[Guillain-Barré syndrome and its variants: Miller-Fisher syndrome. Description of a clinical case in pediatric age.] / La sindrome di Guillain-Barré e le sue varianti: la sindrome di Miller-Fisher. Descrizione di un caso clinico in età pediatrica.

Miller-Fisher syndrome is a rare acquired nerve disease related to Guillain-Barré syndrome. Clinical features include asthenia, ocular muscle weakness with ophthalmoplegia, impaired limb coordination with instability, and absence of tendon reflexes. Swallowing disorders and rarely respiratory failure may be associated. The article aims to summarize, starting from the presentation of a clinical case, the latest updates which, in clinical practice, can be useful for a correct diagnosis and treatment of this condition which concerns both adult and pediatric patients.

Perampanel as precision therapy in rare genetic epilepsies.

OBJECTIVE: Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g., SCN1A), overactive excitatory neurons (e.g., SCN2A, SCN8A), and variants in glutamate receptors (e.g., GRIN2A) hold special interest. We aimed to collect data from a large rare genetic epilepsy cohort treated with perampanel, to detect possible subgroups with high efficacy. METHODS: This multicenter project was based on the framework of NETRE (Network for Therapy in Rare Epilepsies), a web of pediatric neurologists treating rare epilepsies. Retrospective data from patients with genetic epilepsies treated with perampanel were collected. Outcome measures were responder rate (50% seizure reduction), and percentage of seizure reduction after 3 months of treatment. Subgroups of etiologies with high efficacy were identified. RESULTS: A total of 137 patients with 79 different etiologies, aged 2 months to 61 years (mean = 15.48 ± 9.9 years), were enrolled. The mean dosage was 6.45 ± 2.47 mg, and treatment period was 2.0 ± 1.78 years (1.5 months-8 years). Sixty-two patients (44.9%) were treated for >2 years. Ninety-eight patients (71%) were responders, and 93 (67.4%) chose to continue therapy. The mean reduction in seizure frequency was 56.61% ± 34.36%. Sixty patients (43.5%) sustained >75% reduction in seizure frequency, including 38 (27.5%) with >90% reduction in seizure frequency. The following genes showed high treatment efficacy: SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2, and NEU1. Eleven of 17 (64.7%) patients with Dravet syndrome due to an SCN1A pathogenic variant were responders to perampanel treatment; 35.3% of them had >90% seizure reduction. Other etiologies remarkable for >90% reduction in seizures were GNAO1 and PIGA. Fourteen patients had a continuous spike and wave during sleep electroencephalographic pattern, and in six subjects perampanel reduced epileptiform activity. SIGNIFICANCE: Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1, and POLG, suggesting a targeted effect related to glutamate transmission.

[Hashimoto's encephalopathy: when the thyroid gland makes you dream. Description of a clinical case and literature review.] / L'encefalopatia di Hashimoto: quando la tiroide fa sognare Descrizione di un caso clinico pediatrico e revisione della letteratura.

Hashimoto's encephalopathy (HE) is a rare condition in the childhood. It can present with neurological symptoms, psychiatric disorder or seizures. It is more frequently associated with hypothyroidism or euthyroidism, but it can occur, more rarely, even in hyperthyroidism. The presence of serum thyroid (thyroid peroxidase, thyroglobulin) antibodies is a criterion for the diagnosis of HE. We present the case of an 11-years-old girl with HE with seizures associated with hyperthyroidism with an excellent response to a high dose of steroids.

Pediatric Headache in Primary Care and Emergency Departments: Consensus with RAND/UCLA Method.

Headache is the most frequent neurological symptom in childhood and the main reason for admission to pediatric emergency departments. The aim of this consensus document is to define a shared clinical pathway between primary care pediatricians (PCP) and hospitals for the management of children presenting with headache. For the purposes of the study, a group of hospital pediatricians and a group of PCP from the Emilia Romagna's health districts were selected to achieve consensus using the RAND/UCLA appropriateness method. Thirty-nine clinical scenarios were developed: for each scenario, participants were asked to rank the appropriateness of each option from 1 to 9. Agreement was reached if ≥75% of participants ranked within the same range of appropriateness. The answers, results, and discussion helped to define the appropriateness of procedures with a low level of evidence regarding different steps of the diagnostic-therapeutic process: primary care evaluation, emergency department evaluation, hospital admission, acute therapy, prophylaxis, and follow-up. The RAND proved to be a valid method to value appropriateness of procedures and define a diagnostic-therapeutic pathway suitable to the local reality in the management of pediatric headache. From our results, some useful recommendations were developed for optimizing the healthcare professionals' network among primary care services and hospitals.

Clinically Mild Encephalopathy with a Reversible Splenial Lesion Caused by Influenza B Virus in an Unvaccinated Child.

Reversible lesions involved in the splenium of corpus callosum (RESLES) are a rare clinic-radiological condition, whose pathogenesis could be related to infectious events (such as in mild encephalopathy with reversible splenial lesion-MERS), epilepsy or metabolic/electrolyte disorders. MERS is characterized by an acute mild encephalopathy associated with lesions in the splenium of corpus callosum on brain magnetic resonance imaging. Viral infections are commonly associated with this condition and type A influenza is the most common cause. The prognosis is generally favorable with spontaneous resolution of clinical and radiological abnormalities. We report a case report of type B influenza MERS in an 8-year-old unvaccinated girl with complete clinical and radiological recovery.

[The diagnostic framework of optic neuritis: description of a case in adolescence]. / L'inquadramento diagnostico della neurite ottica: descrizione di un caso in età adolescenziale.

The case of a 13-year-old girl who presented a recurrence of left retrobulbar optic neuritis, 3 years after the previous episode, is described. The clinic, the imaging and the laboratory tests carried out allow to classify the pathology as an isolated recurrent optic neuritis. Recurrent optic neuritis cases require careful evaluation to exclude the forms that are part of certain systemic pathologies. These are in addition to multiple sclerosis, also new demyelinating disorders such as NMOSD (NeuroMyelitis Optica Spectrum Disorder), the forms of CRION (Chronic Relapsing Inflamatory Optic Neuritis) as well as the ADEM-ON (Acute Disseminated Encephalomyelitis - Optic Neuritis) that must necessarily enter in differential diagnosis for clinical features, neurological image and possible positivity of specific auto-antibodies. In pediatric-adolescent age some forms of optic neuritis can still be isolated and not necessarily underlie a systemic pathology.

[Encephalitis by type B influenza: a pediatric clinical case and literature review.] / L'encefalopatia da influenza tipo B: descrizione di un caso clinico pediatrico e revisione della letteratura.

We report the case of a 6-year-old girl who presented with encephalitis during type B influenza. The clinical picture was characterized by an alteration of the state of consciousness associated with focal neurological signs with electroencephalographic changes and brain MRI. Clinical improvement was rapid and without neurological outcomes. The clinical characteristics, the pathogenic mechanisms, the prognosis and the therapy of neuroinfluenza cases are described.

8q12 microduplication including CHD7: clinical report on a new patient with Duane retraction syndrome type 3.

BACKGROUND: A novel multiple congenital anomalies syndrome has been recently identified in four patients carrying a 8q12 microduplication sharing the smallest region of overlap (SRO, size 1.6 Mb) including five genes CA8, ASPH, RAB2B, CLVS1 and CDH7. The phenotype is mainly characterized by neurodevelopmental delay, heart defects, facial features and Type 1 Duane anomaly. Increasing dosage of CDH7 was proposed to be responsible for the recurrent pattern of MCA. RESULTS: High resolution array-CGH analysis identified a 4.2 Mb de novo interstitial duplication of the 8q12.1-q12.3 chromosome region in a boy with developmental delay, dysmorphic features, type 3 Duane anomaly. This duplication includes several genes and spans the SRO. DISCUSSION: The present case represents a further patient with an interstitial duplication of chromosome 8q12 and several shared clinical features. Although more cases are needed to delineate the full-blown phenotype of 8q12 duplication syndrome, published data and present observations suggest that it results in a clinically recognizable phenotype. The presence of Duane anomaly in four out of five described patients with a 8q12 duplication definitely rules against the possibility of its being a chance finding unrelated to the imbalance and points toward a pathogenic role. Gene content analysis of the duplicated region and review of the literature suggest that gain-of-dosage of the CHD7 gene may be a good candidate for the main clinical features of the syndrome.

Focal seizures with affective symptoms are a major feature of PCDH19 gene-related epilepsy.

PURPOSE: Mutations of the protocadherin19 gene (PCDH19) cause a female-related epilepsy of variable severity, with or without mental retardation and autistic features. Despite the increasing number of patients and mutations reported, the epilepsy phenotype associated with PCDH19 mutations is still unclear. We analyzed seizure semiology through ictal video-electroencephalography (EEG) recordings in a large series of patients. METHODS: We studied 35 patients with PCDH19 gene-related epilepsy and analyzed clinical history and ictal video-EEG recordings obtained in 34 of them. KEY FINDINGS: Clusters of focal febrile and afebrile seizures had occurred in 34 patients, at a mean age of 10 months. The predominant and more consistent ictal sign was fearful screaming, occurring in 24 patients (70.5%); it was present since epilepsy onset in 12 and appeared later on, during the course in the remaining 12 patients. In infancy, fearful screaming mainly appeared within the context of seizures with prominent hypomotor semiology, whereas during follow-up it was associated with prominent early motor manifestations. In 16 patients, seizures were video-EEG recorded both at onset and during follow-up: in five patients (31%) seizure semiology remained identical, in 7 (44%) semiology varied and in four patients it was unclear whether ictal semiology changed with age. Three patients (9%) had both focal and generalized seizures, the latter consisting of absences and myoclonus. Ictal EEG during focal seizures showed a prominent involvement of the frontotemporal regions (22 patients). About 45% of patients had an alternating EEG pattern, with the ictal discharge migrating from one hemisphere to the contralateral during the same ictal event. Status epilepticus occurred in 30% of patients. Cognitive impairment occurred in 70%, ranging from mild (42%) to moderate (54%) and severe (4%); autistic features occurred in 28.5%. Direct sequencing detected 33 different heterozygous candidate mutations, 8 of which were novel. Mutations were missense substitutions (48.5%), premature termination (10 frameshift, 4 nonsense, and 2 splice-site mutations; 48.5%), and one in-frame deletion. Thirty candidate mutations (91%) were de novo. No specific genotype-phenotype correlation could be established, as missense and truncating mutations were associated with phenotypes of comparable severity. SIGNIFICANCE: Most patients with PCDH19 mutations exhibit a distinctive electroclinical pattern of focal seizures with affective symptoms, suggesting an epileptogenic dysfunction involving the frontotemporal limbic system. Awareness of this distinctive phenotype will likely enhance recognition of this disorder.