Sporadic Infantile Epileptic Encephalopathy Caused by Mutations in PCDH19 Resembles Dravet Syndrome but Mainly Affects Females

Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism

Influenza A(H1N1)–Associated Ischemic Stroke in a 9-Month-Old Child

International audienc

Influenza A(H1N1)–Associated Ischemic Stroke in a 9-Month-Old Child

International audienc

Prognostic factors for the sequelae and severity of Guillain‐Barré syndrome in children

International audienceIntroduction: Guillain-Barré syndrome (GBS) is an inflammatory polyradiculoneuritis.Our aim in this study was to describe the clinical characteristics and the long-termsequelae of GBS in a French pediatric population.Methods: In this multicenter, retrospective study we evaluated clinical signs, radio-logical examinations, laboratory tests, treatments, and outcomes.Results: One hundred ten children were included in this investigation. These childrenpresented with walking difficulties, muscle weakness, and cranial nerve impairment.Electrodiagnostic testing revealed 70% with acute inflammatory demyelinating poly-radiculoneuropathy (AIDP) and 16% with acute motor axonal neuropathy (AMAN).One hundred children received immunoglobulins. At follow-up, 77% were cured,whereas 9% had sequelae, associated with an axonal form (P < .01) and a short inter-val between symptom onset and hospitalization (P < .01). The need for intubationwas correlated with peripheral facial paralysis (P < .01) and dysautonomia (P < .01).Discussion: Although AIDP and AMAN present in a similar way, the axonal form isassociated with a worse outcome

Prognostic factors for the sequelae and severity of Guillain‐Barré syndrome in children

International audienceIntroduction: Guillain-Barré syndrome (GBS) is an inflammatory polyradiculoneuritis.Our aim in this study was to describe the clinical characteristics and the long-termsequelae of GBS in a French pediatric population.Methods: In this multicenter, retrospective study we evaluated clinical signs, radio-logical examinations, laboratory tests, treatments, and outcomes.Results: One hundred ten children were included in this investigation. These childrenpresented with walking difficulties, muscle weakness, and cranial nerve impairment.Electrodiagnostic testing revealed 70% with acute inflammatory demyelinating poly-radiculoneuropathy (AIDP) and 16% with acute motor axonal neuropathy (AMAN).One hundred children received immunoglobulins. At follow-up, 77% were cured,whereas 9% had sequelae, associated with an axonal form (P < .01) and a short inter-val between symptom onset and hospitalization (P < .01). The need for intubationwas correlated with peripheral facial paralysis (P < .01) and dysautonomia (P < .01).Discussion: Although AIDP and AMAN present in a similar way, the axonal form isassociated with a worse outcome

Case Report: Successful Cerebral Revascularization and Cardiac Transplant in a 16-Year-Old Male With Syndromic BRCC3-Related Moyamoya Angiopathy.

International audienceBackground: BRCC3/MTCP1 deletions are associated with a rare familial moyamoya angiopathy with extracranial manifestations. Case: We report the case of an adolescent male presenting with progressive and symptomatic moyamoya angiopathy and severe dilated cardiomyopathy caused by a hemizygous deletion of BRCC3/MTCP1. He was treated for renovascular hypertension by left kidney homograft and right nephrectomy in infancy and had other syndromic features, including cryptorchidism, growth hormone deficiency, and facial dysmorphism. Due to worsening of the neurological and cardiac condition, he was treated by a direct superficial temporal artery to middle cerebral artery bypass to enable successful cardiac transplant without cerebral damage. Conclusions: BRCC3-related moyamoya is a devastating disease with severe heart and brain complications. This case shows that aggressive management with cerebral revascularization to allow cardiac transplant is feasible and efficient despite end-stage heart failure

Long‐term outcomes of paediatric Guillain–Barré syndrome

International audienceAim: To study long-term sequelae in children with Guillain-Barré syndrome (GBS).Method: This was a prospective observational study with children from two French tertiary centres. Data were from clinical and several standardized scales or questionnaires.Results: Fifty-one patients were included with a median follow-up of 6 years 4 months (range 3-20 years) after the acute phase. The sequelae rate was 67% (95% confidence interval [CI] 53-78) and did not vary with time. Most children had minor sequelae (Guillain-Barré Syndrome Disability Score [GBSDS] = 1); only one was unable to run (GBSDS = 2). The most frequent complaints were paraesthesia (43%), pain (35%), and fatigue (31%). The neurological examination was abnormal in 18% of children, autonomy was compromised in 14%, and symptoms of depression occurred in 34%. The factors associated with late-onset sequelae were correlated with severity during the initial phase (i.e. initial GBSDS &gt;4, odds ratio 6.6, 95% CI 1.8-33; p = 0.009). The predictive factors of more severe late-onset conditions were initial severity (p = 0.002) and sex (female patients; p = 0.01).Interpretation: Two-thirds of children with GBS had late-onset sequelae following an episode, often minor, but sometimes with continuing effects on their everyday lives. Particularly affected were those who had severe GBS during the acute phase and who lost the ability to walk.What this paper adds: Two-thirds of children with Guillain-Barré syndrome (GBS) had persistent sequelae. Sequelae were often minor, but daily repercussions of them were sometimes serious. Sequelae were significantly associated with severe GBS during the acute phase

Case Report: Successful Cerebral Revascularization and Cardiac Transplant in a 16-Year-Old Male With Syndromic BRCC3-Related Moyamoya Angiopathy.

International audienceBackground: BRCC3/MTCP1 deletions are associated with a rare familial moyamoya angiopathy with extracranial manifestations. Case: We report the case of an adolescent male presenting with progressive and symptomatic moyamoya angiopathy and severe dilated cardiomyopathy caused by a hemizygous deletion of BRCC3/MTCP1. He was treated for renovascular hypertension by left kidney homograft and right nephrectomy in infancy and had other syndromic features, including cryptorchidism, growth hormone deficiency, and facial dysmorphism. Due to worsening of the neurological and cardiac condition, he was treated by a direct superficial temporal artery to middle cerebral artery bypass to enable successful cardiac transplant without cerebral damage. Conclusions: BRCC3-related moyamoya is a devastating disease with severe heart and brain complications. This case shows that aggressive management with cerebral revascularization to allow cardiac transplant is feasible and efficient despite end-stage heart failure

Cerebrospinal fluid YKL‐40 level evolution is associated with autoimmune encephalitis remission

Abstract Objective Because of its heterogeneity in clinical presentation and course, predicting autoimmune encephalitis (AIE) evolution remains challenging. Hence, our aim was to explore the correlation of several biomarkers with the clinical course of disease. Methods Thirty‐seven cases of AIE were selected retrospectively and divided into active (N = 9), improved (N = 12) and remission (N = 16) AIE according to their disease evolution. Nine proteins were tested in both serum and cerebrospinal fluid (CSF) at diagnosis (T0) and during the follow‐up (T1), in particular activated MMP‐9 (MMP‐9A) and YKL‐40 (or chitinase 3‐like 1). Results From diagnosis to revaluation, AIE remission was associated with decreased YKL‐40 and MMP‐9A levels in the CSF, and with decreased NfL and NfH levels in the serum. The changes in YKL‐40 concentrations in the CSF were associated with (1) still active AIE when increasing >10% (P‐value = 0.0093); (2) partial improvement or remission when the changes were between +9% and −20% (P‐value = 0.0173); and remission with a reduction > −20% (P‐value = 0.0072; overall difference between the three groups: P‐value = 0.0088). At T1, the CSF YKL‐40 levels were significantly decreased between active and improved as well as improved and remission AIE groups but with no calculable threshold because of patient heterogeneity. Conclusion The concentration of YKL‐40, a cytokine‐like proinflammatory protein produced by glial cells, is correlated in the CSF with the clinical course of AIE. Its introduction as a biomarker may assist in following disease activity and in evaluating therapeutic response

Paediatric optic neuritis: factors leading to unfavourable outcome and relapses

Objectives To identify prognostic factors associated with poor visual recovery and chronic relapsing diseases, for example, multiple sclerosis (MS), in children with optic neuritis (ON) at onset.Methods This multicentre retrospective study included 102 children with a first ON episode between 1990 and 2012. The primary criterion was poor visual recovery determined by visual acuity, and the secondary was relapses following ON.Results Median age was 11 years, 66% were girls and mean follow-up was 24 months. 58% of children were diagnosed with idiopathic isolated ON, 22% had MS, 5% had Devic's neuromyelitis optica and 6% chronic relapsing inflammatory ON. Complete visual acuity recovery rate was 57% (95% CI=[46%-69%]) at 6 months and 71% (95% CI=[60%-81%]) at 1 and 2 years but was lower in MS (p&lt;0.01), with recovery rate of only 27% (95% CI=[12%-54%]) at 1year. Age 10 years, optic disc pallor at funduscopy and MS were the principal factors associated with poor visual recovery. Age 10 years, abnormal brain MRI at onset and oligoclonal banding were significantly associated with MS (p&lt;0.01).Conclusion Age 10, optic disc pallor and MS were associated with poor recovery. Better identification of these patients may help to adapt treatment and lead to a prospective treatment study