Histologic Examination of Peripheral Nerves

Michal Miko , Ivan Varga , in Nerves and Nerve Injuries, 2015

Holmes Silver Impregnation Method

The Holmes silver impregnation method serves for the demonstration of neurofibrils in tissue section. This is essentially a modified Bodian stain and is particularly useful when combined with Luxol fast blue stain. The results of the Bodian method are somewhat inconsistent because protargol solution never reaches the alkalinity necessary for optimal impregnation, so an advanced technique by developing a buffered impregnating solution has been developed. This is an argyrophil silver method, requiring chemical reduction to be used. Note that salts of chrome and osmium cannot be used. As a result, neurofibrils are stained brown or black; of course, myelin sheaths of myelinated peripheral nerve are not visible ( Figure 6.8).

Figure 6.8. Micrograph of a part of a nerve fascicle from a peripheral nerve shows parallel-oriented nerve fibers—an impregnation method for visualization of neurofibers inside the axoplasm. The myelin sheaths around fibers are not visible (orig. magn. 1000   ×).

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Neuropathology of Multiple Sclerosis

Bogdan F. Gh. Popescu , Claudia F. Lucchinetti , in Multiple Sclerosis, 2016

Introduction

Multiple sclerosis (MS) is an inflammatory demyelinating disease of unknown cause. Two cardinal features dominate the neuropathology of MS: demyelination and inflammation (Sobel & Moore, 2008 ). Demyelination translates into the loss of the myelin sheath that surrounds the axons in the central nervous system (CNS). On tissue slides, demyelination is identified as plaques or lesions: regions of CNS which lose the blue color that the Luxol fast blue stain normally confers to myelin and lose their immunoreactivity for myelin proteins ( Kuhlmann, Lassmann, & Bruck, 2008). Activated microglia and macrophages, and lymphocytes, mainly T cells, form the bulk of the inflammatory infiltrates. Fewer B cells, plasma cells, and polymorphonuclear leukocytes can also be present in MS lesions. Demyelination and inflammation are associated with reactive astrocytosis, axonal damage, and relative axonal preservation (Kuhlmann et al., 2008; Popescu & Lucchinetti, 2012b; Sobel & Moore, 2008). MS lesions are disseminated throughout the CNS but have a predilection for optic nerves, subpial spinal cord, brain stem, cerebellum, periventricular white matter, and cortical gray matter (Sobel & Moore, 2008). Plaques evolve differently during early versus chronic disease phases, and within each phase, different types and stages of demyelinating activity are evident.

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Peripheral Nerve Sheath Tumors

Bernd W. Scheithauer , ... Robert J. Spinner , in Practical Surgical Neuropathology, 2010

Pathogenesis

Reinnervation of the distal stump of a transected nerve requires an influx of Schwann cells and axons after the distal segment has been vacated of its cellular debris (axons and myelin sheaths)—a process termed wallerian degeneration. It is seen in as little as 24 hours after transection. The color of the myelin degradation product varies from blue in an early phase on Luxol fast blue (LFB) stain to red on periodic acid–Schiff (PAS) stain with progression. At approximately 1 month, macrophages will have removed most axonal and myelin debris. Cords and tubes of basement membrane-enshrouded Schwann cells termed "bands of Bungner" await the ingrowth of new axons.

Between 1 and 3 months after nerve injury, the stumps of proximal axons become expanded and organelle-rich. Neurites emerge from the expansion under the influence of nerve growth factor, elaborated by Schwann cells and trophic factors of macrophage origin. Growing 1 to 2   mm a day, the new axons cross the gap, reach the distal nerve segment, and colonize the band of Bungner. If the process is misdirected, connections cannot be firmly established, and the new axons atrophy.

Traumatic neuromas are essentially aborted attempts at regeneration in instances in which the distal stump is too far removed to establish continuity or when it is interfered with by tissue destruction and inflammatory reaction.

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Nanomedicine and Neuroprotection in Brain Diseases

Hari Shanker Sharma , ... Aruna Sharma , in Progress in Brain Research, 2021

3.5.3.1.2 Immunohistochemistry

Random serial sections fixed with either Somogyi or paraformaldehyde fixatives were used for immunohistochemistry for Albumin, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and amyloid beta peptide (AβP) using commercial protocol as described earlier (Sharma et al., 1992a,b, 1993, 2015a,b, 2016a,b, 2018, 2019a,b,c, 2020a,b,c). For myelin examination Luxol Fast Blue (LFB) stain was also used and compared with the MBP immunostaining (Sharma et al., 2011a,b).

In brief, recombinant rabbit anti-bovine monoclonal albumin antibody (1500, Abcam, EPR12774, Cambridge, UK); recombinant rabbit monoclonal anti-GFAP-antibody GFAP (1500, ab68428, EPR1034Y, Cambridge, MA, USA); recombinant rabbit monoclonal anti-myelin basic protein antibody (1200, ab 133620, EPR 6652, Cambridge, UK); recombinant rabbit monoclonal anti-beta amyloid antibody (16000 ab 205340, mOC23, Cambridge, MA, USA) was employed on paraffin sections to visualize immunoreaction product using Avidin-Biotin-complex (ABC technique, Burlingame, CA, USA) according to commercial protocol (Sharma et al., 1993, 2016a,b, 2018, 2019a,b,c, 2020a,b,c). Myelin was also visualized using LFB staining as described earlier (Sharma et al., 1992a,b, Sharma et al., 2011a,b). No significant differences between immunostaining of albumin, AβP, GFAP or MBP were detected in tissue sections either produced after Somogyi or paraformaldehyde fixatives (Sharma HS, unpublished observation).

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Pathology of Noninfectious Diseases of the Laboratory Primate

Lewis Anne D. , Colgin Lois M.A. , in The Laboratory Primate, 2005

Miscellaneous

Storage diseases

Lysosomal storage diseases affecting only nervous tissue are rare in nonhuman primates. Globoid cell leukodystrophy caused by deficient galactocerebrosidase activity has been documented in a family of rhesus macaques (Baskin et al., 1998 ). The three affected infants presented with tremors, hypertonia, incoordination, poor weight gain and died within the first four months of life. Grossly, one had enlarged peripheral nerves. Microscopically, there was rarefaction of the white matter of the cerebrum, cerebellum and spinal cord. High numbers of periodic acid-Schiff positive macrophages and multinucleated globoid cells were present. Luxol fast blue stains revealed a marked decrease in myelin.

Cerebral venous thrombosis

Cerebral venous thrombosis has been infrequently reported in rhesus macaques (Cork and Adams, 1993; Sheffield et al., 1981). Clinical signs are variable and may be inapparent. Animals may present with mild to moderate neurological and cognitive deficits. Signs referable to an acute onset cerebral vascular accident may be seen. Abnormal gaits have been reported (Cork and Adams, 1993) and seizures have been observed (Sheffield et al., 1981). Grossly, the white matter of the cerebrum contains multiple hemorrhagic foci (Figure 4.17). Chronic lesions appear as tan to brown foci. Lesions predominate in the white matter but can extend to the gray matter. The cerebellum is only rarely affected and the spinal cord is not affected (Cork and Adams, 1993). Acute and chronic lesions generally coexist and this temporal feature, as well as the lesion distribution, characterizes this entity. Microscopically, cerebral veins are often ectatic, congested and/or contain fibrin thrombi. There is rarefaction of the surrounding white matter that stains poorly for myelin (Cork and Adams, 1993), a gemistocytic astrogliosis, hemorrhage and accumulations of hemosiderin-laden macrophages. In more chronic lesions, veins may contain organized, fibrotic and occlusive thrombi that are often recanalized and occasionally mineralized. The etiology is unknown. Some macaques have a history of clinical disease, which could lead to hemoconcentration or a hypercoagulable state such as diarrhea (Cork and Adams, 1993; Sheffield et al., 1981). Presumably, these conditions alter cerebral hemodynamics resulting in thrombosis. Others lack any predisposing history. Risk factors in humans include regional infections, oral contraceptives, pregnancy, genetic prothrombotic conditions, mechanical factors (trauma, neurosurgery, lumbar puncture), some chemotherapeutic regimens and systemic disease (vasculitis, neoplasia, hematologic disorders, congestive heart failure, nephrotic syndrome) (Carvalho et al., 2001; Stam, 2003).

Figure 4.17. Brain, transverse section, cerebral venous thrombosis, rhesus macaque. Multifocal venous thrombosis and hemorrhage are concentrated in the white matter bordering the gray matter.

Cerebral hemorrhage

Cerebral hemorrhage and malacia were reported in two cynomolgus macaques with hypernatremia resulting from accidental water deprivation (Harber et al., 1996). Microscopic findings included areas of necrosis and hemorrhage with an acute inflammatory infiltrate and venous thrombi, both fibrinous and organizing. Unlike cerebral venous thrombosis, the gray matter rather than the white matter was primarily involved. These lesions are similar to those described in humans with hypernatremia (cited in Harber et al., 1996). The vascular changes are postulated to occur because of the close vascular attachments of the brain to the cranium. Hypernatremia causes cellular dehydration with overall shrinkage of the brain and consequent tearing of vessels resulting in hemorrhage and thrombosis.

Neoplasia

Nervous system neoplasms are rare and some that appear in the literature include astrocytomas in rhesus macaques, a cynomolgus macaque and baboon (Herring et al., 1990; Lowenstine, 1986; McClure, 1975; Yanai et al., 1992), neurohypophyseal astrocytoma in a rhesus macaque (HogenEsch et al., 1992), meningioma in a baboon (Lowenstine, 1986), olfactory nerve esthesioblastoma in a cynomolgus macaque (Beniashvili, 1989), medulloblastoma in a baboon (Berthe et al., 1980), choroid plexus lipoma in a baboon (Fiori et al., 1994), and an oligodendroglioma in an owl monkey (cited in Weller, 1994).

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Brain Banking

Maree J. Webster , Sanghyeon Kim , in Handbook of Clinical Neurology, 2018

The samples

All brains in the SMRI collection were obtained by pathologists in designated medical examiner offices. All participating pathologists were trained in standardized collection techniques. Written permission to remove the brain for research purposes and to request all medical and psychiatric records was obtained from the next of kin (Torrey et al., 2000 ). For the SNC one hemisphere of each brain was fixed in 10% buffered formalin and the areas in most demand were dissected out and embedded in paraffin. The other hemisphere was cut into 1-cm-thick coronal slabs and frozen in a mixture of isopentane and dry ice. Right and left hemispheres were randomly alternated for fixing and freezing. In order to provide as many samples as possible from each collection and to satisfy as many researchers and techniques as possible, fixed and frozen sections from the brain areas in most demand were placed on to glass slides. For each brain area, one to two sections every half-millimeter were stained with Nissl and/or Luxol fast blue stain and an atlas constructed.

Thus, when distributing sections from all 60 brains it was possible to match the exact anatomic level across all 60 cases. This is particularly important when distributing sections of anatomically heterogeneous regions such as the amygdala and thalamus. In addition, RNA, DNA, and protein were extracted from various cortical areas and distributed in microgram amounts. Methods were also developed to extract RNA and protein directly from anatomically defined areas and specific nuclei from the frozen slides. RNA levels were measured by quantitative polymerase chain reaction, in situ hybridization, microarray techniques, and, more recently, RNA-sequencing. Protein levels were measured by Western blot and enzyme-linked immunosorbent assays. Cytoarchitectural studies measured cell size, number, and density using histologic stains and immunohistochemistry. Receptor-binding studies were also conducted.

For the AC, which contains a large number of cases, fewer sections were cut and more aliquots of RNA, DNA, and protein have been provided. Many high-throughput genomic (RNA, miRNA, DNA, epigenetic) and proteomic studies have been conducted on the AC.

The majority of studies conducted to date with the SNC were done on the frontal cortex. Figure 13.1A shows that, of the 3258 individual data sets from the SNC that are currently in the SNC Integrative Database (SNCID), 995 were conducted on the frontal cortex (including Brodmann area (BA) 8, 9, 10, and 46 and orbital frontal cortex). The next two most commonly assayed areas from the SNC are the thalamus and hippocampus, with 627 and 385 data sets respectively. For the AC (Fig. 13.1B) the vast majority of studies have been conducted on the hippocampus, with 1246 data sets, followed by the frontal cortex, with 770. The frontal cortex and hippocampus have been the areas in most demand as they have long been considered the anatomic areas most likely involved in the pathophysiology of mental disorders. Studies using neuropsychologic tests and functional brain-imaging technologies have shown that brain activity differences occur most commonly in the frontal lobes and hippocampus in these disorders (Schobel et al., 2009; Barch and Ceaser, 2012; Kraguljac et al., 2013). Cognitive processes that are mediated by the frontal cortex, such as memory, attention, and higher-order processing, are functions that are aberrant in these illnesses. Similarly, the hippocampus is involved in memory and responsivity to stress and emotions that are also aberrant in these illnesses (Green, 2006; Kuipers et al., 2006).

Fig. 13.1

Fig. 13.1. The total number of neuropathology markers from each brain area currently deposited in the Stanley Neuropathology Consortium Integrative Database from the Stanley Neuropathology Consortium (SNC) (A) and the Array Collection (AC) (B) and the percentage of markers that were significantly different in at least one diagnostic group as compared to controls in each brain area for the SNC (C) and AC (D).

Almost all areas of the brain have been sampled at least once in the SNC; however, some potentially relevant areas, e.g., the insular cortex, have very few data sets. The "other" brain category listed not only includes data from other brain areas such as the midbrain, pituitary, and corpus callosum, but also from serum, cerebrospinal fluid (CSF), liver, and spleen that were collected on all cases.

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Acquisition Methods, Methods and Modeling

R. Turner , in Brain Mapping, 2015

Introduction

In human brain, the combination of lipids and proteins known collectively as myelin comprises about half of the dry weight of white matter (Siegel, Agranoff, & Gavulic, 1999). The myelin content of gray matter, which is always lower than in white matter, varies strikingly between cortical areas, reaching a maximum in the primary motor cortex and a minimum in several prefrontal regions.

Broadly speaking, the dry-weight composition of myelin is about 30% protein (including myelin basic protein), about 20% cholesterol, about 20% galactolipids containing sulfur in their head groups, and about 30% phospholipids. The nonmyelin components of white matter are similar, but the proportion of galactolipids is strikingly lower than that of myelin. Gray matter contains comparatively more protein and less lipid and has a higher water content (80%) compared with white matter (70%).

Historically, most of the anatomical research on myelin has been carried out using histological techniques: brain tissue is fixed using formalin or other fixatives such as Bodian No. 2, then sliced with a macrotome into sections about 40   μm thick, and then finally stained to reveal the presence of myelin. Popular stains for myelin include the Gallyas silver stain, Luxol fast blue, and Weigert's method. In addition, immunohistochemical stains can be used, such as MBP IHC antibody, which selectively stains myelin basic protein.

It should be noted that some fixatives, such as those containing ethanol or acetic acid, are incompatible with MRI scanning, because their proton spectra have two closely spaced peaks, giving a blurred double image. Furthermore, the quality of myelin staining depends on the appropriate combination of fixative and stain – some stains give very disappointing results when the wrong fixative has been used. Formalin fixation enables reasonably good-quality MR imaging of cadaver brain, although the relaxation times are considerably reduced due to the molecular cross-linking that accompanies fixation. After the tissue has been sectioned, staining for myelin basic protein then provides satisfactory micrographs.

What appears on such micrographs (see, e.g., Figure 1 showing a Gallyas-stained section of human brain) is a dense stain in white matter and lighter staining in gray matter. The pattern of staining in gray matter is strikingly well organized. Everywhere in the cortex reveals fibers radial to the cortical surface and, in addition, two tangential bands, known as the bands of Baillarger, after their discoverer in 1840. Patches of the cortex up to 20   mm across often have a consistent pattern of myelin staining, with boundaries where an abrupt change into another pattern marks a different cortical area. The cortical myelin staining pattern has been described as myeloarchitectonics since Oscar Vogt so named it in 1903, and the history of myeloarchitecture has been excellently reviewed by Nieuwenhuys (Geyer & Turner, 2013). Spatial differences in myeloarchitecture enable a detailed classification of the cortex into areas that are likely to have common functional properties (see Geyer & Turner, 2013).

Figure 1. Micrograph of human brain tissue stained for myelin using the Gallyas silver stain technique.

It is a remarkable characteristic of magnetic resonance imaging of the brain, first pointed out by Young et al. (1981), that excellent contrast between gray matter and white matter image intensities can be observed in images that are sensitive to differences in the longitudinal relaxation time T 1 ( Figure 2 ). But it has taken many years to better understand the biophysical origins of the T 1 differences between white matter and gray matter. This would be surprising if it were not for the fact that myeloarchitecture has itself been sadly neglected in neuroanatomy, neurology, cognitive science, and neuroradiology for close to a century, since the initial pioneering work of Thudichum (1884), Vogt and Vogt (1919), and Flechsig (1920). It is only recently that imaging neuroscientists (Geyer, Weiss, Reimann, Lohmann, & Turner, 2011; Glasser & Van Essen, 2011; Sereno, Lutti, Weiskopf, & Dick, 2013) have begun to realize the enormous scientific value of mapping myelin in human brain and spatially tracking its changes over time in response to development, maturation, and learning. This article will summarize research on the development, roles, and importance of myelin in the brain and discuss recent work that may lead to a quantitative noninvasive evaluation of cortical and white matter myelination using MRI techniques.

Figure 2. Map of T 1 in the normal human brain, from the Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig. The data were acquired using the MP2RAGE sequence at 7   T, with isotropic spatial resolution of 0.5   mm. An axial slice is shown, from a whole-brain data set acquired in 45   min.

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Biopsy Pathology of Neurodegenerative Disorders in Adults

M. Joe Ma , in Practical Surgical Neuropathology, 2010

Histopathology

Microscopically, brains from DLB patients contain abundant Lewy bodies in cell bodies of medium-sized or small neurons in neocortex (particularly in layers V and VI), paralimbic cortex, amygdala, basal nucleus of Meynert, dorsal raphe nucleus, substantia nigra, locus ceruleus, brainstem reticular formation, and in neurites at the dorsal motor nucleus of the vagus (medulla oblongata). On H&E stain, cortical Lewy bodies are often subtle, measure 3 to 20   μm in diameter, and are ill-defined, round or oval (sometimes curved or serpiginous), pale eosinophilic cytoplasmic inclusions with or without vague dense centers (Fig. 25-6A ). They are single and often push and indent the eccentric neuronal nuclei. Adding Luxol fast blue stain to H&E makes cortical Lewy bodies somewhat more distinct ( Fig. 25-6B).

Classic Lewy bodies found in brainstem, on the other hand, are discrete, perfectly round, eosinophilic, and occasionally concentric and laminated structures with dense cores and peripheral halos (Fig. 25-6C, lower right). Multiple classic Lewy bodies can exist in a large neuron. Oval pale amphophilic cytoplasmic masses, known as "pale bodies" and believed to be precursors of Lewy bodies, can sometimes be seen in large nigral neurons (Fig. 25-6C, upper left). Larger, oval and often serpiginous, densely eosinophilic or pale intraneuritic inclusions seen in the dorsal motor nucleus of the vagus and the basal nucleus of Meynert in these patients are also considered variants of Lewy bodies.

Lewy bodies are minimally argyrophilic (Fig. 25-6D) and are immunoreactive to antibodies against ubiquitin and α-synuclein (Fig. 25-6E). In addition to these two main constituents, several other proteins have been found in Lewy bodies, including neurofilament and αB-crystallin. Ultrastructurally, Lewy bodies consist of straight filaments of 10   nm in diameter arranged either haphazardly (cortical Lewy bodies) or radially around a core of granular and vesicular structures (classic Lewy bodies). Other neuropathologic features include ubiquitinated Lewy neurites, often most prominent in the neuropil of CA2/3 sectors of the hippocampus and amygdala, and varying degrees of spongiform change (Fig. 25-6F) in mesotemporal and paralimbic cortices (rarely in other cortical areas) that mimics prion diseases. If spongiform change is present in the neuropil, immunohistochemical confirmation of many cortical Lewy bodies and, more importantly, absence of deposition of abnormal prion protein is very helpful in reaching the correct diagnosis (although it is theoretically possible to have coexisting DLB and a prion disease).

Paraffin sections of a neocortical brain biopsy sample from a DLB patient cut perpendicular to the cortical surface should show many cortical Lewy bodies in deep cortical layers on routine H&E stain (with or without Luxol fast blue) and on more sensitive immunohistochemical stains for α-synuclein or ubiquitin. There are no established quantitative diagnostic criteria for DLB, but the density of neocortical Lewy bodies found in DLB often exceeds 1/hpf. Otherwise the cortex and subcortical white matter appear normal or show mild gliosis.

Brain biopsy is not indicated for pure idiopathic Parkinson disease. Mild to moderate dementia appears at late stages of idiopathic Parkinson disease in up to 40% of patients. The DLB Consortium utilizes the term Parkinson disease with dementia instead of DLB when the dementia appears 1 year or longer after the initial appearance of parkinsonism. 21 Classic Lewy bodies in idiopathic Parkinson's disease are found mainly in residual pigmented neurons of degenerated substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, and other brainstem nuclei, as well as in the basal nucleus of Meynert. Rare cortical Lewy bodies can be found, especially in paralimbic cortex. Although some researchers have found a good correlation between densities of cortical Lewy bodies and degrees of clinical dementia in Parkinson's disease patients, 28 varying and usually low densities of paralimbic and neocortical Lewy bodies can be found in patients with idiopathic Parkinson disease and no dementia. 29 Otherwise, neocortex usually appears normal. In Parkinson disease with dementia, neocortical pathology overlaps with that of DLB in terms of density and distribution of Lewy bodies. 30, 31 Also, patients with idiopathic Parkinson disease have an increased predilection for AD, such that superimposed dementia may also be explained by AD in such cases.

In DLB or idiopathic Parkinson disease patients with coexistent or, rarely, isolated autonomic failure (gastrointestinal dysmotility and dysphagia), Lewy bodies are found in sympathetic neurons of thoracic and upper lumbar spinal cord, and in neurons of the dorsal motor nucleus of the vagus and the myenteric ganglia in the gut.

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Neuropathology

Matthew D. Cykowski , in Neurology Secrets (Sixth Edition), 2017

Demyelinating Disease and White Matter Neuropathology

210.

What is a demyelinating disease?

These are diseases associated with myelin loss in the central or peripheral nervous system, typically without loss of axons or neurons. The prototypical disease is multiple sclerosis (MS) (central demyelination). Charcot–Marie–Tooth disease is an example of a peripheral disturbance in myelination. Other diseases may affect both central and peripheral myelination (e.g., leukodystrophies).

211.

How does MS appear macroscopically?

The demyelinating lesions of MS are appreciated as discolored, tan lesions in a periventricular distribution. The loss of phospholipid content in normal myelin is what gives these lesions their tan appearance. These plaques are sharply demarcated from adjacent white matter. An important finding in MS plaques is that they neither follow a vascular distribution (as would be seen in hypoxic/ischemic injury) nor occur in an anatomically restricted pathway (as would be seen in Wallerian degeneration).

212.

How do MS plaques appear histologically?

The appearances are highly variable and depend on the age of the lesion. In general, the loss of myelin (highlighted on Luxol fast blue [LFB] special stain and also apparent on H&E) and rarefied parenchyma is sharply demarcated with respect to uninvolved white matter. At the periphery of the plaque, a proliferation of normal oligodendroglial cells may be identified. Within the area of demyelination, a mature-appearing lymphocytic infiltrate is present (usually these are T cells) in a perivascular distribution, and plasma cells may also be present. Activated microglia and macrophages will be present with the latter engulfing myelin debris (occasionally highlighted by LFB stain as LFB-positive debris within the macrophage cytoplasm). Stains that highlight the course of axons (e.g., neurofilament) typically show that axons are intact without the axonal retraction balls seen in lesions resulting in axonal transection (exceptions do exist).

213.

What is the name of the characteristic, multinucleated cell type of a demyelinating lesion? How specific is this finding?

Multinucleated, bizarre astrocytes in demyelinating lesions are named Creutzfeldt cells. Each of these cells has multiple small micronuclei and due to their abundant cytoplasm these cells can be quite large and appear alarming. These cells are not specific to MS and may be seen in glioblastoma in particular; however, for any board examination, demyelination is always the first choice if Creutzfeldt cells are present.

214.

What is a demyelinating pseudotumor? Who described this entity?

This is a fulminant form of MS, also called "tumefactive" MS, wherein the demyelinating focus creates a tumor-like mass lesion that may be mistaken for high-grade glioma. This entity was first described by John Kepes, a Hungarian-born neuropathologist who spent the majority of his career at the University of Kansas.

215.

How is demyelinating pseudotumor recognized?

The imaging is characteristic in that horseshoe- or C-shaped enhancement is identified in the cerebral white matter with the nonenhancing end directed toward the ventricular surface. Most critically, on intraoperative consultation (see preceding description of frozen sections), the critical cell of a demyelinating lesion—the macrophage—is present. This is one of the reasons why neuropathologists tread very carefully at the time of intraoperative consultation whenever a macrophage-rich lesion is identified on cytologic or frozen section preparations.

216.

What serologic finding is common to neuromyelitis optica spectrum disorder?

The presence of aquaporin-4 antibodies.

217.

What is the neuropathologic basis of central pontine myelinolysis (CPM)?

Classically, CPM is characterized by myelin loss with macrophage accumulation in the central basis pontis. At low-power magnification it may appear similar to a brainstem infarct. However, neuronal loss and axonal destruction, which would be expected in infarct, are not present in CPM.

218.

What is the differential diagnosis of diffuse petechial hemorrhage involving the white matter?

The differential is extensive but includes rickettsial infection (Rocky mounted spotted fever), acute disseminated encephalomyelitis, coagulopathy, malaria, and fat emboli (as might follow a motor vehicle accident with long bone fracture).

219.

What is radiation necrosis of white matter, and how does it look macroscopically and microscopically?

Radiation necrosis is necrosis of normal brain tissue (not tumor!), typically in the white matter adjacent to the angle of the lateral ventricles. It occurs in patients who have undergone radiotherapy for a high-grade glioma, metastasis, or lymphoma. Macroscopically, the tissue is necrotic appearing, friable, and yellow, similar to the appearance of cornbread dressing (minus the flavorful ingredients). Microscopically, it is characterized by bland, eosinophilic necrosis with thick-walled vessels demonstrating fibrinoid necrosis of the vessel wall and perivascular hemorrhage.

References available online at expertconsult.com .

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