Neurotoxic fragrance produces ceroid and myelin disease.

Acetyl ethyl tetramethyl tetralin (AETT), a component of soaps, deodorants, and cosmetics, produces hyperirritability and limb weakness in rats repeatedly exposed to the compound. Brain, spinal cord, and peripheral nerves are discolored blue, show progressive neuronal ceroid degeneration, and develop spectacular myelin bubbling. These neurotoxic properties of AETT provide the basis for industry's decision to withdraw the compound from consumer products. In addition, AETT offers the experimentalist a new probe to explore the etiology and pathogeneses of human ceroid and myelin diseases.

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.

Nickel-induced changes and reappraisal of Rosenthal fibers in focal CNS lesions.

Nickel (Ni) wire implants into the CNS of Lewis rats induce the formation of structures morphologically similar to Rosenthal fibers (RF) seen in human conditions. We describe in detail the time courses of Ni-induced changes in rat astrocytes and compare the Ni-induced RF with RF occurring in focal lesions. Immunocytochemistry at the level of electron microscopy suggests that the Ni-induced RF are largely made up of plasma proteins. We suggest that the mechanism of RF formation and possibly the protein composition of RF depends on the condition in which they are found.

Cerebral granular cell tumor: immunohistochemical and electron microscopic study.

A rare intracerebral granular cell tumor (GCT) was studied by immunocytochemical and ultrastructural methods. The tumor was composed of two cell types--filament-rich and granular cells. Granular cells contained PAS-positive, diastase-resistant granules that ultrastructurally corresponded to autophagic cytosegresomes. Glial fibrillary acidic protein, the intermediate filament protein specific for astrocytes, was demonstrated in the filament-rich and, to a lesser extent, in the granular cells. Unlike noncerebral GCT, neither S-100 protein nor vimentin was detected in the tumor cells. On the other hand, both cerebral and noncerebral GCT were labeled immunocytochemically with peanut lectin (Arachis hypogaea). The results suggest that cerebral GCT share some features with noncerebral GCT, but differ in other respects. They further suggest that GCT may be derived from different cell types depending on the tissue of origin, and that cerebral GCT may be derived from astrocytes.

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.

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.

Selective vacuolar myopathy with atrophy of type II fibers. Occurrence in a childhood case of acid maltase deficiency.

A 12-year-old boy being examined for vague chest pains was found to be suffering from acid maltase deficiency. Unlike previously reported cases in which vacuolization was most commonly noted in type I fibers, type II fibers were selectively involved in this patient and were atrophic Type I fibers were spared, or occasionally contained one or more small globular structures consisting of large, complex aggregates of lysosomal profiles.

Peripheral neuropathy in cerebrotendinous xanthomatosis.

We performed a sural nerve biopsy in a patient with cerebrotendinous xanthomatosis (CTX) because of electrophysiologic evidence of peripheral neuropathy. The sections showed a striking loss of myelinated axons, the distribution of which suggested a compressive and/or ischemic process. Biochemical analysis disclosed large amounts of cholestanol, a cholesterol derivative that characteristically accumulates in CTX. However, the biochemical abnormality was not associated with any obvious structural alterations in the myelin lamellae or with abnormal storage material in Schwann's cells.

Atypical psychosis with disseminated subpial demyelination.

A 34-year-old woman experienced three episodes of an atypical psychosis, characterized by confusion, agitation, delusional thinking, paranoid ideation, and auditory hallucinations, during the 14 months prior to her death. Findings of gross examination of the brain and spinal cord were unremarkable. Histologic examination revealed scattered subpial foci of demyelination throughout the brain stem, with involvement of the hippocampal formation bilaterally. Although occasional active lesions at early stages of development were noted, most lesions were gliotic and therefore quiescent. This case and one similar example of disseminated subpial demyelination found in the literature probably represent an unusual variant of multiple sclerosis.

Hereditary sensory neuropathy with deafness: a familial multisystem atrophy.

We report a 39-year-old woman with hereditary sensory neuropathy-type I (HSN-I) and deafness--Hicks' disease. The cochlea showed cell loss in the organ of Corti, and spiral ganglia and atrophy of acoustic nerves. Morphometric and quantitative studies of the ventral cochlear nucleus disclosed mild changes resulting from transynaptic atrophy. There was, however, neuronal as well as severe dendritic loss and gliosis in the auditory and sensory cortex that could not have been caused by their functional deprivation or have resulted from a chain reaction of transynaptic atrophy, since their corresponding lower relay nuclei did not display significant atrophy. The finding of cell loss and gliosis in the thalamus in nuclei that do not subserve these two pathways as well as in the red nuclei, inferiro olivary nuclei, and claustrum suggested that HSN-I with deafness is nosologically related to familial multisystem atrophy.

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.

Reduced somatostatin-like immunoreactivity in cerebral cortex in nonfamilial dysphasic dementia.

A nonfamilial syndrome is described in two middle-aged men who presented with progressive aphasia without incipient signs of cognitive impairment. In each case, 2 years elapsed before progressive functional decline or behavioral disabilities supervened. Radiologic studies documented asymmetric left cerebral atrophy that was progressive. The structure of the language disintegration was distinctive and not like that in Alzheimer's disease. Pathologic studies performed at postmortem examination of one patient documented asymmetric cerebral atrophy with nonspecific histopathologic changes. Biochemical studies revealed normal tissue levels of choline acetyltransferase activity, but reduced somatostatin-like immunoreactivity. Since cerebral somatostatin is largely present in intrinsic cortical neurons, while cholinergic innervation is largely derived from the basal forebrain, these findings suggest that nonfamilial dysphasic dementia may be an example of a distinct class of dementia due to intrinsic cortical degeneration, with sparing of the basal forebrain.

Behr syndrome: a clinicopathologic report.

Two sisters had Behr syndrome; autopsy was performed on one. The autopsy revealed central atrophy of the optic nerves and total disarray of the normal laminar pattern of the lateral geniculate nucleus, dropout of neurons, and gliosis. There were numerous axonal spheroids in the neuropil. Similar spheroids with cell loss and gliosis were also observed in other thalamic nuclei and, rarely, in the pallida. We raise the possibility that Behr syndrome is a manifestation of a heterogeneous group of disorders, and suggest relationship of this particular disease to infantile neuroaxonal dystrophy.

Primary medullary hypertensive hemorrhage.

A 33-year-old man with untreated hypertension had sudden onset of signs and symptoms suggestive of a dorsal lateral medullary syndrome. He died after 27 days. Postmortem studies revealed intramedullary hemorrhage with extension into the fourth ventricle and hypertensive cardiovascular disease.

Klüver-Bucy syndrome and amyotrophic lateral sclerosis: a case report with biochemistry, morphometrics, and Golgi study.

We studied a patient with amyotrophic lateral sclerosis and the Klüver-Bucy syndrome. At autopsy there was extensive degeneration of the limbic system with the brunt of the changes in the medial temporal lobe, especially the entorhinal cortex and subiculum. Degenerative changes were also seen in the substantia nigra and lower motor neurons. Morphometric and biochemical studies implied a disease process that affected small, possibly somatostatinergic, cortical neurons. These latter findings and the lobar distribution of cortical atrophy were consistent with Pick's disease, but Pick bodies and ballooned neurons were not present.

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.

Spinal cord pathology in pediatric acquired immunodeficiency syndrome.

We examined the spinal cords from 15 consecutive autopsies of infants and children with AIDS using a battery of histochemical and immunocytochemical stains, and in four cases, electron microscopy. Corticospinal tract (CST) signs were a notable clinical finding in 14; however, the age of onset, rate of progression, severity of dysfunction, and duration varied among patients. Ten cases had pathologic changes in the CST. In four of the ten cases, the changes were consistent with an "axonopathy" since axons and myelin were both diminished in the CST. These cases may represent CST wallerian degeneration, since they had marked injury to cerebral white matter in the form of chronic inflammation with multinucleated cells, gliosis, and myelin pallor. In five cases, with an average age at death of 31 months, the CST showed poor myelination with relative preservation of axons. These cases may represent delayed myelination or possibly cytokine-mediated injury to newly formed myelin since the CST is one of the last tracts to myelinate in the spinal cord. One child with primary CNS lymphoma had a complicated pattern of spinal injury due to unilateral CST wallerian degeneration possibly superimposed upon delayed myelination, in addition to patchy areas of demyelination associated with perivascular lymphomatous infiltrates. Four children with mild CST signs, ranging in age from 5 to 6 months, had CST myelin pallor that was consistent with the degree of myelination expected for age. We did not find vacuolar myelopathy similar to that seen in adult AIDS, but did note focal vacuolar changes in the thoracic posterior columns in the oldest child.

Progressive dementia, visual deficits, amyotrophy, and microinfarcts.

Data from three patients and 22 previously reported cases suggest that cerebral microinfarction causes a recognizable clinical syndrome. All cases present with stroke, followed by progressive dementia and often with visual field deficits, peripheral vascular disease, and signs of motor neuron dysfunction. The average age at onset is 45, and most patients have been men. Many patients have had valvular or ischemic heart disease; in one of our cases, mitral stenosis caused embolic microinfarcts.

Familial multisystem atrophy with possible thalamic dementia.

We studied a family with progressive dementia, optic atrophy, and spastic paraparesis. Autopsy of one family member revealed multisystem atrophy with widespread degeneration of the thalamus and marked attenuation of hemispheric white matter to account for the dementia. This family may suffer from a unique disorder, but the findings overlap with other reported cases of thalamic dementia or familial spastic paraparesis.

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.