), general quality of life estimated by children (PedsQL) and parents (PedsQL-P), anxiety and depression (SAFA-A; SAFA-D) scales. We also evaluated headache frequency and the presence and severity of allodynia and pericranial tenderness. Results: No difference was detected in Total Pain Catastrophizing score (PCS-C) between chronic and episodic migraine groups (ANOVA F = 0.59, p = 0.70); the PedMIDAS, the PedsQL-P for physical functioning and the Total Tenderness Score were discriminant variables between episodic and chronic migraine. The PCS-C was not correlated with migraine related disability as expressed by Ped MIDAS, but it was significantly correlated with general low quality of life, allodynia, pericranial tenderness, anxiety, and depression. Conclusion: Pain catastrophizing seems a mental characteristic of a clinical phenotype with psychopathological traits and enhanced expression of central sensitization symptoms. This clinical profile causes general decline in quality of life in the child judgment, with a probable parents' underestimation. In childhood age, it would not be a feature of chronic migraine, but the possibility that it could predict this evolution is consistent and worthy of further prospective evaluation.

Headache attributed to aeroplane travel: the first multicentric survey in a paediatric population affected by primary headaches.

BACKGROUND: This multicentric survey investigates the prevalence and characteristics of Airplane Headache in children affected by primary headaches. METHODS: Patients with symptoms of Airplane Headache were recruited from nine Italian Pediatric Headache Centres. Each patient was handed a structured questionnaire which met the ICHD-III criteria. RESULTS: Among 320 children suffering from primary headaches who had flights during their lifetime, 15 (4.7%) had Airplane Headache, with mean age of 12.4 years. Most of the patients were females (80%). The headache was predominantly bilateral (80%) and localized to the frontal area (60%); it was mainly pulsating, and lasted less than 30 min in all cases. Accompanying symptoms were tearing, photophobia, phonophobia in most of the cases (73.3%). More than 30% of patients used medications to treat the attacks, with good results. CONCLUSION: Our study shows that Airplane Headache is not a rare disorder in children affected by primary headaches and highlights that its features in children are peculiar and differ from those described in adults. In children Airplane Headache prevails in females, is more often bilateral, has frequently accompanying symptoms and occurs at any time during the flight. Further studies are needed to confirm the actual frequency of Airplane Headache in the general pediatric population not selected from specialized Headache Centres, with and without other concomitant headache condition, and to better clarify the clinical characteristics, pathophysiology and potential therapies.

Symptoms of central sensitization and comorbidity for juvenile fibromyalgia in childhood migraine: an observational study in a tertiary headache center.

BACKGROUND: Central sensitization is an important epiphenomenon of the adult migraine, clinically expressed by allodynia, pericranial tenderness and comorbidity for fibromyalgia in a relevant number of patients. This study aimed to evaluate the frequency and the clinical characteristics of allodynia, pericranial tenderness, and comorbidity for Juvenile Fibromialgia (JFM) in a cohort of migraine children selected in a tertiary headache center. METHODS: This was an observational cross-sectional study on 8-15 years old migraine patients. Allodynia was assessed by a questionnaire. Pericranial tenderness and comorbidity for JFM as well as their possible association with poor quality of life and migraine related disability, and with other clinical symptoms as anxiety, depression, sleep disorders and pain catastrophizing, were also evaluated. RESULTS: One hundred and fifty one patients were selected, including chronic migraine (n°47), migraine without aura (n° 92) and migraine with aura (n° 12) sufferers. Allodynia was reported in the 96,6% and pericranial tenderness was observed in the 68.8% of patients. Pericranial tenderness was more severe in patients with more frequent migraine and shorter sleep duration. Allodynia seemed associated with anxiety, pain catastrophizing and high disability scores. Comorbidity for JFM was present in the 0.03% ofpatients. These children presented with a severe depression and a significant reduction of quality of life as compared to the other patients. CONCLUSIONS: This study outlined a relevant presence of symptoms of central sensitization among children with migraine. Severe allodynia and comorbidity for JFM seemed to cause a general decline of quality of life, which would suggest the opportunity of a routine assessment of these clinical features.

Survey on treatments for primary headaches in 13 specialized juvenile Headache Centers: The first multicenter Italian study.

AIM: The purpose of this retrospective multicenter study was to evaluate the use and the self-perceived efficacy and tolerability of pharmacological and non-pharmacological treatments in children and adolescents with primary headaches. METHODS: Study of a cohort of children and adolescents diagnosed with primary headache, consecutively referred to 13 juvenile Italian Headache Centers. An ad hoc questionnaire was used for clinical data collection. RESULTS: Among 706 patients with primary headaches included in the study, 637 cases with a single type of headache (migraine 76% - with and without aura in 10% and 67% respectively; tension-type headache 24%) were selected (mean age at clinical interview: 12 years). Acetaminophen and non-steroidal anti-inflammatory drugs (in particular ibuprofen) were commonly used to treat attacks, by 76% and 46% of cases respectively. Triptans were used overall by 6% of migraineurs and by 13% of adolescents with migraine, with better efficacy than acetaminophen and non-steroidal anti-inflammatory drugs. Preventive drugs were used by 19% of migraineurs and by 3% of subjects with tension-type headache. In migraineurs, flunarizine was the most frequently used drug (18%), followed by antiepileptic drugs (7%) and pizotifen (6%), while cyproheptadine, propanolol and amitriptyline were rarely used. Pizotifen showed the best perceived efficacy and tolerability. Melatonin and nutraceuticals were used by 10% and 32% of subjects, respectively, both for migraine and tension-type headache, with good results in terms of perceived efficacy and tolerability. Non-pharmacological preventive treatments (i.e. relaxation techniques, biofeedback, cognitive-behavioral therapy, acupuncture) were used only by 10% of cases (migraine 9%, tension-type headache 15%). DISCUSSION: Non-steroidal anti-inflammatory drugs, especially ibuprofen, should be preferred to acetaminophen for acute attacks of migraine or tension-type headache, because they were usually more effective and well tolerated. Triptans could be used more frequently as first or almost second choice for treating migraine attack in adolescents. Non-pharmacological preventive treatments are recommended by some pediatric guidelines as first-line interventions for primary headaches and their use should be implemented in clinical practice. Prospective multicenter studies based on larger series are warranted to better understand the best treatment strategies for young people with primary headaches.

Laser Evoked Potentials in Early and Presymptomatic Huntington's Disease.

Pain was rarely studied in Huntington's disease (HD). We presently aimed to extend our previous study on pain pathways functions by laser evoked potentials (LEPs) to a larger cohort of early unmedicated HD patients and a small group of presymptomatic HD (PHD) subjects. Forty-two early HD patients, 10 PHD patients, and 64 controls were submitted to LEPs by right-hand stimulation. Two series of 30 laser stimuli were delivered, and artifact-free responses were averaged. The N1, N2, and P2 latencies were significantly increased and the N2P2 amplitude significantly reduced in HD patients compared to controls. In the HD group, the LEPs abnormalities correlated with functional decline. PHD subjects showed a slight and insignificant increase in LEPs latencies, which was inversely correlated with the possible age of HD clinical onset. Data of the present study seem to suggest that the functional state of nociceptive pathways as assessed by LEPs may be a potential biomarker of disease onset and progression. The assessment of pain symptoms in premanifest and manifest HD may also open a new scenario in terms of subtle disturbances of pain processing, which may have a role in the global burden of the disease.

Migraine and Central Sensitization: Clinical Features, Main Comorbidities and Therapeutic Perspectives.

UNLABELLED: Migraine is a very common neurologic disorder, characterized by recurrent attacks of severe headache, autonomic nervous system dysfunction and in some patients by an aura. BACKGROUND: Migraine is a very common neurologic disorder of neuro-vascular origin, being amongst the 20 most disabling diseases. Migraine attacks are characterized by severe headache, associated to autonomic nervous system dysfunction and in some patients by aura. Pathophysiology and Role of Central Sensitization: Abnormal neuronal excitability may subtend altered processing of sensory stimuli, leading to cortical spreading depression and trigeminal activation. A dysfunction of pain modulation enhances central sensitization phenomena, contributing to acute allodynia and headache persistence. The peculiarity of migraine pain facilitates the use of analgesics, and causes an adjunctive invalidating tendency toward drug over-use. Comorbidity: Chronic migraine patients are frequently affected by diffuse pain, framed in fibromyalgia diagnosis. This comorbidity seems to be supported by common pathophysiological mechanisms. It may aggravate migraine invalidity being worth of consideration for therapeutic management. Migraine Management: Acute and preventive treatments need to be tailored to single cases. Main comorbidity and factors facilitating central sensitization should be taken into account. The management of migraine patients should include a link between headache centers and general practitioner, in order to provide for a better patient information and treatment just at the onset of the disease. CONCLUSIONS: Despite its high epidemiologic impact, migraine is frequently underestimated and destined to evolve into chronic form and drugs abuse. A more focused attention to factors facilitating central sensitization and invalidating comorbidities, should reduce the global burden of the disease. KEY WORDS: migraine, pathophysiology, central sensitization, fibromyalgia comorbidity, acute and preventive therapy, patients - centered approach.