(BQ) Part 2 book Escourolle poirier’s manual of basic neuropathology presentation of content: Acquired metabolic disorders, hereditary metabolic diseases, congenital malformations and perinatal diseases, pathology of skeletal muscle, pathology of peripheral nerve, diseases of the pituitary gland.
9 Acquired Metabolic Disorders L E I L A C HI M E LLI AND F R A N Ç O I S E G R AY A WIDE range of systemic acquired metabolic diseases can also affect the central and/or peripheral nervous system (e.g hypoxia, hypoglycemia, disorders of serum electrolytes, vitamin deficiencies, and exogenous intoxications) By and large, the morphologic manifestations of most of these diseases in the various organs of the body are nonspecific In the central nervous system (CNS), on the other hand, lesions may find expression via selective involvement of some brain regions with simultaneous complete preservation of others, a phenomenon often referred to as selective vulnerability The pathogenesis of the predisposition to injury of some anatomical areas and/or of some specific, largely neuronal, cell types varies considerably from one disease to another and is undoubtedly multifactorial in all Differences in the vascular patterns of irrigation and resulting alterations in regional perfusion may explain, at least partly, the phenomenon of selective vulnerability in some disorders Regional variations in the biochemical characteristics of neuronal populations or, most likely, in the distribution of receptors for various excitatory amino acids may also play a role in some others CEREBRAL HYPOXIA The brain normally receives about 15% of the cardiac output, consumes about 20% of the blood oxygen, and consumes about 10% to 20% of the blood glucose Different states of deficient oxygen supply and utilization or deficient substrate may produce prominent cerebral hypoxic changes: • Anoxic or hypoxic hypoxia results from decreased pulmonary access to oxygen This may be due to insufficient oxygen in the inspired air It also may result from upper airway obstruction or may accompany pulmonary disorders that impede the uptake of oxygen In rare instances (i.e., hyperthermia) it may be due to increased metabolic demand • 205 • Anemic hypoxia results from decreased oxygen transport, either from reduced hemoglobin levels or reduced capacity of the hemoglobin molecule to transport oxygen, as occurs in carbon monoxide poisoning • Stagnant hypoxia results from reduction or cessation of blood flow This can be the result of impaired cardiac output producing global ischemia, or can be localized as is the case in brain infarcts The cerebral lesions that result from stagnant hypoxia are due to a combination of an inadequate supply of oxygen and glucose and an accumulation of lactic acid • Histotoxic hypoxia results from exposure to intoxicants, such as cyanide or hydrogen sulfide, which render the neural parenchyma incapable of utilizing oxygen and substrates • Oxyachrestic hypoxia results from severe hypoglycemia, where oxygen is not utilized because of the severe metabolic substrate deficiency 1.1 Basic Cellular Reactions to Injury The basic cellular reactions to injury (see Chapter 1) seen in cerebral hypoxia mostly involve neurons (ischemic nerve cell change); glial cells may also be affected and this may be manifest, for example, as glial necrosis, reactive gliosis, or rod-shaped microglia and macrophage proliferation 1.2 Selective Tissue Lesions The cellular changes resulting from hypoxia are maximal in those areas of the brain that are regarded as showing selective vulnerability In the cerebral cortex, the neuronal changes are more pronounced in the third, fifth, and sixth layers of the neocortex In addition, the changes are more severe in the depths of sulci than along the banks or the apices of the gyri Widespread, severe destruction of the deeper layers of the cortex leads to laminar (or pseudo-laminar) necrosis (Fig. 9.1) This descriptive term applies to a phenomenon whereby the distribution of the necrosis is confined to one or more layers of the isocortex and may be especially evident in the parietal and occipital lobes, where impaired perfusion may exacerbate the effects of hypoxia In the most severe cases, the cortical necrosis is not selective 206 • FIGURE 9.1 Laminar cortical necrosis This is often most severe in the posterior frontal and parietal lobes The hippocampus (Ammon’s horn) often shows selective involvement by hypoxia This is most evident in the CA1 sector (an area that corresponds to what is anatomically defined as Sommer’s sector) (Fig. 9.2A, B) The CA3 area (also referred to as the endplate) is often less severely affected The CA2 area tends to be relatively resistant to hypoxic changes The regional variation in the susceptibility of the pyramidal hippocampal neurons is now best explained by implicating the distribution of excitotoxic receptors as an important pathogenetic factor Among the basal ganglia, the pallidum (especially the medial portion) (Fig. 9.3), the striatum, especially the lateral half of the putamen, and the thalamus are selectively vulnerable to hypoxia The mammillary bodies may be especially vulnerable when hypoxia occurs in infancy In the cerebellum, cortical involvement is frequent and affects chiefly the Purkinje cells with secondary proliferation of Bergmann glia The dentate nucleus is also frequently involved In the brainstem, the medullary olives are vulnerable areas In children, the brainstem is sometimes severely damaged, especially the medial and lateral reticular formations and the adjacent cranial nerve nuclei Various types of white matter lesions may be seen in isolation in response to anoxia or in association with gray matter damage Some white matter lesions consist predominantly of extravasation of edema fluid due to increased vascular permeability but with preservation of endothelial cells These lesions currently are designated as reversible E S C O U R O L L E & P O I R I E R ’ S M A N U A L O F B A S I C N E U R O P AT H O L O G Y https://kat.cr/user/Blink99/ A B FIGURE 9.2 Cerebral anoxia, involvement of the hippocampus (A) Gross appearance (B) Microscopy Note the cell loss from the CA1 sector and to a lesser extent the endplate (Luxol fast blue myelin stain) leukoencephalopathy and may be seen in hypoxia and other acquired metabolic disturbances or intoxications Other white matter lesions, often designated collectively as hypoxic encephalopathy, consist of varying proportions of demyelination and white matter necrosis The degree of severity of these lesions ranges from small, perivascular foci of demyelination, to focal plaque-like areas of demyelination and necrosis, and up to large confluent areas of demyelination and necrosis The lesions tend to be most severe deep in the white matter and are often associated with relative preservation of the subcortical “U” fibers (Fig. 9.4) that interval, a variable degree of cerebral swelling may be observed In cases of sudden death or where only moderate cerebral hypoxia has occurred, unquestionable signs of hypoxia may be discerned solely on histological examination; these changes consist of ischemic neurons in the most vulnerable areas, where they are difficult to detect before to 12 hours of survival beyond the insult Depending on the mechanism of cerebral anoxia, separate and distinctive patterns of ischemic changes are recognized 1.3 Variation of Lesions According to Etiology A survival time of approximately 48 hours is necessary for macroscopically visible lesions of cerebral hypoxia to become apparent Before FIGURE 9.3 Bilateral necrosis of the pallidum, gross appearance FIGURE 9.4 Whole-brain section showing extensive white matter demyelination with preservation of the U fibers in hypoxic leukoencephalopathy (Loyez stain) Chapter Acquired Metabolic Disorders • 207 C E RE BRAL I N FA R C TS Cerebral infarcts are the result of localized ischemic hypoxia due to vascular occlusion (see Chapter 4) Infarcts and/or ischemic lesions in the boundary zone areas are the result of global oligemic hypoxia, especially in the setting of low cerebral blood flow of sudden onset, even of short duration These lesions are one of the possible consequences of acute heart failure (cardiogenic shock), drug-induced hypotension, or general anesthesia C ARDI OVASCU L A R A R R ES T Cardiovascular arrest exceeding three to four minutes at normal temperature ordinarily causes diffuse cortical lesions and Ammon’s horn involvement; the distribution and extent of damage in the basal ganglia and in the brainstem vary (Fig 9.5) Comparable lesions are caused by profound hypoglycemia (vide infra) and status epilepticus 3 C ARBON MONO X I D E P O I S O NI N G Carbon monoxide (CO) is produced by incomplete combustion of carbon-containing substances Humans are exposed to CO mainly through automobile exhaust, improperly ventilated stoves or heaters, and tobacco smoke The toxic effects of CO result primarily from the decreased capacity of blood to transport oxygen At autopsy examination, the brain of an individual who dies within a few hours of intoxication is diffusely swollen and congested The blood within vessels has the characteristic cherry-red color of FIGURE 9.5 Diffuse cortical and basal ganglia lesions in a case of delayed death following cardiovascular arrest 208 • carboxyhemoglobin; that hue is also imparted to the external and cut surface of the brain (Fig. 9.6) Scattered petechial hemorrhages also may be present With prolonged formalin fixation, the red discoloration becomes less prominent Some individuals who seem to recover clinically from acute toxic exposure to CO may, some days to weeks later, develop a neurological syndrome that includes neuropsychiatric manifestations including personality changes, parkinsonism, dementia, incontinence, and frank psychosis In these cases, different combinations of the neuropathological abnormalities described below may be found Pallidal necrosis is most often observed in fatal cases of CO intoxication occurring after some delay after the insult (6 or more days) Microscopic foci of ischemic or hemorrhagic necrosis may develop even sooner The pallidal lesions are usually bilateral but are often asymmetrical The necrosis usually involves the anterior portion and inner segment of the pallidum but may extend into the outer segment or dorsally into the internal capsule Although pallidal necrosis is characteristic of and frequently seen in delayed deaths from CO, it may also be seen in other conditions associated with hypoxia or anoxia (Figs 9.3, 9.7, and 9.8) The selective involvement of the globus pallidus in CO poisoning has been FIGURE 9.6 Macroscopic image of the brain from patient with acute CO poisoning The postmortem blood CO saturation was 60%.The cherry-red color of the carboxyhemoglobin imparts a red hue to the entire brain E S C O U R O L L E & P O I R I E R ’ S M A N U A L O F B A S I C N E U R O P AT H O L O G Y https://kat.cr/user/Blink99/ FIGURE 9.7 Coronal section showing bilateral pallidal necrosis This can be seen following delayed death from CO or other hypoxic conditions attributed to selective vulnerability of pallidal neurons, the result of hypotension and impaired circulation through the pallidal branches of the anterior choroidal arteries, or the relatively high iron content of this portion of the brain, which somehow renders the structure especially susceptible Other gray matter regions involved include the neocortical and hippocampal neurons, and the cerebellar Purkinje cells and granule cells, where there may be focal neuronal loss Lesions of the white matter are also encountered in individuals who die some time after CO poisoning These lesions consist of varying degrees of demyelination and associated necrosis There may be small perivascular foci found in the deep white matter, large confluent areas that extend from the frontal to occipital poles in the periventricular white matter, or sharply demarcated foci of demyelination with relative sparing of axons in the deep white matter (“Grinker’s myelinopathy”) (Fig. 9.8) All these lesions tend to spare the arcuate fibers 1.3.4 CYANIDES Cyanides are histotoxic or cytotoxic agents, the toxicity of which is due to bonding between the cyanide ion and the ferric iron of intracellular cytochrome oxidase This reaction leads to cessation of cellular respiration Acute intoxication can result from either ingestion or inhalation of cyanides and causes respiratory arrest Rarely, survivors of cyanide intoxication may develop parkinsonism or dystonia When death is acute, the brain may be edematous and in some cases focal subarachnoid hemorrhages FIGURE 9.8 CO poisoning Necrosis of the pallidum and white matter necrosis in a case of Grinker myelinopathy (Loyez stain) develop If death occurs some time later, the brain may show foci of necrosis in the basal ganglia and white matter and loss of Purkinje cells 1.3.5 HYPOGLYCEMIA Glucose is the principal source of energy in the CNS Neuronal stores of glucose and glycogen are relatively small and need practically continuous replenishment A decrease of glucose level under 1.5mmol/L (25 to 30mg/100mL) leads to brain damage within one to two hours The most common cause of hypoglycemia is an excess of exogenous insulin The effects of hypoglycemia are not due just to the energy deficit Releases of aspartate and to a lesser extent release of glutamate probably contribute to neuronal damage through excitotoxic mechanisms In acute hypoglycemia, the lesions are similar to those of acute hypoxia but not identical In general, the pattern of injury is that of selective degeneration of neurons rather than frank necrosis of all other cellular components Affected neurons are shrunken with hypereosinophilic cytoplasm Initially, the nucleus is pyknotic, as seen in anoxia, but later may become eosinophilic and appears to blend in with the cytoplasm (nuclear dropout) The topography of the lesions is roughly similar to that in hypoxia, but Purkinje cells may be relatively spared Chapter Acquired Metabolic Disorders • 209 In long-term survivors of severe hypoglycemia who then come to postmortem examination, the cerebral cortex may appear thinned and the hippocampi shrunken and discolored The white matter is reduced in bulk and the ventricles are dilated There may be marked atrophy of the caudate nucleus and putamen On microscopic study, the cerebral cortex shows laminar neuronal loss and gliosis associated with capillary proliferation There is often dense subpial gliosis The hippocampal pyramidal cell layer and subiculum are replaced by a loose meshwork of glial tissue The white matter is usually rarefied and gliotic The caudate nucleus and putamen are diffusely gliotic The globus pallidus is relatively spared Moderate neuronal loss and gliosis may be evident in the thalamus As in acute hypoglycemia, the cerebellar cortex, including the Purkinje cells, is relatively spared HYPE R T HE RM I A Acute hyperthermia or heat stroke is a thermal insult to the cerebral thermoregulatory system controlling heat production and heat dissipation The thermal insult may be endogenous in “exertional heat stroke” or environmental “classic heat stroke.” It is also a feature of malignant hyperthermia, an autosomal dominant disorder of the skeletal muscle characterized by a hypermetabolic response to commonly used inhalation anesthetics and depolarizing muscle relaxants Clinically heat stroke is defined as a syndrome characterized by elevated core body temperature over 40° Celsius and neurological dysfunction Neuropathological studies are relatively few Abnormalities similar to those of hypoxic–ischemic damage, probably resulting from a combination of cardiovascular collapse and an increased metabolic rate, have been described Severe diffuse loss of Purkinje cells with consequent degeneration of the cerebellar efferent pathways is known to occur, but often in the absence of injury to Ammon’s horn and other areas susceptible to hypoxia FIGURE 9.9 Cross-section of pons from patient with CPM Note the ill-defined brown discoloration of the demyelinative lesion complication of the rapid rise in osmolality that accompanies excessively rapid correction or over-correction of chronic hyponatremia The clinical manifestations vary according to the size of the lesion—from asymptomatic to coma In life, the diagnosis can be made by MRI At autopsy, the typical CPM lesion appears as a discolored, destructive area in the basis pontis that may be centrally cavitated (Fig. 9.9) The lesions are often triangular, T-shaped, or diamond-shaped and vary from a few millimeters across (Fig. 9.10) to lesions that involve nearly the entire basis pontis Even when the lesion is extensive, generally at least a thin rim of intact tissue with myelin preservation ELECTROLYTIC DISTURBANCES 2.1 Central Pontine Myelinolysis Central pontine myelinolysis (CPM) is a monophasic demyelinating disease that predominantly involves the basis pontis It usually occurs as a 210 • FIGURE 9.10 (Loyez stain) Triangular lesion of limited CPM E S C O U R O L L E & P O I R I E R ’ S M A N U A L O F B A S I C N E U R O P AT H O L O G Y https://kat.cr/user/Blink99/ anatomically by close apposition of gray and white matter structures 2.2 Disorders of Iron Metabolism FIGURE 9.11 Large section of pons from a patient with extensive CPM (Loyez stain for myelin) is present at the lateral and ventral margins of the basis pontis (Fig. 9.11) Demyelination is usually maximal in the middle and rostral portions of the pons Lesions may extend to the middle cerebellar peduncles Histologically, the CPM lesion is characterized by demyelination with relative preservation of axons and neuronal perikarya (Fig 9.12) Acute lesions contain numerous lipid-laden macrophages but few or no inflammatory cell infiltrates Occasionally foci of necrosis and cavitation are present in the center of the more severe lesions Sometimes, especially in more severe cases, CPM is accompanied by extrapontine demyelinated lesions These may involve the subcortical white matter, striatum, anterior commissure, internal and external capsules, lateral geniculate bodies, and cerebellar folia As is the case in the pons, these extrapontine sites of involvement are characterized In primary or secondary hemochromatosis, the blood–brain barrier provides effective protection against the diffusion of protein-bound iron into the CNS Therefore, hemosiderin iron deposits are limited to regions of the CNS devoid of the blood– brain barrier, including the choroid plexuses, the area postrema, the pineal gland, adenohypophysis, dorsal root ganglia, and a number of vestigial remnants such as the paraphysis and the subfornical organ These regions have a gross rusty appearance and show marked Prussian blue reaction with ferrocyanide 2.3 Disorders of Calcium Metabolism Massive perivascular deposits including calcium (Fig. 9.13A) but also iron (Fig. 9.13B) and other minerals may be observed in the basal ganglia and sometimes in the dentate nucleus, the white matter, and Ammon’s horn (so-called Fahr syndrome) in a variety of circumstances, including hypoparathyroidism and conditions accompanied by hypercalcemia VITAMIN DEFICIENCY DISORDERS 3.1 Thiamine Deficiency FIGURE 9.12 Microscopic section of pons from a patient with CPM Note the intact neuron in the midst of an area of demyelination (Klüver-Barrera stain) The Wernicke-Korsakoff syndrome is caused by thiamine (vitamin B1) deficiency from inadequate intake (beriberi, prolonged intravenous therapy without vitamin supplementation), significant nutritional deficit as in fasting or famine, gastric absorption defect such as in hyperemesis gravidarum, gastrointestinal neoplasms, and gastric plication for morbid obesity The distribution of the lesions of Wernicke encephalopathy is characteristic (Figs 9.14 and 9.15] and accounts for the symptoms, which include disturbances of wakefulness, hypertonia, and ocular palsies They are found in the periventricular areas, including the medial aspect of the thalamus, hypothalamus, and mammillary bodies, the Chapter Acquired Metabolic Disorders • 211 A B FIGURE 9.13 (A) Massive perivascular mineral deposits in a case of Fahr disease (H&E) (B) Iron perivascular deposits in the same patient revealed by Perl’s method for iron periaqueductal region at the level of the third cranial nerve, the reticular formations of the midbrain, caudal portion of the corpora quadrigemina, and the floor of the fourth ventricle The mammillary bodies are the most frequently affected structures and are involved in virtually all cases The changes vary with the stage and severity of the disease At gross examination, when patients die during the acute stages of the disease, petechial hemorrhages involve predominantly the mammillary bodies (Fig. 9.16) and sometimes may be more extensive (Fig. 9.15) In contrast, the lesions may be inconspicuous grossly Patients with less severe, chronic, or previously treated disease may have mildly atrophic mammillary bodies that are gray to brown in color as a result of hemosiderin deposition (Fig. 9.17) A narrow band of tissue immediately adjacent to the ventricular system and around the aqueduct usually remains unaffected At microscopy, the acute lesions display edema, petechial hemorrhages, myelin loss, and reactive astrocytosis Neurons are generally preserved Swelling and hyperplasia of endothelial cells make the capillaries abnormally prominent (Fig. 9.18) The perivascular spaces may contain lipid-laden macrophages Extravasated erythrocytes and hemosiderin-laden macrophages are seen in the cases with grossly discernible petechial hemorrhages In the chronic stages of the disease and in treated patients the affected regions may show little more than mild loss of neurons and gliosis Central chromatolysis of neurons may result from associated niacin deficiency (see below) Korsakoff psychosis is defined clinically as retrograde amnesia and an impaired ability to acquire new information and is usually encountered in alcoholic patients with chronic Wernicke encephalopathy The pathological basis of that syndrome is debated It does not seem to result from the lesions of the mammillary bodies only Involvement of the medial dorsal nuclei (Figs 9.15A and 9.19) and/or midline region of the thalamus plays an important causative role, according to some authors Thiamine deficiency also produces peripheral neuropathy, including beriberi neuropathy and at least some cases of so-called alcoholic polyneuropathy 3.2 Pellagra FIGURE 9.14 Topographical distribution of the lesions in Wernicke encephalopathy 212 • Pellagra is clinically manifest typically by dermatitis, diarrhea, and dementia The disease has long been recognized among malnourished individuals who depended on corn as a major part of their diet It E S C O U R O L L E & P O I R I E R ’ S M A N U A L O F B A S I C N E U R O P AT H O L O G Y https://kat.cr/user/Blink99/ A B C D FIGURE 9.15 Wernicke encephalopathy: topographical distribution of the lesions (Loyez stain) (A) Periventricular hemorrhagic thalamic lesions (B) Lesions in the tegmentum of the midbrain at the level of the third cranial nerve nuclei (C) Hemorrhages in the tegmentum of the upper pons (D) Hemorrhagic lesions in the medullary floor of the fourth ventricle FIGURE 9.16 Acute Wernicke encephalopathy Note the petechial hemorrhages in the mammillary bodies and, to a lesser extent, the walls of the third ventricle FIGURE 9.17 Shrunken, discolored mammillary bodies in a patient who had been treated for previous episodes of Wernicke encephalopathy Chapter Acquired Metabolic Disorders • 213 dorsal nucleus of the vagus, the gracile and cuneate nuclei, the nucleus ambiguus, the trigeminal nerve nuclei, the oculomotor nuclei, the reticular formations, and the anterior horn motor neurons of the spinal cord In some cases of niacin deficiency there may be degeneration of the posterior columns and corticospinal tracts 3.3 Vitamin B12 deficiency FIGURE 9.18 Microscopic appearance of the mammillary bodies from a patient with Wernicke encephalopathy Note the petechial hemorrhages and the swelling of the endothelial cells results from lack of P-P (pellagra preventive) factor (nicotinic acid or niacin) It is now known that deficiency of niacin itself, or of tryptophan, an amino acid precursor of niacin that is deficient in corn, leads to pellagra The disease has become very rare as the result of enriching common foods, such as bread, with niacin This vitamin deficiency is now encountered most often in patients with chronic alcoholism In these patients the disease may be clinically atypical, lacking the characteristic skin lesions The neuropathological changes resulting from niacin deficiency consist of isolated neuronal changes of central chromatolysis type (Fig. 9.20), without associated glial or vascular alterations They affect, in decreasing order of frequency, the Betz cells of the cerebral motor cortex, the pontine nuclei, the FIGURE 9.19 Petechial hemorrhages and myelin loss in the thalamus from a patient with Korsakoff syndrome 214 • Vitamin B12 is obtained primarily from meat and dairy products The vitamin must be bound to “intrinsic factor,” a glycoprotein produced by the gastric parietal cells, prior to being absorbed by the body through the ileum Most cases of vitamin B12 deficiency actually result from inadequate production of intrinsic factor In pernicious anemia, this is due to autoimmune atrophic gastritis, more rarely to gastric neoplasms or gastrectomy Vitamin B12 deficiency also can result from impaired ileal absorption, in individuals with malabsorption syndromes, intestinal tuberculosis, regional enteritis, or lymphomas Rarely the cause of the deficiency is the result of competitive utilization of the vitamin within the intestine by the fish tapeworm (Diphyllobothrium latum) or bacterial overgrowth in intestinal blind loops or diverticula Very similar changes (“vacuolar myelopathy”) have been observed in AIDS patients, resulting from abnormalities of vitamin B12 metabolism Vitamin B12 deficiency affects the hematopoietic (megaloblastic anemia), gastrointestinal (glossitis, anorexia, diarrhea, and weight loss), and nervous systems Neurological complications develop in 40% of untreated cases and can occur in the absence of hematological abnormalities The neuroanatomical/ clinical syndrome of nervous system involvement has been termed subacute combined degeneration of the spinal cord The spinal cord from patients with longstanding severe vitamin B12 deficiency may be mildly shrunken, with discolored posterior and lateral columns Histologically, the earliest lesions consist of vacuolar distention of myelin sheaths, resulting in a characteristic spongy appearance of the affected white matter With further demyelination, lipid-laden macrophages become scattered throughout the lesions Some of the axons traversing the lesions undergo Wallerian degeneration Initially astrocytosis is not marked, but dense gliosis may be seen in patients who have had the disease for a protracted E S C O U R O L L E & P O I R I E R ’ S M A N U A L O F B A S I C N E U R O P AT H O L O G Y https://kat.cr/user/Blink99/ lipid myopathies, 301–302 carnitine deficiency, 301–302 carnitine palmityl transferase deficiency, 302 lipofuscin accumulation, lipoprotein metabolism, 237–240 lissencephaly, 268–270 type I lissencephaly, 268 type II lissencephaly, 268–270 lobar holoprosencephaly, 262 localized myositis, 311 loose reticulated (Antoni B) tissue, 46 Louis-Bar disease, 249–250 Lyme disease, 329 lymphocytic disorders, 146–148 lymphocytic hypophysitis, 356–357 lymphocytic microvasculitis, 330 lymphomas, 54–58, 363 primary CNS lymphomas, 54–55 secondary CNS involvement, 55–56 lymphoplasmacyte-rich meningioma, 50 lymphorrhages, 289 lymphotrophic virus-1-associated myelopathy, 140 lysosomal acid lipase deficiency, 237 lysosomal disorders, 230–240 disorders of cholesterol metabolism, 237–240 abetalipoproteinemia, 238 cerebrotendinous xanthomatosis, 238 ceroid lipofuscinosis, neuronal, 238–240 Tangier disease, 237–238 Wolman disease, 237 gangliosidoses GM1 gangliosidosis type I, 235 GM2 gangliosidosis type II, 234–235 Tay-Sachs disease, 234 lipid metabolism, disorders of, 237–240 lipoprotein metabolism, 237–240 mucopolysaccharidoses, 236–237 sphingolipidoses, 230–238 Fabry disease, 233 Farber lipogranulomatosis, 233 gangliosidoses, 233–235 Gaucher disease, 230–231 Krabbe disease, 231 metachromatic leukodystrophy, 235–236 Niemann-Pick disease, 231–233 lysosomal storage diseases, 230–240 macrophage proliferation and phagocytosis, 13 macrophagic myofasciitis, 310–311 macroscopic examination, CNS, 369–371 histological sampling, 371 inspection, 369 slicing, 369–371 malformations, vascular, 88–90 malignant glioma with PNET-like foci, 26 malignant hyperpyrexia syndrome, 304 malignant lymphomas, neuropathies associated with, 330–331 malignant peripheral nerve sheath tumor, 47–48 mammosomatotrophic cell adenoma, 350 manganese, 220 toxic encephalopathy, 220 MAPK/ERK signaling pathway, 27 maple syrup urine disease, 252 Marburg type MS, 169 Marchiafava-Bignami disease, 217 Marinesco bodies, Markesbery-Griggs distal myopathy, 295 392 • INDEX massive hemispheric infarct, 98 McArdle disease, 246, 303–304 measles encephalitides, 135–137 measles inclusion body encephalitis, 136 Meckel-Gruber syndrome, 258 medulloblastoma, 42–43 anaplastic medulloblastoma, 42 desmoplastic/nodular medulloblastoma, 42 with extensive nodularity, 42 large cell medulloblastoma, 42 with melanotic differentiation, 42–43 with myogenic differentiation, 42 medulloblastoma with extensive nodularity, 42 medulloepithelioma, 43–44 melanomas, 363 melanotic Schwannomas, 46 MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), 301 MEN4, 359–360 meningeal hemangiopericytoma, 51–52 meninges tumors, 48–54 meningiomas, 48–51 WHO grade I meningiomas, 48–50 WHO grade II meningiomas, 50 WHO grade III meningiomas, 50–51 mesencyhmal non-meningothelial tumors adipose tissue lipomas, 52 blood vessel tumors hemangiomas, 53 chondroma, 53 fibrous tumors solitary fibrous tumor, 52–53 muscle tumors Leiomyosarcoma, 53 osteocartilaginous tumors, 53 osteochondroma, 53 osteoma, 53 nonmeningothelial tumors, 51–54 hemangioblastoma, 53–54 meningeal hemangiopericytoma, 51–52 mesencyhmal non-meningothelial tumors, 52–53 primary melanocytic lesions, 53 WHO grade I meningiomas angiomatous meningioma, 49–50 fibrous meningioma, 49 lymphoplasmacyte-rich meningioma, 50 meningothelial meningioma, 49 metaplastic meningiomas, 50 microcystic meningioma, 50 psammomatous meningioma, 49 secretory meningioma, 50 transitional meningioma, 49 WHO grade II meningiomas atypical meningioma, 50 chordoid meningioma, 50 clear cell meningioma, 50 WHO grade III meningiomas anaplastic meningioma, 50–51 papillary meningioma, 51 rhabdoid meningioma, 51 meningioma, 363 meningitis, aseptic, 132 meningocele, 259 meningoencephalocele, 259 meningothelial meningioma, 49 meningovascular neurosyphilis, 121 Menkes disease, 250 mercury, 220 toxic encephalopathy, 220 merosin, 290 merosin-negative congenital muscular dystrophy, 295 merosin-positive congenital muscular dystrophy, 295 MERRF (myoclonus epilepsy with ragged red fibers), 301 mesencyhmal non-meningothelial tumors, 52–53 adipose tissue lipomas, 52 blood vessel tumors hemangiomas, 53 chondroma, 53 fibrous tumors solitary fibrous tumor, 52–53 muscle tumors Leiomyosarcoma, 53 osteocartilaginous tumors, 53 osteochondroma, 53 osteoma, 53 MET, 25 metabolic diseases, hereditary, 227–256 adult polyglucosan body disease, 246–247 amino acid metabolism, 250–253 Canavan disease, 251 Hartnup disease, 252 homocystinuria, 252 hyperglycinemia, 252–253 maple syrup urine disease, 252 phenylketonuria, 251–252 urea-cycle disorders, 253 biochemical abnormalities, 228–229 energy metabolism disorders, 228 intoxication syndromes, 228 lipid metabolism disorders, 228 metal metabolism disorders, 228–229 neurotransmitter metabolism disorders, 228 carbohydrate metabolic disorders, 246–247 cholesterol metabolism abetalipoproteinemia, 238 cerebrotendinous xanthomatosis, 238 ceroid lipofuscinosis, neuronal, 238–240 Tangier disease, 237–238 Wolman disease, 237 copper metabolism, 250 Menkes disease, 250 Wilson disease, 250 defective DNA repair ataxia-telangiectasia, 249–250 Cockayne syndrome, 249 xeroderma pigmentosum, 248–249 enzyme deficiencies, 248–250 defective DNA repair, 248–249 neuroaxonal dystrophies, 248 porphyrias, 250 gangliosidoses GM1 gangliosidosis type I, 235 GM2 gangliosidosis type II, 234–235 Tay-Sachs disease, 234 glycogen metabolic disorders, 246–247 Lafora disease, 246–247 lysosomal disorders, 230–240 cholesterol metabolism, 237–240 lipid metabolism, 237–240 lipoprotein metabolism, 237–240 mucopolysaccharidoses, 236–237 sphingolipidoses, 230–238 metabolic disorders, 246–247 adult polyglucosan body disease, 246–247 glycogenoses, 246 Lafora disease, 246–247 polyglucosan body disease, 246–247 mitochondrial diseases, 244–246 Alpers syndrome, 246 Kearns-Sayre syndrome, 245–246 Leigh disease, 244 mitochondrial encephalopathy, 244–245 myoclonic epilepsy, 245 neuroaxonal dystrophies infantile neuroaxonal dystrophy, 248 neuroaxonal dystrophy, 248 orthochromatic leukodystrophies, 254–256 peroxisomal disorders, 240–244 adrenoleukodystrophy, 242–243 Refsum disease, 243–244 Zellweger syndrome, 242 polyglucosan body disease, 246–247 sphingolipidoses Fabry disease, 233 Farber lipogranulomatosis, 233 gangliosidoses, 233–235 Gaucher disease, 230–231 Krabbe disease, 231 metachromatic leukodystrophy, 235–236 Niemann-Pick disease, 231–233 structural protein disorders, 253–254 Alexander disease, 253 Pelizaeus-Merzbacher disease, 253–254 metabolic disorders, 205–226, 246–247 adult polyglucosan body disease, 246–247 cerebral hypoxia, 205–210 carbon monoxide poisoning, 208–209 cardiovascular arrest, 208 cellular reactions, 206 cerebral infarcts, 208 cyanides, 209 hyperthermia, 210 hypoglycemia, 209–210 tissue lesions, 206–207 electrolytic disturbances, 210–211 calcium metabolism, 211 central pontine myelinolysis, 210–211 iron metabolism, 211 ethanol acute alcohol intoxication, 215 chronic alcoholism, 215–217 glycogenoses, 246 Lafora disease, 246–247 paraneoplastic encephalomyelopathies paraneoplastic cerebellar degeneration, 224 paraneoplastic encephalomyelitis, 224–226 paraneoplastic opsoclonus-myoclonus syndrome, 226 polyglucosan body disease, 246–247 systemic disease, CNS changes, 221–226 hepatic encephalopathy, 221 multifocal necrotizing leukoencephalopathy, 221 paraneoplastic encephalomyelopathies, 221–226 respiratory encephalopathies, 221 toxic encephalopathies, 215–221 aluminum, 219 arsenic, 219–220 ethanol, 215–217 ethylene glycol, 217–218 heavy metals, 219–221 lead, 220 manganese, 220 mercury, 220 metalloids, 219–221 methanol, 217 phenytoin, 218–219 thallium, 220 tin, 220–221 Index • 393 metabolic disorders (Cont.) vitamin deficiency, 211–215 pellagra, 212–214 thiamine deficiency, 211–212 vitamin B12 deficiency, 214–215 metabolic neuropathy, 333–334 diabetes, 333 metachromasia, 235 metachromatic leukodystrophy, 235–236, 342 metal metabolism disorders, 228–229 metalloids, 219–221 toxic encephalopathy, 219–221 metaplastic meningiomas, 50 metastatic neoplasms, pituitary gland, 360 metazoal infections, 128–131 cysticercosis, 129–130 eosinophilic meningitis, 130 hydatidosis, 130 schistosomiasis, 130 Strongyloides stercoralis infection, 131 toxocariasis, 130 trichinosis, 130–131 methanol, 217 toxic encephalopathy, 217 methylator phenotype (G-CIMP), 25 MGMT locus, 25 microcystic meningioma, 50 microglial lesions, 13–14 microglial nodules, 14 microscopic artifacts, 377 microvasculitis, 330 middle-caliber arterioles, 329 systemic vasculitis, 329–330 midline structures, 263–264 anomalies of septum pellucidum, 264 Minamata disease, 220 minicore myopathy, 300 mitochondrial diseases, 244–246 Alpers syndrome, 246 Kearns-Sayre syndrome, 245–246 Leigh disease, 244 mitochondrial encephalopathy, 244–245 myoclonic epilepsy, 245 mitochondrial DNA depletion syndrome 4A, 246 mitochondrial encephalomyelomyopathies, 244–246 mitochondrial encephalomyopathy lactic acidosis stroke (MELAS), 302 mitochondrial encephalopathy, 244–245 mitochondrial myopathies, 300–301 mixed gliomas, 31–32 anaplastic oligoastrocytoma, 32 oligoastrocytoma, 31 mixed meningioma, 49 Miyoshi myopathy, 295 MNGIE syndrome (mitochondrial myopathy, neurogastrointestinal encephalomyopathy), 301 molecular alterations of EGFR amplifi cation and EGFRvIII, 23 monoclonal gammopathies, 331–332 monoclonal gammopathy-associated peripheral neuropathy, 331–332 monoclonal IgM, 331 mononeuropathies, 333 Morel’s laminar sclerosis, 217 morphologic analysis, CNS lesions, 1–18 Morton neuroma, 336 moth-eaten fibers, 283–284 motor neuron diseases, 201–203 394 • INDEX amyotrophic lateral sclerosis, 201–202 gross appearance, 201 microscopic lesions, 201–202 bulbar muscular atrophy, 203 hereditary spastic paraparesis, 203 spinal muscular atrophy, 202–203 X-linked bulbar muscular atrophy, 203 X-linked spinal atrophy, 203 movement disorders, 186–195 akinetic rigid syndromes, 186–193 corticobasal degeneration, 189–191 multiple system atrophy, 191–192 Parkinson disease, 186–188 progressive supranuclear palsy, 188–189 secondary parkinsonian syndromes, 192–193 corticobasal degeneration gross appearance, 190 microscopic lesions, 190–191 Huntington disease gross appearance, 193–194 microscopic lesions, 194 hyperkinetic movement disorders, 193–195 choreoacanthocytosis, 195 HD-like disease, 194 Huntington disease, 193–194 neurodegeneration with brain iron accumulation, 194–195 multiple system atrophy gross appearance, 191 microscopic lesions, 192 Parkinson disease gross appearance, 187 microscopic lesions, 187–188 molecular biology, 188 progressive supranuclear palsy genetics, 189 gross appearance, 188–189 microscopic lesions, 189 secondary parkinsonian syndromes carbon monoxide poisoning, 192 pharmacologic/toxic, 192 postencephalitic parkinsonism, 192 trauma, 193 vascular disease, 192 MPNST See Malignant peripheral nerve sheath tumor MSA See Multiple system atrophy mucopolysaccharidoses, 236–237 multibacillary leprosy, 327 multicore myopathy, 300 multicystic encephalomalacia, 275–276 multifocal necrotizing leukoencephalopathy, 221 multiminicore myopathy, 300 multiple sclerosis, 161–169 acute, 169 cerebral cortex, MS lesions in, 166–167 deep gray matter, MS lesions in, 166–167 etiology, 168–169 inflammation, 162 normal-appearing white, gray matter, 167–168 pathogenesis, 168–169 pathology, 162–168 white matter, demyelinated lesions in, 162–166 multiple system atrophy, 191–192 gross appearance, 191 microscopic lesions, 192 muscle biopsy, 367 muscle tumors Leiomyosarcoma, 53 muscular dystrophies, 280, 289, 293, 295 musculocutaneous (superficial peroneal) nerve, 368 mutation in INI1/SNF5, 44 mutation in serine/threonine kinase, BRA F (V600E), 57 mutation of APC gene, 42 mutations in IDH1/2, 25 mutations of transthyretin ( TT R ) gene, 341 myalgias, 304 myasthenia gravis, 288–289 myasthenic syndromes, 289 Mycobacterium leprae mycoses of the CNS, 125–127 aspergillosis, 126 blastomycosis, 126 candidiasis, 126 chromomycosis, 126 cladosporiosis, 126 coccidioidomycosis, 127 cryptococcosis, 127 histoplasmosis, 127 paracoccidioiodomycosis, 127 pseudiallescheriosis, 127 zygomycosis, 127 mycotic aneurysms, 81 mycotic infections, 125–127 aspergillosis, 126 blastomycosis, 126 candidiasis, 126 chromomycosis, 126 cladosporiosis, 126 coccidioidomycosis, 127 cryptococcosis, 127 histoplasmosis, 127 paracoccidioiodomycosis, 127 pseudiallescheriosis, 127 zygomycosis, 127 myelin protein zero, 337 myeloma with monoclonal IgG, 331 myelomeningocele, 259 myoadenylate deaminase deficiency, 304 myoclonic epilepsy, 245 myoclonic epilepsy ragged red fibers (MERRF), 302 myofibrillar myopathies, 295 myopathy with tubular aggregates, 304 myophosphorylase deficiency, 303–304 myotilin, 290, 294 myotilinopathy, 293 Myotonia congenital, 297 myotonic dystrophy, 296–298 myxopapillary ependymoma, 34 NBAI See Neurodegeneration with brain iron accumulation necrosis, acute neuronal, 2–3 necrotizing changes, 283 Negri bodies, 7, 135–136 nerve cell atrophy, nerve disease, peripheral, 313–342 nerve teasing, 314–316 neural tube closure defects, 258 neuroaxonal dystrophy, 248 infantile neuroaxonal dystrophy, 248 neuroaxonal dystrophy, 248 neurochemical studies, 376 neurocytic tumors, 38 central neurocytoma, 38 cerebellar liponeurocytoma, 38 neurodegeneration with brain iron accumulation (NBAI), 194–195 neuroepithelial tissue tumors, 21–44 astrocytic tumors, 21–29 circumscribed astrocytomas, 26–28 diffusely infiltrating astrocytomas, 21–26 choroid plexus tumors, 34–35 atypical choroid plexus papilloma, 35 carcinoma, 35 papilloma, 35 circumscribed astrocytomas pilocytic astrocytoma, 26–28 pilomyxoid astrocytoma, 28 pleomorphic xanthoastrocytoma, 28 subependymal giant cell astrocytoma, 28–29 CNS primitive neuroectodermal tumors CNS/supratentorial PNET, 43 ependymoblastoma, 44 medulloepithelioma, 43–44 desmoplastic infantile ganglioglioma/astrocytoma, 38 diffusely infiltrating astrocytomas anaplastic astrocytoma, 22–23 diffuse astrocytoma, 21–22 giant cell glioblastoma, 25–26 glioblastoma, 23–25 gliomatosis cerebri, 26 dysplastic gangliocytoma of cerebellum, 37–38 embryonal tumors, 42–44 atypical teratoid/rhabdoid tumor, 44 CNS primitive neuroectodermal tumors, 43–44 medulloblastoma, 42–43 ependymal tumors, 32–34 anaplastic ependymoma, 34 ependymoma, 32–34 myxopapillary ependymoma, 34 subependymoma, 34 gangliocytoma, 36 ganglioglioma, 36–38 astrocytoma, 38 desmoplastic infantile ganglioglioma, 38 dysplastic gangliocytoma of cerebellum, 37–38 gangliocytoma, 36 ganglioglioma, 36–37 glial tumors, 35–36 angiocentric glioma, 35–36 astroblastoma, 36 chordoid glioma of third ventricle, 36 glioneuronal tumors, 38–40 dysembryoplastic neuroepithelial tumor, 38 olfactory neuroblastoma, 40 papillary glioneuronal tumor, 38–39 paraganglioma, 39–40 Rosette-forming glioneuronal tumor of fourth ventricle, 39 medulloblastoma anaplastic medulloblastoma, 42 desmoplastic/nodular medulloblastoma, 42 with extensive nodularity, 42 large cell medulloblastoma, 42 with melanotic differentiation, 42–43 with myogenic differentiation, 42 mixed gliomas, 31–32 anaplastic oligoastrocytoma, 32 oligoastrocytoma, 31 neurocytic tumors, 38 central neurocytoma, 38 cerebellar liponeurocytoma, 38 oligodendroglial tumors, 29–31 anaplastic oligodendroglioma, 31 oligodendroglioma, 29–31 Index • 395 neuroepithelial tissue tumors (Cont.) pineal parenchymal tumors, 40–41 papillary tumor of pineal region, 41 pineal parenchymal tumor of intermediate differentiation, 40 pineoblastoma, 40–41 pineocytoma, 40 neurofibrillary degeneration, Alzheimer, neurofibrillary tangles, Alzheimer disease, 176–178 neurofibroma, 46–47 neurohypophysis tumors, pituitary gland, 360–363 neuromuscular transmission defects, 288–289 Lambert-Eaton syndrome, 289 myasthenia gravis, 288–289 neuromyelitis optica, 171–172 neuronal ceroid lipofuscinosis, 342 neuronal cytoplasmic inclusions (NCIs), 182 neuronal intranuclear inclusion disease, neuronal intranuclear inclusions, 183 neuronal lesions, 2–10 acute neuronal necrosis, 2–3 Alzheimer neurofibrillary degeneration, apoptosis, axonal alterations, 8–10 binucleated neurons, central chromatolysis, 3–4 fenestrated neurons, granulovacuolar degeneration, intraneuronal inclusion bodies, 5–8 nerve cell atrophy, neuronal storage, 4–5 neuropil, programmed cell death, vacuolated neurons, neuronal necrosis, 2–3 neuronal storage, 4–5 neuropathic beriberi, 334 neuropathological techniques, 365–377 artifacts, 377 macroscopic artifacts, 377 microscopic artifacts, 377 autopsy brain, 366 peripheral nervous system, 366 skeletal musculature, 366 spinal cord, 365–366 biopsy procedures brain biopsy, 368 muscle biopsy, 367 peripheral nerve biopsy, 368 stereotactic biopsy, 368 brain bank, 377 electron microscopy, 374 embedding, 371–377 celloidin embedding, 373–374 frozen sections, 374 paraffin embedding, 372–373 fixation of tissues, 369 histoblot, 376 immunohistochemistry, 374–375 macroscopic examination, CNS, 369–371 histological sampling, 371 inspection, 369 slicing, 369–371 PET blot, 376 removal methods, 365–368 autopsy, 365–367 biopsy procedures, 367–369 396 • INDEX surgical specimens, 367 sectioning, 371–377 in situ hybridization, 375 staining, 371–377 neuropathy, 341 neuropil, neurosurgical specimens, 367 neurosyphilis, 120–122 and HIV infection, 122 meningovascular neurosyphilis, 121 parenchymatous neurosyphilis, 122 neurotransmitter metabolism disorders, 228 neurulation failure, 258–261 cranial NTDs, 258–259 spinal NTDs, 259–261 NF2 gene, 34, 45, 47 NF2 tumor suppressor gene, 34 Niemann-Pick disease, 231–233, 342 NIID (neuronal intranuclear inclusion disease), nocardiosis, 120 nodular focal myositis, 310 nodular medulloblastoma, 42 non-infectious CNS vasculitides, 109–110 non-Langerhans cell histiocytoses, 57–58 nonaccidental injury, 75 Nonaka distal myopathy, 295 Nonaka myopathy, 310 nondystrophic myotonias, 296–298 nonmeningothelial tumors, 51–54 hemangioblastoma, 53–54 meningeal hemangiopericytoma, 51–52 mesencyhmal non-meningothelial tumors, 52–53 adipose tissue lipomas, 52 blood vessel tumors hemangiomas, 53 chondroma, 53 fibrous tumors solitary fibrous tumor, 52–53 muscle tumors Leiomyosarcoma, 53 osteocartilaginous tumors, 53 osteochondroma, 53 osteoma, 53 primary melanocytic lesions, 53 nonspecific CNS involvement in viral infections, 132 acute disseminated encephalomyelitis, 132 acute hemorrhagic leukoencephalopathy of Hurst, 132–133, 170 acute viral lymphocytic meningitis, 132 aseptic meningitis, 132 normal prion protein, 150 Northern epilepsy, 239 NTDs See Neural tube closure defects nuclear anomalies, 283 nuclear bags, 282 nuclear pleomorphism, 21 null cell adenomas, 354 nutritional neuropathy, 333–334 occlusion of aqueduct, 274 octapeptide repeat region insertional mutations, 155–158 in prion diseases, 155–158 oculocraniosomatic syndrome, 301 olfactory neuroblastoma, 40 OLIG2, 23–24 oligoastrocytoma, 31 oligodendrocyte lesions, 13 oligodendroglial tumors, 29–31 anaplastic oligodendroglioma, 31 oligodendroglioma, 29–31 oligodendroglioma, 29–31, 363 olivopontocerebellar atrophy [OPCA], 191, 197 Onchocerca vulvulus, 130 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), 192 onion bulb formation, 324 onion bulbs, 326 ophthalmoplegia plus, 301 opportunistic infections, 144–148 AIDS, 146–148 with combined granulocytic, lymphocytic disorders, 146 granulocytic disorders, 146 lymphocytic disorders, 146–148 opsoclonus-myoclonus syndrome, 226 orthochromatic leukodystrophies, 235, 254–256 osteocartilaginous tumors, 53 osteochondroma, 53 osteoma, 53 osteosarcoma, 363 overexpression of mutant EGFRvIII, 25 overlap myositis, 308–309 ovoids, 320 pachygyria, 268 pachymeningitis, 123 pale infarction, 91–92 pallidal necrosis, 208 papillary craniopharyngioma, 360 papillary ependymomas, 32 papillary glioneuronal tumor, 38–39 papillary meningioma, 51 papillary tumor of pineal region, 41 paracoccodioidomycosis, 127 paraffin embedding, 372–373 paraganglioma, 39–40, 363 paragonimiasis, 130 Paramyotonia congenital, 297–298 paraneoplastic cerebellar degeneration, 224–225 paraneoplastic encephalomyelitis, 224–226 paraneoplastic encephalomyelopathies, 221–226 paraneoplastic cerebellar degeneration, 224 paraneoplastic encephalomyelitis, 224–226 paraneoplastic opsoclonus-myoclonus syndrome, 226 paraneoplastic neuropathies, 330 paraneoplastic opsoclonus-myoclonus syndrome, 226 paraneoplastic sensory neuropathy, 226, 330 parasitic myositis, 306 parenchymatous neurosyphilis, 122 Parkinson disease, 186–188 gross appearance, 187 microscopic lesions, 187–188 molecular biology, 188 paucibacillary leprosy, 327 PDGFRA , 25 PDGRA , 25 pediatric head injury, 75 Pelizaeus-Merzbacher disease, 253–254 pellagra deficiency, 212–214 penetrating injuries, 60, 72–73 peptide-hormone-producing adenomas, 347–354 ACTH-producing adenomas, 351–352 corticotroph cell adenomas, 351 silent corticotroph adenoma, 351–352 GH cell adenomas, 350 acidophil stem cell adenoma, 350 GH-only pituitary adenomas, 350 mammosomatotrophic cell adenoma, 350 mixed GH cell/PRL cell adenoma, 350 perinatal ischemic strokes, 276 perinatal telencephalic leukoencephalopathy, 277 perineurial cells, 336 peripheral nerve, 313–342 amyloid neuropathies acquired amyloid neuropathies, 341 familial amyloid polyneuropathies, 341 anatomy, 317–318 autonomic neuropathy, 340–341 hereditary sensory and autonomic neuropathy, 340–341 hereditary sensory neuropathy, 340–341 HSAN type II, 340 HSAN type III, 340–341 axonal degeneration axonal caliber abnormalities, 320 dying-back neuropathy, 318–319 neuronopathy, 319–320 Wallerian degeneration, 318 cryoglobulinemias, 332–333 demyelinating, 324–325 hematological diseases, 330–333 hereditary neuropathies, 336–342 amyloid neuropathies, 341 disorders of lipid metabolism, 342 giant axonal neuropathy, 339 hereditary ataxia, 339 hereditary motor, sensory neuropathy, 336–338 infantile neuroaxonal dystrophy, 339–340 porphyria, 341–342 tomaculous neuropathy, 338–339 hereditary sensory neuropathy HSAN type II, 340 HSAN type III, 340–341 immunopathological disorders inflammatory demyelinating polyradiculoneuropathy, 326–327 sarcoidosis, 327 infection, neuropathies due to AIDS, 327–329 borreliosis, 329 leprosy, 327 inflammatory polyneuropathies, 325–330 immunopathological disorders, 325–327 infection, neuropathies due to, 327–329 vasculitic neuropathies, 329–330 leprosy intermediate forms of leprosy, 327 multibacillary leprosy, 327 paucibacillary leprosy, 327 malignant lymphomas, neuropathies associated with, 330–331 metabolic neuropathy, 333–334 diabetes, 333 monoclonal gammopathies, 331–332 peripheral neuropathy, 331–332 morphometric analysis methods, 316–317 neoplasm invasion of nerve, 333 neoplasms, 330–333 nutritional neuropathy, 333–334 paraneoplastic neuropathies, 330 peripheral nerve biopsy, 313–317 biopsy site, 313–314 frozen sections, 316 indications, 313 methods, 314–317 molecular analysis, 316 plastic embedding, 314 quantitative analysis, 316–317 routine histology, 314 Index • 397 peripheral nerve (Cont.) primary axonal degeneration, 318–321 axonal degeneration, 318–320 primary segmental demyelination, 321–324 acute segmental demyelination, 323 onion bulb formation, 324 remyelination, 323 Schwann cell proliferation, 324 reactions to disease, 318–325 toxic neuropathies, 334–335 accidental exposure, 334–335 arsenic, 334 diphtheria toxin, 334 hexane, 335 hexane and related compounds, 335 industrial exposure, 334–335 lead, 334–335 organophosphorus compounds, 335 therapeutic agent complications, 335–340 traumatic neuropathies, 335–336 vasculitic neuropathies microvasculitis, 330 polyarteritis nodosa, 329–330 peripheral nerve biopsy, 313–317, 368 biopsy site, 313–314 frozen sections, 316 indications, 313 methods, 314–317 morphometric analysis, 316–317 molecular analysis, 316 plastic embedding, 314 quantitative analysis, 316–317 routine histology, 314 peripheral nerve disease, 313–342 amyloid neuropathies acquired amyloid neuropathies, 341 familial amyloid polyneuropathies, 341 axonal degeneration axonal caliber abnormalities, 320 dying-back neuropathy, 318–319 neuronopathy, 319–320 Wallerian degeneration, 318 cryoglobulinemias, 332–333 disease reactions, primary segmental demyelination onion bulb formation, 324 remyelination, 323 hematological diseases, 330–333 hereditary neuropathies, 336–342 amyloid neuropathies, 341 disorders of lipid metabolism, 342 giant axonal neuropathy, 339 hereditary ataxia, 339 hereditary motor, sensory neuropathy, 336–338 infantile neuroaxonal dystrophy, 339–340 porphyria, 341–342 tomaculous neuropathy, 338–339 hereditary sensory and autonomic neuropathy, 340–341 HSAN type II, 340 HSAN type III, 340–341 immunopathological disorders sarcoidosis, 327 subacute/chronic inflammatory demyelinating polyradiculoneuropathy, 326–327 infection, neuropathies due to AIDS, 327–329 borreliosis, 329 leprosy, 327 398 • INDEX inflammatory polyneuropathies, 325–330 immunopathological disorders, 325–327 infection, neuropathies due to, 327–329 vasculitic neuropathies, 329–330 leprosy intermediate forms of leprosy, 327 multibacillary leprosy, 327 paucibacillary leprosy, 327 malignant lymphomas, neuropathies associated with, 330–331 metabolic neuropathy, 333–334 diabetes, 333 methods, morphometric analysis, 316–317 monoclonal gammopathies, 331–332 monoclonal gammopathy-associated peripheral neuropathy, 331–332 neoplasm invasion of nerve, 330–333 nutritional neuropathy, 333–334 paraneoplastic neuropathies, 330 peripheral nerve biopsy, 313–317 biopsy site, 313–314 frozen sections, 316 indications, 313 methods, 314–317 molecular analysis, 316 plastic embedding, 314 quantitative analysis, 316–317 routine histology, 314 primary axonal degeneration, 318–321 axonal degeneration, 318–320 primary segmental demyelination, 321–324 acute segmental demyelination, 323 Schwann cell proliferation, 324 toxic neuropathies, 334–335 accidental exposure, 334–335 arsenic, 334 diphtheria toxin, 334 hexane, 335 industrial exposure, 334–335 lead, 334–335 organophosphorus compounds, 335 therapeutic agent complications, 335–340 traumatic neuropathies, 335–336 vasculitic neuropathies microvasculitis, 330 polyarteritis nodosa, 329–330 peripheral nerve sheath tumors, 44–48 intraneural perineurioma, 47 malignant peripheral nerve sheath tumor, 47–48 neurofibroma, 46–47 Schwannoma, 44–46 cellular Schwannomas, 46 melanotic Schwannomas, 46 plexiform Schwannomas, 46 peripheral nervous system autopsy, 366 perivascular microglia, 13 periventricular hemorrhages, 276 periventricular leukomalacia (PVL), 277 periventricular nodular heterotopia, 265–266 peroneus brevis muscle, 368 peroxisomal disorders, 240–244 adrenoleukodystrophy, 242–243 Refsum disease, 243–244 Zellweger syndrome, 242 PET blot, 376 phenylketonuria, 251–252 phenytoin, 218–219 toxic encephalopathy, 218–219 phosphofructokinase deficiency, 304 phytanic acid oxidase deficiency, 243–244 Pick bodies, 5, 180 Pick cells and FTDP-17, 180 Pick disease, 179–180 pigmentary orthochromatic leukodystrophy of Van Bogaert and Nyssen, 256 PIK3CA, 25 pilocytic astrocytoma, 26–28 pilomyxoid astrocytoma, 28 pineal parenchymal tumors, 40–41 papillary tumor of pineal region, 41 pineal parenchymal tumor, 40 pineoblastoma, 40–41 pineocytoma, 40 pineoblastoma, 40–41 pineocytoma, 40 pituitary adenoma, 346 pituitary aplasia, 359 pituitary carcinoma, 354 pituitary gland, 343–363 ACTH-producing adenomas corticotroph cell adenomas, 351 silent corticotroph adenoma, 351–352 adenomas, 347–356 aplasia, 359 atypical adenoma, 354 carcinoma, 354 chordoma, 362 craniopharyngioma, 360 cysts, 358 developmental disorders, 358–359 ectopic adenoma, 354 empty sella syndrome, 359 germ cell tumors, 362 GH cell adenomas acidophil stem cell adenoma, 350 GH-only pituitary adenomas, 350 mammosomatotrophic cell adenoma, 350 mixed GH cell/PRL cell adenoma, 350 granular cell tumors, 360–362 hamartoma, 362–363 hyperpituitarism, 347–356 hyperplasia, 347–356 hypopituitarism, 356–358 hypoplasia, 359 hypothalamus tumors, 360–363 inflammatory lesions, 356–358 giant cell granuloma, 358 granulomatous hypophysitis, 357 idiopathic, 356–358 lymphocytic hypophysitis, 356–357 primary, 356–358 secondary hypophysitis, 358 xanthomatous hypophysitis, 357 invasive adenomas, 354 lesions, 345–347 metastatic neoplasms, 360 neurohypophysis tumors, 360–363 peptide-hormone-producing adenomas, 347–354 ACTH-producing adenomas, 351–352 GH cell adenomas, 350 gonadotroph cell adenoma, 352 with neuronal metaplasia, 352–354 plurihormonal adenoma, 350 prolactin cell adenoma, 347–349 thyrotroph cell adenoma, 352 pituitary diseases in familial syndromes, 359–360 type multiple endocrine neoplasia syndrome (MEN1), 359 plasmacytoma, 362 Rathke’s pouch, cleft persistence, 358 Rathke’s pouch remnants, persistence of, 358 sellar region tumors, 360–363 vascular lesions, 356–358 apoplexy, 358 infarction, 358 Sheehan syndrome, 358 plasmacytoma, pituitary gland, 362 pleomorphic xanthoastrocytoma (PXA), 28 plexiform Schwannomas, 46 plurihormonal adenoma, 350 PNETs See CNS primitive neuroectodermal tumors POEMS syndrome, 331–332 poliomyelitis, 133–134 polyarteritis nodosa, 329–330 polyglucosan bodies, 304 polyglucosan body disease, 246–247 polyglucosan myopathy, 304 polyglutamine diseases, 174 polymicrogyria, 266–268 polymyositis, 307 polyneuropathies, 325–330 immunopathological disorders, 325–327 inflammatory demyelinating polyradiculoneuropathy, 326–327 sarcoidosis, 327 infection, neuropathies due to, 327–329 AIDS, 327–329 borreliosis, 329 leprosy, 327 inflammatory, 325–330 immunopathological disorders, 325–327 infection, neuropathies due to, 327–329 vasculitic neuropathies, 329–330 leprosy intermediate forms of leprosy, 327 multibacillary leprosy, 327 paucibacillary leprosy, 327 vasculitic neuropathies, 329–330 microvasculitis, 330 polyarteritis nodosa, 329–330 POMGnT1, 294 Pompe disease, 246, 303 POMT1, 294 POMT2, 294 porencephaly, 274–275 porphyria, 250, 341–342 posterior fossa arachnoid cyst, 274 postinfectious perivenous encephalitis, 132 postmortem autolysis, 365 postsynaptic congenital myasthenic syndromes, 289 postvaccinial perivenous encephalitis, 132 potassium-aggravate dmyotonia, 297 presynaptic congenital myasthenic syndrome, 289 primary amyloidosis, 341 primary axonal degeneration, 318–321 axonal caliber abnormalities, 320 dying-back neuropathy, 318–319 neuronopathy, 319–320 Wallerian degeneration, 318 primary CNS lymphomas, 54–55 primary lateral sclerosis, 201 primary melanocytic lesions, 53 primary neoplasms, CNS, 21–54 primary progressive MS (PPMS), 162 Index • 399 primary segmental demyelination, 321–324 acute segmental demyelination, 323 onion bulb formation, 324 remyelination, 323 Schwann cell proliferation, 324 prion diseases, 149–160 abnormal prion protein, 150–151 acquired prion diseases, 156–158 Creutzfeldt-Jakob disease, 157–158 kuru, 156–157 biology, 149–151 diagnostic methods, PrPsc, 151 familial prion diseases, 153–156 cerebral amyloid angiopathy, 155 familial Creutzfeldt-Jakob disease, 154–155 fatal familial insomnia, 156 octapeptide repeat region insertional mutations, 155–158 infectious agent, 149–150 normal prion protein, 150 sporadic Creutzfeldt-Jakob disease, 151–153 variably protease-sensitive prionopathy, 153 variant Creutzfeldt-Jakob disease, 158–160 prion protein, 149–150 prion protein gene, 150 prion protein gene polymorphisms, 151 prionopathy, variably protease-sensitive, 153 PRL cell adenoma See Prolactin cell adenoma PRNP mutations, 154 PRNP polymorphisms, 150 programmed cell death (apoptosis), progranulin, 181 progressive distal axonopathy, 318–319 progressive multifocal leukoencephalitis, 142–143 progressive muscular atrophy, 201 progressive rubella panencephalitis, 139 progressive supranuclear palsy, 188–189 cell biology, 189 genetics, 189 gross appearance, 188–189 microscopic lesions, 189 prolactin cell adenoma, 347–349 prolactinoma, 347–349 PROMM (proximal myotonic myopathy), 297 prosencephalon development, 261–264 holoprosencephalies, 262–263 midline structures, 263–264 anomalies of septum pellucidum, 264 protein, prion abnormal, 150–151 normal, 150 protein disorders, 253–254 Alexander disease, 253 Pelizaeus-Merzbacher disease, 253–254 protein misfolding cyclical amplifi cation (PMCA) reaction, 150 protein storage myopathies, 300 proteinopathies, 173 protozoal infections, 125–128 amebiasis, 125 cerebral malaria, 125 toxoplasmosis, 125–128 trypanosomiasis, 128–129 PrP Sc isotypes, 151 PrPc See Normal prion protein psammomatous meningioma, 49 pseudoallescheriosis, 127 pseuomyopathic changes, 288 PTEN tumor suppressor gene, 25 400 • INDEX pyogenic infections, 114–117 acute bacterial meningitis, 115–116 brain abscesses, 116–117 empyema, 115 epidural abscesses, 115 septic embolism, 117 subdural abscesses, 115 suppurative intracranial phlebitis, 117 quality control of samples, 377 quantitative analysis peripheral nerve biopsy, 316–317 rabies, 135 ragged red fiber, 285, 301 RAS/MAPK signaling pathway, 37 Rasmussen encephalitis, 144, 271 Rathke’s pouch cleft persistence, 358 remnant persistence, 358 RB, 23 RB1, 25 RB pathway, 25 rectal biopsy, 368 Refsum disease, 243–244, 342 regeneration fascicles, 322 relapsing/remitting MS (RRMS), 161 removal en bloc of cervical spine, 367 removal methods, 365–368 autopsy, 365–367 brain, 366 peripheral nervous system, 366 skeletal musculature, 366 spinal cord, 365–366 biopsy procedures, 367–369 brain biopsy, 368 muscle biopsy, 367 peripheral nerve biopsy, 368 stereotactic biopsy, 368 surgical specimens, 367 removal of eyes, 367 remyelination, 323 remyelination in MS lesions, 166 resident microglia, 13 respiratory encephalopathies, 221 retinal/pineal specific transcription factor, CRX, 40 rhabdoid meningioma, 51 rhabdomyolysis, 304–305 rhabdomyosarcoma, 53 rheumatic fibromyalgia, 304 rheumatoid arthritis, 330 rhombencephalosynapsis, 273–274 rickettsiosis, 144 Riley-Day syndrome, 340–341 rimmed vacuoles, 284, 296, 310 ring fibers, 284 ringbinden, 284 RNA viruses, encephalitides, 133–140 rod cell proliferation, 14 Rosenthal fibers, 12, 253 Rosette-forming glioneuronal tumor of fourth ventricle, 39 RRMS, 162 rubella panencephalitis, 139 ruptured intervertebral disc, 74 S100 protein, 51 saccular aneurysm, 77–81 Sanfilippo disease, 237 sarcoglycanopathies, 293 sarcoglycans, 290 sarcoidosis, 123, 310, 327 sarcomas, 363 sarcoplasmic masses, 284 scalp lesions, 60 Schilder type of MS, 169 Schindler disease, 248, 339 schistosomiasis, 130 Schwannoma, 44–46 cellular Schwannomas, 46 melanotic Schwannomas, 46 plexiform Schwannomas, 46 sCJD See Sporadic Creutzfeldt-Jakob disease sclerosing panencephalitis, 135 secondary alpha-dystroglycanopathies, 295 secondary amyloidosis, 341 secondary cerebellar atrophies, 198 crossed cerebellar atrophy, 198 pseudohypertrophy of inferior olive, 198 secondary neoplasms of CNS, 58 secondary Parkinsonian syndromes, 192–193 carbon monoxide poisoning, 192 pharmacologic/toxic, 192 postencephalitic parkinsonism, 192 trauma, 193 vascular disease, 192 secondary progressive MS (SPMS), 161–162 secretory meningioma, 50 sectioning brain, 371–377 SEGA See Subependymal giant cell astrocytoma segmental demyelination, 323 acute segmental demyelination, 323 onion bulb formation, 324 remyelination, 323 Schwann cell proliferation, 324 Seitelberger disease, 248 selective vulnerability, 205 sellar region tumors, pituitary gland, 360–363 semilobar holoprosencephalies, 262 septic embolism, 117 septum pellucidum anomalies, 264 serine/threonine kinase BRA F, 27 SHH-PTCH-SMO signaling pathway, 42 shigellosis, Bordetella pertussis infection, melioidosis, 123 Shulman syndrome, 310 Shy-Drager syndrome, 191 silent corticotroph adenoma, 351–352 Sjögren syndrome, 330 Skein-like inclusions, skeletal muscle, 278–312 biopsy, 278–281 site of biopsy, 278 techniques, 279–280 biopsy techniques immunohistochemistry, 280 muscle enzyme histochemistry, 279–280 congenital myopathies, 298–300 endocrine myopathies steroid myopathy, 304 thyroid myopathy, 304 genetically determined disease, 289–304 congenital myopathies, 298–300 metabolic myopathies, 300–304 muscular dystrophies, 289–298 myofibrillar myopathies, 300 glycogenoses Forbes disease, 303 McArdle disease, 303–304 Pompe disease, 303 Tarui disease, 304 idiopathic inflammatory myopathies dermatomyositis, 306–307 eosinophilic myositis, 310 fasciitis, 310 immune-mediated necrotizing myopathy, 307–308 inclusion body myositis, 309–310 localized myositis, 311 macrophagic myofasciitis, 310–311 nodular focal myositis, 310 overlap myositis, 308–309 polymyositis, 307 sarcoidosis, 310 vasculitis involving skeletal muscle, 311–312 inclusion body myositis, 310 inflammatory myopathies, 305–312 bacterial myositis, 306 fungal myositis, 306 idiopathic inflammatory myopathies, 306–312 inflammatory myopathies caused by microorganisms, 305–306 parasitic myositis, 306 viral myositis, 305–306 interstitial changes, 285 lipid myopathies carnitine deficiency, 301–302 carnitine palmityl transferase deficiency, 302 metabolic myopathies endocrine myopathies, 304 glycogenoses, 302–304 lipid myopathies, 301–302 malignant hyperpyrexia syndrome, 304 mitochondrial myopathies, 300–301 myalgias/cramps syndromes, 304 muscle fiber changes, 281 atrophy, 282 deficiency, 282–283 hypertrophy, 282 muscle fiber structural anomalies, 283–285 shape variations, 281 size variations, 281 muscle fiber structural anomalies basophilic fibers, 283 inclusions, 284 moth-eaten fibers, 283–284 necrotizing changes, 283 nuclear anomalies, 283 ragged red fibers, 285 split fibers, 283 target fibers, 283 tubular aggregates, 285 vacuoles, 284–285 muscular dystrophies autosomal dystrophies, 293–296 Becker muscular dystrophy, 291–293 central core disease, 299–300 centronuclear or myotubular myopathy, 299 congenital fiber type disproportion, 300 congenital muscular dystrophies, 295–296 distal myopathies/muscular dystrophies, 295 Duchenne muscular dystrophy, 291 dystrophic myotonias, 296–298 facio-scapulo-humeral muscular dystrophy, 296 limb-girdle muscular dystrophies, 293–294 Index • 401 skeletal muscle (Cont.) myotonic dystrophy, 296–298 nemaline myopathy, 298–299 nondystrophic myotonias, 296–298 oculopharyngeal dystrophy, 296 related disorders, 298 x-linked Emery-Dreifuss muscular dystrophy, 293 x-linked muscular dystrophies, 291–293 neurogenic atrophy, 285–288 acute neurogenic processes, 288 chronic neurogenic processes, 288 denervation atrophy, 286 grouping of fibers of same histochemical type, 286–288 infants, 288 target fibers, 288 neuromuscular transmission defects, 288–289 Lambert-Eaton syndrome, 289 myasthenia gravis, 288–289 rhabdomyolysis, 305 structural anomalies inclusions, 284 lateral sarcoplasmic masses, 284 toxic myopathies, 304–305 skeletal musculature autopsy, 366 skin biopsy, 368 skull lesions, 61 SMA (Kugelberg-Welander disease), 202, 288 SMA (Werdnig-Hoffmann disease), 202, 288 small angulated fibers, 281, 286 small cell GBM, 26 small intraparenchymal hemorrhages, 110 small vessel disease, 107–112 parenchymal changes, 110–112 arteriopathic leukoencephalopathies, 112 cerebral microbleeds, 110–111 lacunar infarcts, 111–112 small intraparenchymal hemorrhages, 110 vascular diseases, 107–110 CADASIL, 107–109 systemic disorders, 109 vasculitis, 109–110 vasculitis infectious vasculitides, 109 non-infectious CNS vasculitides, 109–110 smear preparations, 367 sparganosis, 130 spheroid body myopathy, 300 sphingolipidoses, 230–238 Fabry disease, 233 Farber lipogranulomatosis, 233 gangliosidoses, 233–235 GM1 gangliosidosis type I, 235 GM2 gangliosidosis type II, 234–235 Tay-Sachs disease, 234 Gaucher disease, 230–231 Krabbe disease, 231 metachromatic leukodystrophy, 235–236 Niemann-Pick disease, 231–233 sphingomyelin lipidosis, 231–233 Spielmeyer-Sjögren-Vogt disease, 239 spina bifida, 259 spinal cord, arterial organization, 104–105 spinal cord autopsy, 365–366 spinal cord injuries, 74–75 spinal cord injury without radiographic abnormality (SCIWORA), 75 spinal cord tuberculomas, 118 402 • INDEX spinal dysraphism, 259 spinal intramedullary infarcts, 104–107 arterial organization of spinal cord, 104–105 etiology, 107 microscopic features, 105 topographical features, 105 spinal muscular atrophy, 202–203 spinocerebellar ataxias (SCA), 199 split fibers, 283 spongiform change, 149–150 spongiform encephalopathies, 149–150 spongy degeneration of CNS, 251 spongy leukodystrophy, 251 sporadic Creutzfeldt-Jakob disease, 151–153 sporadic degenerative ataxia, 200–201 sporadic fatal insomnia, 150 stagnant hypoxia, 206 staining of tissue, 371–377 Steele-Richardson-Olszewski syndrome, 188 stereotactic biopsy, 368 steroid myopathy, 304 storage material, 12–13 striatonigral degeneration, 191 stroke, mitochondrial encephalopathy, 244–245 Strongyloides stercoralis, 130–131 structural protein disorders, 253–254 Alexander disease, 253 Pelizaeus-Merzbacher disease, 253–254 subacute/chronic inflammatory demyelinating polyradiculoneuropathy, 326–327 subacute combined degeneration of spinal cord, 214 subacute necrotizing encephalomyelopathy, 301 subacute necrotizing encephalopathy, 244 subacute necrotizing encephalopathy infantile, 244 subacute necrotizing myopathy, 305 subarachnoid hemorrhage, 67, 76–90 berry aneurysm, 77–81 dissecting aneurysms, 81–82 fusiform aneurysms, 82–83 infective aneurysm, 81 inflammatory aneurysm, 81 saccular aneurysm, 77–81 subcortical band heterotopia, 265 subdural abscesses, 115 subdural hemorrhage, 64–66 subdural hygroma, 66–67 subependymal giant cell astrocytoma, 28–29 subependymoma, 34 sudanophilic leukodystrophy, 235 sulfatides, 235 suppurative intracranial phlebitis, 117 supratentorial lesions, 17 sural nerve, 368 surgical specimens, 367 Swiss-cheese artifact, 377 synuclein, syringomyelia, 260–261 systemic disease, CNS changes, 221–226 hepatic encephalopathy, 221 multifocal necrotizing leukoencephalopathy, 221 paraneoplastic encephalomyelopathies, 221–226 paraneoplastic cerebellar degeneration, 224 paraneoplastic encephalomyelitis, 224–226 paraneoplastic opsoclonus-myoclonus syndrome, 226 respiratory encephalopathies, 221 systemic lupus erythematosus, 330 systemic vasculitis, 329–330 T-cell leukemia, 140 T8 encephalitis, 148 Tangier disease, 237–238, 342 tanycytic ependymomas, 33 targetoid fiber, 283 Tarui disease, 304 tau protein, 12 tauopathy, 174 Tay-Sachs disease, 234 TDP43, 181 telethonin, 290, 294 temozolomide, 31 Thai stages, 178 thalamic variant of sCJD, 152 thallium, 220 toxic encephalopathy, 220 thiamine deficiency, 211–212 third ventricle, chordoid glioma, 36 Thomsen disease, 298 thorn-shaped astrocytes, 190 thyroid myopathy, 304 thyrotroph cell adenoma, 352 tick-bite meningoradiculoneuritis, 329 tigroid demyelination, 249 tigroid leukodystrophy, 253 tin, 220–221 toxic encephalopathy, 220–221 tissue fixation, 369 titin, 290, 294 tomacula, 324 tomaculous neuropathy, 338–339 tonsil biopsy, 159 touch preparations, 367 toxic encephalopathies, 215–221 aluminum, 219 arsenic, 219–220 ethanol, 215–217 acute alcohol intoxication, 215 chronic alcoholism, 215–217 ethylene glycol, 217–218 heavy metals, 219–221 lead, 220 manganese, 220 mercury, 220 metalloids, 219–221 methanol, 217 phenytoin, 218–219 thallium, 220 tin, 220–221 toxic myopathies, 304–305 toxic neuropathies, 334–335 accidental exposure, 334–335 arsenic, 334 diphtheria toxin, 334 hexane, 335 industrial exposure, 334–335 lead, 334–335 organophosphorus compounds, 335 therapeutic agent complications, 335–340 toxin-induced neurological disease, 123–124 toxocariasis, 130 toxoplasma, 306 toxoplasmosis, 125–128 TP53, 22, 25, 31 TP53 gene, 25 TP53 signaling, and reduced signaling of RB pathway, 25 transitional meningioma, 49 transitional schlerosis, 169 transmissible spongiform encephalopathies, 149–150 transthyretin, 341 traumatic axonal injury (TAI), 69 traumatic brain injury, 59–75 blast injuries, 73 chronic traumatic encephalopathy, 73–74 classification, 59–60 diffuse brain injury, 68–72 brain swelling, 72 diffuse traumatic axonal injury, 69–72 diffuse vascular injury, 72 ischemia, 68–69 diffuse traumatic axonal injury axonal injury in mild head injury, 71 focal axonal injury, 71–72 focal injury, 60–68 contusions, 61–62 intracranial hemorrhage, 62–68 lacerations, 61–62 scalp lesions, 60 skull lesions, 61 intracranial hemorrhage brainstem lesions, 68 extradural hemorrhage, 63–64 intracerebral hemorrhage, 67 intraventricular hemorrhage, 67 subarachnoid hemorrhage, 67 subdural hemorrhage, 64–66 subdural hygroma, 66–67 vascular, 67–68 pediatric head injury, 75 penetrating injuries, 72–73 spinal cord injuries, 74–75 traumatic encephalopathy, 73–74 traumatic neuropathies, 335–336 Trichinella spiralis, 306 trichinosis, 130–131 Triethyl-tin, 220 TRIM32, 294 trypanosomiasis, 128–129 TSC1 gene, 28 TSC2 gene, 28 tuberculoid leprosy, 327 tuberculosis, 117–119 brain tuberculomas, 118 spinal cord tuberculomas, 118 tuberculous abscess, 118–119 tuberculous epidural abscess, 117–119 tuberculous meningitis, 117–118 tuberculous subdural abscesses, 117–119 tuberculous abscess, 118–119 tuberculous epidural abscess, 117–119 tuberculous meningitis, 117–118 tuberculous subdural abscesses, 117–119 tuberous sclerosis, 271 tubular aggregates, 285 tufted astrocytes, 12, 190 tumor suppressor gene, 22 tumors of CNS, 20–58 astrocytic tumors circumscribed astrocytomas, 26–28 diffusely infiltrating astrocytomas, 21–26 choroid plexus tumors atypical papilloma, 35 carcinoma, 35 papilloma, 35 Index • 403 tumors of CNS (Cont.) circumscribed astrocytomas pilocytic astrocytoma, 26–28 pilomyxoid astrocytoma, 28 pleomorphic xanthoastrocytoma, 28 subependymal giant cell astrocytoma, 28–29 classification, 20–21 CNS primitive neuroectodermal tumors CNS/supratentorial PNET, 43 ependymoblastoma, 44 medulloepithelioma, 43–44 diffusely infiltrating astrocytomas anaplastic astrocytoma, 22–23 diffuse astrocytoma, 21–22 giant cell glioblastoma, 25–26 glioblastoma, 23–25 gliomatosis cerebri, 26 embryonal tumors atypical teratoid/rhabdoid tumor, 44 CNS primitive neuroectodermal tumors, 43–44 medulloblastoma, 42–43 ependymal tumors anaplastic ependymoma, 34 ependymoma, 32–34 myxopapillary ependymoma, 34 subependymoma, 34 ganglioglioma, 36–37 desmoplastic infantile ganglioglioma/astrocytoma, 38 dysplastic gangliocytoma of cerebellum, 37–38 gangliocytoma, 36 glial tumors angiocentric glioma, 35–36 astroblastoma, 36 chordoid glioma, third ventricle, 36 glioneuronal tumors dysembryoplastic neuroepithelial tumor, 38 olfactory neuroblastoma, 40 papillary glioneuronal tumor, 38–39 paraganglioma, 39–40 Rosette-forming glioneuronal tumor of fourth ventricle, 39 histiocytic tumors, 56–58 Langerhans cell histiocytosis, 56–57 non-Langerhans cell histiocytoses, 57–58 lymphomas, 54–58 primary CNS lymphomas, 54–55 secondary CNS involvement, 55–56 medulloblastoma anaplastic medulloblastoma, 42 desmoplastic/nodular medulloblastoma, 42 with extensive nodularity, 42 large cell medulloblastoma, 42 with melanotic differentiation, 42–43 with myogenic differentiation, 42 meninges tumors, 48–54 meningiomas, 48–51 nonmeningothelial tumors, 51–54 meningiomas WHO grade I meningiomas, 48–50 WHO grade II meningiomas, 50 WHO grade III meningiomas, 50–51 mesencyhmal non-meningothelial tumors adipose tissue lipomas, 52 blood vessel tumors hemangiomas, 53 chondroma, 53 fibrous tumors solitary fibrous tumor, 52–53 muscle tumors Leiomyosarcoma, 53 osteocartilaginous tumors, 53 404 • INDEX osteochondroma, 53 osteoma, 53 mixed gliomas anaplastic oligoastrocytoma, 32 oligoastrocytoma, 31 neurocytic tumors central neurocytoma, 38 cerebellar liponeurocytoma, 38 neuroepithelial tissue tumors, 21–44 astrocytic tumors, 21–29 choroid plexus tumors, 34–35 desmoplastic infantile ganglioglioma/astrocytoma, 38 dysplastic gangliocytoma of cerebellum, 37–38 embryonal tumors, 42–44 ependymal tumors, 32–34 gangliocytoma, 36 ganglioglioma, 36–38 glial tumors, 35–36 glioneuronal tumors, 38–40 mixed gliomas, 31–32 neurocytic tumors, 38 oligodendroglial tumors, 29–31 pineal parenchymal tumors, 40–41 nonmeningothelial tumors hemangioblastoma, 53–54 meningeal hemangiopericytoma, 51–52 mesencyhmal non-meningothelial tumors, 52–53 primary melanocytic lesions, 53 oligodendroglial tumors anaplastic oligodendroglioma, 31 oligodendroglioma, 29–31 peripheral nerve sheath tumors, 44–48 intraneural perineurioma, 47 malignant peripheral nerve sheath tumor, 47–48 neurofibroma, 46–47 Schwannoma, 44–46 pineal parenchymal tumors papillary tumor of pineal region, 41 pineal parenchymal tumor of intermediate differentiation, 40 pineoblastoma, 40–41 pineocytoma, 40 primary neoplasms, 21–54 Schwannoma cellular Schwannomas, 46 melanotic Schwannomas, 46 plexiform Schwannomas, 46 secondary neoplasms, 58 WHO grade I meningiomas angiomatous meningioma, 49–50 fibrous meningioma, 49 lymphoplasmacyte-rich meningioma, 50 meningothelial meningioma, 49 metaplastic meningiomas, 50 psammomatous meningioma, 49 secretory meningioma, 50 transitional meningioma, 49 WHO grade II meningiomas atypical meningioma, 50 chordoid meningioma, 50 clear cell meningioma, 50 WHO grade III meningiomas anaplastic meningioma, 50–51 papillary meningioma, 51 rhabdoid meningioma, 51 Type atrophy, 282 Type atrophy, 282 Type fiber atrophy, 305 Type multiple endocrine neoplasia syndrome (MEN1), 359 Type 2B deficiency, 283 type grouping, 286–288 Type I fiber predominance, 283 Type IV glycogenosis, 304 ubiquitin, Udd myopathy, 295 ulegyria, 276 Ullrich/Bethlem myopathies, 296 uncommitted/undiff erentiated cells, 270 urea-cycle disorders, 253 uremic neuropathy, 334 vacuolar myopathy with lysosomal hyperactivity, 305 vacuolated neurons, vacuoles, 284–285 valosin-containing protein (VCP), 181 variably protease-sensitive prionopathy, 153 variant Creutzfeldt-Jakob disease, 158–160 vascular cognitive impairment, 185 vascular dementia, 185 vascular disease, 76–113 CADASIL, 107–109 cerebral amyloid angiopathy complications, 88 etiology, 86–87 pathology, 87–88 cerebral infarcts carotid territory, 97–100 complications of therapy, 102–104 vertebrobasilar territory, 100–102 hemodynamic factors anastomotic pathways of vascular supply, 93 occlusion site, 93–94 occlusion type, 94 hypertension evolution, 84–85 mechanisms, 83–84 topography, 85–86 infarction, 90–107 anemic infarction, 91–92 atherosclerosis, 94–96 cardiac emboli, 97 cerebral infarcts, 97–104 etiology, 92–97 hemodynamic factors, 93–94 hemorrhagic infarction, 92 pale infarction, 91–92 spinal intramedullary infarcts, 104–107 intracerebral hemorrhage, 76–90 intraparenchymal hemorrhage, 83–90 cerebral amyloid angiopathy, 86–88 hypertension, 83–86 hypertensive cerebrovascular disease, 83–86 systemic disease, 90 vascular malformations, 88–90 parenchymal changes arteriopathic leukoencephalopathies, 112 cerebral microbleeds, 110–111 lacunar infarcts, 111–112 small intraparenchymal hemorrhages, 110 pathology, 112–113 small vessel disease, 107–112 parenchymal changes, 110–112 vascular diseases, 107–110 spinal intramedullary infarcts arterial organization of spinal cord, 104–105 etiology, 107 microscopic features, 105 topographical features, 105 subarachnoid hemorrhage, 67, 76–90 berry aneurysm, 77–81 dissecting aneurysms, 81–82 fusiform aneurysms, 82–83 inflammatory/infective aneurysms, 81 saccular aneurysm, 77–81 systemic disorders, 109 vascular malformations arteriovenous malformations, 88–89 capillary telangiectases, 90 cavernous hemangiomas, 90 venous angiomas, 89–90 vasculitis, 109–110 infectious vasculitides, 109 non-infectious CNS vasculitides, 109–110 vascular lesions, pituitary gland, 358 apoplexy, 358 infarction, 358 Sheehan syndrome, 358 vascular malformations, 88–90 arteriovenous malformations, 88–89 capillary telangiectases, 90 cavernous hemangiomas, 90 venous angiomas, 89–90 vascular supply, anastomotic pathways, 93 vascular tumors, 363 vasculitic neuropathies, 329–330 microvasculitis, 330 polyarteritis nodosa, 329–330 vasculitis involving skeletal muscle, 311–312 vasogenic edema, 14 venous angiomas, 89–90 ventricle, chordoid glioma, 36 vertebral dysraphism, 259 vertebral fracture, 74 vertebrobasilar territory infarcts, 100–102 VHL tumor suppressor, 54 viral inclusions, viral infections, 131–144 DNA viruses CMV infection, 142 HSV encephalitis, 140–142 progressive multifocal leukoencephalitis, 142–143 VZV infection, 142 encephalitides DNA viruses, 140–143 RNA viruses, 133–140 infective viral encephalitis, 133–144 encephalitis, 143–144 encephalitis lethargica, 143 Rasmussen encephalitis, 144 nonspecific CNS involvement, 132 acute disseminated encephalomyelitis, 132 acute hemorrhagic leukoencephalopathy of Hurst, 132–133, 170 acute viral lymphocytic meningitis, 132 aseptic meningitis, 132 RNA viruses arbovirus encephalitides, 134–135 henipaviruses, 137–139 human T-cell leukemia/lymphotrophic virus-1-associated myelopathy, 140 Index • 405 viral infections (Cont.) infection by human immunodeficiency virus, 139–140 measles encephalitides, 135–137 poliomyelitis, 133–134 progressive rubella panencephalitis, 139 rabies, 135 viral lymphocytic meningitis, 132 viral myositis, 305–306 virological studies, 377 vitamin B12 deficiency, 214–215 vitamin deficiencies, 211–215 pellagra, 212–214 thiamine deficiency, 211–212 vitamin B12 deficiency, 214–215 von Economo encephalitis, 143 VZV infection, 142 encephalitides, 142 Waldenström macroglobulinemia, 332 Walker-Warburg syndrome, 258, 270, 295 watershed infarct or boundary-zone infarct, 98–99 Wegener granulomatosis, 330 Welander, Udd, and Markesbery-Griggs distal myopathies, 295 Welander myopathy, 295 Werdnig-Hoffmann disease, 288 Wernicke-Korsakoff encephalopathy, 216 Wernicke-Korsakoff syndrome, 211 Whipple disease, 119–120 white matter, developing brain, lesions of, 277 406 • INDEX Wilson disease, 250 Wilson hepatolenticular degeneration, 221 WNT-β-catenin pathway, 42 Wolman disease, 237 X-linked bulbar muscular atrophy, 203 X-linked muscular dystrophies, 291–293 Becker muscular dystrophy, 291–293 central core disease, 299–300 centronuclear or myotubular myopathy, 299 congenital muscular dystrophies, 295–296 distal myopathies/muscular dystrophies, 295 Duchenne muscular dystrophy, 291 dystrophic myotonias, 296–298 Emery-Dreifuss muscular dystrophy, 293 facio-scapulo-humeral muscular dystrophy, 296 limb-girdle muscular dystrophies, 293–294 nemaline myopathy, 298–299 nondystrophic hereditary myotonias, 298 oculopharyngeal dystrophy, 296 related disorders, 298 X-linked spinal atrophy, 203 xanthomatosis, cerebrotendinous, 238 xanthomatous hypophysitis, 357 xeroderma pigmentosum, 248–249 YWHAE, 268 Zellweger syndrome, 242, 266 zygomycosis, 127 ... • 21 5 A B C FIGURE 9 .21 Subacute combined degeneration of the spinal cord (A) Klüver-Barrera stain showing spongy appearance of the white matter in the central part of the posterior column of. .. concentric bodies on electron microscopy) 2. 1.6 .2 GM2 gangliosidosis type II (Sandhoff disease) and GM2 gangliosidosis AB variant Sandhoff disease (GM2 gangliosidosis type II) results from mutations... consist of loss of Purkinje cells with proliferation of Bergmann glia and variable depopulation of the internal granular cells They are associated with lesions of the dorsal laminae of the inferior