Isabelle Jambaqué

Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation.

X-LINKED adrenoleukodystrophy is an inherited peroxisomal disease caused by a defective gene located within the Xq28 region of the X chromosome.1 Childhood adrenoleukodystrophy is characterized by ...

Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy

BACKGROUND The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration. METHODS 12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment. FINDINGS MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal. INTERPRETATION 5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.

Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis

Vigabatrin has been shown to be efficient in infants with infantile spasms and tuberous sclerosis, in open studies. In order to compare vigabatrin to oral steroids, a prospective randomized multicenter study was implemented using both drugs as monotherapy in newly diagnosed patients with infantile spasms and tuberous sclerosis. Eleven infants received vigabatrin (150 mg/kg per day) and 11 hydrocortisone (15 mg/kg per day) for 1 month. Spasm free patients continued vigabatrin or progressively stopped hydrocortisone in 1 month, non-responders were crossed to the other drug for a new 2 month-period. All vigabatrin patients (11/11) were spasm-free versus 5/11 hydrocortisone infants (P < 0.01). Seven patients were crossed to vigabatrin (six for inefficacy, one for adverse events) and became also totally controlled. Mean time to disappearance of infantile spasms was 3.5 days on vigabatrin versus 13 days on hydrocortisone (P < 0.01). Five patients exhibited side effects on vigabatrin but nine on hydrocortisone (P = 0.006). Vigabatrin should therefore be considered as the first choice treatment for infantile spasms due to tuberous sclerosis.

Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes

PURPOSE To analyze the relationship between craniospinal irradiation (CSI) and intellectual outcome in children with posterior fossa (PF) tumors. METHODS AND MATERIALS A neuropsychological evaluation was performed retrospectively in 31 children, aged 5-15 years, who had received radiotherapy for PF tumors, and who had been off therapy for at least 1 year. Factors evaluated for impact on intellectual outcome were: socioeconomic status, disease presentation, histology, complications, chemotherapy, age at radiotherapy, interval between radiotherapy and testing, and radiation doses and volumes. Patients were divided into 3 subgroups according to the CSI doses (0 Gy [i.e., PF irradiation only], 25 Gy, and 35 Gy), with 11, 11, and 9 patients, respectively. RESULTS Long-term cognitive impairment occurred in most of the patients, even after PF irradiation only. Moreover, there was a significant correlation between the full-scale IQ score (FSIQ) and the CSI dose, with mean FSIQ scores at 84.5 (SD = 14.0), 76.9 (SD = 16.6), and 63.7 (SD = 15.4) for 0 Gy, 25 Gy, and 35 Gy of CS1, respectively. A marked drop in verbal comprehension scores was noted in children who had received the higher dose. CONCLUSION This preliminary study further supports the rationale for de-escalation of CSI doses and volumes in standard-risk PF tumors.

Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients

Vigabatrin (VGB) has demonstrated high efficacy in infantile spasms (IS) due to tuberous sclerosis. Our first objective was to evaluate the cognitive long term effect outcome of children whose refractory spasms definitely disappeared when VGB was given as an add on drug. Our second objective was to determine the response of generalized epilepsy (infantile spasms) compared to partial epilepsy on cognitive impairment. A non selected series of 13 children underwent psychometric and behavioural evaluation before VGB initiation at a mean of 3 years on VGB treatment. Eight of them could perform detailed neuropsychological tests at follow-up. Seven had infantile spasms (Group I), they all were spasm free before 2 years of age and five remained with rare partial seizures (mean age, 5.5 years). Six others had partial epilepsy without spasms (Group II) and five remained with rare seizures (mean age, 7.5 years). Patients of Group I experienced dramatic changes. Developmental quotient (DQ) significantly rose in six out of seven by ten to more than 45 points (P = 0.03) and autistic behaviour disappeared in five out of the six who presented with. The four tested children had normal verbal level after 5 years and could integrate at school but they remained with marked visuospatial disabilities. By contrast, patients of Group II remained with an unchanged DQ of about 60 so that both groups had similar DQ levels on follow-up. The cessation of spasms with VGB is therefore associated with significant improvement of cognition and behaviour in children with tuberous sclerosis. Controlling secondary generalization induced by infantile spasms seems to be a key factor for mental development.

Verbal and visual memory impairment in childrem with epilepsy

Verbal and visual memory performances were evaluated in 60 epileptic children and 60 normal control subjects with Signorets Memory Battery scale. Eighteen patients had idiopathic generalized epilepsy and 42 had partial epilepsy, mostly of the temporal (n = 28) and frontal (n = 10) lobes. Memory scores were statistically lower in epileptics than in controls and significant differences were found within each group: (1) children with idiopathic generalized epilepsy had a slight depression of visual memory; (2) memory disorder was more severe in partial epilepsy; and (3) children with left and right temporal lobe epilepsy had marked memory deficits related to hemispheric specialization.

Deficits in executive functions and motor coordination in children with frontal lobe epilepsy

Frontal lobe dysfunction in adults has been associated with impairments of planning abilities, working memory, impulse control, attention and certain aspects of motor coordination. However, very few studies have attempted to assess these functions in children suffering from frontal lobe epilepsy. The aim of the present study was to determine whether some or all of the components of the frontal lobe syndrome are present in children with this disorder. For this purpose, a neuropsychological test battery was administered to 32 unresected epileptic children, aged 8-16 years: 16 with frontal lobe epilepsy (FLE), eight with temporal lobe epilepsy (TLE) and eight with generalized epilepsy whose principal manifestations were typical absences (GEA). The performances of the three epileptic groups were further compared to normative data derived from 200 French-speaking, healthy children aged 7-16 years, except for standardized tests for which the norms provided in the manual were used. The three epilepsy groups did not differ with respect to conceptual shift and recency memory. However, the FLE children showed deficits in planning and impulse control. Furthermore, they had significantly more coordination problems and exhibited greater rigidity than the other epilepsy groups on the motor tests. These problems were more marked in younger FLE children (8-12 years). The latter were also more impaired on verbal fluency measures. No differences were observed with respect to gender, localization of the epileptic abnormality (unilateral versus bilateral) or medication (monotherapy versus polytherapy). The findings reveal similarities between the neuropsychological profiles of FLE children and adults with frontal lobe lesions.

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.

Vertical Parasagittal Hemispherotomy: Surgical Procedures And Clinical Long-Term Outcomes In A Population Of 83 Children

OBJECTIVE Hemispherotomy techniques have been developed to reduce complication rates and achieve the best possible seizure control. We present the results of our pediatric patients who underwent vertical parasagittal hemispherotomy and evaluate the safety and global long-term outcome of this technique. METHODS Eighty-three patients underwent vertical parasagittal hemispherotomy by the same neurosurgeon (OD) between 1990 and 2000. We reviewed all patients between 2001 and 2003 for a standard global evaluation. The general principle is to achieve, through a posterior frontal cortical window, the same line of disconnection as performed with the classic hemispherectomy, while leaving the majority of the hemisphere intact along with its afferent and efferent vascular supply. METHODS Seventy-four percent of the patients were seizure-free; among them, 77% were seizure-free without further drug treatment. Twelve percent rarely had seizures (Engel Class II) and 14% continued to have seizures (Engel Class III or IV). The results varied according to the etiology, but this variation was not statistically significant. The early postoperative course was uneventful for 94% of the children, and shunt placement was necessary in 15%. We found a correlation between the preoperative delay and the Vineland Adaptive Behavior score: children with a longer duration of seizures had lower performances. CONCLUSION Vertical parasagittal hemispherotomy is an effective surgical technique for hemispheric disconnection. It allows complete disconnection of the hemisphere through a cortical window with good results in terms of seizure outcome and a comparably low complication rate.

Devastating epileptic encephalopathy in school-aged children (DESC): A pseudo encephalitis

PURPOSE To describe the characteristics of a previously overlooked devastating epileptic encephalopathy that presents as intractable bilateral perisylvian epilepsy starting with prolonged status epilepticus (SE) in normally developing school-aged children. METHODS Retrospective study over 7 years of all normally developing children admitted in our institution for a prolonged SE following non-specific febrile illness with at least one seizure recorded on EEG. RESULTS Fourteen children were included at a median age of 7.5 years (4-11) (median follow-up of 4 years (1-7)). Intractable SE lasted 4-60 days (median 30). CSF cell count was normal in five cases and moderately increased in the others. During SE, seizures were recorded in 11 patients and involved temporal lobes in 7; the other 4 patients exhibited perisylvian clinical features with secondary generalization. Intractable epilepsy followed SE in all cases without any latent period. Persisting seizures were recorded in 10 patients and involved temporo-perisylvian regions in 8, frontal regions in 2; 3 others had perisylvian ictal semiology. Spiking was bilateral in 10 cases. MRI showed bilateral hippocampal hypersignal and/or atrophy in 10 cases (extended to the neocortex in 3). All children had major cognitive sequelae. When feasible (six patients), detailed neuropsychology suggested fronto-temporal impairment. CONCLUSIONS Among so called grey matter encephalitis patients, we identified a recognizable pattern we propose to call Devastating Epileptic encephalopathy in School-age Children (DESC) that begins with prolonged SE triggered by fever of unknown cause, and persists as intractable perisylvian epilepsy with severe cognitive deterioration.