Massimo Mastrangelo

Seizure and EEG Patterns in Angelman's Syndrome

We studied the seizure and polygraphic patterns of 18 patients with Angelmans syndrome. All patients showed movement problems. Eleven patients were also reported to have long-lasting periods of jerky movements. The polygraphic recording showed a myoclonic status epilepticus in nine of them. Seven patients had partial seizures with eye deviation and vomiting, similar to those of childhood occipital epilepsies. These seizures and electroencephalographic patterns suggest that Angelmans syndrome occurs in most of the patients as a nonprogressive, age-dependent myoclonic encephalopathy with a prominent occipital involvement. These findings indicate that, whereas ataxia is a constant symptom in Angelmans syndrome, the occurrence of a transient myoclonic status epilepticus may account for the recurrence of different abnormal movements, namely the jerky ones. (J Child Neurol 1995;10:467-471).

PRRT2 Mutations are the major cause of benign familial infantile seizures

Mutations in PRRT2 have been described in paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with choreoathetosis (PKD with infantile seizures), and recently also in some families with benign familial infantile seizures (BFIS) alone. We analyzed PRRT2 in 49 families and three sporadic cases with BFIS only of Italian, German, Turkish, and Japanese origin and identified the previously described mutation c.649dupC in an unstable series of nine cytosines to occur in 39 of our families and one sporadic case (77% of index cases). Furthermore, three novel mutations were found in three other families, whereas 17% of our index cases did not show PRRT2 mutations, including a large family with late‐onset BFIS and febrile seizures. Our study further establishes PRRT2 as the major gene for BFIS alone. Hum Mutat 33:1439–1443, 2012.

Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance

To dissect the genetics of benign familial epilepsies of the first year of life and to assess the extent of the genetic overlap between benign familial neonatal seizures (BFNS), benign familial neonatal‐infantile seizures (BFNIS), and benign familial infantile seizures (BFIS).

Complex Segmental Duplications Mediate a Recurrent dup(X)(p11.22-p11.23) Associated with Mental Retardation, Speech Delay, and EEG Anomalies in Males and Females

Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8-9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome.

Recommendations for the management of febrile seizures : Ad hoc Task Force of LICE Guidelines Commission

Febrile seizures are the most common seizure disorder in childhood, affecting 2–5% of children. Simple febrile seizure is defined as a short (<15 min) generalized seizure, not recurring within 24 h, that occurs during a febrile illness not resulting from an acute disease of the nervous system in a child aged between 6 months and 5 years, with no neurologic deficits and no previous afebrile seizures. These recommendations address the instructions for management of the first febrile seizures, giving criteria for hospital admission, diagnosis, differential diagnosis, and treatment of a prolonged seizure. The authors stressed the benign prognosis of the majority of cases and the risk factors for recurrence of febrile seizures and appearance of epilepsy later on. Both continuous and intermittent anticonvulsant therapy are efficacious in preventing single febrile seizures, but side effects may be so important to overcome the benefits. These treatments are indicated in very selected patients.

The visual system in eyelid myoclonia with absences.

To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]).

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.

Neonatal suppression-burst without epileptic seizures: expanding the electroclinical phenotype of STXBP1-related, early-onset encephalopathy

Early-onset epileptic encephalopathies (EOEEs) are characterised by epileptic seizures beginning in the first months of life, abnormal background EEG activity, and are associated with severe developmental delay and poor prognosis. Mutations and deletions in the STXBP1 gene are associated with Ohtahara syndrome, also known as “early infantile epilepticencephalopathy”. We report an infant affected by EOEE with a 9q34.11 deletion that encompassed the genes STXBP1 and SPTAN1. The infant presented with neonatal encephalopathy without epileptic seizures and an EEG pattern varying from highly discontinuous to suppression-burst. This was followed by West syndrome at 2 months with atypical hypsarrhythmia and spasms, easily controlled by therapy. Our findings suggest that molecular analysis of STXBP1 should be considered for newborns affected by neonatal encephalopathy associated with a peculiar EEG pattern, even in the absence of neonatal epileptic seizures.

Acute neonatal encephalopathy and seizures recurrence: A combined aEEG/EEG study

PURPOSE To evaluate amplitude-integrated EEG (aEEG) in comparison with conventional (cEEG) for the identification of electrographic seizures in neonates with acute neonatal encephalopathies. METHODS Thirty-one conventional cEEG/aEEG long-term recordings from twenty-eight newborns were reviewed in order to assess the electrographic seizure detection rate and recurrence in newborns. Two paediatric neurologists and one neonatologist, blinded to the raw full array cEEG, were asked to mark any events suspected to be an electrographic seizures on aEEG. They were asked to decide if the displayed aEEG trace showed the pattern of a single seizure (SS), repetitive seizures (RS) or status epilepticus (SE). Their ability to recognize electrographic seizures on aEEG was compared to seizures identified on full array cEEG. RESULTS 25 of the 31 long-term cEEGs recordings showed electrographic seizures. The two paediatric neurologists and the neonatologist identified SE in 100% of the reviewed traces using aEEG alone while they identified 49.4% and 37.5% of electrographic seizures using aEEG alone. Overall, the correct identification ranged from 23.5% to 30.7% for SS and 66% for RS. The inter-observer agreement (k) for the identification of SE for the two paediatric neurologists and the neonatologist was 1.0. Overall the inter-observer agreement (k) for the detection of SS, RS and SE of the two paediatric neurologists was 0.91. CONCLUSIONS In our study the observers identified SE in 100% of the reviewed traces using raw aEEG alone, thus aEEG might represent a useful tool to detect SE in the setting of NICU. SS may not be reliably identified using aEEG alone. Simultaneous recording of the raw cEEG/aEEG provides a good level of sensitivity for the detection of neonatal electrographic seizures.

Early onset absence epilepsy with onset in the first year of life: A multicenter cohort study.

Absence epilepsy with onset before age 4 years, or early onset absence epilepsy (EOAE), has been rarely reported, and children with onset in the first year of life are considered almost exceptional. We aimed to report the clinical and electrophysiologic features of a cohort of children with absence epilepsy starting within the first year of life.