Prestatus and status dystonicus in children and adolescents.

AIM: To critically analyse the management of status dystonicus and prestatus dystonicus in children and adolescents, in order to examine clinical features, acute management, and risk of relapse in a paediatric cohort. METHOD: Clinical, demographic, and therapeutic features were analysed according to disease severity. Risk of subsequent relapse was estimated through Kaplan-Meier curves. RESULTS: Thirty-four patients (eight females, 26 males) experiencing 63 episodes of acute dystonia exacerbations at a tertiary referral Italian hospital were identified. Mean age at status dystonicus presentation was 9 years 11 months (11y at inclusion in the study). Onset of dystonia dated back to infancy in most cases. Fourteen patients experienced two or more episodes. Infections were the most common trigger (48%). Benzodiazepines were the most commonly used drugs for acute management. Stereotactic pallidotomy was performed in six cases during status dystonicus, and in two additional patients it was electively performed after medical management. The probability of survival free from status dystonicus relapses was 78% after 4 months and 61% after 27 months. INTERPRETATION: Dystonia exacerbations are potentially life-threating emergencies, with a considerable risk of relapse. Nevertheless, no obvious factors for relapse risk stratification exist. Pallidotomy is a feasible option in medical refractory status dystonicus for patients with limited deep brain stimulation applicability, but the risk of recurrence is elevated. WHAT THIS PAPER ADDS: Acute exacerbations may affect up to 10% of children with dystonia. Infections are the most common precipitant factor. In about 30% of the cases, intensive care unit admission is needed. Subsequent relapses are common, reaching 25% risk at 1 year. Pallidotomy can be considered in medical-refractory cases with no deep brain stimulation applicability.

CHD2 variants are a risk factor for photosensitivity in epilepsy.

Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2.17 × 10(-5)). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3.50 × 10(-4)). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research into human cortical excitability.

Pallidotomy for medically refractory status dystonicus in childhood.

AIM: Status dystonicus is a rare and potentially fatal condition of continuous and generalized muscle contraction that can complicate dystonia. As status dystonicus is usually refractory to traditional pharmacological therapy, alternative and invasive strategies have been developed, but so far there are no guidelines on status dystonicus management. Pallidotomy has shown good results in status dystonicus treatment. METHOD: We report indications, surgical strategy, and outcome of bilateral pallidotomy in four pediatric patients (four males; mean age at surgery 11y 5mo) with secondary dystonia, who developed refractory status dystonicus. Pallidotomy was performed in the area corresponding to the mid portion of the globus pallidus internus. RESULTS: This procedure allowed patients to recover the pre-status dystonicus condition, controlling dystonic postures and movements of trunk and limbs. Moreover oromandibular dystonia, which is resistant to conservative approaches and deep brain stimulation, was significantly reduced. No postoperative complications were registered. INTERPRETATION: Our study suggests pallidotomy as a feasible treatment in patients with secondary dystonia complicated by status dystonicus.

The development of the International Classification of Functioning, Disability and Health for Child and Youth (ICF-CY) Core Sets: a systematic review.

PURPOSE: The aim of this systematic review is to verify the development of the International Classification of Functioning, Disability and Health for Child and Youth (ICF-CY), investigating methodology and how many core sets have been created. METHODS: Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to carry out the systematic review. Six bibliographic databases were searched: MEDLINE, SCOPUS, Web of Sciences, CINHAL, PEDro, and OT Seeker. Papers included in the study have the following characteristics: (a) pediatric population with different health conditions, (b) assessment of ICF domains, (c) development of ICF-CY core set in different health conditions, and (d) recommendation for clinical uses. RESULTS: Search strategies allowed to identify 270 research papers. After the elimination of duplicates, 154 articles were analyzed. Finally, 28 records were included for qualitative synthesis. Twelve different ICF-CY Core Sets were identified. Autism spectrum disorder, attention-deficit/hyperactivity disorder, and cerebral palsy were the main health conditions studied at international level. Most of the studies involved international experts using Cieza' methodology to inform ICF-CY Core Set. CONCLUSIONS: After 15 years since the adoption of ICF-CY, it still finds some barriers to use. Concrete actions should be taken to develop further core sets following a rigorous methodology and to contribute implementing the ICF framework.Implication for rehabilitationIn 15 years since the implementation of International Classification of Functioning, Disability and Health for Child and Youth (ICF-CY), only 12 core sets have been developed.To develop ICF-CY Core Set, health professionals should follow methodology described by Cieza et al.Strong collaboration between low- and middle-income countries and high-income countries are recommended.

Convulsions associated with gastroenteritis in the spectrum of benign focal epilepsies in infancy: 30 cases including four cases with ictal EEG recording.

Benign convulsions associated with gastroenteritis are now recognized as a clinical entity, characterized by an acute cluster of afebrile seizures during an episode of mild diarrhoea with excellent prognosis. We observed 30 children who each experienced at least two seizures associated with mild gastroenteritis. The inclusion criteria were: afebrile seizures during gastroenteritis, dehydration at ≤ 5%, normal neurological findings, normal psychomotor development and no underlying pathology according to laboratory and neuroimaging studies. Mean age was 21 months (range: 6-38). Familial history for epilepsy was positive in 3/30 (10%) and for febrile convulsions in 11/30 (36.6%). Seizure onset was mainly on the third day of gastroenteritis. Seizures were described as generalised by parents in 16/30 patients (53.3%). We directly observed seizures in 14/30 patients (47.7%), and the semiology was partial with secondary generalisation. Focal onset was confirmed in two patients by EEG and in two patients by video-EEG recording. Twenty of 30 patients (66.6%) received antiepileptic drugs during the acute phase. Ten patients (33.3%) received no treatment. During follow-up (mean duration: 53 months), one patient had an isolated afebrile seizure and two others a febrile seizure. At the end of follow-up, antiepileptic treatment was withdrawn for all but two patients. None developed epilepsy. Although the pathogenesis of this clinical entity is unknown, we hypothesize that mild gastroenteritis may provoke a transient brain dysfunction which in turn provokes seizures in children with genetically determined susceptibility.

Headache, epilepsy and photosensitivity: how are they connected?

Although headache and epilepsy have often been associated, the precise electroclinical and pathophysiological interaction between these disorders and in particular its relations with photosensitivity is as yet to be fully understood in adults or children. The association between headache and epilepsy commonly occurs in all types of epilepsy and not only in occipital epilepsy. Generally, peri-ictal headache is often neglected, regardless of its severity, because patients are more concerned about their seizures. Altered cerebral cortex excitability may be the link between these two conditions and photosensitivity shows this. The physician should bear this association in mind when dealing with epileptic and migraine patients so as to be able to offer such patients an accurate diagnosis and appropriate treatment; this should be borne in mind when declaring epileptic patients 'seizure free'. To date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may, on occasion, be the sole ictal epileptic manifestation. Lastly, studies designed to investigate the triggering role of photosensitivity in both headache and epilepsy are warranted.

Phenomenology and clinical course of movement disorder in GNAO1 variants: Results from an analytical review.

GNAO1 variants were recently discovered as causes of epileptic encephalopathies and heterogeneous syndromes presenting with movement disorders (MDs), whose phenomenology and clinical course are yet undefined. We herein focused on GNAO1-related MD, providing an analytical review of existing data to outline the main MD phenomenology and management, clinical evolution and genotype-phenotype correlations. Reviewing 41 previously published patients and assessing 5 novel cases, a comprehensive cohort of 46 patients was analyzed, reassuming knowledge about genotypes, phenotypes, disease course and treatment of this condition. GNAO1-related MD consisted of a severe early-onset hyperkinetic syndrome, with prominent chorea, dystonia and orofacial dyskinesia. Symptoms are poorly responsive to medical therapy and fluctuate, with critical and life-threatening exacerbations, such as status dystonicus. The presence of a choreiform MD appears to be predictive of a higher risk of movement disorder emergency. Surgical treatments are sometimes effective, although severe disabilities persist. Differently from the early infantile epileptic encephalopathy phenotype (associated with loss of function variants), no clear correlation between genotype and MD phenotype emerged, although some variants recurred more frequently, mainly affecting exons 6 and 7.

Clinical and genetic analysis of a family with two rare reflex epilepsies.

PURPOSE: To determine clinical phenotypes, evolution and genetic background of a large family with a combination of two unusual forms of reflex epilepsies. METHOD: Phenotyping was performed in eighteen family members (10 F, 8 M) including standardized EEG recordings with intermittent photic stimulation (IPS). Genetic analyses (linkage scans, Whole Exome Sequencing (WES) and Functional studies) were performed using photoparoxysmal EEG responses (PPRs) as affection status. RESULTS: The proband suffered from speaking induced jaw-jerks and increasing limb jerks evoked by flickering sunlight since about 50 years of age. Three of her family members had the same phenotype. Generalized PPRs were found in seven members (six above 50 years of age) with myoclonus during the PPR. Evolution was typical: Sensitivity to lights with migraine-like complaints around adolescence, followed by jerks evoked by lights and spontaneously with dropping of objects, and strong increase of light sensitivity and onset of talking induced jaw jerks around 50 years. Linkage analysis showed suggestive evidence for linkage to four genomic regions. All photosensitive family members shared a heterozygous R129C mutation in the SCNM1 gene that regulates splicing of voltage gated ion channels. Mutation screening of 134 unrelated PPR patients and 95 healthy controls, did not replicate these findings. CONCLUSION: This family presents a combination of two rare reflex epilepsies. Genetic analysis favors four genomic regions and points to a shared SCNM1 mutation that was not replicated in a general cohort of photosensitive subjects. Further genetic studies in families with similar combination of features are warranted.

Long-term follow-up in children with benign convulsions associated with gastroenteritis.

BACKGROUND: The outcome of benign convulsions associated with gastroenteritis (CwG) has generally been reported as being excellent. However, these data need to be confirmed in studies with longer follow-up evaluations. AIM: To assess the long-term neurological outcome of a large sample of children presenting with CwG. METHODS: We reviewed clinical features of 81 subjects presenting with CwG (1994-2010) from three different Italian centers with a follow-up period of at least 3 years. RESULTS: Follow-up period ranged from 39 months to 15 years (mean 9.8 years). Neurological examination and cognitive level at the last evaluation were normal in all the patients. A mild attention deficit was detected in three cases (3.7%). Fourteen children (17.3%) received chronic anti-epileptic therapy. Interictal EEG abnormalities detected at onset in 20 patients (24.7%) reverted to normal. Transient EEG epileptiform abnormalities were detected in other three cases (3.7%), and a transient photosensitivity in one (1.2%). No recurrence of CwG was observed. Three patients (3.7%) presented with a febrile seizure and two (2.5%) with an unprovoked seizure, but none developed epilepsy. CONCLUSIONS: The long-term evaluation of children with CwG confirms the excellent prognosis of this condition, with normal psychomotor development and low risk of relapse and of subsequent epilepsy.

Long-term outcome of pattern-sensitive epilepsy.

PURPOSE: To evaluate the long-term outcome of patients with pattern-sensitive epilepsy. METHODS: We prospectively studied 35 patients (21 females and 14 males) with pattern-sensitive epilepsy (follow up > or = 5 years; mean 13.9; range 6.4 - 27.6). All cases had regular clinical examinations and serial electroencephalographic (EEG) recordings. Photosensitivity and pattern sensitivity were ascertained neurophysiologically in all cases. Outcome was evaluated according to the following variables: duration of photosensitivity, rate of remission (seizure-free period > or = 2 years), withdrawal of therapy, and recurrence after drug discontinuation. RESULTS: The epilepsy was generalized in 18 cases (17 idiopathic, one symptomatic) and partial in 17 (13 idiopathic, four symptomatic). Sixteen patients (46%) had a family history of seizures. The mean age at the last examination was 21.4 years (range 11.2-35.5 years). Five patients (14%) had only reflex seizures. The most common type of spontaneous seizures was generalized (60%), whereas reflex seizures were more frequently partial (74%). Mean epilepsy duration was 8.7 +/- 6.3 years. Patients with only reflex seizures were instructed to avoid precipitating stimuli and were not treated with antiepileptic drugs. Treatment was gradually withdrawn in 10 out of 30 treated patients, with relapse in only two cases. At the end of follow up, 28 patients (80%) were seizure-free. CONCLUSION: The long-term outcome of patients with pattern-sensitive epilepsy indicates a good prognosis with a favorable course for both spontaneous and reflex seizures.