¾ Central nervous system ¾ Peripheral nervous system Pathology of the Nervous System JANTIMA TANBOON,MD 27/10/51 Jantima Tanboon, MD 2 Normal cells Neuron Glia Macroglia: ectoderm Microglia: mesoderm Choroid plexus Neuropil Meningothelial cells Virchow-Robin space 27/10/51 missinglink.ucsf.eduJantima Tanboon, MD /www.lab.anhb.uwa.edu.au3 27/10/51 Jantima Tanboon, MD 4 Neuron Nuclei, ganglia Cell body (perikaryon), processes Eccentric nucleus Prominent nucleolus Abundant Nissl substance Microtubule, neurofilament, prominent golgi, rER, synaptic specialization NFP, NeuN, synaptophysin 27/10/51NFP, NeuN, synaptophysinJantima Tanboon, MD 5 27/10/51 Jantima Tanboon, MD 6 1 Glia Astrocytes Round-oval nuclei Macroglia <- neuroectoderm Pale chromatin Astrocytes,Oligodendrocytes, Ependyma Gray/white matter Protoplasmic: gray Microglia <- bone marrow Fibrous: gray/white Inflammation, repair, fluid balance, energy Star shape GFAP, Golgi method metabolism 27/10/51 Jantima Tanboon, MD 7 27/10/51 Jantima Tanboon, MD 8 Astrocytes Oligodendrocytes Processes Processses wrap neural axons DNeuron Like Schwann cells in PNS Metabolic buffers Multiple internodes Small round lymphocyte-like nuclei Detoxifiers Linear arrays Nutrient suppliers Electrical insulator DCapillaries Barriers: blood, CSF, brain Repair, scar formation/ fibroblast 27/10/51 Jantima Tanboon, MD 9 27/10/51 Jantima Tanboon, MD 10 27/10/51 Jantima Tanboon, MD 11 27/10/51 Jantima Tanboon, MD 12 2 Ependymal cells Line ventricular system 27/10/51 Jantima Tanboon, MD 13 27/10/51 Jantima Tanboon, MD 14 Microglia Mesoderm- bone marrow Macrophages of CNS Injury response 1. Proliferation 2. Developing elongated (rod cells)- syphillis 3. Microglial nodules 4. Neuronophagia 27/10/51 Jantima Tanboon, MD 15 27/10/51 Jantima Tanboon, MD 16 Reaction of neurons to injury Acute neuronal change (red neuron) Acute neuronal change (red neuron) Acute CNS hypoxic/ ischemic Subacute and chronic neuronal injury (degeneration) H+E 12-24 hrs Axonal reaction Shrinkage cell body Subcellular alteration in organelles and cytoskeletal Nuclear pyknosis Neurodegenerative changes Loss of nucleolus Loss of Nissl substance 27/10/51 Jantima Tanboon, MD 17 27/10/51 Jantima Tanboon, MD 18 3 Subacute and chronic neuronal injury (degeneration) Cell loss Reactive gliosis (early detect) Axonal reaction Regeneration of axon->Axonal spheroids Increase protein synthesis-> sprouting Enlarge, round up cell body Peripheral nuclear displacement Dispersion of Nissl substance to periphery Central chromatolysis 27/10/51 Jantima Tanboon, MD 19 27/10/51 Jantima Tanboon, MD 20 Subcellular alteration in organelles and Reaction of Astrocytes to injury cytoskeletal Lipofuscin, proteins, CHO Gliosis***-indicator of CNS injury Viral inclusion Cellular swelling z Intranuclear z Intracytoplasmic Rosenthal fibers Neurodegenerative changes Corpora amylacea Neurofibrillary tangles-Alzheimer Glial cytoplasmic inclusion Lewy body- Parkinson Alzheimer type II astrocyte Abnormal vacuolation- CJD 27/10/51 Jantima Tanboon, MD 21 27/10/51 Jantima Tanboon, MD 22 Gliosis Astrocyte: hypertrophy hyperplasia Nucleus: eccentric, enlarged vesicular, prominent nucleolus Scant->bright pink cytoplasm Gemistocytic astrocyte Glial fibrils Bergmann gliosis 27/10/51 Jantima Tanboon, MD 23 27/10/51 Jantima Tanboon, MD 24 4 Rosenthal fibers Corpora amylacea Thick elongated brightly eosinophilic Concentrically lamellated round faintly basophilic, Irregular contour within astrocytic process PAS positive 5-50µm Long standing gliosis Heat shock protein, ubiquitin Pilocytic astrocytoma Astrocytic end process Craniopharyngioma z Subpial Syrinx cavities z Perivascular zone Alexander disease Advance age αB-crystallin, hsp27, ubiquitin Adult polyglucosan body Lafora body (cytoplasm) 27/10/51 Jantima Tanboon, MD 25 27/10/51 Jantima Tanboon, MD 26 Alzheimer type II astrocyte Gray matter Nucleus 2-3 times> normal Pale staining central chromatin Unrelated to Alzheimer disease Hyperamonemia Chronic liver disease Wilson disease Hereditary disorder of Urea cycle 27/10/51 Jantima Tanboon, MD 27 27/10/51 Jantima Tanboon, MD 28 Cerebral edema Vasogenic edema Disrupted normal BBB vascular permeability Intercellular space Localized/generalized Cytotoxic edema Neuronal/glial/endothelial injury Intracellular Generalized hypoxic/ischemic 27/10/51 Jantima Tanboon, MD 29 27/10/51 Jantima Tanboon, MD 30 5 Increase intracranial pressure Subfalcine (cingulate)herniation Herniation ACA compromised Subfalcine (cingulate) Transtentorial Tonsillar herniation (uncinate, mesial temporal) Life-threatening Tonsillar herniation Life-threatening Brain stem compression Respiratory and cardiac center in medulla 27/10/51 Jantima Tanboon, MD 31 27/10/51 Jantima Tanboon, MD 32 Transtentorial (uncinate, mesial temporal) herniation CNIII compressed -> pupil dilate z Impair ipsilateral ocular movement PCA compressed->primary visual cortex z Contralateral peduncle compress z Kernohan’s notch z Ipsilateral hemiparesis Hemorrhage in midbrain, pons z Secondary brain stem (Duret hemorrhage) 27/10/51 Jantima Tanboon, MD 33 27/10/51 Jantima Tanboon, MD 34 Hydrocephalus Accumulation of excessive CSF Impaired flow Impaired absorption Overproduction Hydrocephalus ex vacuo CSF Produced: Choroid plexus Absorbed: Arachnoid granulation 27/10/51 Jantima Tanboon, MD 35 27/10/51 Jantima Tanboon, MD 36 6 Noncommunicating hydrocephalus Neural tube defects Congenital malformation 1. Anencephaly Tumor Inflammation 2. Encephalocele Hemorrhage 3. Spina bifida*(spinal dysraphism) 4. Myelomeningocele Communicating hydrocephalus Maternal blood: AFP, acetylcholinesterase Subarachnoid hemorrhage Folate deficiency Meningitis Metastasis to subarachnoid space Subsequent pregnancy 4-5% 27/10/51 Jantima Tanboon, MD 37 27/10/51 Jantima Tanboon, MD 38 Forebrain anomaly 1. Polymicrogyria 2. Megalencephaly 3. Microencephaly* 4. Lissencephaly 5. Neuronal heterotopia 6. Holoprocencephaly 7. Agenesis of corpus callosum 27/10/51 Jantima Tanboon, MD 39 27/10/51 Jantima Tanboon, MD 40 Posterior fossa anomaly Arnold-Chiari malformation z Type I: less severe, tonsils z Type II: vermis z Small posterior fossa, large foramen magnum, low insertion of tent z caudal displacement of medulla, tectum malformation, aqueduct stenosis, cerebralheterotopia, hydromyelial Dandy-Walker malformation 27/10/51 Jantima Tanboon, MD 41 27/10/51 Jantima Tanboon, MD 42 7 Arnold- Chiari malformation Dandy-Walker malformation Enlarged posterior fossa, Agenesis of vermis, Midline cyst Type I Type II 27/10/51 Jantima Tanboon, MD 43 27/10/51 Jantima Tanboon, MD 44 Direct parenchymal injury Hydromyelia Syringomyelia Contusion: bruising Laceration: tearing Syringo bulbia 27/10/51 Jantima Tanboon, MD 45 27/10/51 Jantima Tanboon, MD 46 Contusion Plaque jaune Contusion 27/10/51 Jantima Tanboon, MD 47 27/10/51 Jantima Tanboon, MD 48 8 Diffuse axonal injury Diffuse axonal injury Deep centroaxial white matter region 27/10/51 Jantima Tanboon, MD 49 27/10/51 Jantima Tanboon, MD 50 Traumatic vascular injury 27/10/51 Jantima Tanboon, MD 51 27/10/51 Jantima Tanboon, MD 52 Epidural hematoma Subdural hematoma ¾ Associated skull fracture Potential spaces-> Bridging veins Elder, infant ¾ Middle meningeal artery ¾ Acute subdural hematoma ¾ Chronic subdural hematoma ¾ Lucid interval 27/10/51 Jantima Tanboon, MD 53 27/10/51 Jantima Tanboon, MD 54 9 Chronic subdural hematoma Subarachnoid hemorrhage Multiple episode of rebleeding Trauma Organizing Aneurysm/Vascular malformation 1wk -> Clot lysis 2wks -> Fibroblast from meninges to hematoma 2-3 months -> Early development of hyalinized connective tissue 27/10/51 Jantima Tanboon, MD 55 27/10/51 Jantima Tanboon, MD 56 Trauma sequele Cerebrovascular disease Post traumatic hydrocephalus Cerebrovascular accident (CVA) Punch-drunk syndrome (dementia pugilistica) Ischemia and infarction z Hydrocephalus z Global cerebral ischemia z Thining of corpus callosum z Focal cerebral ischemia z DAI z Neurofibrillary tangles Intracranial hemorrhage z Diffuse Aβ-plaque z Intraparenchymal (intracerebral) hemorrhage Epilepsy z Rupture Berry aneurysm Brain tumor (meningioma) Infectious disease z Vascular malformation Psychiatric disorder Hypertensive cerebrovascular disease 27/10/51 Jantima Tanboon, MD 57 27/10/51 Jantima Tanboon, MD 58 Global cerebral ischemia Diffuse hypoxic/ischemic encephalopathy Low flow Respirator brain Border zone (watershed) infarction Most susceptible z Pyramidal cells of Sommer sector (CA1) of the hippocampus, Purkinje cell of cerebellum, 27/10/51 pyramidal neuronJantima in Tanboon,neocortex MD 59 27/10/51 Jantima Tanboon, MD 60 10 1. Early change: 12-24 hrs Red neuron Neutrophils 2. Subacute change: 24hrs-2 wks Necrosis Macrophage Vascular proliferation Gliosis 3. Repair: after 2 weeks Remove all necrotic tissue Loss normal organized CNS structure Gliosis Pseudolaminar necrosis 27/10/51 Jantima Tanboon, MD 61 27/10/51 Jantima Tanboon, MD 62 Focal cerebral ischemia MCA* Embolization* z Cardiac mural thrombi: MI, valvular disease, AF z Thromboemboli: atheromatous plaque z Paradoxical emboli z Emboli associated with Sx z Other material (tumor, fat, air) In situ thrombosis z Atherosclerosis: carotid bifurcation, origin of MCA, basilar artery 27/10/51 Jantima Tanboon, MD 63 27/10/51 Jantima Tanboon, MD 64 Non hemorrhagic infarcts First 6 hrs: difficult 48 hrs: pale soft swollen, indistinct GW junctio