Neuronal Inclusion Bodies in Degenerative Diseases
Neuronal cytoplasmic inclusion bodies are the distinguishing features of several important neurodegenera-tive diseases. Some are identified in hematoxylin-eosin HE -stained sections, others only in silver-stained sections, and still others with immunohistologic stains see Fig. 2.3 . The molecular components of these inclusions are identified using immunohistochemical stains. Some Diseases with Neurofibrillary Tangles Parkinson-Dementia-ALS complex of Guam Progressive supranuclear palsy...
Leigh Syndrome
Leigh syndrome LS or subacute necrotizing encepha-lomyopathy, is genetically heterogenous, caused by mutations in the nuclear gene coding for SORF1 and mutations in the mitochondrial gene coding for ATPase 6. The inheritance is mendelian autosomal recessive or X-linked recessive or maternal. The biochemical defect results from defects in the OXPHO system and the pyruvate dehydrogenase complex. The disease commonly affects infants and young children, rarely adolescents or adults. It presents...
Ischemic Stroke Cerebral Infarction
The brain requires a constant and adequate blood flow to supply oxygen and glucose essential for its high energy metabolism. A constant blood flow is assured by an autoregulatory mechanism of arteries and arterioles they constrict in response to rising systemic blood pressure and dilate in response to falling systemic blood pressure. This mechanism operates while the arterial pressure remains between 50 and 160 mm Hg. One- Atherosclerosis of cerebral arteries. A. Severe atheromatosis of basal...
Prion Diseases Transmissible Spongiform Encephalopathies
Animal Prion Diseases Human Prion Diseases Prion diseases, a group of fatal neurodegenerative diseases affecting both humans and animals, are unique in that they can be both infectious transmissible and heritable. The causative pathogen is a proteinaceous infectious agent termed prion protein PrPsc sc refers to scrapie . PrPsc is a protease-resistant isoform of a cellular prion protein PrPc c refers to cellular that is normally folded in the membranes of the neurons and glial cells of the...
Amebiasis
Infections by one of the three species of amebae Naegleria fowleri, Acanthamoeba sp., and Entamoeba histolytica are rare but detrimental. Immunocompromised individuals are at risk for the infection. Naegleria fowleri is found in freshwater and soil. It infects the nasal cavity and reaches the brain along the olfactory nerves to produce a fulminant hemorrhagic meningoencephalitis with PNLs. Acanthamoeba sp. are found in fresh- and seawater. They reach the brain via the bloodstream, producing a...
Permanent Global Ischemia Brain Death
The difference between the mean systemic arterial blood pressure and the intracranial pressure ICP pressure of the CSF maintains the cerebral perfusions pressure CPP . A drop in arterial blood pressure or an increase in ICP depresses blood perfusion. When the CPP suddenly drops below a critical value about 40 mm Hg , cerebral circulation gradually ceases. If blood flow is not restored, the nonperfused brain suffers total and irreversible damage, eventually leading to irreversible cessation of...
Mucopolysaccharidoses
Mucopolysaccharides MPS or glycosaminoglycans GAGs consist of polysaccharide chains attached to a polypeptide core. Due to deficient activities of specific enzymes, MPSs accumulate in visceral organs and mesenchymal tissues and are excreted in urine. The mucopolysaccharides that are stored and excreted in urine are dermatan sulfate, heparan sulfate, and chon-droitin sulfate. Mucopolysaccharidoses, common lysosomal diseases, affect chiefly infants and young children and are transmitted in an...
Bibliography Efy
Bernat, J. L. 1997 . Systemic hypoperfusion brain injury In K. M. A. Welch, D. J. Caplan, et al. Eds. Primer on cerebrovascular diseases pp. 289-292 . San Diego Academic Press. Ginsberg, M. D., Hedley-Whyte, E. T., amp Richardson, E. P., Jr. 1976 . Hypoxic-ischemic leukoencephalopathy in man. Arch Neurol, 33, 5-14. Hogan, R. E. 2001 . Mesial temporal sclerosis Clinicopathological correlations. Arch Neurol, 58, 1484-1486. Kinney H. C., Samuels, M. A. 1994 . Neuropathology of the persistent...
Pathology Vtn
Grossly, multiple focal areas of demyelination, called plaques, are the pathologic hallmark of the disease. The location, number, size, and shape of the plaques vary greatly from case to case. Plaques typically occur within the white matter, but may also be found within gray structures, such as the cerebral cortex, thalamus, and basal ganglia. Preferential sites are the optic nerves and chiasma, the periventricular and periaqueductal regions, Postinfectious and postvaccination encephalomyelitis...
Adult Adrenomyeloneuropathy
Adult adrenomyeloneuropathy presents with a slowly progressive spastic paraparesis and peripheral neuropathy. It may be associated with cerebral ALD. Demyelin-ation is prominent in the spinal cord, particularly in the posterior columns and pyramidal tracts, but lympho-cytic infiltrations are rare or absent. Adrenal insufficiency is variably present. Usually it is severe in AMN, in which the testes are also involved. The atrophic adrenal cortex contains ballooned eosino-philic cells, and some...
Transtentorial Uncal and Hippocampal Herniation
A hemispheric mass lesion displaces the uncus and all or part of the hippocampus through the tentorial opening. Subsequently, the oculomotor nerve-roots are pressed against the rigid tentorial edge or the petrocli-noid ligament. The rostral brainstem with the aqueduct is compressed and displaced to the opposite side. This displacement allows the tentorial edge to lacerate the pyramidal fibers in the opposite pedunculus, producing the Kernohan's notch see the section Localizing Features .
Lysosomal Carbohydrate Diseases
Deficiencies of lysosomal enzymes necessary for the degradation of complex carbohydrates result in an accumulation of nondegraded products in various tissues and cells. Such products are the mucopolysaccharides, the mucolipids, the glycoproteins, and the glycogen. The diseases affect chiefly infants and children. Despite genetic and enzymatic heterogeneity, many diseases share facial and skeletal abnormalities, multiorgan manifestations, and urinary excretion of abnormal metabolites,...
Acute Disseminated Postinfectious and Postvaccination Encephalomyelitis
Acute disseminated postinfectious and postvaccination encephalomyelitis develops 1 to 3 weeks following a Balo's concentric sclerosis shows zones of myelin losses alternating with zones of intact myelin in a circular fashion myelin stain . viral or bacterial infection such as measles, varicella, rubella, influenza, mumps, infectious mononucleosis, or scarlet fever, or it develops following vaccination for rabies, smallpox, measles, typhoid, and paratyphoid. The onset is acute with headaches,...
Herpes Simplex Virus1 Infection
Herpes simplex virus-1 infection is the major cause of sporadic and malignant encephalitis, chiefly in adults and young subjects. The infection is acquired by exposure to contaminated saliva or respiratory secretion. The virus initially causes a nasopharyngitis. By retrograde axonal transport, it reaches the trigeminal ganglia, where it becomes latent. Reactivation of the virus produces herpes vesicles on the lips cold sore or oral mucosa. The brain is infected by spread of the virus along the...
Diseases with Akinetic Rigidity Idiopathic Parkinsons Disease
Idiopathic Parkinson's disease iPD , the most common movement disorder and a major cause of neurologic Akinetic-rigid form Parkinson's disease Progressive supranuclear palsy Dementia with parkinsonism linked to chromosome 17 Striatonigral degeneration Corticobasal degeneration Postencephalitic parkinsonism Parkinsonism-dementia complex of Guam Hyperkinetic form Huntington's disease Dystonias disability in the elderly, may affect individuals of 40 to 60 years of age, but it is seen primarily in...
Metachromatic Leukodystrophy Sulfatide Lipidosis
Metachromatic leukodystrophy or sulfatide lipidosis is an autosomal recessive disorder affecting chiefly infants, but juvenile and adult variants are also known. It is caused by deficiency of the lysosomal enzyme arylsulfa-tase A ASA . The ASA gene is located on chromosome 22. ASA normally degrades the myelin sulfatides to cerebroside and inorganic sulfate Table 9.6 . A deficiency of the enzyme ASA results in the excessive accumulation of sulfatides in the myelin, rendering it chemically...
HIVImmunosuppressionRelated Nervous System Diseases
This group of diseases comprises numerous opportunistic infections and the primary CNS lymphoma. A great number of pathogens, dormant in the neural tissue, become reactivated by the immunosuppressed HIV-encephalitis. Microglial nodules with multinucleated giant cells A in the white matter HE and B brainstem Holmes H-E . C. Expression of HIV p24 antigen in cells of microglial nodule immunostain . HIV-encephalitis. Microglial nodules with multinucleated giant cells A in the white matter HE and B...
Astrocytes
The role of astrocytes begins during brain development, when the radial astrocytes guide the migrating neurons. After birth, the astrocytes are important in a number of physiologic processes They provide support and nutrients to the neurons, protect them from excitotoxic neurotransmitters, contribute to the blood-brain barrier, and maintain homeostasis in the extracellular compartment. Astrocytes are star-shaped. In HE-stained section, only the nucleus is visible it is medium-sized, round or...
Neuronal Lipidoses
These diseases are inherited in an autosomal recessive mode except for the Fabry's disease, which has an X-linked recessive inheritance. They affect chiefly infants and children and may also occur in juveniles and adults. The diseases display both similar and distinctive clinical features. Generally, infantile diseases with onset at 6 months to 2.5 years manifest with loss of already acquired psychomotor skills, growth retardation, visual impairment, and often seizures. Death occurs within 1 to...
Cerebral Pathology In Chronic Epilepsy
Hypoxic-ischemic lesions often are encountered in the brains of patients who suffer from epilepsy with generalized tonic-clonic seizures and status epilepticus. The lesions result from respiratory and circulatory Prolonged coma following cardiac arrest. Chronic cortical pan-necrosis. Three-month survival in a 69-year-old man. A. Transverse section of the cerebral hemispheres shows thinning and sponginess of the cortex, necrosis of the basal ganglia, and focal softening of the white matter. The...
NewVariant CJD
In 1994 and1995, a little less than 10 years after the outbreak of BSE in Europe, a new variant of CJD nvCJD was recognized in the United Kingdom and France. The disease is distinguished by an earlier onset of behavioral changes and psychiatric symptoms, followed by cerebellar dysfunction and myoclonus. Later in the course, dementia develops. The course is protracted. Bilateral pulvinar hyperintensities on MRI are held to be characteristic. Because PrPsc is detectable in lymphoid tissue,...
Oligodendrocytes
In standard preparations, oligodendrocytes are recognized by their small, round, dark nuclei, rich in chromatin. The small perikaryons, with few and short processes, are visualized using silver stains. In the gray matter, oligodendrocytes serve as satellite cells around the neurons and regulate the perineuronal environment. In the white matter, oligodendrocytes are aligned along the myelin sheaths as interfascicular glia Fig. 2.7 . The major function of interfascicular oligodendrocytes is the...
Anthrax Meningoencephalitis
Infection with Bacillus anthracis is acquired through cutaneous contact, inhalation, or ingestion. The bacilli Acute purulent leptomeningitis caused by P-hemolytic streptococci in a 71-year-old man. A. Thick yellow exudate fills the subarachnoid space over the lateral aspects of the cerebral hemispheres. B. Dense exudate of PNLs, a few lymphocytes and erythrocytes, and some fibrin fills the subarachnoid space HE . Acute purulent leptomeningitis caused by P-hemolytic streptococci in a...
Pathologic Features 1
Grossly, the brain shows variable atrophy of the convolutions, subcortical gray structures, and hemispheric white matter Fig. 7.1 . The histologic hallmark of the disease is microvacuolation and spongiform degenera Creutzfeldt-Jakob disease. A. Severe diffuse cerebral atrophy. B. Cerebral cortex showing microvacuolation and neuronal losses and C prominent astrocytic proliferation HE . tion of the cerebral and cerebellar cortex and, variably, of the subcortical gray structures. The vacuoles are...
Myelin
Myelin ensheathes the nerve fibers in a spiral lamellar fashion, promoting a faster and more effective conduction of nervous impulses along the nerve fibers. It is produced by the oligodendrocytes during development of the brain and spinal cord and maintained by them after completion of myelination Fig. 2.10 . The major chemical components of myelin are lipids, which constitute about 70 to 85 . The sphingolipids and cholesterol are the most important of these. The remaining 15 to 30 of myelin...
Death of the Neurons
Neurons die in one of two ways through apoptosis or necrosis. Apoptosis, or programmed cell death, is genetically regulated and commonly occurs in degenerative diseases. During brain development, the apoptosis of excess neurons is physiologic. In apoptotic cell death, the nuclear chromatin condenses into masses of various sizes and shapes, the nuclear membrane buds and fragments. These nuclear buds, along with cytoplasmic buds, form the apoptotic bodies, which then are phago-cytosed by...
Meningovascular Syphilis
Meningovascular syphilis manifests 5 to 7 years after the initial infection and presents with meningeal and multifocal cerebral and or spinal cord symptoms and signs. The pathology is characterized by a proliferative endarteritis of the small, medium, and large arteries Heubner endarteritis . A prominent endothelial proliferation along with mononuclear cell infiltrates in the media and adventitia lead to severe luminal narrowing and, eventually, occlusion and subsequent infarctions Fig. 6.25 ....
Cryptococcosis
Cryptococcosis torulosis is the most prevalent cerebral mycosis. Cryptococcus neoformans, in yeast form, measures 5 to 12 microns. It is surrounded by a polysac-charide capsule that stains with Alcian blue and mucicarmine it appears as a halo in sections stained with silver Fig. 6.21 . The primary infection is commonly a granuloma-tous inflammation in the lungs. The fungi reach the brain by hematogenous dissemination and produce a granulomatous meningoencephalitis with thick, gelatinous...
Acknowledgments
My thanks to the histologic technicians, photographers, and secretaries for their valuable contribution to this work. I am indebted to Tariq I. Hassan, M.D., Associate Professor of Neurology at the Chicago Medical School at Rosalind Franklin University and Chief of Staff at the Veterans Administration Medical Center at North Chicago for his continuous support for the Neuropathology Laboratory. My special thanks to Frederick Sierles, Professor of Psychiatry at the Chicago Medical School at...
Anomalies of Basal Cerebral Arteries
The persistence of the embryonic origin of the posterior cerebral artery from the carotid artery is a common incidental autopsy finding Fig. 4.35 . Subsequently, the supply territory of the posterior cerebral artery becomes liable to circulatory insufficiency in the carotid artery. In hypoplasia of one vertebral artery, the basilar artery is the continuation of the normal vertebral artery. Dolichoectasia in an 83-year-old man. A. The basilar artery is tortuous, its wall is thin and soft, and...
Enteroviruses
Enteroviruses are spread through the respiratory route or through fecal contamination hand-to-mouth . Poliovirus causes poliomyelitis, chiefly a childhood disease, which, before the introduction of the Salk vaccine, had a high mortality rate. The virus spreads from the oropharynx to the gastrointestinal tract and from there to the lymphoid tissue. Here, it replicates and disseminates to the nervous tissue via the bloodstream. Within the nervous tissue, the virus selectively affects the motor...
Purulent Leptomeningitis
Purulent leptomeningitis refers to an inflammation of the pia and arachnoid with a purulent exudate in the subarachnoid space. Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae are responsible for about 75 of these infections. 6 mos.-2 yrs. Children-young adults Adults B. streptococcus Listeria monocytogenes Staphylococcus aureus Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Purulent leptomeningitis occurs at all ages from birth through old...
Pathology of the Neurons
The reactions of neurons to disease manifest in alterations in the size, shape, and staining properties of the Neuronal alterations. A. Vacuolated swollen motor neuron in medulla. B. Chronic atrophy of pyramidal neuron The perikaryon is shrunken, the dendrites are corkscrew-like, and the nucleus is densely basophilic. C. Axonal or retrograde changes in hypo-glossal neuron caused by tumorous infiltration of the nerve roots. The swollen perikaryon is rounded, the dendrites are retracted, the...
Cytoplasmic argyrophilic and tau positive inclusions
These features are characteristic of several neurodegen-erative diseases collectively referred to as tauopathies see Fig. 2.6 . Viral nuclear inclusions. These inclusions are found in herpes simplex encephalitis, subacute sclerosing panen-cephalitis, and in progressive multifocal leukoencepha-lopathy, in which the astrocytes are transformed into large atypical cells. Neoplastic transformation. Astrocytes have the capacity to proliferate into a variety of relatively benign or malignant...
Vasogenic Edema
Intracranial expanding mass lesions, such as neoplasms, abscesses, granulomas, and hematomas, induce a vasogenic edema, which, if not resolved, leads to herniations, vascular lesions, and bony erosions Table 2.7 . Hernia-tions and vascular lesions are particularly important, because they create serious clinical situations, and death can ensue. Initially, the edema surrounds the mass lesion then gradually propagates further along the fiber tracts, ultimately becoming generalized. The severity of...
Dolichoectasia
Dolichoectasia is the diffuse elongation, distention, and tortuosity of the extracranial and intracranial cerebral arteries the vertebrobasilar and the posterior cerebral arteries are affected most often. Atherosclerosis accentuates the anomaly. Histologically, the arterial wall is thin and the elastica is disrupted or virtually absent Fig. 4.34 . Dolichoectasia is associated with ischemic stroke, subarachnoid hemorrhage, and various symptoms caused by the pressure exerted on adjacent...
Introduction to Clinical Neuropathology
The objectives of the neuropathologic examination are twofold First, to identify and localize any lesion s , interpret histologic changes and ultimately, formulate a diagnosis. Second, to correlate the location and histopathologic features of the lesion s with the clinical presentation. Fulfilling these goals requires familiarity with the anatomy and histology of the nervous system. For this purpose, photographs of representative brain and spinal cord slices and myelin-stained sections are...
Cerebral Changes In Physiologic Aging
Aging is an inescapable natural biologic process affecting all organ systems of the body. This process, regulated by genetic factors longevity genes and influenced by environmental factors, begins after age 50 to 60 years or later. Aging of the central nervous system primarily A. Normal pressure hydrocephalus in a 60-year-old man with gait difficulties over the years and memory decline. MRI shows enormously enlarged ventricles and only mildly enlarged subarachnoid space. B. Hydrocephalus ex...
TransSynaptic Degeneration
In trans-synaptic degeneration or transneuronal atrophy, those neurons that lose their chief or only afferent connection that is, their synaptic input atrophy. Particular sites of trans-synaptic neuronal atrophy are a the lateral geniculate bodies following degeneration of the ganglion cells of the retina, optic nerve, or optic tract Anterograde or Wallerian degeneration. A. Lacunar infarct in the internal capsule. B. Degeneration of the ipsilateral pyramidal tract in the medulla myelin stain ....