Recurrent pericarditis in a patient with Bardet-Biedl syndrome: A case report.

Bardet-Biedl syndrome is a rare autosomal recessive disorder characterized by rod-cone dystrophy, renal dysfunction, obesity, learning difficulties, hypogonadism, polydactyl, and many other minor features that can affect the cardiovascular, locomotive, neurological, and endocrine systems. We report the case of a 16-year-old boy affected by Bardet-Biedl syndrome who presented with recurrent pericarditis with an optimal response to treatment with Anakinra. To our knowledge, this is the first description of an association between Bardet-Biedl syndrome and recurrent pericarditis.

Long-term follow-up in pediatric patients with paroxysmal hypothermia (Shapiro's syndrome).

INTRODUCTION: Shapiro syndrome (SS) is characterized by spontaneous recurrent episodes of hypothermia, hyperhidrosis and corpus callosum (CC) agenesis. Less than 60 cases have been reported to date and the pathogenic mechanism as well as the prognosis of this syndrome are still debated. We describe the clinical features and long-term follow-up of a pediatric cohort of SS patients. METHODS: We collected 13 (10 novel) pediatric cases of SS and report their long-term follow-up and neurological outcome. RESULTS: All patients experienced recurring hypothermia, with body temperature below 35 °C during the episodes, often accompanied by hyperidrosis. CC agenesis was an inconstant structural feature in the present series (2/13 patients). Seven patients received antiepileptic drugs (AEDs) or other drug therapy for a mean period of 12 months. At long-term follow-up (mean = 61 months, range: 60-96), all individuals were free from episodes of paroxysmal hypothermia independently from previous AED use or other drug therapy. CONCLUSION: Paroxysmal hypothermia, the core symptom of SS, behaved as a age-dependent feature in our cohort, supporting a good long-term prognosis for SS. A prompt diagnosis of SS is crucial to avoid unnecessary diagnostic investigations.

De novo 12q22.q23.3 duplication associated with temporal lobe epilepsy.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Seizure 50 (2017) 80-82, http://dx.doi.org/10.1016/j.seizure.2017.06.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype.

BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported. RESULTS: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype. CONCLUSION: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.

De novo 12q22.q23.3 duplication associated with temporal lobe epilepsy.

PURPOSE: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and may be associated with acquired central nervous system lesions or could be genetic. Various susceptibility genes and environmental factors are believed to be involved in the aetiology of TLE, which is considered to be a heterogeneous, polygenic, and complex disorder. Rare point mutations in LGI1, DEPDC5, and RELN as well as some copy number variations (CNVs) have been reported in families with TLE patients. METHODS: We perform a genetic analysis by Array-CGH in a patient with dysmorphic features and temporal lobe epilepsy. RESULTS: We report a de novo duplication of the long arm of chromosome 12. CONCLUSION: We confirm that 12q22-q23.3 is a candidate locus for familial temporal lobe epilepsy with febrile seizures and highlight the role of chromosomal rearrangements in patients with epilepsy and intellectual disability.

A novel Xp22.13 microdeletion in Nance-Horan syndrome.

BACKGROUND: Nance-Horan syndrome (NHS) is a rare X-linked developmental disorder characterized by congenital cataract, dental anomalies and facial dysmorphisms. Notably, up to 30% of NHS patients have intellectual disability and a few patients have been reported to have congenital cardiac defects. Nance-Horan syndrome is caused by mutations in the NHS gene that is highly expressed in the midbrain, retina, lens, tooth, and is conserved across vertebrate species. Although most pathogenic mutations are nonsense mutations, a few genomic rearrangements involving NHS locus have been reported, suggesting a possible pathogenic role of the flanking genes. METHODS: Here, we report a microdeletion of 170,6 Kb at Xp22.13 (17.733.948-17.904.576) (GRCh37/hg19), detected by array-based comparative genomic hybridization in an Italian boy with NHS syndrome. RESULTS: The microdeletion harbors the NHS, SCLML1, and RAI2 genes and results in a phenotype consistent with NSH syndrome and developmental delay. CONCLUSION: We compare our case with the previous Xp22.13 microdeletions and discuss the possible pathogenetic role of the flanking genes. Birth Defects Research 109:866-868, 2017. © 2017 Wiley Periodicals, Inc.

Preliminary assessment of the feasibility of using AB words to assess candidacy in adults.

BACKGROUND: Adult cochlear implant (CI) candidacy is assessed in part by the use of speech perception measures. In the United Kingdom the current cut-off point to fall within the CI candidacy range is a score of less than 50% on the BKB sentences presented in quiet (presented at 70 dBSPL). GOAL: The specific goal of this article was to review the benefit of adding the AB word test to the assessment test battery for candidacy. RESULTS: The AB word test scores showed good sensitivity and specificity when calculated based on both word and phoneme scores. The word score equivalent for 50% correct on the BKB sentences was 18.5% and it was 34.5% when the phoneme score was calculated; these scores are in line with those used in centres in Wales (15% AB word score). CONCLUSION: The goal of the British Cochlear Implant Group (BCIG) service evaluation was to determine if the pre-implant assessment measures are appropriate and set at the correct level for determining candidacy, the future analyses will determine whether the speech perception cut-off point for candidacy should be adjusted and whether other more challenging measures should be used in the candidacy evaluation.

Safety of Overnight Switch from Brand-Name to Generic Levetiracetam.

BACKGROUND AND OBJECTIVE: Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. The objective of this study was to evaluate the safety and tolerability of the brand-to-generic levetiracetam switch in patients with focal or generalized epilepsy. METHODS: A prospective study in patients with primary, cryptogenic or symptomatic epilepsy, who were taking branded levetiracetam and were switched to generic levetiracetam. Patients were consecutively recruited from January 2013 to January 2015. We evaluated efficacy, tolerability and compliance before switching (T0) and after 6 months of therapy (T1). Evaluations were scheduled as follows: baseline, 7 and 15 days, 1, 3 and 6 months. At each visit clinical diary seizures, physical and neurological examination, laboratory parameters and electroencephalogram were evaluated. RESULTS: Fifty-nine patients, equally mixed by sex, were included in the study. Mean age was 26.1 years. Forty-seven per cent of the patients enrolled received levetiracetam as monotherapy. One patient was lost during the follow-up: so at T1 we had 58 patients (28 monotherapy and 30 polytherapy). At T0 and at T1, there was no statistically significant difference in terms of seizure frequency and intensity, occurrence of adverse events, laboratory parameters and electroencephalographic features. Two patients stopped treatment with the generic (both at 3 months after the switch) and restarted therapy with brand levetiracetam because of seizure increase. At the end of the study, the switchback rate was 3.4%. CONCLUSIONS: No increase of seizures and adverse effects were observed when branded levetiracetam was interchanged to a generic equivalent. More studies should be conducted with a larger series of patients to confirm these results.

Assessment and Outcome in Non-Traditional Cochlear Implant Candidates.

The objectives of this study were to assess: (i) patient expectations met as a measure of outcome in early-deafened, late-implanted (non-traditional) cochlear implant recipients and (ii) pre-implantation predictive factors for postoperative speech perception. The notes of 13 recipients were retrospectively reviewed. The mean age at onset of profound deafness was 1.5 years (range 0-6). The mean age at implantation was 37 years (range 22-51 years). Patient expectations were assessed pre-operatively and 1 year after implantation. They were met or exceeded in 129/140 (92%) domains overall. A higher Speech Intelligibility Rating and audiovisual City University of New York sentence score before implantation were found to be positive predictive factors for improved speech discrimination after cochlear implantation.

Epileptic encephalopathy with continuous spike and wave during sleep associated to periventricular leukomalacia.

Periventricular leukomalacia is the most common type of brain injury in premature infants. Our aim is to describe the frequency and the features of epilepsy in a single-center population of 137 children with periventricular leukomalacia. Forty-two of the 137 (31%) patients presented epilepsy. Twelve percent of these patients presented West syndrome, whereas 19% showed a pattern of continuous spike-waves during slow sleep syndrome. In the latter group, outcome was frequently unfavorable, with a greater number of seizures and more drug resistance. A significant association was found between epilepsy and neonatal seizures, spastic tetraplegia, and mental retardation. Although less common than in other forms of brain injury, epilepsy is nevertheless a significant complication in children with periventricular leukomalacia. The fairly frequent association with continuous spike-waves during slow sleep syndrome deserves particular attention: electroencephalographic sleep monitoring is important in order to provide early treatment and prevent further neurologic deterioration.

Improving the nurse-family partnership in community practice.

BACKGROUND: Evidence-based preventive interventions are rarely final products. They have reached a stage of development that warrant public investment but require additional research and development to strengthen their effects. The Nurse-Family Partnership (NFP), a program of nurse home visiting, is grounded in findings from replicated randomized controlled trials. OBJECTIVE: Evidence-based programs require replication in accordance with the models tested in the original randomized controlled trials in order to achieve impacts comparable to those found in those trials, and yet they must be changed in order to improve their impacts, given that interventions require continuous improvement. This article provides a framework and illustrations of work our team members have developed to address this tension. METHODS: Because the NFP is delivered in communities outside of research contexts, we used quantitative and qualitative research to identify challenges with the NFP program model and its implementation, as well as promising approaches for addressing them. RESULTS: We describe a framework used to address these issues and illustrate its use in improving nurses' skills in retaining participants, reducing closely spaced subsequent pregnancies, responding to intimate partner violence, observing and promoting caregivers' care of their children, addressing parents' mental health problems, classifying families' risks and strengths as a guide for program implementation, and collaborating with indigenous health organizations to adapt and evaluate the program for their populations. We identify common challenges encountered in conducting research in practice settings and translating findings from these studies into ongoing program implementation. CONCLUSIONS: The conduct of research focused on quality improvement, model improvement, and implementation in NFP practice settings is challenging, but feasible, and holds promise for improving the impact of the NFP.

EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement.

Pontocerebellar hypoplasia (PCH) type 1 is characterized by the co-occurrence of spinal anterior horn involvement and hypoplasia of the cerebellum and pons. EXOSC3 has been recently defined as a major cause of PCH type 1. Three different phenotypes showing variable severity have been reported. We identified a homozygous mutation [c.395A > C/p.D132A] in EXOSC3 in four patients with muscle hypotonia, developmental delay, spinal anterior horn involvement, and prolonged survival, consistent with the "mild PCH1 phenotype". Interestingly, isolated cerebellar hypoplasia limited to the hemispheres or involving both hemispheres and vermis was the main neuroradiologic finding, whereas the pontine volume was in the normal range for age. These findings strongly suggest that analysis of the EXOSC3 gene should be recommended also in patients with spinal anterior horn involvement and isolated cerebellar hypoplasia.

Expanded spectrum of Pelizaeus-Merzbacher-like disease: literature revision and description of a novel GJC2 mutation in an unusually severe form.

Homozygous or compound heterozygous mutations in the GJC2 gene, encoding the gap junction protein connexin47 (Cx47), cause the autosomal recessive hypomyelinating Pelizaeus-Merzbacher-like disease (PMLD1, MIM# 608804). Although clinical and neuroradiological findings resemble those of the classic Pelizaeus-Merzbacher disease, PMLD patients usually show a greater level of cognitive and motor functions. Unpredictably a homozygous missense GJC2 mutation (p.Glu260Lys) was found in a patient presenting with a very severe clinical picture characterised by congenital nystagmus and severe neurological impairment. Also magnetic resonance imaging was unusually severe, showing an abnormal supra- and infratentorial white matter involvement extending to the spinal cord. The novel p.Glu260Lys (c.778G>A) mutation, occurring in a highly conserved motif (SRPTEK) of the Cx47 extracellular loop-2 domain, was predicted, by modelling analysis, to break a 'salt bridge network', crucial for a proper connexin-connexin interaction to form a connexon, thus hampering the correct formation of the connexon pore. The same structural analysis, extended to the previously reported missense mutations, predicted that most changes were expected to have less severe impact on protein functions, correlating with the mild PMLD1 form of the patients. Our study expands the spectrum of PMLD1 and provides evidence that the extremely severe clinical and neuroradiological PMLD1 form of our patient likely correlates with the predicted impairment of gap junction channel assembly resulting from the detrimental effect of the new p.Glu260Lys mutant allele on Cx47 protein.

Anti-glutamic acid decarboxylase limbic encephalitis without epilepsy evolving into dementia with cerebellar ataxia.

OBJECTIVES: To expand the spectrum of the clinical presentation of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis and to improve the recognition of this entity. DESIGN: Case study. SETTING: University hospital. PATIENT: An 11-year-old-girl with progressive mood and behavioral disorder, speech impairment, and short-term memory impairment who manifested cerebellar ataxia with nystagmus during the disease course. INTERVENTIONS: Blood and cerebrospinal fluid analysis including autoantibodies, electroencephalography, brain and spinal magnetic resonance imaging, and cognitive and neuropsychological assessment were performed. High-dose methylprednisolone sodium succinate pulses, cycles of intravenous immunoglobulins, mycophenolate mofetil, and rituximab as well as antipsychotics and benzodiazepine were administered. RESULTS: Diagnosis of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis was made. The clinical features during the first months of disease included only mood, behavioral, and memory impairment. After 5 months, despite immunotherapies, cerebellar ataxia with nystagmus appeared with brain magnetic resonance imaging evidence of cerebral atrophy. No clinical or infraclinical seizures were recorded during follow-up. CONCLUSIONS: Anti-glutamic acid decarboxylase antibodies-related limbic encephalitis can present with only behavioral or neuropsychological symptoms without any epileptic disorder. Moreover, cerebellar ataxia related to anti-glutamic acid decarboxylase antibodies can be observed in patients with limbic encephalitis during the disease course.

Whole blood fatty acid composition differs in term versus mildly preterm infants: small versus matched appropriate for gestational age.

To investigate the associations between whole blood fatty acid (FA) profile and restricted intrauterine growth, any small for gestational age (SGA) infant born in our maternity ward through 1 y was matched with two appropriate for gestational age (AGA), of the same GA +/- 0.5 wk, infants, further subdivided into term and preterm. Whole blood was collected at d 4 on a strip and FA % composition assessed by means of gas chromatography. The whole sample consisted of 28 SGA versus 56 AGA born at term and 20 SGA versus 40 AGA born preterm at around 35 wks. Parent FA of the n-6 and n-3 FA families were higher in preterm groups, whereas docosahexaenoic acid was higher in term AGA (median % values, 3.9 versus 3.7 in term SGA, 2.8 in preterm AGA, and 2.5 in preterm SGA, p < 0.001). Term AGA had markedly higher values for the docosahexaenoic acid/alpha-linolenic acid ratio (median value: 91, versus 18 in term SGA, 12 in preterm AGA, and 10 in preterm SGA, p < 0.001). Term SGA had significantly lower levels of total monounsaturated FA and higher levels of eicosapentaenoic acid. Therefore, the 4-d whole blood FA pattern is associated with both GA and birth weight.