Pretreatment neuropsychological deficits in children with brain tumors.

Treatment of childhood brain cancer has been associated with long-term cognitive morbidity in children. In the present study, the cognitive status of children with brain tumors was examined prior to any treatment to single out the role of tumor and tumor-related factors in cognitive deficits. Eighty-three children with newly diagnosed brain tumors (mean age, 8.6 years; range, 7 months to 16.6 years; median, 9.4 years) completed an extensive battery of age-related tests to assess cognitive function before any therapeutic intervention. Magnetic resonance imaging (MRI) was used to determine tumor site and volume and tumor-related factors. Performance under test was compared with symptom duration, neurological status, epilepsy, and MRI. Cognitive difficulties are detected at diagnosis in as many as 50% of patients for some cognitive domains; 6% of patients present with true-diagnosed mental retardation. The location of the tumor is the principal determinant of cognitive deficits, with major impairment in children with cortical tumors. Symptom duration and the presence of epilepsy are significantly associated with neuropsychological disabilities, while neuroradiological tumor-related variables do not correlate clearly with neurocognitive performance. The knowledge of the pre-existing cognitive deficits is critical to evaluate the results of treatment, providing a baseline for assessing the true impact of therapy in determining cognitive decline. In addition, the study suggests that some clinical variables require careful monitoring, because they could be specifically implicated in the neuropsychological outcome; the efforts to reduce the impact of these factors could ameliorate long-term prognosis.

Developmental plasticity after right hemispherectomy in an epileptic adolescent with early brain injury.

OBJECTIVES: The authors present the case of an adolescent affected with refractory epilepsy due to a neonatal ischemic infarction of the right medial cerebral artery. Hemiplegic since the first months of life, she began presenting motor partial seizures associated with drop attacks at 4.5 years; these were initially well controlled by antiepileptic drugs, but at 10 years seizures appeared again and became refractory. Thus, at 14 years and 10 months, she was submitted to a right hemispherectomy that made her rapidly seizure free. In the post-surgical follow-up lasting 5 years, neuropsychological serial assessments showed an impressive progressive improvement of cognitive skills, namely, visuospatial abilities. This case seems to challenge the widely spread feeling that functional catch-up in brain-injured children could only occur early in life. In effect, the astonishing recovery especially of visuospatial skills in our case occurred in adolescence after a late surgical intervention of right hemispherectomy. METHODS: Different neuropsychological aspects are discussed. The reorganisation process recovered the spatial and linguistic abilities as well as the verbal and visuospatial memory; however, there was a persistent impairment of complex spatial and perceptual skills as well as recall abilities. Despite the deficit of complex visual stimuli processing, the patient showed a good performance in the recognition of unknown faces. CONCLUSIONS: Probably, the absence of seizures in the first 4 years of life could have allowed a generally adequate compensatory reorganisation, successively masked by the persistent and diffuse epileptic disorder. The seizure control produced by surgery eventually made evident the effectiveness of the brain reorganisation.

Sleep disorders in Sanfilippo syndrome: a polygraphic study.

OBJECTIVE: A high prevalence of sleep disorders is reported in patients affected by Mucopolysaccharidosis III (Sanfilippo syndrome). These disorders have never been investigated by prolonged, objective, and instrumental evaluations. The present work is based on sleep duration and structure in Sanfilippo patients. STUDY DESIGN: The features of sleep/wake cycle in 6 Sanfilippo patients and 6 healthy controls were evaluated by means of sleep diaries and 48 hour ambulatory EEG and polygraphic recordings. Statistical analysis was performed by means of the U-test (Mann-Whitney). RESULTS: Four out of six Sanfilippo patients, the oldest patients in our sample, showed an extremely irregular sleep pattern, with several sleep episodes of inconstant duration, irregularly distributed along 24 hours. The two younger patients showed sleep maintenance insomnia with several nocturnal awakenings. CONCLUSIONS: These results suggest that sleep disruption in Sanfilippo syndrome consists of an irregular sleep/wake pattern, which at its onset might appear as a disorder of initiating or maintaining sleep. This could explain why same patients do not respond to conventional hypnotics. The present observation might suggest attempting therapies aimed at resynchronization, such as behavioral treatment, light therapy or melatonin.

Reversible aphasic disorder induced by lamotrigine in atypical benign childhood epilepsy.

PURPOSE: We studied an eleven year-old girl with atypical, benign partial epilepsy who acutely presented a severe aphasia associated with marked EEG deterioration after lamotrigine administration. A parallel monitoring of language disorders and EEG changes during the gradual withdrawal of lamotrigine was performed in order to evaluate their possible correlation with lamotrigine administration. METHODS: Detailed neuropsychological and linguistic examinations in association with awake and sleep EEG were periodically performed. RESULTS: The evolution of the aphasic disorder was closely related to the EEG abnormalities, and disappeared after the withdrawal of lamotrigine. CONCLUSIONS: We considered the hypothesis that our case could be an expression of a paradoxical reaction to lamotrigine, in which the transitory aphasic disorder was sustained by an epileptiform electric activation.

Surgical treatment of temporal tumors associated with epilepsy in children.

Seizures are a frequent sign of cerebral supratentorial tumors in children, especially when the location of the neoplasm is the temporal lobe. We report a series of 37 pediatric patients with temporal epileptogenic tumors. They represent 80.4% of children affected by temporal neoplasms, confirming the high incidence of seizures when neoplasms are located in this cerebral area. There was a slight male predominance. Epilepsy was the first symptom in all the patients of our series, as well as the only clinical manifestation present until surgery in 62% of patients. In the remaining children, hemiparesis, intracranial hypertension, psychosocial or neuropsychological disabilities, and delayed milestones arose before diagnosis and surgical treatment. The most frequent type of seizures was the partial complex (56%), but simple partial or generalized fits, as well as more than one type of seizures, were observed. The medial temporal structures were those more commonly involved, although seizures were observed also in cases where they were spared by tumors located exclusively in the temporal neocortex. On histology, most of the tumors showed a benign phenotype. Tumor resection was complete in 60% of cases; the excision of the tumor was incomplete in subjects whose lesion involved surgically inaccessible cerebral regions, as language areas, insular structures, and basal nuclei. As for epilepsy, 26 among the 32 long-term survivors can be classified in class I of Engel's classification; 4 of them did not receive any antiepileptic treatment. Four patients showed a significant reduction in the frequency of their fits. In 2 subjects, only the frequency of seizures was minimally reduced after tumor excision; in both, a partial removal of their tumor was performed. The relationship among the results on epilepsy and the extent of surgery removal of the tumor, brain tissue removal if any, frequency of seizures in the preoperative period and the time interval between the first epileptic manifestation and surgery show that the most significant prognostic element predictive of a good control of seizures is radical resection of the tumor.

Is ESES/CSWS a strictly age-related disorder?

OBJECTIVES: We report on a case of ESES/CSWS observed in a patient of 21 years and still persisting at the age of 25. Cases of ESES/CSWS have never been previously described in adult patients. ESES/CSWS is considered to be related to the degree of maturation of the central nervous system, and therefore strictly age-related. METHODS: Our case of ESES/CSWS was observed in a 2 1 year old woman referred for cognitive and behavioral disorders. She had previously had epileptic fits, but was seizure free at that time. The patient underwent a full-night polygraphic recording , which showed typical ESES/CSWS pattern, with a Spike-and-Wave Index >8 5%. Polysomnography was repeated 9 times in a 4 year follow-up, during which the ESES/CSWS condition persisted, despite the pharmacological treatments. The patient also underwent cerebral magnetic resonance imaging and fludeoxyglucose F 18 positron emission tomography (PET). RESULTS: The PET study revealed reduced metabolic activity within the lower gyrus of the right parietal lobe, but no significant difference between subcortical structures and cortical mantle was seen. MRI scans were normal. CONCLUSIONS: This observation suggests that ESES/CSWS might not always be an age-related condition. Sleep EEG recordings should always be performed in patients with behavioral disorders and a history of epileptic fits.

Neuro-cognitive development and epilepsy outcome in children with surgically treated hemimegalencephaly.

We performed a long-term follow-up of 10 patients with hemimegalencephaly and refractory epilepsy, after having treated them with hemispherectomy. Before surgery, 9 patients presented with delayed motor and cognitive development. Surgery was performed between age 5 months and 4 years and 8 months; the mean postsurgical follow-up was 5 years and 2 months. The epilepsy improved in most cases: 6 patients became seizure-free and 2 presented only dystonic fits. The cognitive outcome was less favourable, even though some improvement of cognitive competence was found in all. The neurological deficit did not increase after surgery, and the quality of life improved significantly. A good cognitive development before surgery, less severe morphological changes in neuroimaging, and functional and anatomical integrity of the "healthy" hemisphere seem to be associated with a better cognitive outcome.

Linguistic and non-linguistic abilities in a patient with early left hemispherectomy.

A patient who underwent early removal of the left hemisphere because of Sturge-Weber syndrome was submitted to detailed linguistic and visuospatial batteries. The performances were compared to performances of subjects matched for age, education and IQ, but without focal cerebral lesions. Language was mildly impaired but to the same extent as in IQ controls. On the contrary, visuospatial abilities were clearly worse than in IQ controls, and the most preserved visuospatial abilities seemed to be the less sophisticated ones. Non literal comprehension of language, a function generally attributed to the right hemisphere, was intact. This same pattern, that is, preservation of language and impairment of visuospatial abilities, also seems to occur in subjects who have undergone surgical removal of the right hemisphere; in other words, the cognitive pattern seems the same regardless of which hemisphere is removed. These observations suggest that no matter which hemisphere is removed, functional reorganisation follows a hierarchical criterion which privileges the linguistic function, and the visuospatial functions most essential for independent survival.

Effect of acetyl-L-carnitine on hyperactivity and spatial memory deficits of rats exposed to neonatal anoxia.

The effect of acetyl-L-carnitine (ALC) on behavioral deficits following neonatal anoxia (N2 100% for 25 min at 30 h after birth) was studied in the rat. Transient hyperactivity at P20-P45 postnatal days and permanent spatial memory deficits were shown by anoxic rats. A chronic ALC treatment (50 mg/kg per die injected intraperitoneally from P2, after anoxia, to P60) significantly reduced the transient increase in sniffing, rearing and locomotory activity of anoxic rats, but, mostly, ameliorated the spatial memory performances in a maze at P30-P40 and in a water maze at P50-P60. No behavioral changes were seen in ALC-treated animals that received sham-exposure at birth. On the basis of these results, the use of ALC for the treatment of perinatal asphyctic insults in children is suggested.

Changes in open field behavior, spatial memory, and hippocampal parvalbumin immunoreactivity following enrichment in rats exposed to neonatal anoxia.

Behavioral and neurochemical changes following enriched housing were studied in Wistar rats neonatally exposed to anoxia (100% N2 for 25 min at approximately 30 h after birth) or to sham treatment. Neonatal anoxia provoked transient hyperactivity during the P25-P40 period, and spatial memory disturbances persisting into adult life. Enriched housing, from P21, at weaning, to P60, improved behavior in open field and spatial memory abilities in a water maze, reducing the deficits that followed neonatal anoxia. Changes in the expression of the calcium binding protein parvalbumin were present in the CA1, CA3, and DG regions of the hippocampus in both sham-treated and anoxic rats exposed to enrichment. The present findings give further support to the evidence of a positive effect of enriched housing on behavior and learning of normal and lesioned animals, which is sustained by modifications in the neuronal activity, and suggest that modifications in the environment can be useful to counteract the development of some neurological disturbances that follow neonatal insults, e.g., perinatal asphyxia.

Neonatal anoxia induces transitory hyperactivity, permanent spatial memory deficits and CA1 cell density reduction in developing rats.

Physical and reflex development, spontaneous behavior in open field and spatial memory abilities have been studied in rats after neonatal anoxia. Histological analysis of the hippocampal fields have been carried out in selected animals at the end of the testing period. No differences between control and anoxic rats were recorded in the physical and reflex development. Hyperactivity in open field was present in anoxic animals only transiently between P20 and P45. Spatial memory abilities, tested at two developmental stages by means of a maze and a water maze, appeared to be defectual not only during the hyperactivity period but also in adulthood. The histological analysis of the different hippocampal fields demonstrated a significant difference between anoxic and control rats in the cell density of the CA1 field. The present data demonstrate that neonatal anoxia, besides determining only transitory defects in open field behavior, profoundly affects cognitive abilities and cell density in CA1 hippocampal field. These results might be of relevance in the interpretation of the substrate of the cognitive impairment seen in hyperactive children that are exposed to hypoxia at birth.