Maria Spanò

Topiramate as add-on drug in severe myoclonic epilepsy in infancy: an Italian multicenter open trial

PURPOSE This study was to evaluate the efficacy and safety of topiramate (TPM) in patients with severe myoclonic epilepsy in infancy (SMEI) and refractory seizures. METHODS We performed a prospective multicentric open label add-on study in 18 patients (age 2-21 years, mean 9 years) with SMEI and refractory seizures of different types. TPM was added to one or two other baseline drugs and the efficacy was rated according to seizure type and frequency. RESULTS TPM was initiated at a daily dose of 0.5-1 mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24 h up to a maximum daily dose of 12 mg/kg. After a mean period of 11.9 months (range 2-24 months), three patients (16.7%) had 100% fewer seizures and ten patients (55.5%) had a more than 50% seizure decrease. In no patient there was a seizure worsening. Mild to moderate adverse events were present in four patients (22.2%), represented by weight loss, hypermenorrhoea, renal microlithiasis, nervousness and dysarthric speech. CONCLUSION TPM may be a useful drug in patients with SMEI, being particularly effective against generalized tonic-clonic seizures. Further studies are needed to evaluate the early use of this drug in such a severe syndrome.

Autosomal recessive congenital cerebellar atrophy: A clinical and neuropsychological study

Congenital cerebellar atrophy associated with a non-progressive cerebellar syndrome and mild cognitive retardation is described in seven cases, four of them familial. Their occurrence is consistent with an autosomal recessive inheritance. Clinical and neuroimaging data seem to exclude supratentorial changes. Even though it is not possible to definitely rule out a possible role of the forebrain in determining the mental defect, the neuropsychological study supplies arguments stressing the relationship between cerebellar defect and cognitive development.

CONGENITAL MUSCULAR DYSTROPHY WITH DEFECTIVE α-DYSTROGLYCAN, CEREBELLAR HYPOPLASIA, AND EPILEPSY

Congenital muscular dystrophies (CMDs) with hypoglycosylation of α-dystroglycan (α-DG) are heterogeneous disorders often involving brain, eyes, and muscle. Mutations in 6 known or putative glycosyltransferase genes have been identified: Protein-O-mannosyl transferase 1 ( POMT1 ), Protein-O-mannosyl transferase 2 ( POMT2 ), Protein-O-mannose1,2-N-acetylglucosaminyltransferase 1 , Fukutin , Fukutin-related protein , and LARGE . Mutations in each of these genes have been associated with a wide range of phenotypes ranging from the severe Walker–Warburg syndrome (WWS) to milder variants of limb girdle muscle dystrophy.1 We report 4 cases of CMD with a distinctive phenotype characterized by cognitive impairment, microcephaly, cerebellar hypoplasia, feeding difficulties, and progressive myoclonic epilepsy. Mutations in the 6 known genes were ruled out in these patients. ### Case reports. All 4 patients originated from the same area in Calabria, in Southern Italy. Two were sporadic cases, both girls (patients 1 and 2), and 2 were brothers born to first-degree cousins (patients 3 and 4). Clinical features were similar in all patients. #### Onset. There were reduced fetal movements and weak cry, difficulty in swallowing, severe hypotonia, and muscle weakness at birth. #### Developmental milestones and progression. None acquired head control or any other milestone with the exception of patient 2, who acquired head control at 12 months and sat with support after 18 months for a short period. Cognitive development was severely impaired with absent speech. All patients had microcephaly and myopathic face, generalized muscle wasting, and severe hypotonia. They were able to …

Alternating hemiplegia of childhood successfully treated with topiramate: 18 months of follow-up

Alternating hemiplegia of childhood (AHC) is a rare neurologic syndrome with recurrent hemiplegic attacks shifting from one side to the other and lasting from minutes to several days. The attacks typically begin in infancy, are triggered by emotion or fatigue, and disappear during sleep.1 Additional features are pendular nystagmus, tonic/dystonic attacks, dyspneic episodes, mental retardation, and epilepsy. The etiology of AHC is unknown. Some consider it a variant of migraine1 and differentiation from familial hemiplegic migraine (FHM) may be difficult.2 The majority of AHC cases are sporadic, although a few familial cases have been reported, including one family with a mutation in the ATP1A2 FHM2 gene.2,3 There is no standard therapy for AHC. Flunarizine is the most frequently used drug.1 Topiramate (TPM) is a relatively new agent effective in the prophylactic treatment of both epilepsy and migraine.4,5 It inhibits carbonic anhydrase and displays modulatory effects on voltage-gated Na+ and Ca …

Mechanisms and evolution of the brain damage in neonatal post-hemorrhagic hydrocephalus

There are three main mechanisms of poor outcome in children with post-hemorragic hydrocephalus: (1) brain injuries due to ventricular dilatation, (2) shunt-related complications, and (3) primary cerebral hypoxic-ischemic and hemorrhagic lesions. The authors give a short up-to-date report, focusing mainly on the third mechanism, with reference to personal studies.

Type I hyperprolinemia and proline dehydrogenase (PRODH) mutations in four Italian children with epilepsy and mental retardation.

Type I hyperprolinemia (HPI) is an autosomal recessive disorder caused by proline oxidase deficiency. This enzyme is encoded by the proline dehydrogenase (PRODH) gene on 22q11. The functional consequences of different PRODH mutations on proline oxidase activity have been characterized in vitro. Few patients with HPI with epilepsy and cognitive/behavioral disturbances have been described so far. We screened four Italian children with HPI presenting epilepsy, mental retardation, and behavioral disorders for PRODH gene mutations, and attempted a genotype–phenotype correlation.

A new form of alpha-dystroglycanopathy associated with severe drug-resistant epilepsy and unusual EEG features

We describe two unrelated girls with congenital muscular dystrophy associated with alpha-dystroglycan deficit with no identified genetic defect, both presenting severe drug-resistant epilepsy with predominant myoclonic seizures and an unusual similar EEG pattern. Severe epilepsy has been unusually described in patients with congenital muscular dystrophies, mainly associated with Walker-Warburg, Fukuyama and muscle-eye-brain diseases.