Publications by authors named "Antonia Parmeggiani"

44 Publications

Phonic and Motor Stereotypies in Autism Spectrum Disorder: Video Analysis and Neurological Characterization.

Brain Sci 2021 Mar 28;11(4). Epub 2021 Mar 28.

Child Neurology and Psychiatry Unit, IRCCS Institute of Neurological Sciences of Bologna, 40138 Bologna, Italy.

Stereotypies are among the core symptoms of Autism spectrum disorder (ASD) and can cause significant clinical impairment. At present, phonic stereotypies in ASD have been scarcely explored. This study investigates the frequency, variability, and typologies of phonic and motor stereotypies in children with ASD and their association with clinical neurological variables. We examined 35 patients by recording standardized video sessions and administering the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). Phonic stereotypies were present in 83.0% of the patients. The most prevalent subtypes were noncommunicative vocalizations (60.0%), single syllables (37.1%), and echolalic stereotypies (22.9%). Noncommunicative vocalizations were more frequent in nonverbal patients (OR = 4.629, = 0.008), while echolalic stereotypies were more represented in verbal patients (OR = 0.279, = 0.028). Patients with intellectual disability (ID) showed a higher number (F(1,26) = 9.406, = 0.005) and variability (F(1,25) = 7.174, = 0.013) of motor stereotypies, with a higher number (F(1,26) = 13.268, = 0.005) and variability (F(1,26) = 9.490, = 0.005) of stereotypies involving the head/trunk/shoulders category. Patients with guttural stereotypies showed a higher variability of total motor stereotypies (OR = 1.487, = 0.032) and self-directed motor stereotypies (OR = 4.389, = 0.042). These results, combined with a standardized video-analysis, document the frequency and variability of phonic stereotypies among children with ASD. Correlations between specific phonic stereotypies and verbal abilities should be investigated further.
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http://dx.doi.org/10.3390/brainsci11040431DOI Listing
March 2021

Autism spectrum disorder and anorexia nervosa: an Italian prospective study.

Ital J Pediatr 2021 Mar 9;47(1):59. Epub 2021 Mar 9.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Background: Potential overlaps exist between psychopathological features of Anorexia Nervosa (AN) and Autism Spectrum Disorder (ASD). The impact of malnutrition on autistic traits in patients with AN should be considered. This study investigates possible associations among the psychopathology of Eating Disorders (EDs), ASD traits and BMI in a group of young patients with AN, using the EDI-3 (Eating Disorder Inventory-3) test and gold-standard measures for ASD.

Methods: Prospective study involving 23 inpatients admitted to an Italian Centre for paediatric ED. ASD traits and ED psychopathology were assessed administering the ADOS-2 (Autism Diagnostic Observation Schedule-2), AQ (Autism Quotient) and EDI-3 tests. Both present and past autistic traits were investigated using different versions of AQ. Correlations were adjusted for BMI, Obsessive Compulsive Disorder (OCD) comorbidity and concurrent antipsychotic treatments.

Results: An ASD diagnosis was possible in 22% of patients. Significant correlations were documented between ASD traits and ED psychopathology: AQ total-Interpersonal problems (IPC) (p = 0.041); AQ total-Global psychological maladjustment (GMPC) (p = 0.027); AQ social skills-Ineffectiveness (IC) (p = 0.018); AQ social skills-IPC (p = 0.019); AQ social skills-Affective problems (APC) (p = 0.025); AQ social skills-GMPC (p = 0.007); AQ attention switching-IPC (p = 0.020); ADOS-2 imagination-IC (p = 0.035). These correlations were independent of BMI, OCD and antipsychotic treatments.

Conclusions: ASD traits presented high prevalence in a group of young inpatients with AN. These traits were significantly correlated to 4 specific EDI-3 subscales and independent of BMI. This is the first study to investigate the relationship between ASD traits as measured with gold-standard measures, EDI-3 scores, and BMI.
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http://dx.doi.org/10.1186/s13052-021-01006-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945370PMC
March 2021

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift.

J Pers Med 2021 Jan 25;11(2). Epub 2021 Jan 25.

Neonatal Intensive Care Unit, Department of Surgical Sciences, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, 09100 Cagliari, Italy.

The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called 'First 1000 Days') are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.
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http://dx.doi.org/10.3390/jpm11020070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912683PMC
January 2021

Quadriceps muscle strength in Duchenne muscular dystrophy and effect of corticosteroid treatment.

Acta Myol 2020 Dec 1;39(4):200-206. Epub 2020 Dec 1.

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Italy.

Objectives: In Duchenne muscular dystrophy, quadriceps weakness is recognized as a key factor in gait deterioration. The objective of this work was three-fold: first, to document the strength of the quadriceps in corticosteroid-naïve DMD boys; second, to measure the effect of corticosteroids on quadriceps strength; and third, to evaluate the correlation between baseline quadriceps strength and the age when starting corticosteroids with the loss of ambulation.

Methods: Quadriceps muscle strength using hand-held dynamometry was measured in 12 ambulant DMD boys who had never taken corticosteroids and during corticosteroid treatment until the loss of ambulation.

Results: Baseline quadriceps muscle strength at 6 years of age was 28% that of normal children of the same age; it decreased to 15% at 8 years and to 6% at 10 years. The increase in quadriceps muscle strength obtained after 1 year of corticosteroid treatment had a strong direct correlation with the baseline strength (R = 0.96). With corticosteroid treatment, the age of ambulation loss showed a very strong direct relationship (R = 0.92) with baseline quadriceps muscle strength but only a very weak inverse relationship (R = -0.73) with the age of starting treatment. Age of loss of ambulation was 10.3 ± 0.5 19.1 ± 4.7 (P < 0.05) in children with baseline quadriceps muscle strength less than or greater than 40 N, respectively.

Conclusions: Corticosteroid-naïve DMD boys have a quantifiable severe progressive quadriceps weakness. This long-term study, for the first time, shows that both of the positive effects obtained with CS treatment, i.e. increasing quadriceps strength and delaying the loss of ambulation, have a strong and direct correlation with baseline quadriceps muscle strength. As such, hand-held dynamometry may be a useful tool in the routine physical examination and during clinical trial assessment.
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http://dx.doi.org/10.36185/2532-1900-023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783426PMC
December 2020

Pervasive refusal syndrome or anorexia nervosa: a case report with a successful behavioural treatment.

Eat Weight Disord 2020 Aug 20. Epub 2020 Aug 20.

Regional Centre for Feeding Eating Disorders, Child Neurology and Psychiatry Unit, Department of Medical and Surgical Sciences, S. Orsola Malpighi Hospital, University of Bologna, Bologna, Italy.

Purpose: Pervasive refusal syndrome (PRS) is a rare psychiatric disease that affects children. It was first described by Lask in 1991 (Arch Dis Child 66:866-869, 1991). Recently, Otasowie and Collaborators reported a systematic review about PRS. Despite this, PRS has not yet been classified in DSM-5 and ICD-11 and the lack of evidence-based treatment makes this syndrome a real challenge for clinicians. The aim of this paper is to present our experience through the description of a case report and its treatment.

Methods And Results: The case reported is a girl aged 11 years that fits the clinical picture described in the literature of PRS. In previous reports, behavioural treatment was not used or appreciated; our case adds new knowledge regarding the PRS diagnosis and the successful behavioural treatment during hospitalization, which we describe in all its phases.

Conclusion: PRS is a rare, life-threatening syndrome; it would be extremely important to have an official and evidence-based treatment guide.

Level Of Evidence: Level V, case report.
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http://dx.doi.org/10.1007/s40519-020-00991-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439801PMC
August 2020

Corrigendum to "Challenges in the clinical interpretation of small de novo copy number variants in neurodevelopmental disorders" [Gene 706 (2019) 162-171].

Gene 2020 04 6;735:144393. Epub 2020 Feb 6.

Unit of Medical Genetics, Department of Medical and Surgical Sciences, Policlinico St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.gene.2020.144393DOI Listing
April 2020

Early features of autism spectrum disorder: a cross-sectional study.

Ital J Pediatr 2019 Nov 14;45(1):144. Epub 2019 Nov 14.

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria Infantile, Bologna, Italia.

Background: Autism spectrum disorder is characterized by impairment in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests and activities. It is important to detect this condition as soon as possible and promptly begin targeted treatments. This study aimed to report on age at onset, early signs, and mode at onset in 105 Italian patients with autism spectrum disorder, searching for correlations with a series of clinical and instrumental variables.

Methods: This retrospective cross-sectional study considered the following five categories of symptoms at onset: language, social interaction and relationships, stereotyped behavior and activities, motor skills, and regulation. Three modes of presentation were considered: a delay, a stagnation, or a regression of development, which were defined modes of onset of autism spectrum disorder. The age at onset, the category of clinical features, and the mode at onset were considered in the entire sample and statistically analyzed for several clinical variables. Statistical analysis was performed utilizing Fisher Exact test and Chi Square test.

Results: The first symptoms between 7 and 12 months were evident in 41.9% of cases, and between 13 and 24 months in 27.6%; no significant differences for the age at onset related to diagnosis, etiopathogenesis, early onset epilepsy, and intelligence quotient level emerged. Social interaction and relationships (93.3%) and language (92.4%) were the categories of early signs more represented in our sample. Delay in spoken language (to be understood as both verbal production and verbal comprehension) was one of the most common (even though not specific) symptoms prompting initial medical consultation for a possible diagnosis of autism spectrum disorder. At onset, patients without intellectual disability manifested stagnation more often than delay or regression of development; patients with a severe/profound intellectual disability more frequently showed delay or regression of development. Language signs at onset were less frequent in cases with regression, whereas motor skill disorders prevailed in cases with delay at onset. Feeding problems were more numerous in cases with delay and stagnation of development.

Conclusions: These data contribute to identifying an early trend of autism spectrum disorder, useful also for pediatricians.
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http://dx.doi.org/10.1186/s13052-019-0733-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857294PMC
November 2019

The effect of chronic neuroglycopenia on resting state networks in GLUT1 syndrome across the lifespan.

Hum Brain Mapp 2020 02 11;41(2):453-466. Epub 2019 Nov 11.

Neurology Unit, OCSAE Hospital, AOU Modena, Modena, Italy.

Glucose transporter type I deficiency syndrome (GLUT1DS) is an encephalopathic disorder due to a chronic insufficient transport of glucose into the brain. PET studies in GLUT1DS documented a widespread cortico-thalamic hypometabolism and a signal increase in the basal ganglia, regardless of age and clinical phenotype. Herein, we captured the pattern of functional connectivity of distinct striatal, cortical, and cerebellar regions in GLUT1DS (10 children, eight adults) and in healthy controls (HC, 19 children, 17 adults) during rest. Additionally, we explored for regional connectivity differences in GLUT1 children versus adults and according to the clinical presentation. Compared to HC, GLUT1DS exhibited increase connectivity within the basal ganglia circuitries and between the striatal regions with the frontal cortex and cerebellum. The excessive connectivity was predominant in patients with movement disorders and in children compared to adults, suggesting a correlation with the clinical phenotype and age at fMRI study. Our findings highlight the primary role of the striatum in the GLUT1DS pathophysiology and confirm the dependency of symptoms to the patients' chronological age. Despite the reduced chronic glucose uptake, GLUT1DS exhibit increased connectivity changes in regions highly sensible to glycopenia. Our results may portrait the effect of neuroprotective brain strategy to overcome the chronic poor energy supply during vulnerable ages.
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http://dx.doi.org/10.1002/hbm.24815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313681PMC
February 2020

Challenges in the clinical interpretation of small de novo copy number variants in neurodevelopmental disorders.

Gene 2019 Jul 11;706:162-171. Epub 2019 May 11.

Unit of Medical Genetics, Department of Medical and Surgical Sciences, Policlinico St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. Electronic address:

In clinical genetics, the need to discriminate between benign and pathogenic variants identified in patients with neurodevelopmental disorders is an absolute necessity. Copy number variants (CNVs) of small size can enable the identification of genes that are critical for neurologic development. However, assigning a definite association with a specific disorder is a difficult task. Among 328 trios analyzed over seven years of activity in a single laboratory, we identified 19 unrelated patients (5.8%) who carried a small (<500 kb) de novo CNV. Four patients had an additional independent de novo CNV. Nine had a variant that could be assigned as definitely pathogenic, whereas the remaining CNVs were considered as variants of unknown significance (VUS). We report clinical and molecular findings of patients harboring VUS. We reviewed the medical literature available for genes impacted by CNVs, obtained the probability of truncating loss-of-function intolerance, and compared overlapping CNVs reported in databases. The classification of small non-recurrent CNVs remains difficult but, among our findings, we provide support for a role of SND1 in the susceptibility of autism, describe a new case of the rare 17p13.1 microduplication syndrome, and report an X-linked duplication involving KIF4A and DLG3 as a likely cause of epilepsy.
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http://dx.doi.org/10.1016/j.gene.2019.05.007DOI Listing
July 2019

Disability and inclusive education in an Italian Region: analysis of the data for the school year 2012-2013.

Minerva Pediatr 2017 Feb 17. Epub 2017 Feb 17.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Background: In Italy, pupils with disabilities enroll in mainstream schools and attend the ordinary classes at all educational levels. For the past twelve years, the Region Emilia Romagna has witnessed an increase in the number of children who are in need of special support. The aim of the study was to identify the causes of disability in children attending public schools during the school year 2012-2013.

Methods: The study was designed as a cross-sectional survey. Data were obtained from the Regional Education Department, and divided into categories based on clinical diagnoses. Statistical analyses were performed to analyze the distribution of the diagnostic categories among Provinces and school grades. The most recurrent combinations of illnesses were identified.

Results: Intellectual disability was the most common cause of impairment (38,5%), often associated with epilepsy and autism. Hyperkinetic disorder associated with specific disorders of scholastic skills was the most recurrent combination of diagnoses. Rare diseases were diagnosed in 4,1%, whereas 5,0% of cases were affected by Psychopathological disorders.

Conclusions: Our study is the first in Italy for its focus on the causes of children's disabilities in an Italian region. Being familiar with the causes of disability affecting the children of a territory is important to allocate the available resources efficiently, and to ensure all children's effective social integration.
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http://dx.doi.org/10.23736/S0026-4946.17.04747-8DOI Listing
February 2017

Brain correlates of spike and wave discharges in GLUT1 deficiency syndrome.

Neuroimage Clin 2017 21;13:446-454. Epub 2016 Dec 21.

Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; N.O.C.S.A.E. Hospital, AUSL Modena, 41100 Modena, Italy.

Purpose: To provide imaging biomarkers of generalized spike-and-wave discharges (GSWD) in patients with GLUT1 deficiency syndrome (GLUT1DS).

Methods: Eighteen GLUT1DS patients with pathogenetic mutation in SLC2A1 gene were studied by means of Video-EEG simultaneously recorded with functional MRI (VideoEEG-fMRI). A control group of sex and age-matched patients affected by Genetic Generalized Epilepsy (GGE) with GSWD were investigated with the same protocol. Within and between groups comparison was performed as appropriated. For GLUT1DS, correlations analyses between the contrast of interest and the main clinical measurements were provided.

Results: EEG during fMRI revealed interictal GSWD in 10 GLUT1DS patients. Group-level analysis showed BOLD signal increases at the premotor cortex and putamen. With respect to GGE, GLUT1DS patients demonstrated increased neuronal activity in the putamen, precuneus, cingulate cortex, SMA and paracentral lobule. Whole-brain correlation analyses disclosed a linear relationship between the GSWD-related BOLD changes and the levels of glycorrhachia at diagnosis over the sensory-motor cortex and superior parietal lobuli.

Conclusion: The BOLD dynamics related to GSWD in GLUT1DS are substantially different from typical GGE showing the former an increased activity in the premotor-striatal network and a decrease in the thalamus. The revealed hemodynamic maps might represent imaging biomarkers of GLUT1DS, being potentially useful for a precocious diagnosis of this genetic disorder.
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http://dx.doi.org/10.1016/j.nicl.2016.12.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233795PMC
November 2017

Long-term follow-up of cognitive functions in patients with continuous spike-waves during sleep (CSWS).

Epilepsy Behav 2016 07 27;60:211-217. Epub 2016 May 27.

Child Neurology and Psychiatry Unit, Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi of Bologna and Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, Bologna, Italy. Electronic address:

Continuous spike-waves during sleep (CSWS) are associated with several cognitive, neurological, and psychiatric disorders, which sometimes persist after CSWS disappearance. The purpose of this retrospective study was to investigate the correlation between general (clinical and instrumental) and neuropsychological findings in CSWS, to identify variables that predispose patients to a poorer long-term neuropsychological outcome. Patients with spikes and waves during sleep with a frequency ≥25/min (spikes and waves frequency index - SWFI) were enrolled. There were patients presenting abnormal EEG activity corresponding to the classic CSWS and patients with paroxysmal abnormalities during sleep <85% with SWFI ≥25/min that was defined as excessive spike-waves during sleep (ESWS). Clinical and instrumental features and neuropsychological findings during and after the spike and wave active phase period were considered. A statistical analysis was performed utilizing the Spearman correlation test and multivariate analysis. The study included 61 patients; the mean follow-up (i.e., the period between SWFI ≥25 first recording and last observation) was 7years and 4months. The SWFI correlated inversely with full and performance IQ during CSWS/ESWS. Longer-lasting SWFI ≥25 was related to worse results in verbal IQ and performance IQ after CSWS/ESWS disappearance. Other variables may influence the neuropsychological outcome, like age at SWFI ≥25 first recording, perinatal distress, pathologic neurologic examination, and antiepileptic drug resistance. This confirms that CSWS/ESWS are a complex pathology and that many variables contribute to its outcome. The SWFI value above all during CSWS/ESWS and long-lasting SWFI ≥25 after CSWS/ESWS disappearance are the most significant indexes that appear mostly to determine cognitive evolution. This finding underscores the importance of EEG recordings during sleep in children with a developmental disorder, even if seizures are not reported, as well as the importance of using therapy with an early efficacy.
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http://dx.doi.org/10.1016/j.yebeh.2016.04.006DOI Listing
July 2016

The syndrome of polymicrogyria, thalamic hypoplasia, and epilepsy with CSWS.

Neurology 2016 Mar 4;86(13):1250-9. Epub 2016 Mar 4.

From the Pediatric Neurology Unit and Laboratories, A. Meyer Children's Hospital (E.B., M.F., F.Z., E.P., C.B., R.G.), and Department of Statistics, Computer Science and Applications "G. Parenti" (L.G.), University of Florence; Department of Translational Research and New Surgical and Medical Technologies (M.C.), University of Pisa; Unit of Neuroradiology (M.C.), Pisa University Hospital "Azienda Ospedaliero-Universitaria Pisana"; Child Neurology and Psychiatry Unit (A. Posar, M.S.), IRCCS Institute of Neurological Sciences of Bologna; Departments of Biomedical and Neuromotor Sciences (A. Posar, M.S.) and Medical and Surgical Sciences (A. Parmeggiani, G.A.), University of Bologna; Child Neurology and Psychiatry Unit (A. Parmeggiani), Policlinico S. Orsola-Malpighi, Bologna; IRCCS Stella Maris Foundation (E.B., A.R.F., R.G.), Calambrone, Pisa, Italy; and the Epilepsy Unit, Department of Neurology (J.S.-P.), Hospital Vall Hebron, Barcelona, Spain.

Objective: We explored the long-term follow-up of continuous spike-and-wave complexes during sleep (CSWS) in polymicrogyria and the anatomic volumetric variables that influence the risk of developing this age-related epileptic encephalopathy.

Methods: We performed prospective follow-up of 27 patients with polymicrogyria/CSWS (mean follow-up 14.3 years; range 2-31 years) and comparative volumetric analysis of the polymicrogyric hemispheres and ipsilateral thalami vs 3 subgroups featuring polymicrogyria without CSWS, benign rolandic epilepsy (BRE), and headache. Receiver operator characteristic analysis of the power of volumetric values was determined to predict CSWS.

Results: CSWS peaked between 5 and 7 years (mean age at onset 4.7 years). Remission occurred within 2 years from onset in 21%, within 4 years in 50%, and by age 13 years in 100%. We found smaller thalamic and hemispheric volumes in polymicrogyria/CSWS with respect to polymicrogyria without CSWS (p = 0.0021 for hemispheres; p = 0.0003 for thalami), BRE, and controls with headache (p < 0.0001). Volumes of the malformed hemispheres and ipsilateral thalami reliably identified the risk of incurring CSWS, with a 68-fold increased risk for values lower than optimal diagnostic cutoffs (436,150 mm(3) for malformed hemispheres or 4,616 mm(3) for ipsilateral thalami; sensitivity 92.54%; specificity 84.62%). The risk increased by 2% for every 1,000 mm(3) reduction of the polymicrogyric hemispheres and by 15% for every 100 mm(3) reduction of ipsilateral thalami.

Conclusions: The polymicrogyria/CSWS syndrome is likely caused by a cortico-thalamic malformation complex and is characterized by remission of epilepsy within early adolescence. Early assessment of hemispheric and thalamic volumes in children with polymicrogyria and epilepsy can reliably predict CSWS.
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http://dx.doi.org/10.1212/WNL.0000000000002526DOI Listing
March 2016

Prognostic factors of drug-resistant epilepsy in childhood: An Italian study.

Pediatr Int 2015 Dec 5;57(6):1143-8. Epub 2015 Nov 5.

Child Neurology and Psychiatry Service, Neurological Clinic, IRCCS Institute of Neurological Sciences of Bologna.

Background: Epilepsy is drug resistant in 30-40% of cases. We studied, retrospectively, the prognostic factors of drug resistance (DR) during a 15 year period, in an Italian sample of patients with childhood epilepsy.

Methods: A total of 117 patients were divided into two groups: one with DR, and the other without DR. The two groups were compared at the following time points: epilepsy onset (T0), and at 2, 5, 8 and 10 years after seizure onset (T2, T5, T8 and T10, respectively) using Fisher's exact test and randomization test. Multiple logistic regression analysis was then used to identify the most reliable predictive model of DR.

Results: Positive neurological examination at onset, symptomatic/probable symptomatic etiology, lack of response to the first drug, seizure clustering during follow up, intelligence quotient ≤ 70, altered neuropsychological examination at onset, and presence of cerebral lesions were predominant in cases of DR. The most reliable combinations of predictors of DR included partial or no response to the first drug, presence of seizure clustering during follow up, altered neurological examination at onset, and long latency between epilepsy onset and first drug at T2; partial or absent response to the first drug and positive magnetic resonance imaging (MRI) at T5; positive MRI and absence of generalized seizures at T8; and positive MRI at T10. DR also sometimes appeared after discontinuation of an effective therapy.

Conclusions: Predictive factors of DR can be recognized in a large number of patients with epilepsy at disease onset, although the current possibility of predicting epilepsy outcome remains limited. In the long term, evidence of cerebral lesions appears to become the most significant prognostic factor.
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http://dx.doi.org/10.1111/ped.12705DOI Listing
December 2015

Homozygous NOTCH3 null mutation and impaired NOTCH3 signaling in recessive early-onset arteriopathy and cavitating leukoencephalopathy.

EMBO Mol Med 2015 Jun;7(6):848-58

U.O. Genetica Medica, Policlinico Sant'Orsola-Malpighi, Bologna, Italy Dipartimento di Scienze Mediche Chirurgiche (DIMEC), University of Bologna, Bologna, Italy

Notch signaling is essential for vascular physiology. Neomorphic heterozygous mutations in NOTCH3, one of the four human NOTCH receptors, cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Hypomorphic heterozygous alleles have been occasionally described in association with a spectrum of cerebrovascular phenotypes overlapping CADASIL, but their pathogenic potential is unclear. We describe a patient with childhood-onset arteriopathy, cavitating leukoencephalopathy with cerebral white matter abnormalities presented as diffuse cavitations, multiple lacunar infarctions and disseminated microbleeds. We identified a novel homozygous c.C2898A (p.C966*) null mutation in NOTCH3 abolishing NOTCH3 expression and causing NOTCH3 signaling impairment. NOTCH3 targets acting in the regulation of arterial tone (KCNA5) or expressed in the vasculature (CDH6) were downregulated. Patient's vessels were characterized by smooth muscle degeneration as in CADASIL, but without deposition of granular osmiophilic material (GOM), the CADASIL hallmark. The heterozygous parents displayed similar but less dramatic trends in decrease in the expression of NOTCH3 and its targets, as well as in vessel degeneration. This study suggests a functional link between NOTCH3 deficiency and pathogenesis of vascular leukoencephalopathies.
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http://dx.doi.org/10.15252/emmm.201404399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459822PMC
June 2015

Autosomal dominant lateral temporal epilepsy (ADLTE): novel structural and single-nucleotide LGI1 mutations in families with predominant visual auras.

Epilepsy Res 2015 Feb 16;110:132-8. Epub 2014 Dec 16.

CNR-Neuroscience Institute, Section of Padua, Padova, Italy. Electronic address:

Purpose: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by prominent auditory or aphasic symptoms. Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE patients.

Methods: Twenty-four ADLTE families and 140 sporadic LTE patients with no evidence of point mutations in LGI1 were screened for copy number alterations using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained familial and sporadic LTE patients were clinically investigated, and interictal EEG and MRI findings were obtained; probands were tested for LGI1 mutations by direct exon sequencing or denaturing high performance liquid chromatography.

Results: We identified a novel microdeletion spanning LGI1 exon 2 in a family with two affected members, both presenting focal seizures with visual symptoms. Also, we identified a novel LGI1 missense mutation (c.1118T > C; p.L373S) in a newly ascertained family with focal seizures with prominent visual auras, and another missense mutation (c.856T > C; p.C286R) in a sporadic patient with auditory seizures.

Conclusions: We describe two novel ADLTE families with predominant visual auras segregating pathogenic LGI1 mutations. These findings support the notion that, in addition to auditory symptoms, other types of auras can be found in patients carrying LGI1 mutations. The identification of a novel microdeletion in LGI1, the second so far identified, suggests that LGI1 microrearrangements may not be exceptional.
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http://dx.doi.org/10.1016/j.eplepsyres.2014.12.004DOI Listing
February 2015

Neuropsychological implications of adjunctive levetiracetam in childhood epilepsy.

J Pediatr Neurosci 2014 May;9(2):115-20

Child Neurology and Psychiatry Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy ; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Introduction: Levetiracetam (LEV) is an effective antiepileptic drug also used in childhood and adolescence. Literature data regarding the long-term effects of LEV in childhood epilepsy and based on extensive neuropsychological evaluations using standardized tools are still scanty. Our study aimed to address this topic.

Materials And Methods: We studied 10 patients with epilepsy characterized by focal or generalized seizures (4 boys, 6 girls; mean age: 10 years 8 months; range: 6 years 2 months - 16 years 2 months), treated with adjunctive LEV during a follow-up of 12 months. In 6 patients electroencephalogram (EEG) showed continuous spike and waves during sleep. Using standardized tools, we performed seriated assessments of cognitive and behavioral functioning in relation to seizure and EEG outcome.

Results: Six patients completed the trial after 12 months of treatment; 1 patient dropped out of the study after 9 months, 3 patients after 6 months. Adjunctive LEV was effective on seizures in 3/10 patients and on EEG in 2/10 patients, and was well tolerated in all examined cases. Overall, no worsening of cognitive or behavioral functions has been detected during the period of the study; even at 6 and 12 months from baseline, an improvement in patients' abstract reasoning has been found, that was not related to seizure or EEG outcome.

Conclusions: In our population of children and adolescents, LEV had no adverse cognitive or behavioral effects, short- or long-term. We found an improvement of abstract reasoning, regardless of seizure and EEG outcome.
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http://dx.doi.org/10.4103/1817-1745.139282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166830PMC
May 2014

Co-occurring malformations of cortical development and SCN1A gene mutations.

Epilepsia 2014 Jul 5;55(7):1009-19. Epub 2014 Jun 5.

Pediatric Neurology Unit and Laboratories, Children's Hospital Meyer-University of Florence, Florence, Italy.

Objective: To report on six patients with SCN1A mutations and malformations of cortical development (MCDs) and describe their clinical course, genetic findings, and electrographic, imaging, and neuropathologic features.

Methods: Through our database of epileptic encephalopathies, we identified 120 patients with SCN1A mutations, of which 4 had magnetic resonance imaging (MRI) evidence of MCDs. We collected two further similar observations through the European Task-force for Epilepsy Surgery in Children.

Results: The study group consisted of five males and one female (mean age 7.4 ± 5.3 years). All patients exhibited electroclinical features consistent with the Dravet syndrome spectrum, cognitive impairment, and autistic features. Sequencing analysis of the SCN1A gene detected two missense, two truncating, and two splice-site mutations. Brain MRI revealed bilateral periventricular nodular heterotopia (PNH) in two patients and focal cortical dysplasia (FCD) in three, and disclosed no macroscopic abnormality in one. In the MRI-negative patient, neuropathologic study of the whole brain performed after sudden unexpected death in epilepsy (SUDEP), revealed multifocal micronodular dysplasia in the left temporal lobe. Two patients with FCD underwent epilepsy surgery. Neuropathology revealed FCD type IA and type IIA. Their seizure outcome was unfavorable. All four patients with FCD exhibited multiple seizure types, which always included complex partial seizures, the area of onset of which co-localized with the region of structural abnormality.

Significance: MCDs and SCN1A gene mutations can co-occur. Although epidemiology does not support a causative role for SCN1A mutations, loss or impaired protein function combined with the effect of susceptibility factors and genetic modifiers of the phenotypic expression of SCN1A mutations might play a role. MCDs, particularly FCD, can influence the electroclinical phenotype in patients with SCN1A-related epilepsy. In patients with MCDs and a history of polymorphic seizures precipitated by fever, SCN1A gene testing should be performed before discussing any epilepsy surgery option, due to the possible implications for outcome.
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http://dx.doi.org/10.1111/epi.12658DOI Listing
July 2014

Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions.

BMC Neurol 2014 May 28;14:116. Epub 2014 May 28.

UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria, Bologna, Italy.

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype.

Case Presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present.

Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.
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http://dx.doi.org/10.1186/1471-2377-14-116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047257PMC
May 2014

Life-threatening complications of posterior reversible encephalopathy syndrome in children.

Eur J Paediatr Neurol 2014 Sep 25;18(5):632-40. Epub 2014 Apr 25.

Child Neurology Unit, University of Bologna, S. Orsola Malpighi Hospital, Via Massarenti 11, Bologna, Italy.

Background: Although the posterior reversible encephalopathy syndrome (PRES) is considered to have a benign clinical outcome, the presentation of PRES can be associated with life-threatening complications such as severe cerebral hemorrhage, cerebellar herniation and refractory status epilepticus (SE). The aim of this paper is to report incidence, clinical features and outcome of life-threatening complications related to PRES in children.

Methods: Patients who suffered from life-threatening complications were retrospectively identified from a group composed by 27 consecutive children diagnosed with PRES in our hospital between 2000 and 2012. The clinical, radiological and EEG features and the outcome of these patients were evaluated and compared to the characteristics of patients with no complications.

Results: Five patients (18%) presented life-threatening complications: 2 cerebral hemorrhages with mass effect and midline shift (1 massive intraparenchymal hemorrhage and 1 subdural hemorrhage and intraparenchymal hemorrhage), 2 transforaminal cerebellar herniations and 1 refractory SE. Two children died because of complications and 2 children required urgent neurosurgical intervention. The infratentorial involvement at onset of PRES and the observation of focal neurological deficits other than visual disturbances were significantly more frequent in children with life-threatening complications (p < 0.01).

Conclusions: PRES is associated with a non-negligible incidence of life-threatening complications. A careful clinical, neuroradiological and EEG monitoring is necessary in order to improve the outcome especially in the case of focal neurological deficits and infratentorial involvement.
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http://dx.doi.org/10.1016/j.ejpn.2014.04.014DOI Listing
September 2014

Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients.

EMBO Mol Med 2014 Jun 6;6(6):795-809. Epub 2014 Apr 6.

Unit of Medical Genetics, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital University of Bologna, Bologna, Italy.

Intellectual disability (ID) and autism spectrum disorders (ASDs) are complex neuropsychiatric conditions, with overlapping clinical boundaries in many patients. We identified a novel intragenic deletion of maternal origin in two siblings with mild ID and epilepsy in the CADPS2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2DR). Mutation screening of 223 additional patients (187 with ASD and 36 with ID) identified a missense change of maternal origin disrupting CADPS2/D2DR interaction. CADPS2 allelic expression was tested in blood and different adult human brain regions, revealing that the gene was monoallelically expressed in blood and amygdala, and the expressed allele was the one of maternal origin. Cadps2 gene expression performed in mice at different developmental stages was biallelic in the postnatal and adult stages; however, a monoallelic (maternal) expression was detected in the embryonal stage, suggesting that CADPS2 is subjected to tissue- and temporal-specific regulation in human and mice. We suggest that CADPS2 variants may contribute to ID/ASD development, possibly through a parent-of-origin effect.
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http://dx.doi.org/10.1002/emmm.201303235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203356PMC
June 2014

A novel null homozygous mutation confirms CACNA2D2 as a gene mutated in epileptic encephalopathy.

PLoS One 2013 16;8(12):e82154. Epub 2013 Dec 16.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy ; Dipartimento di Scienze Biomediche e Neuromotorie (DIBINEM), University of Bologna, Bologna, Italy.

Contribution to epileptic encephalopathy (EE) of mutations in CACNA2D2, encoding α2δ-2 subunit of Voltage Dependent Calcium Channels, is unclear. To date only one CACNA2D2 mutation altering channel functionality has been identified in a single family. In the same family, a rare CELSR3 polymorphism also segregated with disease. Involvement of CACNA2D2 in EE is therefore not confirmed, while that of CELSR3 is questionable. In a patient with epilepsy, dyskinesia, cerebellar atrophy, psychomotor delay and dysmorphic features, offspring to consanguineous parents, we performed whole exome sequencing (WES) for homozygosity mapping and mutation detection. WES identified extended autozygosity on chromosome 3, containing two novel homozygous candidate mutations: c.1295delA (p.Asn432fs) in CACNA2D2 and c.G6407A (p.Gly2136Asp) in CELSR3. Gene prioritization pointed to CACNA2D2 as the most prominent candidate gene. The WES finding in CACNA2D2 resulted to be statistically significant (p = 0.032), unlike that in CELSR3. CACNA2D2 homozygous c.1295delA essentially abolished α2δ-2 expression. In summary, we identified a novel null CACNA2D2 mutation associated to a clinical phenotype strikingly similar to the Cacna2d2 null mouse model. Molecular and statistical analyses together argued in favor of a causal contribution of CACNA2D2 mutations to EE, while suggested that finding in CELSR3, although potentially damaging, is likely incidental.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082154PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864908PMC
September 2014

Neuropsychological findings in childhood narcolepsy.

J Child Neurol 2014 Oct 28;29(10):1370-6. Epub 2013 Nov 28.

IRCCS Institute of Neurological Sciences of Bologna, Italy Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.

Narcolepsy with cataplexy is a severely disabling disorder very often arising in childhood. Data on neuropsychological impairment in children are scant. We administered standardized neuropsychological tests to 13 children with narcolepsy with cataplexy. Overall, our patients displayed multiple patterns of cognitive and behavioral dysfunction, and often academic failure (7 cases out of 13). All children had a normal full intelligence quotient (IQ), but 3 patients presented a significantly higher and 2 a significantly lower Verbal IQ compared to Performance IQ, respectively. Mean sleep latency was significantly correlated (P < .05) to alertness functions. Eight patients displayed behavioral problems: emotional symptoms and conduct problems prevailed. Childhood narcolepsy with cataplexy represents a risk factor for subtle and heterogeneous cognitive impairments potentially resulting in academic failure, despite the normal IQ. These children also have a certain psychopathological risk. All this seems to be at least partially detached from the direct effects of daytime sleepiness.
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http://dx.doi.org/10.1177/0883073813508315DOI Listing
October 2014

Neuropsychological impairment in early-onset hydrocephalus and epilepsy with continuous spike-waves during slow-wave sleep: A case report and literature review.

J Pediatr Neurosci 2013 May;8(2):141-5

Child Neurology and Psychiatry Unit, IRCCS Institute of Neurological Sciences of Bologna, Bologna Italy ; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Epilepsy with continuous spike-waves during slow-wave sleep (CSWS) is often characterized by a severe cognitive and behavioral impairment. Symptomatic cases also include patients with an early-onset hydrocephalus, but in literature detailed neuropsychological data on these subjects are not available. We describe the results of serial cognitive assessments in a girl with shunted early-onset hydrocephalus, followed by partial epilepsy complicated with CSWS at 4 years 10 months, in which a dramatic cognitive and behavioral deterioration occurred few months after CSWS onset. Adrenocorticotropic hormone treatment improved both clinical and electroencephalogram picture, but an impairment of visual perception, visual-motor coordination and executive functions persisted after CSWS disappearance. We hypothesize, in this case, an involvement of right occipital-parietal lobe and prefrontal lobe.
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http://dx.doi.org/10.4103/1817-1745.117850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783725PMC
May 2013

The characteristics and activities of child and adolescent mental health services in Italy: a regional survey.

BMC Psychiatry 2012 Jan 30;12. Epub 2012 Jan 30.

IRCCS Centro San Giovanni di Dio-Fatebenefratelli, Brescia-Italy.

Background: To date, no studies have assessed in detail the characteristics, organisation, and functioning of Child and Adolescent Mental Health Services (CAMHS). This information gap represents a major limitation for researchers and clinicians because most mental disorders have their onset in childhood or adolescence, and effective interventions can therefore represent a major factor in avoiding chronicity. Interventions and mental health care are delivered by and through services, and not by individual, private clinicians, and drawbacks or limitations of services generally translate in inappropriateness and ineffectiveness of treatments and interventions: therefore information about services is essential to improve the quality of care and ultimately the course and outcome of mental disorders in childhood and adolescence.The present paper reports the results of the first study aimed at providing detailed, updated and comprehensive data on CAMHS of a densely populated Italian region (over 4 million inhabitants) with a target population of 633,725 subjects aged 0-17 years.

Methods: Unit Chiefs of all the CAMHS filled in a structured 'Facility Form', with activity data referring to 2008 (data for inpatient facilities referred to 2009), which were then analysed in detail.

Results: Eleven CAMHS were operative, including 110 outpatient units, with a ratio of approximately 20 child psychiatrists and 23 psychologists per 100,000 inhabitants aged 0-17 years. All outpatient units were well equipped and organized and all granted free service access. In 2008, approximately 6% of the target population was in contact with outpatient CAMHS, showing substantial homogeneity across the eleven areas thereby. Most patients in contact in 2008 received a language disorder- or learning disability diagnosis (41%). First-ever contacts accounted for 30% of annual visits across all units. Hospital bed availability was 5 per 100,000 inhabitants aged 0-17 years.

Conclusion: The percentage of young people in contact with CAMHS for mental disorders is in line with those observed in previous epidemiological studies. The overall number of child psychiatrists per 100,000 inhabitants is one of the highest in Europe and it is comparable with the most well equipped areas in the US. This comparison should be interpreted with caution, however, because in Italy, child psychiatrists also treat neurological disorders. Critical areas requiring improvement are: the uneven utilisation of standardised assessment procedures and the limited availability of dedicated emergency services during non-office hours (e.g., nights and holidays).
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http://dx.doi.org/10.1186/1471-244X-12-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310734PMC
January 2012

Phosphatase and tensin homolog (PTEN) gene mutations and autism: literature review and a case report of a patient with Cowden syndrome, autistic disorder, and epilepsy.

J Child Neurol 2012 Mar 29;27(3):392-7. Epub 2011 Sep 29.

Child Neurology and Psychiatry Unit, Department of Neurological Sciences, University of Bologna, Italy.

Phosphatase and tensin homolog (PTEN) gene mutations are associated with a spectrum of clinical disorders characterized by skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Autism has rarely been described in association with these variable clinical features. At present, 24 patients with phosphatase and tensin homolog gene mutation, autism, macrocephaly, and some clinical findings described in phosphatase and tensin homolog syndromes have been reported in the literature. We describe a 14-year-old boy with autistic disorder, focal epilepsy, severe and progressive macrocephaly, and multiple papular skin lesions and palmoplantar punctate keratoses, characteristic of Cowden syndrome. The boy has a de novo phosphatase and tensin homolog gene mutation. Our patient is the first case described to present a typical Cowden syndrome and autism associated with epilepsy.
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http://dx.doi.org/10.1177/0883073811420296DOI Listing
March 2012

Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy.

Epilepsy Res 2011 Mar 18;94(1-2):110-6. Epub 2011 Feb 18.

CNR-Institute of Neurosciences, Section of Padua, Padova, Italy.

The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio=2.25; 95% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim=0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio=12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy.
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http://dx.doi.org/10.1016/j.eplepsyres.2011.01.010DOI Listing
March 2011

Epilepsy and trimethylaminuria: A new case report and literature review.

Brain Dev 2011 Aug 20;33(7):593-6. Epub 2010 Oct 20.

Child Neurology and Psychiatry Unit, Department of Neurological Sciences, University of Bologna, Italy.

Trimethylaminuria is a metabolic disorder characterized by the excessive excretion of trimethylamine in bodily secretions, which confers a very unpleasant odour resembling that of dead fish. Literature reports only two cases affected by trimethylaminuria and epilepsy. We describe a third patient who, from the age of seven, was affected by temporal focal seizures with nocturnal episodes of nausea, vomiting, anxiety and autonomic activation followed by headache. EEG showed focal paroxysmal abnormalities prevailing on the right temporo-parieto-occipital regions. We began administering levetiracetam and seizures stopped. Our patient also showed learning disabilities despite a normal intelligence quotient (IQ), while another described patient had an IQ varying from borderline to mild mental retardation. We discuss the association between trimethylaminuria and epilepsy, and formulate some hypotheses on the relationship between trimethylamine convulsive effect and the anticonvulsive role of levetiracetam.
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http://dx.doi.org/10.1016/j.braindev.2010.09.007DOI Listing
August 2011

Epilepsy and EEG paroxysmal abnormalities in autism spectrum disorders.

Brain Dev 2010 Oct 5;32(9):783-9. Epub 2010 Aug 5.

Autism Centre, Child Neurology and Psychiatry Unit, Department of Neurological Sciences, University of Bologna, Italy.

The occurrence of epilepsy in autism is variable; nevertheless, EEG paroxysmal abnormalities (PA) are frequently recorded in patients with autism, although the influence of epilepsy and/or EEG PA on the autistic regression has not been clarified yet. We examine a large sample of 345 inpatients with autism, divided into three groups: (1) patients without epilepsy and EEG PA; (2) patients with EEG PA but no seizures; (3) patients with epilepsy including febrile convulsions. The prevalence of epilepsy (24.9%) and EEG PA (45.5%) was higher than that reported in the general population. The significant differences among the three groups concerned autistic regression (comparison between groups 1 and 2, p<0.05; comparison between groups 1 and 3, p<0.01), cerebral lesions (comparison between groups 1 and 2, p<0.05; between groups 1 and 3, p<0.001), and symptomatic autism (comparison between groups 1 and 2 as much as comparison between groups 1 and 3, p<0.001), which were prevalent in groups 2 and 3; while severe/profound mental retardation was more frequent in group 3 compared to group 1 (p<0.01). Focal epilepsy (43.0%) and febrile convulsions (33.7%) were frequent in the third group with epilepsy. EEG PA were mainly localized in temporal and central areas (31.4%). Only 2.6% of patients had subcontinuous/continuous EEG PA during sleep. Seizures and EEG PA were not related to autistic regression. EEG PA occurred mainly in childhood, while epilepsy tended to occur (p<0.001) as age increased. The age at onset of seizures had two peaks: between 0 and 5 and between 10 and 15 years with no difference between idiopathic and symptomatic cases. In 58.5% of subjects aged > or = 20 years, epilepsy including febrile seizures occurred at some point of their lives, while cases with only EEG PA were less frequent (9.7%). The relationship among autism, EEG PA and epilepsy should be clarified and investigated. In autism, seizures and EEG PA could represent an epiphenomenon of a cerebral dysfunction independent of apparent lesions.
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http://dx.doi.org/10.1016/j.braindev.2010.07.003DOI Listing
October 2010

Riboflavin prophylaxis in pediatric and adolescent migraine.

J Headache Pain 2009 Oct 1;10(5):361-5. Epub 2009 Aug 1.

Department of Neurological Sciences, University of Bologna, Bologna, Italy.

Migraine is a common disorder in childhood and adolescence. Studies on adults show the effectiveness and tolerability of riboflavin in migraine prevention, while data on children are scarce. This retrospective study reports on our experience of using riboflavin for migraine prophylaxis in 41 pediatric and adolescent patients, who received 200 or 400 mg/day single oral dose of riboflavin for 3, 4 or 6 months. Attack frequency and intensity decreased (P < 0.01) during treatment, and these results were confirmed during the follow-up. A large number of patients (77.1%) reported that abortive drugs were effective for controlling ictal events. During the follow-up, 68.4% of cases had a 50% or greater reduction in frequency of attacks and 21.0% in intensity. Two patients had vomiting and increased appetite, respectively, most likely for causes unrelated to the use of riboflavin. In conclusion, riboflavin seems to be a well-tolerated, effective, and low-cost prophylactic treatment in children and adolescents suffering from migraine.
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http://dx.doi.org/10.1007/s10194-009-0142-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3452096PMC
October 2009