Camillo Mastropaolo

Prognosis after Therapy Discontinuation in Children with Epilepsy

Anticonvulsant therapy was stopped in 191 epileptic children (109 males and 82 females) after a seizure-free period of at least 2 years, independent of EEG findings, followed up for a minimum of 2 years after withdrawal. Overall, 43 (22.5%) had recurrence of seizures; of these, 79% relapsed within the 1st year after drug stopping and 93% within the 2nd year. The probability of remaining seizure free was 97% at the end of the withdrawal period, 82% 1 year later, 79% at 2 years and 77% at 5 years. In order to evaluate the risk of recurrence and the predictive factors of relapse, several parameters were investigated by univariate and multivariate statistical analysis. At univariate analysis, the factors which proved to be significantly correlated to relapses were: age at onset over 4 years, seizure-free time less than 2 years, sudden drug discontinuation, pathological EEG records during seizure-free time and paroxysmal responses to intermittent photic stimulation (IPS). At multivariate analysis, only age at onset, seizure-free time and sudden discontinuation were the factors indicating a significantly higher relapse risk; paroxysmal IPS responses, when analyzed in association with these variables, proved to be significant and increased the predictive value for prognosis of associated factors.

The Free Fraction of Valproic Acid in Tears, Saliva, and Cerebrospinal Fluid

Summary: Valproic acid (VPA) was determined by EMIT® assay in plasma, tears, saliva, and cerebrospinal fluid (CSF) of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios. The VPA CSF/serum ratio was in good agreement with data in the literature. Salivary levels were extremely erratic, while those for tears were much more reliable. Determination of VPA in tears is therefore the best method of studying the VPA free fraction in those cases in which investigations of protein binding of the drug are necessary.

Tears as the best practical indicator of the unbound fraction of an anticonvulsant drug.

Summary: Phenobarbital and carbamazepine concentrations were détérmined by the EMIT* technique in tears, saliva, cerebrospinal fluid (CSF), and plasma of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios for the two agents. The phenobarbital CSF/serum ratio was in good agreement with data in the literature, and the higher ratio found for carbamazepine may be caused by an EMIT assay cross‐reaction for the free fraction of carbamazepine‐10,11‐epoxide. In our hands, tears seem to represent the best practical indicator of the unbound fraction of an anticonvulsant drug, and the noninvasiveness of the method makes it specifically useful in pediatric neurology.

The myoblast defect identified in Duchenne muscular dystrophy is not a primary expression of the DMD mutation

SummaryWe previously proposed the hypothesis that the primary expression of the defect in X-linked Duchenne muscular dystrophy (DMD) occurred in the myoblast, or muscle precursor cell. This was based on the observation that the number of viable myoblasts obtained per gram DMD muscle tissue was greatly reduced and those that grew in culture had decreased proliferative capacity and an aberrant distended flat morphology. Here we test that hypothesis by determining whether the expression of the myoblast defect is X-linked. Muscle cells were obtained from five doubly heterozygous carriers of two X-linked loci, DMD and glucose-6-phosphate dehydrogenase (G6PD), and compared with those from five sex-and age-matched controls heterozygous for G6PD only. A total of 1,355 individual clones were determined to be muscle and evaluated at the single cell level for proliferative capacity, morphology, and G6PD isozyme expression. The results demonstrate that the proportion of defective myoblast clones is significantly increased in DMD carriers. However, since this cellular defect does not consistently segregate with a single G6PD phenotype in the myoblast clones derived from any of the carriers, it is unlikely to be the primary expression of the DMD mutant allele.

Incomplete penetrance with normal MRI in a woman with germline mutation of the DCX gene

X-linked isolated lissencephaly sequence (ILS) and subcortical band heterotopia are allelic human disorders associated with mutations of the DCX gene in both familial and sporadic forms. The authors describe a large Sardinian family in which three brothers with ILS have a missense mutation of the DCX gene. Their mother, a nonmosaic carrier, has a normal phenotype and cranial MRI. Skewed X-inactivation in the lymphocytes was also ruled out. This is the first report of an asymptomatic carrier of a DCX mutation likely due to apparent nonpenetrance.

Diphenylhydantoin and primidone in tears.

Summary: Diphenylhydantoin (PHT) and primidone (PRM) were determined by the EMIT® technique in the plasma, tears, saliva, and CSF of epileptic patients. Results indicate for PHT that tear values are more strictly correlated than are the saliva values to plasma and CSF concentrations. As for PRM, the data obtained show great interindividual variability of concentration in the different body fluids–in agreement with the wide range of both protein binding and half‐life of this drug.

Clinical and EEG findings in eleven patients affected by mitochondrial encephalomyopathy with MERRF-MELAS overlap

A study of mitochondrial DNA disease was carried out on 12 members belonging to three generations of a family from northern Sardinia. On the basis of the diagnostic criteria currently used in the classification of mitochondrial diseases a typical MERRF-MELAS overlap phenotype was seen in 11 patients with the mtDNA tRNA(lys) mutation at nucleotide position 8356. Clinical and instrumental investigations (EEG in particular) were made. Patients were divided into two groups: severely and mildly affected cases. The follow-up was reported. The aim of this study was to identify, through EEG, the early signs of the disease. The EEG findings recorded during the clinical evolution allowed us to recognize four degrees of cerebral involvement, and could also suggest the prognosis.

An AT-deletion causing a frameshift in the arylsulfatase A gene of a late infantile metachromatic leukodystrophy patient

A metachromatic leukodystrophy (MLD) patient affected with the late infantile form was found to be homozygous for an AT-deletion (2324delAT) in the arylsulfatase A gene. The mutation causes a frameshift at the beginning of exon 8 leading to an early termination codon. The parents and unaffected brother of the patient were heterozygous for the microdeletion. The mutation was not detected in another 31 MLD Italian patients. No aberrant transcript caused by the mutation was revealed by the reverse transcription-polymerase chain reaction method.