Heterotopia associated with hippocampal sclerosis: an under-recognized cause of early onset epilepsy in children operated on for temporal lobe epilepsy.

PURPOSE: The aim of this study is to report on 52 children operated on for pharmacoresistant temporal lobe epilepsy, with special emphasis on histopathology and correlation with clinical features. METHODS: Charts were retrospectively analyzed. All children underwent comprehensive clinical, electrophysiological and radiological investigations before surgery. Surgical procedures were tailored according to scalp, foramen ovale and eventually depth electrode recordings. Histopathology was compared with clinical variables (χ (2) and Fisher's exact tests). Outcome was evaluated using the Engel scale. RESULTS: Developmental tumor was found in 14 cases, malformation of cortical development (MCD) in 26, isolated hippocampal sclerosis (HS) in 5 and gliosis in 7. Dual pathology (DP) affected 18 patients and the main extrahippocampal lesion consisted of microscopic sub-cortical heterotopias (HS-HT) for 15 patients who shared a particular clinical pattern: a history of febrile seizures (FS) and/or brain injury, early onset of epilepsy without latent period from FS to the first temporal seizure, and a particularly good outcome following surgery. CONCLUSION: In our pediatric temporal lobe surgery series, the prevalence for MCD and for DP was higher than in adult series. Age at seizure onset depends on pathology, and is earlier when involving the neocortex rather than only the hippocampus. We identify the association HS-HT (the most frequent DP in this series), with particular clinical features.

Immunocytochemical characterization of long-term persistent immune activation in human brain after herpes simplex encephalitis.

The clinical, virological and immunocytochemical features of three children who recovered from acute herpes simplex encephalitis (HSE) before the age of 2 years, and who developed secondary severe focal epilepsy after a symptom-free period, leading to neurosurgery 3-10 years later are described. In one child, relapse of HSE occurred immediately after surgery. In all three patients, brain sample biopsies showed abundant CD3-positive T lymphocytes with a majority of CD8 cells, and abundant activated macrophage-microglial cells, a pattern similar to that found in acute HSE. Herpes simplex virus DNA was retrieved from the tissue biopsy in one case. The long-term persistent cerebral inflammatory process observed after HSE differed from that observed in another chronic viral disease, subacute sclerosing panencephalitis. This inflammatory reaction may be a result either of low-grade viral expression or self-induced immune activation. The role of inflammation in triggering epilepsy remains hypothetical. Solving these issues should have major therapeutic implications. Herpes simplex virus DNA latency in brain may be the source of replicative HSE relapse.

[Cortical heterotopias: animal models and human disease]. / Hétérotopies corticales: modèles animaux et pathologie humaine.

Cortical heterotopia is defined as the misplacement of a group of neurons displaced to a precise localization in the neocortex and results from perturbed migration along the glial guide, either because of glial destruction or molecular anomalies. Heterotopic neurons are rarely dispersed but are rather grouped in nodules or bands. Heterotopic masses may lie in an ependymal or subcortical localization depending on whether they result from lack of migration or an arrested migration. Heterotopias can also occur in intra-cortical or extra-cortical localizations. The cause of heterotopia remains to be elucidated. Two genes situated on chromosome X have been implicated but non-genetic forms attributable to antenatal ischemia or toxic aggression during fetal development have also been observed. The presence of heterotopia is usually associated with epilepsy and sometimes with mental retardation. Seizures may be initiated within the heterotopic region then propagate via long projections to the neocortex which may also be malformed.

Focal cortical dysplasia and hemimegalencephaly: histological and neuroimaging correlations.

BACKGROUND: The classification of cerebral cortical dysplasia is difficult and there are histological similarities between focal cortical dysplasia (FCD) and hemimegalencephaly. Objectives. To correlate the MR features and histological data of cortical dysplasias. MATERIALS AND METHODS: The MR appearances of 17 brains were examined. According to the signal intensity within the pathological area on T2-weighted (T2-W) sequences we selected two groups. RESULTS: Group 1 comprised ten patients with high signal in the dysplastic area on T2-W images. This group included five hemimegalencephalies, three frontal quadramegalencephalies, and one gyral dysplasia. The pathological hemisphere was reduced in size in one case. The cortex was thickened in all cases on T1-weighted (T1-W) images. There was loss of delineation between white matter (WM) and grey matter (GM) in all cases on both T1-W and T2-W sequences. The differential diagnosis with tumour, neoplastic-like malformation or polymicrogyria was questionable. Group 2 comprised seven patients presenting without increased signal within the dysplastic area on T2-W images. WM and GM were of similar signal intensity in six cases, and delineation between white and grey matter was absent in all cases. There were mild abnormalities on T1-W sequences in all cases. The dysplasias were limited to a lobe in five cases and a gyrus in two cases. In all cases, depiction of the malformation was a greater diagnostic problem than the differential diagnosis. CONCLUSIONS: A constant MR sign in our series was the loss of delineation between WM and GM in the dysplastic area. This correlated well with the observed histological disorganisation. Markedly high signal within the dysplastic area seems to be related to myelin abnormalities rather than glial cell abnormalities.

Antenatal thalamic lesions in the newborn: two anatomoclinical cases.

We report two cases of antenatal bilateral thalamic lesions constituted by neuronal loss, gliosis and mineralized glial or neuronal cells. No etiology could be found. Neuroradiological findings were poorly correlated with histological changes. These cases are compared with the few previously reported cases of the same condition. We strongly recommend extensive etiological investigation as recurrence occurred in one family.

[Corpus callosum agenesis and parasagittal interhemispheric cyst]. / Agénésie du corps calleux et kyste interhémisphérique paramédian.

We report the association of a corpus callosum agenesis with a parasagittal interhemispheric cyst, without cortical malformation. This rare malformation is related to an early disorder in embryogenesis. The importance of the anatomic abnormalities compared with the good clinical status is remarkable. MR findings avoid misdiagnosis with a medial interhemispheric cyst associated to corpus callosum agenesis in which the prognosis is unpredictable.

Migrating partial seizures in infancy: a malignant disorder with developmental arrest.

Fourteen infants of both sexes had a previously unreported epileptic condition characterized by nearly continuous multifocal seizures. The first seizures occurred at a mean age of 3 months, without antecedent risk factors. At 1 to 10 months, the seizures became very frequent. They were partial with variable clinical expression, and the EEG showed that the discharges randomly involved multiple independent sites, moving from one cortical area to another in consecutive seizures. Although their topography varied, the EEG ictal pattern of each seizure was very similar. It consisted of rhythmic alpha or theta activity which spread to involve an increasing area of the cortical surface. Patients regressed developmentally and became quadriplegic with severe axial hypotonia. Three patients died at age 7 months and at age 7 and 8 years, respectively. Seizures were controlled in only 2 patients, and only 3 children resumed psychomotor development. Extensive investigation failed to determine an etiology, and there was no familial recurrence. Neuropathological examination of the brain in two cases showed only severe hippocampal neuronal loss and accompanying gliosis.

An unusual presentation of focal cortical dysplasia.

In a case of histologically proved focal cortical dysplasia, there was an absence of cortex-white matter delineation in the right parietooccipital area only on the T2-weighted images. This pattern correlated with the gross and histologic findings obtained on the resected cerebral tissue.

Dysembryoplastic neuroepithelial tumors in two children with neurofibromatosis type 1.

Dysembryoplastic neuroepithelial tumors (DNT) occur mainly in children and are always clinically associated with intractable complex partial seizures. In the first report, which included 39 cases, the patients had no neurological deficit and no stigmata of phacomatosis. In contrast, we observed a DNT in 2 children with a neurofibromatosis type 1. The first patient developed intractable complex partial seizures at age 9 years and was operated at the age of 13 years. Neuroimaging study showed multifocal involvement with three separated lesions in the frontal, parietal and temporal lobes. The second patient was a 16-year-old boy with 5-year history of severe and refractory epilepsy. Magnetic resonance imaging identified a right temporal lesion and the patient underwent a right temporal lobectomy. This unusual association of two cases of DNT with neurofibromatosis type 1 raises the question of whether this association is specific or fortuitous.

Reappraisal of Rasmussen's syndrome with special emphasis on treatment with high doses of steroids.

Eight patients with Rasmussen's syndrome and epilepsia partialis continua were treated with high doses of steroids, including pulses of methylprednisolone and prednisone in decreasing doses. Three patients exhibited clinical, radiological, or histological evidence of bilateral involvement. Epilepsy and focal deficit decreased within six months in seven patients. Only five patients, in whom steroid treatment had begun less than 15 months after the onset of epilepsia partialis continua, experienced a lasting effect although they had periodic episodes of transient relapse. Treatment with high doses of steroids seems advisable during the first year after onset of epilepsia partialis continua, before hemiplegia has developed and in cases with bilateral involvement.

Cardiac rhabdomyoma and tuberous sclerosis in three fetuses: a neuropathological study.

In spite of the development of modern imaging, most lesions of tuberous sclerosis (TS) remain difficult to detect before birth. Particularly, brain involvement at a fetal stage of development is poorly documented. We report three cases of fetuses examined after pregnancy was interrupted because of the detection of cardiac rhabdomyoma. In two of the three cases there were brain lesions suggestive of TS, including cortical tubers, subependymal nodules and scattered bizarre giant cells in the white matter. These observations confirm that brain lesions of TS can be present before birth; they can show, at an early period of development, an aspect quite similar to lesions described at an adult stage. The most characteristic cell abnormality is the so-called balloon cell. The majority of these cells exhibit a strong immunoreactivity with glial antibodies (GFAP, vimentin, S100). Immunoreactivity with neuronal markers (synaptophysin) is present in a small percentage of balloon cells.

Value of magnetic resonance imaging in West syndrome of unknown etiology.

Magnetic resonance imaging (MRI) studies of 46 patients with West syndrome (WS) of unknown etiology were reviewed retrospectively. The criteria for cryptogenic WS were met by 25 and 21 were considered symptomatic because other types of seizure or psychomotor retardation were apparent before spasm onset. Computed tomographic (CT) scans were normal in 38 patients and showed diffuse atrophy in eight symptomatic patients. In five patients, MRI was more informative than CT, demonstrating one case of delayed myelination and four cases of focal lesion. The focal lesion in 2 of these patients was similar on MRI consisting of poor gray-white matter demarcation in the parieto-occipitotemporal region. Surgical resection was performed in one because of intractable seizures, and neuropathological examination revealed cortical dysplasia. The remaining two cases with focal lesion had increased signal intensity on T2-weighted images in the posterior frontal cortex and in the temporal lobe, respectively. Our data indicate that MRI is useful in some cases of WS, especially in demonstrating focal corticosubcortical lesions not visible on CT scan.

Epilepsy and focal gyral anomalies detected by MRI: electroclinico-morphological correlations and follow-up.

The authors studied 10 patients (mean age 15 years 6 months) with localized developmental gyral disorder detected by MRI. There were two groups of major malformations. Seven patients (group 1) had unilateral 'macrogyric-like' insulo-opercular changes, one of whom died early in life and had extensive microgyria. The six others had mental retardation and epilepsy, three of whom had focal neurological signs. Age at onset of epilepsy varied greatly. Clinical and EEG data suggested a wider cerebral involvement than recognized on MRI. The remaining three patients (group 2) had abnormal gyri of variable topography and extension, with bulging grey matter and ventricular deformity. One had mental retardation, another had neurological signs. All had intractable complex partial seizures and focal EEG anomalies correlating with the MRI lesion site, pointing to a well-defined epileptogenic zone. No clinical or EEG evidence of significant malformation in the remaining brain tissue was observed. Ablative surgery was beneficial for one patient; focal cortical dysplasia was the pathological substrate.

Early epileptic encephalopathy with suppression bursts and olivary-dentate dysplasia.

A case of neonatal epileptic encephalopathy with suppression-bursts associated with olivary dentate nuclei dysplasia is reported. This unusual association shows that the so-called Ohtahara syndrome could correspond to several different brain malformations sometimes disclosable only by neuropathological examination.

Unlayered polymicrogyria and agenesis of the corpus callosum: a relevant association?

Three anatomical cases of unlayered polymicrogyria associated with agenesis of the corpus callosum and heterotopias are presented. The cortical dysplasia includes: (1) thin unlayered cortical mantle with radial disposition but no horizontal organisation of the neurons; (2) microgyria with fused molecular layers; and (3) persisting transitory cells in the molecular layer (Cajal-Retzius cells, subpial granular layer). A Golgi study of the cortex in one case shows abnormal orientation of the neuronal dendritic tree in the superficial area along the fused molecular layers. Heterotopias are of two types: scattered neurons in the subcortical region and in layer I; and nodular heterotopias in the paraventricular region and in centrum semi ovale. This type of cortical dysplasia differs from the classical four-layered microgyria and is similar to the cortical anomalies described in Aicardi syndrome. One case presented here has Aicardi syndrome, while the two others, one girl and one boy, do not meet the criteria for Aicardi syndrome; in particular, they do not display chorioretinal lacunae. Nevertheless, this neuropathological association is responsible for severe mental retardation and epilepsy, and incites the search for a genetic origin like that in Aicardi syndrome.

Cerebral lymphoma and HIV encephalitis in a case of paediatric AIDS, with pre-existing multicystic encephalomalacia.

A case of intracerebral malignant B cell lymphoma associated with encephalitis typical of Human Immunodeficiency Virus (HIV) infection is described in a 4 year old child, with post-transfusion Acquired Immune Deficiency Syndrome (AIDS) and severe pre-existing cystic encephalomalacia. This report further documents B cell lymphoma as the commonest cause of an intracerebral mass, and an important cause of death in paediatric AIDS. That more than one pathological process may be responsible for neurological symptoms in paediatric AIDS is also emphasised.

Bilateral porencephalic defect in a newborn after injection of benzol during pregnancy.

Porencephaly is usually considered to be a prenatal brain lesion due to a circulatory failure. We report a case of bilateral porencephaly with heterotopia and absence of the septum pellucidum in a newborn. The mother had received several injections of benzol during pregnancy with an intent of inducing abortion. The possibility of a causal relationship between the administration of benzol and the occurrence of the defect is supported by the existence of previously reported cases of cerebral malformations following maternal exposure to organic solvents.

[Congenital hereditary motor and sensory neuropathy]. / Neuropathies héréditaires sensitivomotrices à début congénital.

The authors report 6 cases of hereditary sensorimotor neuropathy (HSMN) presenting with the following clinical features: (1) severe outcome (3 out of 6 patients died before the age of 4 years), and (2) intellectual impairment (3 out of 6 cases). Histopathological study of nerve biopsies gave heterogeneous results: there was one case of axonal neuropathy (HSMN II of Dyck and Lambert), one case of demyelinating neuropathy with Schwann's cell proliferation (HSMN III of Dyck and Lambert), and one case of giant axonal neuropathy. The last three cases displayed an original pattern hitherto unknown in classical delayed HSMN, with complete disappearance of myelinated sheaths and Schwann's cell proliferation. This particular pattern did not seem to be due to the biopsy being performed at an early stage, since in one case a second biopsy showed the same histological features.

[Delayed measles encephalitis in a leukemic child]. / Encéphalite retardée de la rougeole chez un enfant leucémique.

A case of measles encephalitis of the delayed type in a 5 year-old girl is reported. The encephalitis occurred 6 months after a measles which supervened just after the 18th monthly reinduction treatment for acute lymphoblastic leukemia. The child died one month later. This measles inclusion body encephalitis (MIBE) was confirmed by the presence of intracellular inclusions in the brain cells visualized by electron microscopy. The evidence of viral related intracellular nucleocapsides was confirmed by in situ hybridization. These nucleocapsides were identical to those seen in subacute sclerosing panencephalitis.