Raffaella Cusmai

NEUROPSYCHOLOGICAL ASPECTS OF TUBEROUS SCLEROSIS IN RELATION TO EPILEPSY AND MRI FINDINGS

The neuropsychological performances, outcome of epilepsy and MRI topography of tubers of 23 children with tuberous sclerosis were reviewed. Seven children had normal intelligence, 10 had mental retardation, and six mental retardation and autism. An adverse association was found between the number of lesions and IQ, behaviour and severity of epilepsy. Posterior lesions, in addition to frontal‐lobe dysfunction, were observed in children with autism. Tuberous sclerosis with well‐defined cerebral lesions may represent a model for the relationship between different neuropsychiatric problems.

The ketogenic diet in children, adolescents and young adults with refractory epilepsy: An Italian multicentric experience

PURPOSE This collaborative study by three Italian groups of child neuropsychiatrists was carried on to evaluate the efficacy and safety of the classic 4:1 ketogenic diet as add-on treatment in refractory partial or generalized epilepsy in children, adolescents and young adults. METHODS We performed a prospective add-on study in 56 refractory epilepsy young patients (age 1-23 years, mean 10.4 years), all with both symptomatic and cryptogenic, generalized or partial epilepsies. Child neuropsychiatrists worked with nutritional team for sample selection and patients management. The ketogenic diet was added to the baseline antiepileptic drugs and the efficacy was rated according to seizure type and frequency. During treatment, seizure frequency, side effects, urine and blood ketone levels and other parameters were systematically evaluated. RESULTS Patients have been treated for 1-18 months (mean 5 months). A >50% reduction in seizure frequency was gained in 37.5 and 26.8% of patients after 3 and 6 months, respectively, at 12 months, this number fell by 8.9%. No significant relationship between diet efficacy and seizure or epilepsy type, age at diet onset, sex and etiology of epilepsy was noted. Nevertheless, it seems noteworthy that 64% of our patients with neuronal migration disorders improved on this diet. Adverse effects occurred, mainly in the first weeks of treatment, in 32 patients (57.1%), but were generally mild and transient. In seven patients (12.5%) it was possible to withdraw one to two AED after 3-4 months on ketogenic diet. CONCLUSION This initial experience with the ketogenic diet was effective in difficult-to-treat patients with partial and generalized epilepsies, though its efficacy dropped significantly by 9-12 months.

Genetic and neuroradiological heterogeneity of double cortex syndrome

Mutations in the X‐linked doublecortin gene appear in many sporadic cases of double cortex (DC; also known as subcortical band heterotopia), a neuronal migration disorder causing epilepsy and mental retardation. The purpose of this study was to examine why a significant percentage of sporadic DC patients had been found not to harbor doublecortin mutations and to determine whether clinical features or magnetic resonance imaging scan appearance could distinguish between patients with and without doublecortin mutations. Magnetic resonance imaging scan analysis differentiated patients into the following four groups: anterior biased/global DC with doublecortin mutation (16 of 30; 53%), anterior biased/global DC without mutation (8 of 30; 27%), posterior biased DC without mutation (3 of 30; 10%), and limited/unilateral DC without mutation (3 of 30; 10%). The presence of these atypical phenotypes suggests that other genetic loci or mosaicism at the doublecortin locus may be responsible for this diversity of DC cases. Ann Neurol 2000;47:265–269

The Idiopathic Form of West Syndrome

Summary: The clinical and electroencephalographic data of 31 children with cryptogenic West syndrome (WS), selected from a series of 103 WS patients, with a follow‐up between 4 and 12 years, were studied retrospectively to verify whether this group included patients who fulfilled the criteria for an idiopathic etiology. The results identified a possible idiopathic etiology in 17 patients (55%), who had a family history of other forms of idiopathic epilepsy or febrile convulsions, or who developed, during the follow‐up, an EEG genetic trait such as a photoconvulsive response or spike‐and‐wave discharges, or rolandic spikes. All 17 children had a favorable outcome and all had normal neuropsychological development. Four children (13%) fulfilled the criteria for a true cryptogenic etiology, a causative lesion being suspected, but never proved. At the end of the follow‐up all four had seizures, or developmental delay or both, all signs that suggest an underlying cerebral lesion. The other 10 children, representing 32% of the cryptogenic cases, had a good prognosis, with early disappearance of spasms and hypsarrhythmia, and normal neurological development, but none had an EEG epileptic trait or family history of epilepsy or febrile convulsions; although they could have had an idiopathic WS, this was not proved. We conclude that among the children classified as having a cryptogenic WS, many—in our series at least 55%—fulfill the criteria for an idiopathic etiology.

Infantile ascending hereditary spastic paralysis (IAHSP) Clinical features in 11 families

Objective: To report clinical, neuroradiologic, neurophysiologic, and genetic findings on 16 patients from 11 unrelated families with a remarkable uniform phenotype characterized by infantile ascending hereditary spastic paralysis (IAHSP). Methods: Sixteen patients from 11 families, originating from North Africa and Europe, who presented severe spastic paralysis and ascending progression were studied. Results: Spastic paraplegia started in the first 2 years of life in most patients and extended to the upper limbs by the end of the first decade. The disease progressed to tetraplegia, anarthria, dysphagia, and slow eye movements in the second decade. The clinical course showed a long survival and preservation of intellectual skills. Clinical, neuroradiologic, and neurophysiologic findings were consistent with a relatively selective early involvement of the corticospinal and corticobulbar pathways. No signs of lower motor neuron involvement were observed, whereas motor evoked potentials demonstrated predominant involvement of the upper motor neurons. MRI was normal in young patients but showed brain cortical atrophy in the oldest, predominant in the motor areas, and T2-weighted bilateral hyperintense signals in the posterior arm of the internal capsule. The ALS2 gene, recently found mutated in consanguineous Arabic families with either an ALS2 phenotype or a juvenile-onset primary lateral sclerosis, was analyzed. Alsin mutations were found in only 4 of the 10 families, whereas haplotype analysis excluded the ALS2 locus in one family. Conclusions: The syndrome of IAHSP is genetically heterogeneous, and no clinical sign can help to distinguish patients with and without Alsin mutations.

Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis

In tuberous sclerosis complex, early seizure onset is associated with high risk of intractable epilepsy and cognitive/behavioral impairment. We retrospectively evaluated the long-term outcome of 44 infants presenting with seizures in the first 12 months who received vigabatrin, and were followed up for at least 3.5 years. At the final evaluation 55% of patients were still having seizures, 80% had intellectual disability, and 30% had autism. Sixty-five percent of children who had been treated earlier with vigabatrin after seizure onset achieved seizure freedom, compared with 24% of subjects who received vigabatrin treatment later (P<0.01). Intellectual disability was present in 61% of the children treated early (group A) and in 100% of the children treated later (group B). Nine percent of group A and 52% of group B had autism (P≈0.001). A shorter gap between seizure onset and start of treatment could reduce the risk of epileptic encephalopathy, minimizing the deleterious effect of seizures, but is not able to completely reverse the tuberous sclerosis complex-associated cognitive impairment.

Reflex myoclonic epilepsy in infancy: A new age-dependent idiopathic epileptic syndrome related to startle reaction

Summary Benign myoclonic epilepsy of infancy (BMEI) is an idiopathic disorder characterized by spontaneous myoclonic attacks with onset in the first 2 years of life. We observed 6 neurologically normal infants (aged 6–21 months) with attacks that resembled those of BMEI but that occurred as reflex responses to unexpected auditory and tactile stimuli. Four infants also had rare spontaneous attacks. These reflex attacks consisted of isolated muscle jerks or clusters of up to eight symmetric limb jerks affecting mainly the arms. Five of the children had a family history of epilepsy or febrile convulsions. Myoclonic attacks disappeared in 614months. In 3 patients, the jerks stopped spontaneously; the others responded to valproate (VPA). Myoclonus could be elicited in wakefulness and in sleep. Ictal EEGs showed brief generalized spike‐or polyspike‐and‐wave discharges. Interictal EEGs were normal during wakefulness; during sleep, brief generalized discharges were evident. We propose that reflex myoclonic epilepsy of infancy (RMEI) is a new agedependent idiopathic generalized epileptic (IGE) syndrome, with an apparently good prognosis.

West Syndrome Due to Perinatal Insults

Summary: Clinical, neuroradiological data and outcome of epilepsy of 32 patients with symptomatic infantile spasms caused by perinatal insults are reported. Neuroradiological investigations showed focal as well as diffuse cerebral lesions. Fifteen children had a porencephalic lesion, 12 had periventricular leukomalacia and five had diffuse bilateral cerebral atrophy, associated with status marmoratus in one child and bilateral ulegyria in another. Eight patients (25%) had epilepsy following West syndrome. In the group of 15 children with porencephalic cysts, the lesion was always unilateral, but topography and extension varied. Eight children had circumscribed cysts involving the rolandic or parieto‐occipital regions, and the outcome of epilepsy was favorable. Seven patients had large lesions involving the frontal lobe, associated with unilateral hemispheric atrophy in four cases. These four children had an unfavorable epilepsy outcome. In the 12 patients with periventricular leukomalacia, all premature, eleven had no seizure relapse after the spasms; one of these children had epilepsy. In the five full‐term patients with bilateral and diffuse cerebral lesions, three children had epilepsy at the last observation. In children with leukomalacia and in patients with localized porencephalic lesions the outcome of epilepsy appears to be better than in patients with diffuse cerebral lesions or in children with extensive porencephalic cysts, particularly those involving the frontal lobe.

Spectrum of phenotypes in female patients with epilepsy due to protocadherin 19 mutations.

Purpose:  To describe clinical and neuropsychological features of six consecutive sporadic girls with protocadherin 19 (PCDH19) mutations.

Levetiracetam in juvenile myoclonic epilepsy: long‐term efficacy in newly diagnosed adolescents

The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in juvenile myoclonic epilepsy (JME). The study group consisted of 32 patients with epilepsy (20 males, 12 females) with a mean age of 13 years 3 months (SD 7y 11mo) at seizure onset. LEV was administered as the first drug; all patients were followed up at 6 and 12 months. The dose that achieved seizure control ranged from 1000 to 2500mg/daily. At 6‐month evaluation: 15 patients were seizure free; 14 patients were responders (>50% reduction in seizures); and three patients had marginal effects (<50% reduction of seizures). At 12‐month evaluation: 29 patients were seizure free; three patients were responders. No patients reported adverse events. These data provide preliminary evidence that LEV may be effective for treating patients with newly diagnosed JME.