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.

Neuropsychological performances, quality of life, and psychological issues in pediatric onset multiple sclerosis: a narrative review.

Multiple sclerosis (MS) is primarily a disease diagnosed in young and middle-aged adults. Although MS is a rare condition in pediatric age, an increasing rate of patients is diagnosed under the age of 18. The disabling nature of the disease cannot be reduced only to physical symptoms. Several additional symptoms such as cognitive impairment, fatigue, and psychological symptoms are common features of pediatric MS. The reviewed literature suggests that, despite the lower physical disability, children and adolescents diagnosed with MS are vulnerable to cognitive impairment even in the early stage of the disease. The neuropsychological profile of pediatric MS may resemble that of adult MS, including an impairment in attention/information processing speed, learning, verbal, and visuospatial memory. However, cognitive difficulties in children and adolescents are more likely to involve also general intelligence and linguistic abilities, presumably due to patients' younger age and cognitive growth stage. Cognitive difficulties, beyond physical disability and relapses, may have a considerable impact on learning and school achievement. Depression and fatigue are other highly prevalent disturbances in pediatric MS and may contribute to patients' low functional outcomes. Overall, these manifestations may cause considerable functional impairment on daily activities and quality of life that may require individualized rehabilitative treatment and extensive psychosocial care. Additional neuropsychological research evaluating larger samples, using more homogenous methods, and exploring the role of MS treatment on cognitive and psychological development is required.

Unsatisfactory response to acute medications does not affect the medication overuse headache development in pediatric chronic migraine.

BACKGROUND: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. METHODS: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation. RESULTS: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05). CONCLUSIONS: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities.

Headache attributed to SARS-CoV-2 infection, vaccination and the impact on primary headache disorders of the COVID-19 pandemic: A comprehensive review.

OBJECTIVE: The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders. METHODS: This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords "COVID 19" or "vaccine" and "headache" to assess the appropriateness of all published articles for their inclusion in the review. RESULTS: Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced. CONCLUSIONS: The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

The Enigma of New Daily Persistent Headache: What Solutions for Pediatric Age?

PURPOSE OF REVIEW: To analyze systematically the evidence currently available from the literature regarding the diagnosis, clinical characteristics, treatment and outcome of new daily persistent headache (NDPH). RECENT FINDINGS: NDPH is a primary headache characterized by an abrupt onset with continuous daily pain that can persist for many months. Although self-limiting forms have been described, NDPH is frequently associated with high disability even in children and adolescents. For this reason, it is very important to recognize it from a diagnostic point of view and to treat it. We found little specific data on NDPH in developmental age. Most of the therapy studies have been conducted on adults with conflicting data. Currently, pediatric NDPH therapy is based on experiences in adult patients and in individuals with other forms of primary chronic headache, hence the need for more pediatric studies to fill this information gap.

Age-related sensory neuropathy in patients with spinal muscular atrophy type 1.

INTRODUCTION/AIMS: Spinal muscular atrophy type 1 (SMA 1) is a devastating motor neuron disorder that leads to progressive muscle weakness, respiratory failure and premature death. Although sensory electrophysiological changes have been anecdotally found in pediatric SMA 1 patients, the age of onset of sensory neuropathy remains unknown. METHODS: Sensory nerve conduction studies of the median and sural nerves were performed in 28 consecutive SMA 1 patients of different ages. Sensory nerve conduction velocities and sensory nerve action potential (SNAP) amplitudes recorded in these patients were compared with those obtained from 93 healthy subjects stratified by age. RESULTS: SNAP amplitudes decreased with increasing age in the sural and median nerves, without any significant difference between upper and lower limbs. DISCUSSION: Our data suggest that sural and median nerve SNAP amplitudes are normal in younger patients, while an axonal neuropathy appears in older ones.

Childhood-Onset Multifocal Motor Neuropathy with IgM Antibodies to Gangliosides GM1: A Case Report with Poor Outcome.

BACKGROUND: Multifocal motor neuropathy (MMN) is a slowly progressive motor neuropathy characterized by asymmetric muscle weakness without sensory involvement. Typically, MMN respond completely to treatment with intravenous immunoglobulin (IVIg). MMN is even rarer in the pediatric population, where only five patients have been reported up to now. CASE REPORT: We discuss the 3-year follow-up of a 13-year-old girl with MMN who was positive for IgM antibodies to gangliosides GM1. She was diagnosed with MMN in accordance with the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria. Serological studies revealed that she tested positive for IgM antibodies to GM1. She underwent intravenous methylprednisolone followed by an oral prednisone taper, intravenous immunoglobulin (IVIg), plasma exchange followed by IVIG and prednisone and Rituximab. No improvement was referred. At the present, she shows flaccid tetraplegia, facial diplegia, and bulbar cranial nerve palsy. CONCLUSION: Although childhood onset MMN is rare, most patients reported in literature respond to IVIg treatment. In a few cases, however, IVIg can be ineffective. In our patient, IVIg as well as treatment with prednisolone, plasma exchange and rituximab have failed.

Fingolimod in pediatric multiple sclerosis: three case reports.

Treatment for pediatric-onset multiple sclerosis (POMS) currently reflects treatment for adult-onset MS, despite some differences in its clinical course. First-choice treatment of POMS generally consists of interferon ß-1a or glatiramer acetate, with therapies such as natalizumab or fingolimod reserved for second-choice treatment. In cases of severe disease, both fingolimod and natalizumab can be considered first-choice therapy. This paper presents three case histories of patients with POMS and highlights the different uses of fingolimod within the POMS treatment algorithm. The first and third cases are examples of escalation therapy, both in females aged 16 to 17 years, with fingolimod administering as second choice following disease progression. The second case is an example of using fingolimod as first-choice therapy, given to a 12-year-old male with severe disease. In all three cases, over a period of approximately 1 year after the initiation of fingolimod treatment, there was no further disease progression and no adverse events were recorded.

Early alterations of cortical thickness and gyrification in migraine without aura: a retrospective MRI study in pediatric patients.

BACKGROUND: Migraine is the most common neurological disease, with high social-economical burden. Although there is growing evidence of brain structural and functional abnormalities in patients with migraine, few studies have been conducted on children and no studies investigating cortical gyrification have been conducted on pediatric patients affected by migraine without aura. METHODS: Seventy-two pediatric patients affected by migraine without aura and eighty-two controls aged between 6 and 18 were retrospectively recruited with the following inclusion criteria: MRI exam showing no morphological or signal abnormalities, no systemic comorbidities, no abnormal neurological examination. Cortical thickness (CT) and local gyrification index (LGI) were obtained through a dedicated algorithm, consisting of a combination of voxel-based and surface-based morphometric techniques. The statistical analysis was performed separately on CT and LGI between: patients and controls; subgroups of controls and subgroups of patients. RESULTS: Patients showed a decreased LGI in the left superior parietal lobule and in the supramarginal gyrus, compared to controls. Female patients presented a decreased LGI in the right superior, middle and transverse temporal gyri, right postcentral gyrus and supramarginal gyrus compared to male patients. Compared to migraine patients younger than 12 years, the ≥ 12-year-old subjects showed a decreased CT in the superior and middle frontal gyri, pre- and post-central cortex, paracentral lobule, superior and transverse temporal gyri, supramarginal gyrus and posterior insula. Migraine patients experiencing nausea and/or vomiting during headache attacks presented an increased CT in the pars opercularis of the left inferior frontal gyrus. CONCLUSIONS: Differences in CT and LGI in patients affected by migraine without aura may suggest the presence of congenital and acquired abnormalities in migraine and that migraine might represent a vast spectrum of different entities. In particular, ≥ 12-year-old pediatric patients showed a decreased CT in areas related to the executive function and nociceptive networks compared to younger patients, while female patients compared to males showed a decreased CT of the auditory cortex compared to males. Therefore, early and tailored therapies are paramount to obtain migraine control, prevent cerebral reduction of cortical thickness and preserve executive function and nociception networks to ensure a high quality of life.

Preoperative serum circulating microRNAs as potential biomarkers for chronic postoperative pain after total knee replacement.

BACKGROUND: Chronic postoperative pain affects approximately 20% of patients with knee osteoarthritis after total knee replacement. Circulating microRNAs can be found in serum and might act as biomarkers in a variety of diseases. The current study aimed to investigate the preoperative expression of circulating microRNAs as potential predictive biomarkers for the development of chronic postoperative pain in the year following total knee replacement. METHODS: Serum samples, collected preoperatively from 136 knee osteoarthritis patients, were analyzed for 21 circulatory microRNAs. Pain intensity was assessed using a visual analog scale before and one year after total knee replacement. Patients were divided into a low-pain relief group (pain relief percentage <30%) and a high-pain relief group (pain relief percentage >30%) based on their pain relief one year after total knee replacement, and differences in microRNAs expression were analyzed between the two groups. RESULTS: We found that three microRNAs were preoperatively dysregulated in serum in the low-pain relief group compared with the high-pain relief group. MicroRNAs hsa-miR-146a-5p, -145-5p, and -130 b-3p exhibited fold changes of 1.50, 1.55, and 1.61, respectively, between the groups (all P values < 0.05). Hsa-miR-146a-5p and preoperative pain intensity correlated positively with postoperative pain relief (respectively, R = 0.300, P = 0.006; R = 0.500, P < 0.001). DISCUSSION: This study showed that patients with a low postoperative pain relief present a dysregulation of circulating microRNAs. Altered circulatory microRNAs expression correlated with postoperative pain relief, indicating that microRNAs can serve as predictive biomarkers of pain outcome after surgery and hence may foster new strategies for preventing chronic postoperative pain after total knee replacement (TKR).

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.

Pearl and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part II.

This review focuses on new and/or less standardized event-related potentials methods, in order to improve their knowledge for future clinical applications. The olfactory event-related potentials (OERPs) assess the olfactory functions in time domain, with potential utility in anosmia and degenerative diseases. The transcranial magnetic stimulation-electroencephalography (TMS-EEG) could support the investigation of the intracerebral connections with very high temporal discrimination. Its application in the diagnosis of disorders of consciousness has achieved recent confirmation. Magnetoencephalography (MEG) and event-related fields (ERF) could improve spatial accuracy of scalp signals, with potential large application in pre-surgical study of epileptic patients. Although these techniques have methodological limits, such as high inter- and intraindividual variability and high costs, their diffusion among researchers and clinicians is hopeful, pending their standardization.

Pearls and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part I.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

Hematopoietic Stem Cell Transplantation in Neuromyelitis Optica-Spectrum Disorders (NMO-SD): State-of-the-Art and Future Perspectives.

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune inflammatory disorders of the central nervous system (CNS). Understanding of the molecular basis of these diseases in the last decades has led to an important improvement in the treatment of this disease, in particular, to the use of immunotherapeutic approaches, such as monoclonal antibodies and Hematopoietic Stem Cell Transplantation (HSCT). The aim of this review is to summarize the pathogenesis, biological basis and new treatment options of these disorders, with a particular focus on HSCT applications. Different HSCT strategies are being explored in NMOSD, both autologous and allogeneic HSCT, with the new emergence of therapeutic effects such as an induction of tolerance to auto-antigens and graft versus autoimmunity effects that can be exploited to hopefully treat a disease that still has prognosis.

Cerebellar Transcranial Direct Current Stimulation (ctDCS) Ameliorates Phantom Limb Pain and Non-painful Phantom Limb Sensations.

Phantom limb pain (PLP) is a disabling and intractable sensation arising in about 80% of patients after amputation. The aim of this study was to evaluate the possibility to modulate nociceptive processing and pain perception with cerebellar transcranial direct current stimulation (ctDCS) in patients suffering from painful and non-painful phantom limb sensations. Fourteen upper limb amputees underwent ctDCS (anodal or sham, 2.0 mA, 20 min per day, 5 days a week). Clinical scores and electrophysiological parameters were assessed before tDCS, at the end of the 5-day treatment, 2 and 4 weeks later. Laser-evoked potentials (LEPs) were obtained from the stump using a Nd:YAP laser by pulses with short duration (5 ms) and small diameter spots (5 mm). Changes in visual analogue scores (VAS) were evaluated (chronic pain, paroxysmal pain, stump pain, phantom movements, phantom sensations). Anodal polarization significantly dampened LEP amplitudes (N1, p = 0.021 and N2/P2, p = 0.0034), whereas sham intervention left them unchanged. Anodal ctDCS significantly reduced paroxysmal pain (p < 0.0001), non-painful phantom limb sensations (p < 0.0001) and phantom limb movements (p = 0.0003), whereas phantom limb and stump pain did not change compared to the sham condition. Anodal ctDCS significantly improves both paroxysmal pain and non-painful phantom limb sensations, which are likely induced by maladaptive changes in the sensorimotor network and posterior parietal cortex respectively.

Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a high risk of developing primary headache: A longitudinal study.

BACKGROUND AND AIM: Episodic syndromes that may be associated with migraine are a group of disorders affecting patients with migraine or with an increased risk of presenting it, and likely represent an early life expression of migraine. Cyclic vomiting syndrome and benign paroxysmal torticollis are well characterized and represent a frequent cause of request for specialist consultations. The aim of this study is to longitudinally assess the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy, and to define the main clinical features of the disorder. METHODS: We administered a questionnaire to the parents of all our pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis according to ICHD-3; questions were focused on the main clinical features of the disorder as well as the prognosis, with particular emphasis on the development of headache. RESULTS: For the final analysis we considered 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis. Seventy-nine percent of patients with cyclic vomiting syndrome presented with headache during the follow-up, with a mean age at onset of 6 years; 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up, with a mean age at onset of 5 years. DISCUSSION: Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. In both groups of patients, the vast majority presented with different episodic syndromes that may be associated with migraine at different ages, thus suggesting an age-dependent evolution of migraine-like symptoms before the onset of clear migrainous headache.

Relapse risk factors in anti-N-methyl-D-aspartate receptor encephalitis.

AIM: To identify factors that may predict and affect the risk of relapse in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHOD: This was a retrospective study of an Italian cohort of patients with paediatric (≤18y) onset anti-NMDAR encephalitis. RESULTS: Of the 62 children included (39 females; median age at onset 9y 10mo, range 1y 2mo-18y; onset between 2005 and 2018), 21 per cent relapsed (median two total events per relapsing patient, range 2-4). Time to first relapse was median 31.5 months (range 7-89mo). Severity at first relapse was lower than onset (median modified Rankin Scale [mRS] 3, range 2-4, vs median mRS 5, range 3-5; admission to intensive care unit: 0/10 vs 3/10). At the survival analysis, the risk of relapsing was significantly lower in patients who received three or more different immune therapies at first disease event (hazard ratio 0.208, 95% confidence interval 0.046-0.941; p=0.042). Neurological outcome at follow-up did not differ significantly between patients with relapsing and monophasic disease (mRS 0-1 in 39/49 vs 12/13; p=0.431), although follow-up duration was significantly longer in relapsing (median 84mo, range 14-137mo) than in monophasic patients (median 32mo, range 4-108mo; p=0.002). INTERPRETATION: Relapses may occur in about one-fifth of children with anti-NMDAR encephalitis, are generally milder than at onset, and may span over a long period, although they do not seem to be associated with severity in the acute phase or with outcome at follow-up. Aggressive immune therapy at onset may reduce risk of relapse. WHAT THIS PAPER ADDS: Relapses of anti-N-methyl-D-aspartate receptor encephalitis may span over a long period. Relapses were not associated with severity in the acute phase or outcome at follow-up. Aggressive immune therapy at onset appears to decrease risk of relapse.

Childhood Rapid-Onset Ataxia: Expanding the Phenotypic Spectrum of ATP1A3 Mutations.

ATP1A3 mutations are related to a wide spectrum of clinical conditions, including several defined syndromes as rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), together with many other intermediate phenotypes. Ataxia is always more increasingly reported, either as accessory or prominent sign, in ATP1A3-related conditions, being thus considered as a peculiar feature of this spectrum. Here, we report three cases of childhood rapid-onset ataxia due to two different ATP1A3 variants. Interestingly, two patients (mother and son) showed a variant c.2266C>T (p.R756C), while the third carried the c.2452G>A (p.E818K) variant, commonly described in association with CAPOS syndrome. Our report contributes to extent the phenotypic spectrum of ATP1A3 mutations, remarking childhood rapid-onset ataxia as an additional clinical presentation of ATP1A3-related conditions. Finally, we discussed this phenomenology in the light of translational evidence from a RDP animal model.

Features of aura in paediatric migraine diagnosed using the ICHD 3 beta criteria.

Background In children and adolescents, the prevalence rate of migraine with aura is 1.6%. Few studies concerning migraine with aura features in paediatric population have been reported. Aim The aim of our study was to investigate clinical features of aura in a retrospective cohort of children with migraine with aura. Furthermore, we studied whether the International Classification of Headache Disorder (ICHD) 3 beta version criteria could efficiently detect migraine with aura in a paediatric population. Results We included 164 patients who experienced aura associated with headache (mean age 9.92 ± 2.64 years). When the ICHD-II criteria were used, a final diagnosis of migraine with typical aura was obtained in 15.3% of patients, probable migraine with typical aura in 13.4%, and typical aura with headache in 61.8%, while in in 9.5% of patients the diagnosis was undetermined. According to ICHD-3 beta, we diagnosed migraine with typical aura in 77.7% of patients, probable migraine with typical aura in 13.4%, and an undetermined diagnosis in 9.5% (less than two attacks). Conclusion Aura features did not depend on age and were similar to those of adults. However, the headache could be difficult to classify if headache duration was considered. In this view, the ICHD-3 beta offers the advantage of not considering headache features, including pain duration, for the diagnosis of migraine with typical aura, thus making this diagnosis easier in children and adolescents.