Pathology of the nervous system Markéta Hermanová Meninges meninges CNS trauma nMissile (depressed, penetrating and perforatin injuries) nNon-missile injury: -Primary damage (immediate) -Secondary damage (after the injury) n nPrimary damage includes: -Focal lesions (contusions and lacerations) -Diffuse axonal injury n nSecondary damage includes: -Intracranial haematomas, herniation, infarction, infections - nComplications: -epilepsy, persistent vegetative state and post-traumatic dementis n n n n Brain oedema nDiffuse swelling due to: vasogenic and cytotoxic reasons nFocal swelling due to: focal lesions (cerebral abscesses, haematomas, intracranial neoplasms nConsequences of intracranial space occupying lesions: -Raised intracranial pressure -Intracranial shift and herniation -Epilepsy -Hydrocephalus -Systemic effects nRaised intracranial pressure – clinical picture: -Papillooedema (optic papilla) -Nausea and vomiting -Headache -Impairment of consciousness Intracranial herniation Manifesttion of traumatic intracranial bleeding Site Mechanism Clinical manifestation Extradural space Skull rupture with arterial rupture Lucid interval followed by a rapid increase in intracranial pressure Subdural space Rupture of venous sinuses or small bridging veins due to torsion force Acute presentation with a rapid increase in intrcranial pressure. Chronic presentation with personality change, memory loss and confusion, particularly in the elderly Subarachnoid space Arterial rupture, berry aneurysm of circle of Willis Meningeal irritation with a rapid increase in intracranial pressure Cerebral hemisphere Cortical contusion Rupture of small intrinsic vessels with intracerebral haematoma May cause seizures Increased intracranial pressure with focal deficits, usually fatal. _aneurysm-circ-willis-331f Berry/saccular aneurysm of circle of Willis Spinal cord injuries nOpen injuries due to direct trauma nClosed injuries: -Primary damage: contusions, nerve fiber transection, haemorrhagic necrosis -Secondary damage: extradural haematoma, infarction, infection, oedema nComplications: -Degeneration of damaged nerve fibres (both ascending and descending) -Post traumatic syringomyelia -Systemic effects of paraplegia (urinary tract and chest infections, pressure sores and muscle waiting) nSpinal cord and nerve root compression: -Intervertebral disc prolapse -Neoplasm -Skeletal disorders -Infections (tbc, abscess) -Vascular disorders (arteriovenous malformation, haemorrhage) -Trauma n n n Intervertebral disc prolapse Hydrocephalus -Excess of cerebrospinal fluid (CSF) within the intracranial cavity -Due to obstruction of the CSF pathways (non-communicating, congenital or aquired), impaired CSF absorption, excess CSF production -Produces irreversible brain damage unless the increased intracranial pressure is relieved by surgical drainage Major causes of stroke Cause % Clinical presentation Pathogenesis Predisposing factors Cerebral infarction 82 Slowly evolving signs and symptoms Cerebral hypoperfusion (in AS), emblism, thrombosis Heart disease Hypertension Atheroma Diabetes mellitus Intracerebral haemorrhage 15 Sudden onset of stroke with raised intracranial pressure Rupture of arteriole or microaneurysm Hypertension Vascular malformation Subarachnoid haemorrhage 3 Saudden headache with meningism Rupture of saccular/berry aneurysm of circle of Willis Hypertension Coarctation of the aorta Hypoxic CNS damage: ischaemia – hypoxia – anoxia CNS infections: bacterial infection nFollow the direct spread of infection from the skull, or haematogenous spread n nLeptomeningitis, the most common, in children and in elderly n nComplications: hydrocephalus, cerebral thrombophlebitis, cerebral infarction, abscess, sepsis n nAetiological agents: E. coli, Streptococcus agalactiae, Listeria monocytogenes (in neonates); Neisseria meningitis (2-18 years), Streptococcus pneumoniae (over 30 years), BK (tuberculous meningitis), Treponema palllidum (in syphilis) Purulent meningitis 01 Brain abscess SurgicalPathologyOfTheNervousSystem_121-3 CNS infections: viral infections nInfections spread to the CNS by the haematogenous route or retrograde neural transport n nViral meningitis is a common, self-limiting illness, less severe than bacterial meningitis n nViral encephalitis may result in death or severe disability (virus carried by ticks or mosquitoes) n nReactivation of latent viral infection (e.g. Herpes zoster) may damage the CNS n nCNS involvement in HIV infection: -Cerebral HIV infection (causing progressive dementia) -Multiple opportunistic infections (e.g. Toxoplasma, fungi) -Other viral infections (e.g. CMV) -Primary cerebral lymphoma n CNS infections: viral, fungal and parasitic infections nPrion diseases (prion=pathologic protein) responsible for subacute spongiform encephalopathy, a rare cause of dementia (e.g. Creutzfeldt-Jakob disease and variant CJD („mad cow“ disease) n nAcute disseminated encephalomyelitis, a demyeliting disorder, may result from virus-induced immune reaction (complications of measles, mumps, rubeola; also following vaccination for smallpox and rabies) n nAntenatal viral infections: CMV and rubella virus resulting in a necrotising encephalomyelitis, developlmenta malformations and microcephaly n nFungal infections: Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans,… nParasitic infections: Toxoplasma gondii, Plasmodium falciparum, Trypanosoma rhodesiense……. n n CNS infections common in immunosuppressed patients! Subacute spongiform encephalopathy; Creutzfeldt - Jacob, vacuolar transformation of neurons SurgicalPathologyOfTheNervousSystem_425-8 Demyelinating conditions nDue to immunological, viral or chemical mechanisms nMyelin disintegrated, myelin fragments phygocytosed, remyelination does not occur to any significant extent n nMultiple sclerosis: commonest demyelinating conditions, v.s. autoimmune, with high incidence in northern countries. Clinically: -Limb weakness -Paraesthesiae -Visual abnormalities -Diplopia -Bladder dysfunctions, vertigo n nLeukodystrophies - inherited disorders of myelin synthesis Metabolic disorders nHypoglycaemia (in DM) can result in irreversible neuronal damage and neuronal cell death n nCNS toxins: nmethanol, ethanol, metals and industrial chemicals ndrugs (affecting neuronal development (e.g. phenytoin), affecting mature CNS (e.g. vincristin) - nDeficiency states: malnutrition, vitamin deficiencies (B1, B12) n nInherited metabolic diseases: lysosomal storage diseases due to deficiences of various lysosomal enzymes (sphingolipidosis, mucopolysacharidosis, glycogenosis, ceroid lipofuscinosis) Epilepsy nRepeated seizures due to paroxysmal neurological dysfunction caused by abnormal discharges from neurones in th brain n nGeneralised epilepsy: -Synchronous abnormal discharges due to hyperexcitability of membranes -Often idiopathic, not associated with structural abnormalities in the brain n nFocal epilepsy -Associated with structural abnormalities of the cerebral cortex – epileptogenic lesions -Malformation of cortical development, tumors, glial scars, vascular abnormalities,…. -Some cases treated surgically - nProvoked seizures -Discharges due to acute damage to the brain (head injury, alcohol, metabolic abnormality (e.g. hypoglycaemia) - n 5258-08-IIa-100x Normal cortex Focal cortical dysplasia Congenital abnormalities nKnown causes: -Genetic factors (tuberous sclerosis (AD), aqueduct stenosis (X-linked), Down´s syndrome (trisomy 21)) -Maternal infections (e.g. rubella, CMV) -Irradiation in utero -Toxic, as in fetal alcohol syndrome -Dietary factors (e.g. Folic acid deficiency implicated in neural tube defects) -Metabolic (e.g. Phenylketonuria) - nNeural tube defects nPosterior fossa malformation Neural tube defects Arnold Chiari malformation 1.Involving cerebellum, brainstem, spinal cord 2.Cerebellar tonsils displaced downwards 3.Results in hydrocephalus, communicating 4.Often assoc. with meningomyelocele Posterior fossa malformationst Neurodegenerative disorders nCharacterised by progressive loss of neurons in functionally related areas of the CNS nAetiologically mostly unknown, some are inherited n nMotor neuron disease: -Amyotrophic lateral sclerosis n (both upper and lower motorneurons affected, distal and proximal muscle weakness and wasting spasticity) -Progressive muscular atrophy n (lower motor neuron involvement, weakness an wasting of distal muscles, fasciculations and absent reflexes) -Progressive bulbar pulsy n (cranial nerves involvement results in weakness of the tongue, palate, pharyngeal muscles) n nParkinson´s disease -tremor, bradykinesis, rigidity; manifestation between 45-60 years -caused by progressive loss of pigmented neurones in substantia nigra resulting in relative dopamin deficiency n Motor neuron tract Upper motoneuron Lower motoneuron Dementia nAcquired global impairment of intellect, reason and personality without impairment of consciousness n nDisorders resulting in dementia: nPrimary neurodegenerative diseases -Alzheimer´s d. -Pick´s d. (frontotemporal dementia) -Huntington´s d. (AD, choreiformic movements, jerking dementia) nCerebrovascular disease (e.g. multinffarct dementia) nInfections (e.g. CJD, syphilis, HIV) nSpace occupying diseases (e.g. neoplasms, haematomas) nHydrocephalus nDrugs and toxins nMetabolic disorders (e.g. hypothyreoidism, hypoparathyreoidism, hepatic failure,..) nVitamin deficiences (e.g. B1, B12) nParaneoplastic syndromes (e.g. limbic encephalitis) - n n Brain atrophy – Alzheimer disease 01 -Sporadic and familiar cases -Cortical atrophy -Amyloid angiopathy, neurochemical abnormalities, neuronal loss, amyloid plaques and tangles Cell of origin Tumor Glial cells Astrocytoma (both low grade and high grade) Oligodendroglioma (both low grade and high grade) Glioblastoma (Ependymoma) Primitive neuroectodermal cells Medulloblastoma (CNS; central nervous system, cerebellum) Neuroblastoma (PNS; peripheral nervous system, adrenals) Retinoblastoma …..all mentioned are pediatric tumors Arachnoidal cells Meningioma Nerve sheath cells Schwannoma, neurofibroma Malignant schwannoma, neurofibrosarcoma ANS; autonomous nervous system Paragangliomas, chemodectomas, pheochromocytoma + secondary, metastatic tumors CNS tumors nClinicopathological features: nCNS tumors do not metastasise to othe organs - (only infiltration of adjacent tissues and spreading through - CSF pathways) nLocal effects -Signs related to the site of the tumor -e.g. epilepsy with a temporal lobe tumor, paraplegis in spinal cord tumor nMass effects -Signs and symptoms of space occupying lesions -Vasogenic oedema around CNS tumor -Herniation -Hydrocephalus in posterior fossa tumor Peripheral neuropathy: peripheral nerve disorders nMononeuropathy -a single nerve involved -e.g. carpal tunnel syndrome - nMononeuritis multiplex -Several isolated nerves involved -e.g. polyarteritis nodosa, sarcoidosis n nPolyneuropathy: multiple nerve involvement nMainly motor: e.g. Guillain-Barre sy (autoimmune polyradiculoneuritis) nMainly sensory: carcinomatous neuropathy nSensorimotor: e.g. alcoholism nAutonomic: e.g. diabetes Thank you for your attention….