M2 Pathology Course Phone: Lecture # 72 tiborv@uic.edu Tuesday, February 11, :30 10:20

Transcription

1 Tibor Valyi-Nagy, M.D., Ph.D. UIC College of Medicine Assistant Professor of Pathology, UIC M2 Pathology Course Phone: Lecture # 72 tiborv@uic.edu Tuesday, February 11, :30 10:20 I. Central nervous system (CNS) pathology: special features II. Cells and cellular pathology in the CNS III. Brain herniation and hydrocephalus IV. Malformations and perinatal CNS injury GOALS AND OBJECTIVES: Upon completion of this learning activity participants should be able to: Discuss why the compact, regionally highly specialized structural organization of the CNS is relevant to CNS pathology Discuss the concept of selective vulnerability of neurons to injury Discuss the significance of the postmitotic nature of neurons after embryonic development to CNS pathology Recognize the most common neuronal and glial response types to injury in histologic sections Discuss the pathogenesis of brain herniation Discuss the pathogenesis of hydrocephalus Recognize the major types of CNS malformation ABSTRACT Neuropathology is the study of the etiology, pathogenesis, and structural and functional consequences of disease affecting the central nervous system (CNS: brain and spinal cord) and peripheral nervous system (PNS: peripheral nerves, ganglia, receptors). This lecture will provide an introduction to neuropathology by primarily focusing on some special anatomic and functional organizational features of the CNS that are relevant to CNS pathology. This lecture will also provide background information important for the understanding of the pathologic presentation of specific nervous system diseases by discussing common neuronal and glial response patterns to injury and the pathogenesis of brain herniation and hydrocephalus. Finally, there will be a discussion of the most common CNS malformations and that of perinatal CNS injury. KEYWORDS: selective vulnerability, gliosis, brain herniation, hydrocephalus, neural tube defects, CNS malformations, cerebral palsy READING ASSIGNMENT: Robbins Pathologic Basis of Disease, 6 th edition, 1999, pages:

2 NEUROPATHOLOGY Study of the etiology, pathogenesis, structural and functional consequences of disease affecting: Central nervous system (CNS = brain and spinal cord) Peripheral nervous system (PNS = peripheral nerves, ganglia, receptors) OUTLINE OF NEUROPATHOLOGY LECTURES LECTURE 1: I. CNS pathology: special features II. Cells and cellular pathology in the CNS III. Common pathophysiologic complications: herniation and hydrocephalus IV. Malformations and perinatal CNS injury LECTURE 2: V. CNS trauma VI. Cerebrovascular diseases LECTURE 3: VII. CNS infections VIII. Diseases of myelin LECTURE 4: IX. Neurodegenerative diseases X. Toxic and acquired metabolic diseases LECTURE 5: XI. CNS neoplasia XII. Phacomatoses (Neurocutaneous syndromes) I. CNS PATHOLOGY - SOME SPECIAL FEATURES Compact, regionally highly specialized structure: Small lesions can have severe consequences (examples: pontine hemorrhage, small lacunar infarct involving corpus callosum) Similar clinical syndromes may result from different disease processes affecting same structures (example: dementia due to Alzheimer disease or multiple infarcts) A single disease process affecting different structures may cause different clinical symptoms (example: glioblastoma involving brainstem vs cerebral hemisphere) - 2 -

3 CNS PATHOLOGY - SOME SPECIAL FEATURES - cont. Neurons (functional units of CNS): postmitotic after embryonic development - loss of neurons is permanent Brain consumes 20 % of total body oxygen supply: extreme vulnerability to hypoxia/ischemia Distinctive response patterns to injury: glial responses No conventional lymphatic system: special cerebrospinal fluid circulation Brain enclosed by rigid skull: possibility of herniation II. CELLS AND CELLULAR PATHOLOGY IN THE CNS CNS Most important cell types Neurons Glia (astrocytes, oligodendrocytes, ependymal cells, microglia) Cells of meninges and blood vessels NEURONS Functional units of the CNS: receive, store and transmit information Differ greatly from one another in: cellular architecture, neurotransmitter use, metabolic requirement, blood supply, distribution of interconnections, function Organized into aggregates (nuclei, ganglia), columns, layers Sets of neurons, not necessarily clustered together may share common vulnerability to injury based on common characteristics: basis of selective vulnerability Postmitotic after embryonic development, lost neurons are not replaced CNS neurons: only limited capacity to regenerate axons NEURONAL REACTIONS TO INJURY Acute neuronal injury (red neurons): irreversible injury due to various causes including hypoxia/ischemia, infection, toxins Chromatolysis: reaction within the neuronal cell body to axonal injury Neuronal atrophy: Refers to neuronal loss due to progressive disease of long duration, presents as cell loss often selectively involving functionally related systems of neurons - 3 -

4 INTRANEURONAL INCLUSIONS Intracytoplasmic examples: neurofibrillary tangles, Lewy bodies, Negri bodies Intranuclear example: Cytomegalovirus nuclear inclusions Star-shaped glial cells ASTROCYTES Functions include nutritional supply and insulation of neurons, contribution to blood-brain barrier Play prominent role in response to injury Cytoplasm of resting astrocytes not readily evident Response to tissue injury: hyperplasia and hypertrophy: astrogliosis Highlighted by immunostaining for GFAP OLIGODENDROCYTES Processes wrap around axons of neurons to form myelin Oligodendrocyte injury is a feature of demyelinating diseases (e.g. multiple sclerosis) Nuclei may harbor viral inclusions in progressive multifocal leukoencephalopathy Limited capacity for regeneration EPENDYMAL CELLS Line ventricular chambers, aqueduct, central canal of spinal cord Modulate the transfer of fluid between CSF and parenchyma Reaction to injury: ependymal granulations (loss of ependyma plus subependymal astrogliosis) MICROGLIA Native macrophages of the CNS inconspicuous when resting Reactions to injury: proliferation, microglial nodules, neuronophagia, elongation of nuclei: rod cells - 4 -

5 III. COMMON PATHOPHYSIOLOGIC COMPLICATIONS Brain herniation Hydrocephalus Brain surrounded by rigid skull HERNIATION Rigid barriers divide the cranial cavity into subcompartments (falx cerebri, cerebellar tentorium) Intracranial volume is fixed (brain parenchyma, CSF, blood) Space occupying masses (tumor, hemorrhage, etc.), brain edema, increased CSF lead to increased intracranial pressure and may cause herniation Herniation is displacement of expanding brain to adjacent subcompartments or through the foramen magnum Necrosis of herniated parenchyma COMPLICATIONS OF BRAIN HERNIATION Compression of vessels and consequent infarction (e.g. posterior cerebral artery infarction involving the visual cortex) Nerve compression (e.g. III. Cranial nerve in transtentorial herniation with consequent pupillary dilation and impaired ocular movement) Death (e.g. brainstem compression in tonsillar herniation) HYDROCEPHALUS Hydrocephalus: Accumulation of excessive cerebrospinal fluid (CSF) within the ventricular system of the brain Normal CFS circulation: choroid plexus in ventricles, foramina Luschka and Magendi, subarachnoid space, arachnoid granulations, venous circulation Causes of hydrocephalus: Increased CSF production (e.g. choroid plexus tumors) Obstruction of CSF flow (non-communicating hydrocephalus, e.g. aqueduct destruction by viral infection) Decreased CSF resorption (e.g. due to meningitis) Brain atrophy and compensatory ventricular dilatation (hydrocephalus ex vacuo, e.g. Alzheimer s disease) - 5 -

6 IV.A. CNS MALFORMATIONS Congenital CNS malformation: Morphological CNS defect present at birth due to an abnormal developmental process Causes: unknown in a majority of cases, genetic and chromosomal abnormalities, environmental (e.g. infection, drugs, nutritional), multifactorial Anatomic pattern of malformation reflects the stage of formation of the CNS at the time of injury Important types and examples: Neural tube defects (e.g. anencephaly, myelomeningocele, spina bifida, encephalocele) Forebrain anomalies (e.g. holoprosencephaly, agenesis of the corpus callosum, neuronal migration defects, microencephaly) Posterior fossa defects (Arnold-Chiari and Dandy-Walker malformation) Hydromyelia, syringomyelia NEURAL TUBE DEFECTS Transformation of the neural plate into the neural tube occurs at days of gestation Neural tube defects are due to failure of a portion of the neural tube to close or reopening of a region after successful closure All characterized by abnormalities involving both neural tissue and overlying bone or soft tissues Most common type of CNS malformation, wide geographic and ethnic variation in frequency, recurrence rate: 4-5% Etiology: unknown, some association with chromosomal disorders (trisomy 13), environmental factors (e.g. folate deficiency), interaction of genetic and environmental factors suspected based on research in mice Types of neural tube defects Anencephaly Anencephaly with rachischisis (craniorachischisis): Skull vault and vertebral arches are deficient, replacement of brain with vascular mass (area cerebrovasculosa) Myelomeningocele: herniation of the spinal cord and meningeal tissue through a vertebral defect Meningocele: herniation of meningeal tissue only Spina bifida: Either asymptomatic bony defect only (spina bifida occulta) or disorganized spinal cord with overlying meningeal outpouching Encephalocele (occipital): herniation of brain tissue through a skull defect - 6 -

7 Holoprosencephaly Failure of separation of cerebral hemispheres FOREBRAIN ANOMALIES May be associated with facial abnormalities (e.g. cyclopia) Etiologic associations: Trisomy 13, 18 Sonic hedgehog gene mutations Maternal diabetes mellitus Toxoplasmosis, other infections Agenesis of the corpus callosum. Absence of white matter bundles connecting cerebral hemispheres. Neuronal migration defects: Laminar neuronal heterotopia Nodular neuronal heterotopia Agyria Polymicrogyria POSTERIOR FOSSA ABNORMALITIES Arnold-Chiari malformation (Chiari type II malformation) Small posterior fossa Downward extension of cerebellar vermis through foramen magnum Caudally displaced medulla often associated with: Aqueductal stenosis Hydrocephalus Lumbar myelomeningocele Hydromyelia Dandy-Walker syndrome Agenesis of the cerebellar vermis and fourth ventricular cyst - 7 -

8 HYDROMYELIA, SYRINGOMYELIA Hydromyelia: Multisegmental expansion of the central canal of the spinal cord Syringomyelia: fluid-filled cleft like cavity in spinal cord (not lined by ependyma) 4.B. PERINATAL BRAIN INJURY Important cause of childhood neurological disability Cerebral palsy (a clinical term): non-progressive neurologic motor deficit attributable to insults occurring during the prenatal and perinatal period Most common underlying pathology: hemorrhages and infarctions Premature infants at increased risk for germinal matrix hemorrhage and periventricular infarcts leading to periventricular leucomalacia In term infants: choroid plexus hemorrhage and infarcts involving cerebral cortex, basal ganglia and thalamus Common causes: maternal disease (e.g. hemorrhage, shock, drugs, trauma), placental abnormalities, neonatal disease (e.g. congenital heart disease) - 8 -