Multimodality imaging for focus localization in pediatric pharmacoresistant epilepsy.

UNLABELLED: Multiple structural and functional imaging modalities are available to localize the epileptogenic focus. In pre-surgical evaluation of children with pharmacoresistant epilepsy, investigations with the maximum yield should be considered in order to reduce the complexity of the workup. OBJECTIVE: To determine the extent to which PET, ictal/interictal SPECT and its co-registration with the patient's MRI contributes to correct localization of the epileptogenic focus, surgical intervention and to the post surgical outcome in paediatric patients. METHODS: The study population included children and adolescents with pharmacoresistant epilepsy (n = 50) who underwent preoperative evaluation, surgery and had postoperative follow-up for at least 12 months. Outcome was measured by postoperative seizure frequency using Engel's classification. RESULTS: Thirty-nine patients (78%) became completely seizure free after surgical intervention. The likelihood to benefit from surgical treatment was significantly higher if localization with more imaging modalities (MRI, PET, SPECT) were concordant with respect to the resected brain area (p < 0.01). Preoperative PET examination provided better localizing information in patients with extratemporal epilepsy and/or dysplastic lesions, whereas SPECT was found to be superior to PET in patients with temporal lobe epilepsy and/or tumors (p < 0.05). No significant difference was noted in the surgical outcome in younger or older age group, in children with or without special education needs. CONCLUSION: In paediatric epilepsy pre-surgical evaluation, the combined use of multiple functional imaging modalities for a precise localisation of the epileptogenic focus is worthwhile for both extratemporal and temporal lobe epilepsy, also when EEG and MRI alone are non-contributive, given the potential benefit of complete postoperative seizure control.

Cells with TP53 mutations in low grade astrocytic tumors evolve clonally to malignancy and are an unfavorable prognostic factor.

It is important to understand how low grade tumors recur and progress to malignant lesions since this dramatically shortens patient survival. Here, we evaluated the concept that malignant progression and poor prognosis of low grade astrocytic tumors are TP53 dependent through clonal expansion of mutated cells. TP53 status was established in primary and recurrent tumors from 36 patients with WHO grade II astrocytic tumors and two tumor types were found. Tumors from 14 patients (39%; type 1) had TP53 mutated cells, and 92% of these recurred with 57% progressing to malignancy. The evolution of TP53 mutated cells before and after progression was examined using a clonal analysis procedure in yeast. Malignant progression was accompanied by an increased percentage of mutant TP53 (red) yeast colonies resulting from monoclonal expansion of cells with mutated TP53. The presence of TP53 mutations in WHO grade II astrocytic tumors was associated with malignant progression (P=0. 034, chi2 test) and shorter progression-free survival (PFS; 47.6+/-9. 6 months for TP53-mutated tumors vs 67.8+/-8.2 months for TP53-wild type tumors, P<0.05, log-rank test). Tumors from 22 patients (61%; type 2) were without TP53 mutations, and 64% of these recurred without a change in TP53 status, although 41% progressed to malignancy. This suggests that TP53 mutation is not an initiating or progression event in the majority of low grade astrocytic tumors. Our study also indicates that irradiation for WHO grade II astrocytic tumors might be associated with poor outcome (P<0.0001) and this was independent of TP53 status. These findings have important implications in the clinical management of patients with low grade astocytoma and provide new support to the clonal evolution model for tumor progression.

Familial alternating epilepsia partialis continua with chronic encephalitis: another variant of Rasmussen syndrome?

Two brothers had infantile epilepsia partialis continua alternately involving both sides of the body. The children rapidly developed severe psychomotor regression and cerebral atrophy. A brain biopsy specimen showed evidence of chronic inflammatory changes. Extensive investigation did not provide evidence of a specific viral pathogenesis, mitochondrial disorder, or any identifiable neurodegenerative genetically determined disorder. This illness has the features of Rasmussen chronic encephalitis, in which bilateral involvement is quite unusual. Although few patients with bilateral hemispheral involvement have been described, to our knowledge there have been no reported cases involving affected siblings. The familial disorder described herein may represent yet another variant of the classically sporadic and unilateral childhood form. This group of disorders is probably immunologically determined.

Cerebral amyloid angiopathy.

We studied 24 patients with autopsy-proven cerebral amyloid angiopathy. Eight patients were demented or had some other medical problem and died of pneumonia or systemic disease. Sixteen patients died of intracranial hemorrhage. Amyloid was found in cortical arteries and arterioles of all patients. CT showed diffuse atrophy in demented patients and intracerebral hematomas in the others. The location and size of the hematoma, with cortical and subarachnoid extension, help to differentiate amyloid angiopathy from other causes of intracranial hemorrhage in the elderly.

Intracerebral cavernous angiomas.

We studied 31 patients with histologically verified intracerebral cavernous angiomas. Twenty-two patients were symptomatic; nine were asymptomatic. All 22 symptomatic patients had seizures, three had intracranial hemorrhage, and one had signs of a space-occupying lesion. Twenty-seven lesions were located in the neocortex, three in the brainstem, and one in the cerebellum; all exhibited characteristic gross and microscopic features of cavernous angiomas. CT identified the location and extent of the lesion in 16 of 27 cases. Six of seven lesions demonstrated contrast enhancement, and ten of 27 scans harbored densities consistent with intracerebral calcium. Angiography was performed in 17 cases and was completely normal in eight. MRI revealed mixed signal intensity centrally with a ring of decreased signal intensity peripherally on T2-weighted images and was diagnostic in five cases. Surgical treatment offers an excellent prognosis for seizure control in patients with such lesions.

Aminopterin-like syndrome sine aminopterin associated with translocation involving chromosomes 5 and 10.

We studied a baby born with physical features suggestive of the aminopterin syndrome, but without exposure of the mother to aminopterin during pregnancy. G-banded chromosomes from peripheral blood lymphocytes had a normal 46,XX pattern. However, in 50 skin fibroblasts there was a normal female karyotype in 5 cells and 45 cells showed an apparently balanced reciprocal translocation involving the long arm of chromosome 5 (band q35) and the long arm of chromosome 10 (band q22). The relation of this mosaicism to the abnormal phenotype is unclear.

Optic nerve in globoid leukodystrophy (Krabbe's disease). Ultrastructural changes.

Globoid leukodystrophy (Krabbe's disease) was diagnosed in an infant in whom a progressive neurological disorder and optic atrophy developed. At autopsy, ultrastructural examination of the optic nerves and cerebral white matter revealed characteristic tubular inclusions in globoid-epithelioid cells. Thinning of the nerve fiber and ganglion cell layers of the retina appeared to be due to retrograde degeneration of the optic nerve related to the abnormal metabolism of myelin. We discuss the pathogenesis of the clinical and pathological ocular findings, with regard to the inherited absence of the enzyme galactocerebroside beta-galactosidase and the accumulation in the optic nerve and brain of its substrates, galactocerebroside and psychosine.

Fulminant hepatic failure associated with status epilepticus in children: three cases and a review of potential mechanisms.

Fulminant hepatic failure is a rare complication of status epilepticus. Although many of the anticonvulsants used to treat the seizures are known to have hepatotoxic properties, the exact mechanism leading to massive destruction of the liver following a prolonged seizure remains unclear. Three children are presented who developed fulminant hepatic failure following status epilepticus and subsequently died of multiple organ failure. The literature is reviewed with particular attention to the possible interaction between the anticonvulsants and the metabolic consequences of status epilepticus. We postulate that it is a combination of hypoxia and ischemia that occurs during a prolonged seizure with altered metabolism of free radicals secondary to the anticonvulsant drugs which leads to widespread hepatocyte membrane damage.

Eosinophilic aseptic arachnoiditis. A neurological complication in HIV-negative drug-addicts.

The finding of an eosinophilic aseptic meningitis in IV drug abuse is usually suggestive of an opportunistic infection or an allergic reaction. However, HIV-negative patients are at lower risk for developing these complications. Two young HIV-negative patients, with previous intravenous polytoxicomany, developed cystic arachnoiditis over the spinal cord associated with eosinophilic meningitis. Histology of the meningeal spinal cord lesions revealed a vasculocentric mixed inflammatory reaction. In one patient prednisone led to marked clinical improvement. Since infection, vasculitis, sarcoidosis and previous myelography were ruled out, we believe that the syndrome of eosinophilic aseptic arachnoiditis may be related to an hyperergic reaction in the meniges toward drug-adulterants inoculated through the intravenous route.

Traumatic aneurysm from shaken baby syndrome: case report.

OBJECTIVE AND IMPORTANCE: We present a 6-week-old infant who developed a traumatic aneurysm from clearly documented shaken baby syndrome. Despite the theoretical similarity in the mechanism of such injuries, this is the first aneurysm reported that resulted from such a cause. The infant is also the youngest reported patient to have suffered from a traumatic aneurysm. CLINICAL PRESENTATION: Police records documented shaking of the child as well as direct impact on the child's head. Three weeks later, the patient developed an intracerebral hemorrhage, which was revealed by angiography to have resulted from a pericallosal artery aneurysm. TECHNIQUE: The aneurysm was totally resected through a porencephalic cyst, which had developed secondary to ischemic injury to the brain. CONCLUSION: The temporal course, as well as the location of this traumatic aneurysm, is similar to that in older patients.

Ganglioglioma presenting as a vascular lesion in a 10-year-old boy. Case report.

The authors present the case of a 10-year-old boy admitted for evaluation of a generalized seizure and a history of headaches. Computerized tomography (CT) and gadolinium-enhanced magnetic resonance (MR) imaging demonstrated a large nonhomogeneous contrast-enhancing mass of the left frontal lobe, with a large cystic component. Cerebral angiography revealed the lesion to be highly vascular and fed entirely by the internal carotid artery system. The patient underwent craniotomy and the lesion was completely removed. Neuropathological study revealed that the tumor was a ganglioglioma. On review of the literature, it was found that gangliogliomas often present in the second and third decade, are known to have cystic components, and are contrast-enhancing on CT and MR imaging; however, they are classically known to be avascular on angiography. This case of a markedly vascular ganglioglioma emphasizes that these tumors should be included in the differential diagnosis of vascular supratentorial lesions.

Supratentorial ectopic ependymoma.

BACKGROUND: Ependymomas usually arise from the ventricular surface. METHODS: We report an 11-year-old female who presented with a supratentorial ectopic ependymoma. RESULTS: The patient presented with a two-month-history of progressive headache, nausea and vomiting. Examination revealed papilledema, horizontal nystagmus, diplopia on upward gaze, and right pronator drift. CT scan showed an enhancing left precentral subcortical lesion measuring 3 cm in diameter with associated edema and mass effect. Its medial border was located 3 cm from the ependymal surface of the ventricle. A firm tumour was dissected from the centrum semiovale white matter, and removed in toto as confirmed on MRI. Pathological examination revealed histological, immuno-histochemical and electron microscopic features consistent with an ependymoma. Spine MRI and bone marrow aspirate, as well as lumbar puncture of cytology failed to show any dissemination. CONCLUSION: From the literature review, this represents an exceptional ependymoma located at the distance from the ventricular system or cisterns. Different pathogenic alternatives are discussed.

X-linked hydrocephalus.

Two French-Canadian families with seven cases of hydrocephalus in two generations are presented. The pattern of inheritance is consistent with an X-linked recessive transmission. The clinical and pathologic characteristics of this entity are reviewed. The anomaly of adducted thumbs was present in one patient and its cause is considered. The hypothesis of primary hydrocephalus and secondary compression of the aqueduct as the mechanism for aqueductal stenosis is discussed.

Intraventricular central neurocytoma.

A case of central neurocytoma treated surgically is described. The authors review the literature. Emphasis is placed on radiological and pathological features not previously described. In particular, the intra-operative ultrasound appearance is described. The role of adjunctive radiotherapy is also discussed.

Developmental bilateral perisylvian dysplasia.

Acquired bilateral anterior opercular lesions result in the characteristic Foix-Chavany-Marie syndrome that features expressive dysphasia and pseudobulbar palsy. A developmental congenital variant that represents a restricted disorder of neuronal migration was recently reported. We report a newborn with autopsy-confirmed developmental bilateral perisylvian dysplasia. Polymicrogyria was found on detailed histologic study confirming the only prior pathologic study of this syndrome. The clinical heterogeneity of this disorder with neonatal and childhood modes of presentation is reviewed. Speculation regarding pathogenesis focuses on either a genetically determined selective aberration of neuronal migration or an in utero postmigration vascular accident.

Infantile epileptic encephalopathy (Ohtahara syndrome) and migrational disorder.

A case of early infantile epileptic encephalopathy (EIEE) with suppression-bursts (Ohtahara syndrome) associated with a diffuse cerebral migrational and maturation disorder evident on microscopic examination is reported. Although virtually all reported cases of EIEE are secondary to a congenital or acquired structural malformation of cortical development, EIEE is sometimes identified only by detailed neuropathologic examination, as confirmed by this case report. In addition to the malformation of cortical development, the patient demonstrated an absence of gamma-aminobutyric acid in the cerebrospinal fluid. All children with EIEE should be thoroughly examined by magnetic resonance imaging, cerebrospinal fluid amino acid level determination, and detailed postmortem neuropathologic examination.

Cauda equina histiocytosis X.

A young child was admitted with a cauda equina syndrome believed to be progressive, but unrelated to a congenital anomaly. Magnetic resonance imaging studies revealed the presence of an intradural tumor in the cauda equina. A yellow pasty tumor with nerve root infiltration was identified at surgery. Histologic features were pathognomonic for histiocytosis X. The patient's management and review of the literature are discussed.

Schinzel-Giedion syndrome: further delineation of the phenotype.

We describe a male infant with findings typical of Schinzel-Giedion syndrome. Characteristic features include: midface retraction, widely patent fontanelles, hirsutism, choanal stenosis, hypospadias with chordae, club feet and broad ribs. The patient suffered from seizures and died at 14 months of age of fulminant bronchopneumonia. Pathological examination revealed steatosis in the liver as well as lipid vacuolization of the zona fasciculata of the adrenals.

Combination of immunohistochemistry and ploidy analysis to assist histopathological diagnosis of molar diseases.

BACKGROUND: Differential diagnosis between hydropic abortion, partial mole and complete mole is still a challenge for pathologists but really important for patient management. MATERIAL AND METHOD: In this study, we have evaluated 111 products of conception from the first trimester. Histological analysis was made according to the main diagnostic histopathological features described in the literature and the cases were categorized in hydropic abortus (HA), partial mole (PM) and complete mole (CM). Immunohistochemistry was performed using monoclonal antibody against p57(kip) protein a putative paternally imprinted inhibitor gene and DNA ploidy was analysed in all cases by image cytometry. RESULTS: All 23 HAs presented a diploid DNA content and were p57(kip2) positive. From the 28 CMs, 12 cases (43%) were diploid and 16 cases (57%) were tetraploid but no expression of p57(kip2) was found with positive internal controls. From the 60 PMs, 58 cases were positive for p57(kip2) expression and 53 cases (88%) were triploid, 6 cases (10%) tetraploid and 1 case (2%) diploid. CONCLUSION: This study on 111 cases of early pregnancies confirms the usefulness of immunohistochemistry and cytometry but demonstrates the importance of the combination of both techniques to assist histology for the best reliable diagnosis.