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Background Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, localized at presynaptic terminals of brain and cerebellar neurons, result in clinically variable neurological disorders including hemiplegic migraine (HM) and episodic or progressive adult-onset ataxia (EA2, SCA6). Most recently, CACNA1A mutations have been identified in patients with nonprogressive congenital ataxia (NPCA). Methods We performed targeted resequencing of known genes involved in cerebellar dysfunction, in 48 patients with congenital or early onset ataxia associated with cerebellar and/or vermis atrophy. Results De novo missense mutations of CACNA1A were found in four patients (4/48, ∼8.3%). Three of them developed migraine before or after the onset of ataxia. Seizures were present in half of the cases. Conclusion Our results expand the clinical and mutational spectrum of CACNA1A -related phenotype in childhood and suggest that CACNA1A screening should be implemented in this subgroup of ataxias.

Purpose The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies. Results Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs. Conclusion Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.

Summary Background Epilepsy is a frequent and severe feature of Menkes disease (MD) but only few studies described the long-term evolution of these children. We report a series of 28 epileptic MD patients, with clinical characteristics, EEG abnormalities, brain malformations and long-term outcome. Methods EEG, clinical characteristics and neuroimaging features in 28 MD patients were analyzed at the onset of epilepsy and after long-term follow-up (at least 4 years). We subdivided the patients into two groups: Group 1, 16 patients who received a subcutaneous copper–histidine treatment, and Group 2 including 12 patients who did not get any therapies. Results The large majority of our patients presented at the onset of epilepsy focal seizures (FS) and infantile spasms (IS). Five patients had recurrent status epilepticus (SE). During the follow-up, patients showed multiple seizure types: 6 patients had generalized tonic clonic seizures (GCT), 6 patients presented IS, 10 children had FS, 11 had myoclonic jerks and 3 had SE. Therapy with various antiepileptic drugs had poor efficacy, except in three patients who showed seizure disappearance with consequent discontinuation of antiepileptic therapy. There was no difference of neurological outcome among the two groups analyzed. Conclusions Epilepsy in MD is a difficult to treat problem. At the onset, the most frequent type of seizures are FC and IS; in the next months, other kinds of seizures can appear. Many children are drug resistant. Institution of replacement therapy with copper–histidine seems to be not beneficial for epilepsy.

Background Mutations of protein-rich transmembrane protein 2 ( PRRT2 ) were recently associated to benign familial infantile seizures (BFIS) (MIM 605751 ) and paroxysmal kinesigenic dyskinesias (PKD) (MIM12800). Aims To report mutations of PRRT2 in BFIS, infantile convulsions and choreoathetosis (ICCA), and in sporadic cases affected by benign infantile epilepsy (BIE). Methods A mutational screening of PRRT2 was performed in 5 families, and in 7 sporadic cases affected by BIE. All clinical and neurophysiological details were reviewed. Results Thirty-three members among 5 families were collected. Fifteen individuals had infantile seizures and one had infantile seizures followed by paroxysmal kinesigenic dyskinesia (PKD). We found the c.649_650InsC PRRT2 mutation in all tested patients (13 out of 15). Age at onset ranged from 3.5 to 10 months. Focal seizures, with or without secondary generalization, occurred mainly in cluster. One patient at the age of 11 years presented with PKD successfully treated with carbamazepine. All patients had a normal cognitive development. Two out of 7 non-familial cases (28.5%) carried a de novo PRRT2 mutation: the c.649_650InsC mutation in one with clustered seizures at the age of 5 months and an unreported c.718C-T p.R240X mutation in the other who, after cluster focal seizures at the age of 5 months, experienced absences at the age of 5 years. Conclusion Our findings emphasize that PRRT2 mutations might be responsible of both BFIS and ICCA, but might be causative also for sporadic cases of benign infantile seizures. The phenotypic spectrum comprises BFIS, ICCA, and PKD.

Non ketotic hyperglycinemia is a rare inborn error of glycine metabolism due to deficient activity of glycine cleavage system, a multienzymatic complex consisting of four protein subunits: the P-protein, the H-protein, the T-protein and the L-protein. The neonatal form of non ketotic hyperglycinemia presents in the first days of life with encephalopathy, seizures, multifocal myoclonus and characteristic "hiccups". Rapid progression may lead to intractable seizures, coma and respiratory failure requiring mechanical ventilation. Clinical trial with scavenges drugs decreasing glycine levels such as sodium benzoate, and with drugs reducing NMDA receptors excitatory properties, such as ketamine and dextromethorphan, have been tried but the outcome is usually poor; antiepileptic therapy, moreover, is unable to control epileptic seizures. Ketogenic diet has been successfully tried for refractory epilepsy in pediatric patients. We report three cases affected by neonatal non ketotic hyperglycinemia and early myoclonic encephalopathy treated with ketogenic diet. In our patients ketogenic diet, in association with standard pharmacological therapy, determined dramatic reduction of seizures and improved quality of life.

Patients having a hypothalamic hamartoma frequently present epileptic attacks of laughter, and they later experience multiple additional seizure types, which invariably lead to a severe drug-resistant epilepsy. If this association is now well-known, relationships between the hypothalamic mass and the different types of seizures remain still mysterious. We report the case of a 16-year-old girl suffering from this peculiar epileptic picture, in whom a stereo-EEG study was performed, allowing us to record both the hamartoma, the neighboring hypothalamic structures, and other bilateral cortical areas. It showed that gelastic fits were strictly linked to ictal discharges which began and remained well localized in the hamartoma. Conversely, atonic seizures, which might result from a secondary epileptogenesis, admitted a widely extended bilateral frontal cortical origin, sparing the lesion, and slightly involving the posterior hypothalamus. Stereotactic radiosurgery of the hamartoma proved to be ineffective on both types of seizures, probably because of the too low dose of X-rays delivered (18 grays), as suggested by the absence of hypothalamic mass changes on MRI. Such data, never reported to our knowledge, seem able to contribute to a better understanding of this very peculiar epileptic syndrome, and perhaps to a better adapted therapeutic management.

A group of 10 patients suffering from tuberous sclerosis (TS) and epilepsy was studied by means of topographic mapping of EEG and visual evoked potentials. The localizing ability of the technique was compared to the topography of hyperintense T2-dependent areas seen on magnetic resonance images (MRI). Data were collected from 19 electrodes, free from interictal EEG transients and artifacts, spectral analysis was performed using the FFT algorithm and color maps were produced by specialized equipment. Data were analyzed with respect to the presence of interhemispheric asymmetries and significant differences with age-matched normal controls. The topography of slow frequency components was the best clue for localization, with a concordance between imaging and spectral EEG data in 76% of the lesions detected by MRI. In 7 patients topographic mapping revealed spectral abnormalities in areas where MRI was not able to detect morphological lesions. These abnormalities were characterized by an increased delta (5 patients), theta (4 patients), or lowered ipsilateral alpha (1 patient) power. Although full agreement between imaging and electrophysiological data was not observed, we believe that in patients with TS the study of EEG rhythm activity can add valuable information to the visual inspection of the tracings.

Among 174 cases of infantile spasms examined by CT-scan between January 80 and December 85, 17 (9.8%) had a focal lesion without microcephaly. It consisted of an angioma (1 case), a cortical dysplasia (1 case) and porencephalic lesions (15 cases). In 11 cases with porencephaly, an acute event had occurred between 28 weeks of gestation and 3 months of life. In 7 cases, the lesion extended to the major part of one hemisphere. In the 10 others, it was localized either to the rolandic or to the temporo-occipital regions. In all the cases, the lesion concerned at least one of these areas. It involved the cortex in 15 cases but in the 2 others it seemed to only concern the white matter. The lesion was on the left in 14 cases. After steroids, the epilepsy recurred in 6 cases of which 5 involved the frontal lobe (P less than 0.05). This study seems to show that it is mainly the rolandic and the temporo-occipital areas that favour the occurrence of infantile spasms, whereas extension to the frontal area is responsible of a later partial epilepsy.

We report a 3-year-old child affected by severe encephalopathy, partial seizures with early onset and microcephaly, in whom polymicrogyria was detected by means of magnetic resonance imaging (MRI). We believe that MRI findings may allow an early and confident in vivo diagnosis of this severe and probably not so rare condition.

Three severely asphyxiated full-term newborns showed tomographic findings of bilateral symmetrical hyperdensities restricted to the thalamic region. All these patients had a strikingly similar poor neurological outcome characterized by dystonia, severe mental retardation and acquired microcephaly. We presume that these bithalamic hyperdensities could be an early predictor of the later status marmoratus.