Neuropath II PDF

11/12/2024 Categories of CNS diseases Cerebral edema, herniation and hydrocephalus Vascular diseases...

11/12/2024 Categories of CNS diseases Cerebral edema, herniation and hydrocephalus Vascular diseases Trauma NEUROPATHOLOGY II CNS infections Diseases of myelin Dentistry 6655 Neurodegenerative diseases Neoplasms CNS Infections Routes of entry to the CNS include: CNS INFECTIONS – hematogenous spread – extension of local infections (dental, sinus, middle ear) – direct implantation (trauma) – via peripheral nerves e.g. rabies CNS Infections Acute bacterial meningitis Acute bacterial meningitis: inflammation of Inflammation of leptomeninges, spreads through subarachnoid space (identify in CSF) leptomeninges and subarachnoid space Caused by pyogenic bacteria (e.g. E.coli, S. Cerebral abscess: focal suppurative infection pneumoniae, H. influenzae, N. meningitidis) Risk factors: extremes of age, debilitated state, Encephalitis: diffuse inflammation of brain poor hygiene, crowded living conditions parenchyma; infections, usually viral Presenting signs/symptoms: Fever, headache, stiff neck 1  11/12/2024 Acute bacterial meningitis Acute bacterial meningitis Brain is swollen Meningeal exudate Purulent exudate with large number of under subarachnoid neutrophils and space, over the necrotic cellular cerebral hemispheres debris Purulence within the ventricles Gram stain usually shows organisms Tuberculous Meningitis Tuberculous meningitis (chronic) Lymphocytes, > 2-3 weeks of macrophages, and headache, lethargy, multinucleated giant nausea & vomiting cells (granulomas) Cranial nerve palsies, epilepsy Mycobacteria may be Gelatinous exudate, demonstrable by acid may appear nodular fast stain Cryptococcal Meningitis (chronic meningitis) Cerebral Abscess Usually bacterial Spherical budding (S.milleri), also fungal yeast, found in soil Hematogenous or and bird excrement contiguous spread Low grade fever, (dental root or ear debility, headache infections) Slimy exudate, Fever, focal neurologic deficits (mortality 10%) capsular material Cavity contains pus, Both healthy and surrounded by a thick immunocompromised wall of granulation hosts (e.g. HIV+) can tissue and gliosis be affected 2  11/12/2024 Encephalitis Diffuse inflammation of brain parenchyma Viral in origin (herpes, arboviruses, HIV etc) Herpesviruses – most common Viral inclusion bodies Usually fatal without treatment Herpesvirus; Cowdry type A Encephalitis inclusions Neuronophagia Diseases of Myelin Myelin is derived from oligodendroglial cytoplasmic processes Myelin sheath provides insulation to the neuronal processes Permits rapid conduction of electrical impulses Demyelination disorders: interfere with myelin sheath integrity, disrupt normal propagation of electrical signals 3  11/12/2024 Multiple Sclerosis Most common primary demyelinating disorder Autoimmune (T-cell mediated) plus genetics Adult females (20-40s), waxing/waning course (visual disturbances, speech/gait abnormalities) Irregular areas of demyelination: MS plaques Tx: corticosteroids, Ocrevus (ocrelizumab) early FDA approved disease-modifier Neurodegenerative Diseases Alzheimer’s disease Heterogeneous group of disorders: note Most common cause of dementia, increasing progressive degeneration of neurons in specific incidence with increasing age regions of the brain, spinal cord or both Mostly sporadic (10% familial), etiology unknown Sporadic or familial Grossly, atrophic brain (↓ volume and weight), Dementia (memory impairment & cognitive and ventricular dilatation disorder retain consciousness), movement Microscopically: disorders, tremor and rigidity etc. – senile (neuritic) plaques (aggregates of thickened, Alzheimer’s disease, Parkinson disease and tortuous processes with central amyloid deposits) Huntington’s disease – neurofibrillary tangles (filamentous aggregates within neuronal cytoplasm) Alzheimer’s Disease Alzheimer’s Disease Patients present with irreversible, progressive Senile (neuritic) loss of memory and plaques cognitive functions Grossly, severe atrophy of brain and ventricular dilatation Neurofibrillary tangle 4  11/12/2024 Parkinson Disease Parkinson Disease Degeneration of dopamine-secreting pigmented neurons of substantia nigra in the midbrain Mostly sporadic; 6th decade Rigidity, expressionless face, stooped posture, fine tremor, slower gait Gross: mildly atrophic brain Microscopic: intracytoplasmic, eosinophilic inclusions (Lewy bodies; α-synuclein and other proteins) within pigmented neurons Faces of Parkinson Disease Huntington’s Disease Hereditary, progressively fatal disorder Spontaneous, involuntary movements (chorea) and dementia AD. Gene (huntingtin), chromosome 4, toxic gain-of-function mutation with CAG repeats Gross: atrophy of the basal ganglia (eg., caudate nucleus, putamen and in advanced cases, the globus pallidus) Central Nervous System Tumors 5  11/12/2024 Overall concepts Adult Brain Tumors Primary: Arise from cells of the brain, spinal Astrocytomas – cord or their coverings most common – Symptoms related to site of origin more than tumor type [e.g., increased intracranial pressure (headache), focal deficits, seizure, hydrocephalus etc.] WHO grades II (well – Histologic grade correlates to biologic behavior Astrocytomas graded from I-IV differentiated, III – Rarely metastasize outside the CNS (anaplastic), and IV (glioblastoma) Secondary (metastatic): lung, breast, prostate etc. – Mets to brain: far more common than mets from brain Adults-mostly cerebral hemisphere Astrocytoma (grade II) Astrocytoma Grade III highly cellular with mitotic figures Mild cellularity and nuclear pleomorphism Grade IV Glioblastoma: Adult Brain Tumors Necrosis & microvascular proliferation Oligodendroglioma Cerebral hemisphere, well circumscribed, often calcified Cells with uniform, round nuclei and perinuclear halo (fried egg look) 6  11/12/2024 Adult Brain Tumors Ependymoma: well circumscribed, arise from ventricular wall Most are slow growing (usually grade II) Elongated cells with processes radiating around blood vessels (perivascular pseudorosettes) & true rosettes Perivascular pseudorosettes: A,B True rosettes: C,D Adult Brain Tumors Meningioma Derived from the arachnoid matter Female predominance Firm, lobulated lesions with a pushing border into underlying brain Microscopically: cellular whorls and psammoma bodies are common Meningioma Adult Brain Tumors Metastatic tumors Brain is a common site Cellular whorls for metastatic lesions Often multiple deposits Tumors from the lungs, breast, skin melanomas, kidney, GI most frequent Psammoma bodies 7  11/12/2024 Pediatric Brain Tumors Pediatric Brain Tumors Pilocytic Astrocytoma Medulloblastoma Grade I tumor Cerebellum, aggressive Usually in the growth pattern cerebellum, often cystic Grade IV tumor, small primitive round cells Astrocytes with hair- May disseminate like processes through CSF – Rosenthal fibers Cells may form Homer- Wright rosettes Management of Brain Tumors Depends on location and histologic grade Can the tumor be surgically excised or eliminated with radiation treatment (e.g. stereotactic radiosurgery)? Intrathecal chemotherapy: specific meds depending on cancer type Proton beam radiation therapy 8