Mixed cystic gliosarcoma and primitive neuroectodermal tumor: a case report.

The clinical and pathologic features of a mixed (composite) gliosarcoma and primitive neuroectodermal tumor occurring in a 54-year-old male are presented. A large cyst and the presence of Rosenthal fibers are also unusual features of this tumor. To our knowledge, such a morphologically variegated tumor has not previously been reported.

Bielschowsky bodies (Lafora bodies of Bielschowsky type): report of a case associated with Rosenthal fibers in the brain stem.

Bielschowsky bodies are an uncommon type of polyglucosan body. Similar to Lafora bodies, they are characteristically identified within neuronal perikarya and neurites. However, they lack the diffuse distribution of Lafora bodies, and instead are typically restricted to the external pallidum, often in association with status marmoratus or atrophy of the putamen. Fewer numbers of Bielschowsky bodies have also been identified in other areas such as the substantia nigra, putamen and inner globus pallidus. We report an additional case with Bielschowsky bodies in an 18-year old female with cerebral palsy. This case demonstrated multifocal Bielschowsky bodies and abundant Rosenthal fibers in the midbrain and pons. To our knowledge the association of Bielschowsky bodies with this peculiar distribution of Rosenthal fibers has not previously been reported.

Idiopathic giant-cell granulomatous hypophysitis. Report of a case with autopsy follow-up.

Idiopathic granulomatous inflammation of the pituitary gland occurs rarely, and is usually identified as an incidental finding at autopsy. However, it may present during life as a mass lesion that clinically mimics other more common pituitary gland lesions. We report a 54-year-old woman presenting with acute onset diabetes insipidus whose MRI showed a 1.1 cm pituitary mass, with infundibular thickening and meningeal enhancement. Biopsy demonstrated granulomatous hypophysitis with multinucleate histiocytes. Special studies for infectious organisms were negative. The patient's disease progressed following biopsy, causing complete loss of vision in the right eye. This responded to high-dose steroids and local lowdose radiation. She later developed an acute inferior myocardial infarction. Laboratory tests failed to demonstrate an underlying autoimmune process. While recovering from this myocardial infarction, she succumbed to pulmonary embolism. Autopsy revealed moderate residual chronic infundibular inflammation. No evidence of systemic or residual pituitary granulomatous disease was identified. To the best of our knowledge, this is the first case of idiopathic granulomatous hypophysitis initially diagnosed by biopsy to have post-mortem neuropathologic examination.

Spinal cord glioneuronal tumor with "rosetted" neuropil islands and meningeal dissemination: a case report.

Distinctive glioneuronal tumors arising within the cerebrum and displaying neuropil-like islands and tumor cells immunoreactive for neuronal and glial antigens have recently been described. We report a similar tumor in the cervico-thoracic region of the spinal cord in a 44-year-old woman that recurred 1 year later with dissemination to the lumbar dura and cauda equina. The tumor was composed of "rosetted" neuropil islands displaying immunoreactivity for synaptophysin, whereas the intervening tumor cells were more fibrillar and immunoreactive for GFAP. The tumor cell nuclei immediately surrounding these neuropil islands were immunoreactive to the newly characterized neuronal marker, anti-Hu. While several cases of neurocytomas have been described in the spinal cord, to the best of our knowledge, this is the first example of a glioneuronal tumor with "rosetted" neuropil islands to be reported in the spinal cord.

Melanotic craniopharyngioma: a report of two cases.

We report a 74-year-old woman and a 50-year-old woman with similar histories of headache and visual disturbance who were found to have adamantinomatous craniopharyngiomas which contained melanin pigment. This finding was confirmed by the Masson Fontana method and ultrastructural studies. These are only the second and third cases reported describing melanin pigment within a craniopharyngioma. The finding of melanin in craniopharyngiomas attests to their similarities with odontogenic tumors of the jaw, which can also contain melanin pigment and also supports the hypothesis that the histogenesis of these neoplasms derives from the vestiges of Rathke's pouch epithelium.

Alzheimer's disease pathology in motor cortex in dementia with Lewy bodies clinically mimicking corticobasal degeneration.

We report here a 70-year-old woman whose initial clinical presentation suggested corticobasal degeneration, but autopsy revealed dementia with Lewy bodies (DLB) with severe Alzheimer's disease (AD)-type pathology accentuated in the motor cortex, in conjunction with a high burden of both cortical and brain stem LB. Review of the literature disclosed four patients with AD whose peri-Rolandic region was particularly involved by the disease and who exhibited similar clinical and neuropathological findings as in our patient except they lacked LB. It appears that DLB if associated with severe AD-type pathology can, like some unusual cases of AD, mimic corticobasal degeneration.

Familial arteriopathic leukoencephalopathy: imaging and neuropathologic findings.

We present the clinical, imaging, and neuropathologic data for a family with an autosomal dominant, nonhypertensive, progressive cerebral arteriopathy and leukoencephalopathy. Clinical presentation was characterized by progressive dementia, gait abnormalities, and, in some, Parkinson-like symptoms. MR abnormalities, consisting of white matter T2 hyperintensities and cystic-appearing T1 hypointensities, were present in seven family members. The basal ganglia also showed cystic abnormalities. Neuropathologic examination in two cases revealed numerous lacunar infarctlike lesions, extensive demyelination, and widespread hyalinization of arteriolar walls with karyolysis and granular deposits within the media. These findings appear to constitute further evidence of a genetically determined arteriopathic leukoencephalopathy.

Central neurocytoma: one associated with a fourth ventricular PNET/medulloblastoma and the second mixed with adipose tissue.

We report two cases of central neurocytoma; one located in the right lateral ventricle and associated with a distinctly separate primitive neuroectodermal tumor (PNET)/medulloblastoma of the fourth ventricle, and the other admixed with fat cells and arising from the left lateral and third ventricles with extension into the corpus callosum. We discuss that concurrent occurrences of PNET and adipose tissue are not fortuitous events, but an evidence that neurocytomas and PNETs originate in the residual germinal pool from common progenitor cell rests recapitulating features of developing neurons and with a potential for mesenchymal differentiation.

Isolated meningeal vasculopathy associated with Clostridium septicum infection.

A 28-year-old patient with acute lymphoblastic leukemia and neutropenia developed necrotizing enterocolitis and Clostridium septicum bacteremia, followed by rhabdomyolysis, skin rash, and acute neurologic changes. Numerous cortical leptomeningeal enhancements were present on head MRI. Meningeal and brain biopsy showed segmental, full-thickness lysis of smooth muscle cells of medium-sized meningeal vessels with overall preservation of the structure of the vessel wall.

Pena-Shokeir phenotype associated with bilateral opercular polymicrogyria.

Autopsy examination of an infant with the Pena-Shokeir phenotype revealed bilateral opercular polymicrogyria associated with neuronal loss and ferrugination in the basal ganglia, thalamus, brainstem, and spinal anterior horns. Bilateral opercular polymicrogyria previously has been linked to the developmental form of Foix-Chavany-Marie syndrome, or faciopharyngoglossomasticatory diplegia. In the Pena-Shokeir phenotype, bilateral opercular polymicrogyria may contribute to deficits in swallowing and facial movements. The pattern of brain and spinal cord injury in this case supports previous suggestions that the Pena-Shokeir phenotype (and certain other forms of arthrogryposis multiplex congenita) may be caused by hypoxic-ischemic injury to the developing central nervous system.

Massive leptomeningeal amyloidosis associated with a Val30Met transthyretin gene.

We report a 69-year-old woman of Mexican origin with a 6-year history of progressive paresis, mild peripheral neuropathy, and recent onset of fluctuating mental status. Head and spinal MRI revealed contrast enhancing thickened meninges which on biopsy disclosed amyloid deposition. Immunohistochemistry identified the amyloid as transthyretin (TTR), and polymerase chain reaction/restriction fragment length polymorphism analysis of blood revealed a Val30Met mutation in one of her TTR genes. This mutation causes familial (hereditary) amyloidotic polyneuropathy of the Portuguese type (FAP 1). However, unlike FAP 1, in which peripheral neuropathy is a dominant feature, our patient's clinical manifestations, which included communicating hydrocephalus and myelopathy, were more suggestive of familial oculoleptomeningeal amyloidosis (FOLMA). In summary, the clinical presentation of TTR Met 30 mutation is more varied than previously suspected, and leptomeningeal amyloidosis should be considered in the differential diagnosis of obscure conditions involving meninges.

What can artificial neural networks teach us about neurodegenerative disorders with extrapyramidal features?

Artificial neural networks (ANNs), computer paradigms that can learn, excel in pattern recognition tasks such as disease diagnosis. Artificial neural networks operate in two different learning modes: supervised, in which a known diagnostic outcome is presented to the ANN, and unsupervised, in which the diagnostic outcome is not presented. A supervised learning ANN could emulate human expert diagnostic performance and identify relevant predictive markers in the diagnostic task, while an unsupervised learning ANN could suggest reasonable alternative diagnostic classification criteria. In the present study, we used ANN methodology to try to overcome the neuropathological difficulties in differentiating the subtypes of progressive supranuclear palsy (PSP), and in differentiating PSP from postencephalitic parkinsonism (PEP) and corticobasal degeneration, or Pick's disease from corticobasal degeneration. First, we applied supervised learning ANN to classify 62 cases of these disorders and to identify diagnostic markers that distinguish them. In a second experiment, we used unsupervised learning ANN to investigate possible alternative nosological classifications. Artificial neural networks input data for each case consisted of values representing histological features, including neurofibrillary tangles, neuronal loss and gliosis found in multiple brain sampling areas. The supervised learning ANN achieved excellent accuracy in classifying PSP but had difficulty classifying the other disorders. This method identified a few features that might help to differentiate PEP, supported currently proposed criteria for Pick's disease, corticobasal degeneration and typical PSP, but detected no features to characterize the atypical subtype of PSP. In general, unsupervised learning ANN supported the present nosological classification for PSP, PEP, Pick's disease and corticobasal degeneration, although it overlapped some groups. Artificial neural networks methodology appears promising for studying neurodegenerative disorders.

Corpora amylacea: a marker for mesial temporal sclerosis.

Mesial temporal sclerosis (MTS) is the most frequently encountered abnormality in temporal lobectomies performed for medically intractable seizure disorders. The pathologic diagnosis of MTS relies on the identification of neuronal loss affecting various regions of the hippocampus. However, neuronal loss is often difficult to assess, particularly in lobectomies that are not performed en bloc. Because of this difficulty the presence of hippocampal pathology is often indeterminate. In this report we describe our experience with 73 temporal lobectomies performed for seizure disorders. In 58%, increased numbers of corpora amylacea (CoA) were found in association with MTS. The relationship between CoA and the pathogenetic mechanisms underlying MTS remains speculative. However, the association between MTS and corpora amylacea is important to recognize since the identification of abundant numbers of CoA provides a marker for MTS that can be useful in cases in which neuronal loss and gliosis are difficult to assess. For this purpose, it is strongly recommended that tissues resected from the hippocampus and amygdala for temporal lobe epilepsy be stained with LFB-PAS to highlight CoA.

Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders.

We investigated the validity and reliability of diagnoses made by eight neuropathologists who used the preliminary NINDS neuropathologic diagnostic criteria for progressive supranuclear palsy (PSP) and related disorders. The specific disorders were typical, atypical, and combined PSP, postencephalitic parkinsonism, corticobasal ganglionic degeneration, and Pick's disease. These disorders were chosen because of the difficulties in their neuropathologic differentiation. We assessed validity by measuring sensitivity and positive predictive value. Reliability was evaluated by measuring pairwise and group agreement. From a total of 62 histologic cases, each neuropathologist independently classified 16 to 19 cases for the pairwise analysis and 5 to 6 cases for the group analysis. The neuropathologists were unaware of the study design, unfamiliar with the assigned cases, and initially had no clinical information about the cases. Our results showed that with routine sampling and staining methods, neuropathologic examination alone was not fully adequate for differentiating the disorders. The main difficulties were discriminating the subtypes of PSP and separating postencephalitic parkinsonism from PSP. Corticobasal ganglionic degeneration and Pick's disease were less difficult to distinguish from PSP. The addition of minimal clinical information contributed to the accuracy of the diagnosis. On the basis of results obtained, we propose clinicopathologic diagnostic criteria to improve on the NINDS criteria.

Intracerebral involvement in scleroderma en coup de sabre: report of a case with neuropathologic findings.

Linear scleroderma en coup de sabre (LScs) is a rare disorder not infrequently associated with neurologic symptoms, notably epilepsy. However, histopathologic documentation of intracerebral lesions in LScs is very limited and the etiology of the central nervous system symptoms has therefore never been convincingly established. We describe a 27-year-old woman with LScs and a longstanding history of epilepsy. Radiographic studies demonstrated a focal, intraparenchymal lesion in the left frontal lobe directly subjacent to the area of scleroderma on the forehead and scalp. The resected cerebral lesion revealed localized band-like sclerosis of the leptomeninges and associated vessels, as well as intraparenchymal calcifications and anomalous, ectatic vessels. These findings suggest that LScs may represent a neurocutaneous syndrome of vascular dysplasia similar to the Sturge-Weber syndrome, rather than a localized form of collagen vascular disease, as suggested by some.

Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy).

We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brain-stem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP.

Epstein-Barr virus-associated natural killer-large granular lymphocyte leukemia.

We describe the first case of an Epstein-Barr virus (EBV)-associated natural killer-large granular lymphocyte (NK-LGL) leukemia in the United States to the best of our knowledge. A 29-year-old woman of Japanese descent developed EBV infection after a blood transfusion as indicated by a rise in serum antibody titers. Peripheral blood and bone marrow aspirate smears demonstrated increased LGLs. Flow cytometry showed that these cells expressed NK-associated surface antigens. Cytogenetic analysis of the bone marrow aspirate showed two distinct but related clones with multiple copies of a modified 7 marker chromosome. Death followed colonic perforation. Findings at necropsy included bone marrow lymphocytosis and erythrophagocytosis, a mononucleosis-like lymphadenitis, atypical hepatitis with a mixed, predominantly T-cell infiltrate, interstitial pneumonitis, and multiorgan system vasculitis with perforation of the transverse colon. Epstein-Barr virus transcripts were identified in lymphocytes infiltrating liver and peripheral nerve by in situ hybridization. In addition, Southern blot analyses showed monoclonal bands superimposed on oligoclonal ladders of EBV termini in liver and lymph node. The identical episomal form of EBV was found in the bone marrow, lymph node, and liver. No immunoglobulin (Ig), T-cell receptor beta, or T-cell receptor gamma chain gene rearrangements were identified. These studies support the hypothesis that the LGL population was a neoplastic EBV-related clonal proliferation of NK cells.

Concomitant branching enzyme and phosphorylase deficiencies. An unusual glycogenosis with extensive neuronal polyglucosan storage.

A baby girl was born hypotonic and was respirator-dependent until death at 43 days of age. A muscle biopsy revealed PAS-positive, diastase-resistant sarcoplasmic inclusions with a vaguely fibrillar structure by electron microscopy. Biochemical studies at autopsy disclosed complete absence of branching enzyme in skeletal muscle and heart, and a deficiency of phosphorylase activity in skeletal muscle with a modest reduction in myocardium. Storage material was present in glia and perikarya of neurons, increasing in amount in the rostrocaudal direction, involving most severely the motor neurons in the brain stem and spinal cord, dorsal root ganglia and myenteric plexi. Inclusions were also present in most organs, especially liver and skeletal muscle. Ultrastructurally, the inclusions ranged from granular aggregates of membrane-bound material concentrated in the region of Golgi apparatus to large filamentous bodies similar to polyglucosan bodies. This baby differs from other patients with infantile glycogenosis IV by the severity and onset of symptoms at birth, involvement of neuronal perikarya and widespread extraneural deposits. The combined deficiencies of branching enzyme and phosphorylase may have accounted for the unique clinical and neuropathological findings.