Cerebellar hypoplasia with heterotopic purkinje cells in the molecular layer and preservation of the granule layers associated with severe encephalopathy. A new entity?

We present the case of an infant girl, born to first cousins, with a clinical phenotype consisting of microcephaly, hypotonia, strabismus and severe psychomotor retardation. Magnetic resonance imaging (MRI) showed global cerebellar atrophy involving the vermis and both hemispheres. The patient's serum transferrin levels were consistently unremarkable.

Lethal X-linked microcephaly with dysmorphic features, bilateral optic pathway aplasia and normal eyes.

We describe a family, consisting of two brothers and a maternal uncle who died of an apparently identical condition, within a few days of birth, suggestive of an X-linked mode of inheritance. The propositus (the older sibling) was investigated in detail and showed the following clinical features: microcephaly, facial dysmorphism, malformations of hands and feet, and cryptorchidism. Examination of the brain revealed arhinencephaly, a primitive gyral pattern, arrested cortical maturation, absence of corticofugal tracts and corpus callosum, agenesis of the optic pathway with preserved eyes and oculomotor system, absent auditory pathway, agenesis of the pars compacta of the substantia nigra and severe hypoplasia of the cerebellum and its connections.

alpha-Lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria.

In the present cross-sectional study, the influence of alpha-lipoic acid on markers of oxidative stress, assessed by measurement of plasma lipid hydroperoxides (ROOHs), and on the balance between oxidative stress and antioxidant defence, determined by the ratio ROOH/(alpha-tocopherol/cholesterol), was examined in 107 patients with diabetes mellitus. Patients receiving alpha-lipoic acid (600 mg/day for > 3 months) had significant lower ROOHs and a lower ROOH/(alpha-tocopherol/cholesterol) ratio than those without alpha-lipoic acid treatment [ROOH: 4.76 +/- 2.

The mysterious prion diseases--a historical perspective.

The spongiform encephalopathies are a group of diseases sharing a common pathology and affecting both humans and animals. The human diseases include both sporadic and familiar disorders. Creutzefeld-Jakob disease and kuru are sporadic, familial Creutzfeld-Jakob, fatal familial insomnia and the Gerstmann-Sträussler-Scheinker syndrome are genetic and inherited as autosomal dominants.

Calbindin-D28k in subsets of medulloblastomas and in the human medulloblastoma cell line D283 Med.

Objective: To evaluate the antigenic expression of calbindin-D28k in surgically resected cerebellar medulloblastomas and the human medulloblastoma cell line D283 Med in relation to glial neoplasms, the human glioblastoma (U-251 MG) and rat glioma (C-6) cell lines, and other primary and metastatic brain tumors.

Design: Immunohistochemical staining was performed using an antiserum and a monoclonal antibody against calbindin-D28k on (1) formalin-fixed, paraffin-embedded human, predominantly posterior fossa, brain tumor specimens (49 medulloblastomas, 59 glial and mesenchymal primary central nervous system tumors, 1 posterior fossa rhabdoid tumor, and 34 metastatic tumors); (2) formalin-70% alcohol-, or Bouin's-fixed tumor cell lines (D283 Med, U-251 MG, and C-6) maintained in a three-dimensional gelatin foam (Gelfoam matrix) system, with or without treatment with dibutyryl cyclic adenosine monophosphate; and (3) formalin-fixed, paraffin-embedded C-6 glioma cells transplanted intracerebrally to rats.

Results: Calbindin-D28k immunohistochemical staining was detected in 20 of 49 cerebellar medulloblastomas and in cells of the human medulloblastoma cell line D283 Med grown in gelatin Gelfoam matrices, with or without treatment with dibutyryl cyclic adenosine monophosphate.

A cytomorphological scheme of differentiating neuronal phenotypes in cerebellar medulloblastomas based on immunolocalization of class III beta-tubulin isotype (beta III) and proliferating cell nuclear antigen (PCNA)/cyclin.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III) to that of the proliferating cell nuclear antigen (PCNA)/cyclin in 46 cerebellar neuroblastic tumors (medulloblastomas). Both class III beta-tubulin (beta III) and PCNA/cyclin reactivities were present in all tumors, but the topographic distribution and cytomorphologic features of stained cells varied considerably between classic and desmoplastic medulloblastomas. Four neoplastic phenotypes, representing gradations of neuronal differentiation, were identified: [Allegranza 1991] apolar, blast-like PCNA/cyclin(+) cells devoid of beta III reactivity (Nb1); [Bravo et al.

The stromal Schwann cell during maturation of peripheral neuroblastomas. Immunohistochemical observations with antibodies to the neuronal class III beta-tubulin isotype (beta III) and S-100 protein.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III; analogous to the beta' 1-/beta 2-tubulin isoform) to the Schwann cell-associated S-100 protein focusing on topographic relationships of Schwann-like cells to differentiating neuronal phenotypes during stromal development in human peripheral neuroblastomas. The earliest appearance of Schwann cells in poorly differentiated (classical) neuroblastomas is heralded by S-100 protein-immunoreactive cells in close association with tumor blood vessels. In subsequent stages of maturation, i.

Differential localization of class III, beta-tubulin isotype and calbindin-D28k defines distinct neuronal types in the developing human cerebellar cortex.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III) to that of calbindin-D28k in 40 human fetal and postnatal cerebella ranging from 12 weeks gestation to adulthood. In the external granule layer of the developing cerebellar cortex, beta III staining was present in the premigratory (postmitotic) zone of horizontal neurons but was absent in "epithelioid" cells of the subpial proliferative mitotic zone. In the molecular layer, intense beta III staining was associated with parallel fibers, stellate/basket neurons and migrating fusiform granule neurons.

Symmetrical neurofibroma with Schwann cell predominance and focal formation of microneurinomas.

A case of symmetrical neurofibroma with onion bulbs in various stages of development and progression to microneurinomas is presented. Immunohistochemistry with differentiation and growth factor markers as well as electron microscopy showed a Schwann cell origin of the concentrically arranged cells. The onion bulbs differed from those of hypertrophic neuropathy by their more compact structure.

Gliofibroma: immunohistochemical analysis.

A case of gliofibroma occurring in an adult patient as a large circumscribed supratentorial tumor is reported. The bimorphic pattern was substantiated and further analyzed by immunohistochemistry. Some evidence in favor of collagen production by mesenchymal and/or inflammatory cells leading to a progressive fibrous replacement of the glial cells in this particular tumor type is presented.

Vascular permeability changes in tumours of the peripheral nervous system.

Vascular permeability changes were examined in 34 tumours of the peripheral nervous system by immunohistochemical demonstration of serum proteins as endogenous tracers. The blood-tumour barrier was impaired in the reticular (Antoni type B) portions of neurinomas (Schwannomas) and in cutaneous neurofibromas but was similar to the normal blood-nerve barrier in fibrillary (Antoni type A) neurinomas, in most neurofibromas, in ganglioneuromas and in anaplastic tumours. These differences in permeability are discussed in relation to aspects of pathological tumour vascularization, the histogenesis of microcystic changes, and systemic therapeutic approaches.

Basic fibroblast growth factor and somatomedin C in human medulloepithelioma.

Two published cases of medulloepithelioma, a rare malignant pediatric brain tumor composed of a mixture of primitive neuroepithelium and its differentiated neuronal and glial descendants, were examined by immunohistochemical staining for the presence of growth factors. From a panel of antibodies, those identifying basic fibroblast growth factor and insulin-like growth factor I, formerly known as somatomedin C, were strongly immunoreactive within the neuroepithelial cell population of the tumors. Immunoblots of purified recombinant basic fibroblast growth factor and insulin-like growth factor I showed antibody specificity without cross-reactivity.

The brain in the 18q-syndrome.

The authors describe the cerebral neuropathological findings of a 25 1/2-year-old male with 18q-syndrome. An abnormal gyral pattern, atrophy of the olfactory and optic nerves and small neocerebellar hemispheres with hemispheral lobular sclerosis were noted. Microscopically there were pial glioneuronal heterotopias; misplacement of neurons in the molecular layer of the cortex, as well as in deep white matter; not readily identifiable Betz cells; gliosis of olfactory and optic tracts and elsewhere; and loss of Purkinje cells.

Aqueductal atresia as a feature of arhinencephalic syndromes.

Two cases are presented of aqueductal atresia associated with arhinencephalic syndromes. The first case was one of semilobar holoprosencephaly with occipital encephalocele, the second one of lobar holoprosencephaly (callosal agenesis with interhemispheric cyst). Only the second case was associated with obstructive hydrocephalus.

Focal neuronal gigantism and cerebral cortical thickening after therapeutic irradiation of the central nervous system.

An exceptional type of cortical dysplasia is described in the brain of a 32-year-old woman who had received radiation therapy for a large pituitary adenoma 6 years before death. Markedly thickened gyri of the left inferior frontal, insular, and temporal cortex were found grossly. Microscopically, these gyri showed laminar disorganization and many unusually large and abnormally shaped ganglion cells.

Absence of septum pellucidum and polymicrogyria: a forme fruste of the porencephalic syndrome.

Two cases are presented of absence of the septum pellucidum associated with bilateral polymicrogyria. In one case a circumscribed, completely enclosed cavity was present in the white matter of one cerebral hemisphere, different in structure from typical prenatal porencephaly. It is suggested that these cases represent a "forme fruste" of the syndrome of absent septum, bilateral porencephaly, polymicrogyria and heterotopia and may be ascribed to a similar, if less severe, encephaloclastic process of debatable etiology, operating around the midterm of pregnancy.

Aqueductal obstruction in sarcoidosis.

A 50-year-old woman presented with a severe obstructive hydrocephalus, only temporarily relieved by shunts. The diagnosis of sarcoidosis was suspected but never proven. Autopsy revealed multisystem sarcoidosis as well as widespread involvement of the CNS.

Hemimegalencephaly, hemifacial hypertrophy and intracranial lipoma: a variant of neurofibromatosis.

A case is presented of a 30-year-old, mentally retarded and epileptic patient, with a progressive hemifacial hypertrophy since birth. Repeated biopsies revealed the neurofibromatous nature of her facial lesion. Autopsy also revealed an ipsilateral hemimegalencephaly, as well as meningeal lipomas and osteomas.

Epidermal growth factor receptor in meningiomas is expressed predominantly on endothelial cells.

The immunohistochemistry of the epidermal growth factor receptor (EGFR) was studied with monoclonal antibodies in 12 meningiomas of various histologic subtypes, nine benign and three malignant. Strong immunoreactivity of EGFR epitopes was found in the endothelia of the tumor vasculature in six cases. A much weaker reaction was detected within tumor cells in six cases, in one of which it was diffuse and five focal.

Ectopic midline spinal ganglion in diastematomyelia: a study of its connections.

The connections of an ectopic midline spinal ganglion associated with an asymptomatic sacral diastematomyelia were studied. The ganglion was intercalated in the ventral root of one hemicord and sent its efferents to the dorsal root of the other hemicord. The afferents joined the anterior root to form a midline intradural spinal nerve in the cauda equina.

Lhermitte-Duclos disease. An immunohistochemical study of the cerebellar cortex.

Immunocytochemical studies were carried out on two previously reported autopsy cases of Lhermitte-Duclos disease. The unaffected cerebellar cortex adjacent to the lesions served as control. The findings supported the view, previously expressed by one of the authors, of a heterogeneous neuronal structure of the lesion, consisting of at least two cell types.

The brain in partial trisomy 18: a case report.

This is a clinical and neuropathological report of a 27-year-old male with partial trisomy of the long arm of chromosome 18. Severe psychomotor retardation, blindness, and epilepsy were the major clinical features. Microcephaly, an unusual diverticulum of the left occipital lobe, and severe atrophy of the visual system were the major findings on neuropathological examination.

The cytoskeleton of the human cerebellar cortex: an immunohistochemical study of normal and pathological material.

Monoclonal antibodies to non-phosphorylated and phosphorylated neurofilaments, as well as monoclonal and polyclonal antibodies to other cytoskeletal elements, were applied to the study of the cerebellar cortex of normal and pathological human material. The methods proved to be applicable to formalin fixed paraffin embedded tissue, provided the period of formalin fixation was short. The main difference between normal and pathological material was found in Purkinje cells and their dendrites.

Arhinencephaly. The spectrum of associated malformations.

Eight cases are presented of arhinencephaly and its associated malformations, which included 2 examples of holoprosencephaly and 3 of agenesis of the corpus callosum. Additional features included cortical malformations, anomalies of the long tracts and of the optic pathway, cerebellar hypoplasia and dentato-olivary dysplasia. Each of these components covered a wide spectrum ranging in severity from extreme to minimal.