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.

Progressive unilateral hemispheric atrophy in an infant with neurofibromatosis.

INTRODUCTION: Cerebrovascular diseases are rarely seen in neurofibromatosis type 1. These include vascular occlusive disease, moyamoya vessels, aneurysms, arteriovenous malformations and fistulae. CASE REPORT: We describe the case of an infant with genetically proven neurofibromatosis type 1 and progressive brain hemiatrophy over months, due to primary narrowing of intracranial carotid artery branches, as demonstrated by successive brain imaging. She presented with refractory seizures and a progressive hemiparesis associated with developmental delay. Surgical material from hemispherotomy done at 18 months showed severe abnormalities of the small vessels. CONCLUSION: Cerebrovascular changes seen in neurofibromatosis can be diffuse and progressive, with secondary hemiparesis, epilepsy and developmental delay.

Right-sided diaphragmatic eventration: a rare cause of non-immune hydrops fetalis.

We report 2 cases of non-immune hydrops fetalis (NIHF) in which autopsy findings revealed an association with right-sided congenital diaphragmatic eventration (CDE). Both patients born at 30 weeks of gestation presented with severe generalized skin oedema, pleural effusions and ascites. They both died shortly after birth of cardiorespiratory insufficiency due to lung hypoplasia and low output heart failure. The right thoracic cavity was filled with the membranous but intact right diaphragm covering the herniated visceral organs including parts of the liver, small bowel and colon surrounded by voluminous ascites. In similar fashion to the situation seen in congenital diaphragmatic hernia (CDH), the displaced visceral organs led to impaired lung growth resulting in important lung hypoplasia and obstructed venous return. Extravascular liquid accumulation was probably further aggravated by hypoproteinaemia secondary to liver dysfunction resulting from the venous congestion and cardiac failure. In summary, CDE is a rare condition resulting from impaired ingrowth of muscle fibres into the diaphragm during the first trimester. Prenatal differentiation of CDE from CDH is a real challenge. The association of CDE and NIHF has not been previously described.

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.

The role of posterior fossa decompression in acute cerebellitis.

BACKGROUND: We present two cases of children who were diagnosed with cerebellitis with acute cerebellar swelling. This rare pathology is potentially fatal, and no clear treatment guidelines are described in the literature. DISCUSSION: Considering our experience, we discuss the different therapeutic strategies and propose aggressive surgical measures consisting of external ventricular drainage and posterior fossa decompression in case of failure of early response to medical treatment to limit secondary cerebellar and brainstem lesions.

Repeated surgical excision for an unusual variant of nephroblastoma: case report and review of the literature.

Bilateral fetal rhabdomyomatous nephroblastoma is a rare variant of Wilms' Tumor. The authors report the evolution over 48 months of a 10-month-old baby with bilateral nephroblastoma for which a left nephrectomy was initially performed. A right kidney tumor was enucleated preserving the kidney. The transformation of the primary tumor into a completely differentiated cystic nephroblastoma or nephromalike tumor and the appearance of a metachronous lesion was seen. This report emphasizes the role of nephron-sparing surgery in bilateral Wilms' Tumor when a benign transformation occurs under chemotherapy.

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.

Brain involvement in haemolytic-uraemic syndrome: MRI features of coagulative necrosis.

We describe radiological demonstration of brain involvement in haemolytic-uraemic syndrome (HUS) in two siblings with a very different clinical course. While the brother presented with a mild, reversible encephalopathy, his sister developed high-signal lesions in the cortex, putamen and caudate nucleus on T1-weighted images, seen as dense areas on CT. Biopsy revealed coagulative necrosis due to microthrombosis without haemorrhage, calcification or infection. These findings suggest a possible prognostic role for MRI in cases of encephalopathy due to HUS.

Brainstem Gliomas. A 10-year institutional review.

Case records of 37 patients with a diagnosis of brainstem glioma treated at the Montreal Children's Hospital from June 1989 to June 1999 were reviewed. 15 patients had diffuse pontine gliomas and 22 patients had focal forms of brainstem gliomas. The two groups were compared with respect to age, clinical evolution, radiological appearance, type of surgery practised, histological diagnosis, adjuvant treatments and survival. A non-pontine brainstem location, a cystic or exophytic component, bright enhancement with gadolinium injection, a histological diagnosis of pilocytic astrocytoma or ganglioglioma were favourable prognostic factors. Progression-free survival and overall survival were significantly worse in the group of patients with diffuse pontine gliomas. The relative impact of radical surgery and/or radiotherapy is analysed. Surgery coupled to adjuncts such as navigation, ultrasound and monitoring plays an important role for focal brainstem lesions. Focal/conformal radiotherapy has an adjuvant role but better treatments are needed for the diffuse pontine brainstem lesions.

Dysgenetic mesial temporal sclerosis: an unrecognized entity.

Mesial temporal sclerosis (MTS) is the most frequently encountered lesion in adult patients with intractable temporal epilepsy; it is found in isolation in approximately two-thirds of surgically treated cases. Whereas the exact etiology of MTS is still controversial, several reports suggest that this pathologic lesion is both the cause and the consequence of chronic seizures and develops progressively during childhood secondary to recurrent seizures. In order to evaluate the clinical importance of MTS in children, we retrospectively reviewed the clinical charts of children who underwent surgery for medically intractable temporal epilepsy and report cases presenting an amygdalo-hippocampic dual pathology. Six children aged 1.5-16 years (mean +/- SD: 7.5 +/- 3 years) presenting with partial complex seizures (5 cases) or extension spasms (1 case), with onset from 6 months to the age of 8.5 years (mean seizure onset +/- SD: 3 +/- 5 years) underwent anterior temporal lobectomy including resection of the amygdala and hippocampus. All patients exhibited variable degrees of severity of neuronal loss and gliosis in the amygdala and/or hippocampus. The pathological picture of MTS was not isolated, however. Careful pathological examination has thus shown foci of amygdalo-hippocampic neuronal dysplasia in six patients, with concomitant bilaminated fascia dentata in two cases. Postoperatively, no mortality or morbidity was encountered. After a mean follow-up of 2.5 years, four patients are seizure free. One patient had a 80% rate of improvement in seizure frequency, though still having occasional febrile convulsions. In another patient, complex partial seizures resolved, but rare episodes of absence were still observed. These data are in keeping with the hypothesis that MTS could be secondary to repeated seizures. The analysis of this series of patients could suggest that mesiotemporal dysplastic lesions within the amygdalo-hippocampic structures induce seizures, which, in turn, will favor the development of MTS during childhood. MTS could then lead to synaptic reorganization, which can express abnormal hyperexcitability and result in more recurrent seizures. In this way a vicious circle is set up, which may explain the progression of seizures in some patients.

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.

Cree leukoencephalopathy: neuroimaging findings.

PURPOSE: To describe the computed tomographic (CT) and magnetic resonance (MR) imaging findings in Cree leukoencephalopathy. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records and neuroimaging studies in 12 infants with Cree leukoencephalopathy (CT in 12 infants, MR in six). The diagnosis was established clinically in six patients and at autopsy in the other six. RESULTS: At CT, extensive, diffuse, and symmetric hypoattenuation was seen in the cerebral and cerebellar white matter in all 12 patients. Hypoattenuation was also seen in the corpus callosum in 11 (92%), internal capsule in 10 (83%), globus pallidus in nine (75%), brainstem in nine (75%), and thalamus in four (33%). The caudate nucleus and putamen were spared. On T2-weighted MR images in six patients, the cerebral and cerebellar white matter, including the subcortical arcuate fibers, was hyperintense as were the internal capsule, corpus callosum, corticospinal tracts, and globus pallidus. The thalamus was affected in four (67%) patients, pons in five (83%), and medulla in four (33%). The caudate nucleus and putamen were not affected. CONCLUSION: Cree leukoencephalopathy causes striking symmetric and diffuse involvement of the cerebral and cerebellar white matter and brainstem with sparing of the caudate nucleus and putamen.

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.

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.

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.

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.

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.

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.

Lesionectomy of MRI detected lesions in children with epilepsy.

The results of complete excision of cerebral lesions detected by MRI in 18 children presenting with epilepsy were analyzed. There were 14 boys and 4 girls with a mean age of 9.2 years. The average age of onset of seizures was 6.8 years. The mean time from onset of seizures to surgery was 2.3 years. Often, CT scans suggested that the lesions were indolent. MRI was better in differentiating neoplastic from developmental lesions. Angiography was non-contributory in this series. Interictal EEGs showed epileptiform activity correlating with imaging studies in 54% of children. The lesion was completely surgically excised in all patients. This was confirmed by intra-operative ultrasound and postoperative imaging. Electrocorticography was performed prior to and after the resection, but residual spiking did not lead to further resection. The average postoperative follow-up was 5.7 years. Five patients had low grade astrocytomas, 4 had gangliogliomas, 1 a mixed astrocytoma-oligodendroglioma, 3 had cortical dysplasia, 2 infantile desmoplastic gangliogliomas, 2 hamartomata, and 1 cavernous angioma. Sixteen patients have been seizure-free since surgery. Only 2 have partial seizures. Thus, all patients benefited from the resection, with respect to seizure control. In those with temporal lobe lesions, improvement in IQ was seen postoperatively. Early consideration of surgery in patients with epilepsy and lesions demonstrated by MRI is suggested.