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PATHOPHYSIOLOGY OF THE NERVOUS SYSTEM

Peerayut Sitthichaiyakul, M.D. Department of Pathology, Faculty of Medicine, Naresuan University

NERVOUS SYSTEM

Central nervous system • Brain • Spinal cord Peripheral nervous system • Cranial nerves • Spinal nerves Autonomic nervous system

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CONTENTS

• Central nervous system

• Peripheral nervous system

Central Nervous System

• Mechanism of brain injury • Traumas • Cerebrovascular diseases • CNS infection • Degenerative diseases • Brain tumors

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MECHANISM OF BRAIN INJURY

• Occur in most form of acute brain injury • Oxygenated blood < metabolic demand • Ischemia Inability to generate ATP • Oxygen free radicals, excitary amino acids

and inflammatory cells 2° injury

Cellular Hypoxia and Ischemia

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Cerebral Edema • Vasogenic edema : damage of blood-brain

barrier increase vascular permeability intercellular edema – Cerebral infarction – Intracerebral hemorrhage – Brain tumor – Infection : meningitis, encephalitis, brain

abscess – Trauma – Lead poisoning

• Cytotoxic edema: intracellular accumulation – Hypoxia : cardiac arrest – Hyponatremia – Hemodialysis – Diabetic ketoacidosis

• Interstitial edema: periventricular edema

– Hydrocephalus

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Increased Intracranial Pressure

• ICP is exerted by the contents of the cranium

1. brain tissue 2. cerebrospinal fluid (CSF) 3. blood

• Common cause of increased intracranial pressure – Increased brain tissue volume: tumor hemorrhage infection – Increased cerebrospinal fluid volume hydrocephalus – Increased blood volume increased right atrial pressure

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Brain Herniation

Subfalcine herniation • cingurate lobe of the cerebral hemisphere

herniate through the space between falx cerebri and corpus callosum

• Compress anterior cerebral artery

Uncal herniation • Medial aspect of the temporal lobe herniate

over the edge of the tentorium cerebelli • Compress posterior cerebral artery • Compress brain stem brain stem

hemorrhage

Tonsillar herniation • Cerebellar tonsil herniate through the

foramen magnum • Compress medulla oblongata respiratory

center

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Hydrocephalus

• Noncommunicating hydrocephalus • Congenital malformation • Tumor • Inflammation • Hemorrhage

• Communicating hydrocephalus • Subarachnoid hemorrhage • Meningitis • Metastasis to subarachnoid space

TRAUMA

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Skull Fracture

• Linear fracture

• Depressed fracture

• Comminuted fracture

• Diastatic fracture

• Compound fracture

• Location – Fall while alert occipital region – Fall whlie loss of consciousness : syncopal

attack frontal region

• Clinical finding – Asymptomatic – Lower cranial nerve or cervicomedullary

dysfunction – CSF discharge fome nose or ear route of

organisms to meninges

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Traumatic Vascular Injury

• Epidural hematoma • Subdural hematoma • Subarachnoid hemorrhage

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Epidural hematoma

• Associated with skull fracture • Bleeding from middle minigeal artery • Bleeding into space between periosteum and dura Clinical findings • < 30 ml. asymptomatic • 30-50 ml. space-occupying lesion increased intracranial pressure compress venous sinus circulatory stagnation cerebral ischemia and edema brain herniation • > 60 ml brain herniation

Subdural hematoma

• Bleeding from bridging vein • Bleeding between dura mater and arachnoid layer • Acute subdural hematoma • Chronic subdural hematoma Clinical findings • Asymptomatic • Stretching of the meninges headache • Irritation of the cortex seizure • Growth of fibroblasts and hyalinized connective

tissue rebleeding chronic subdural hematoma

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Subarachnoid hemorrhage • Bleeding between arachnoid layer and pia mater • Traumatic subarachnoid hemorrhage bleeding

from bridging vein • Other cause

– Ruptured berry aneurysm : most common cause • Ruptured occur at any time • ⅓ associated with acute increase in intracranial

pressure – Ruptured arteriovenous malformation

CEREBROVASCULAR DISEASES

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• Third leading cause of death • Leading cause of serious disability • Risk factors:

– Hypertension – Diabetes mellitus – Hyperlipidemia – Cigarette smoking – Advancing age – Family history

• Two process depend on pathophysiology 1. Ischemia and infarction - Global cerebral ischemia/infarction hypoxic encephalopathy - Focal cerebral ischemia/infarction obstruction of local blood

supply 2. Hemorrhage

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Global cerebral ischemia (hypoxic/ischemic encephalopathy) – Shock – Cardiac arrest – Severe hypotension

• Survive vegetative state – Severe impaired neurologic function, coma

Cerebral Infarction

Focal cerebral ischemia 1. thrombosis 2. embolism • Thrombosis

– Atherosclerosis – Arteritis from syphilis, TB, Toxoplasma, CMV – Collagen-vascular diseases – Hematologic diseases with hypercoagulable

states – Drug abuse

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• Embolism – Cardiac mural thrombi: most common cause myocardial infarction valvular heart diseases atrial fibrillation – Atheromatous plaque – Paradoxical emboli – Emboli associated with cardiac surgery – Tumor emboli – Fat emboli – Air emboli

Clinical features • Neurologic deficit • Depend on

– Site of obstruction – Size of infarction Small cerebral infarction asymptomatic focal neurologic deficit Large cerebral infarction cerebral edema brain herniation

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• Hypertension : the most common cause arteriosclerosis of blood vessels small microaneurysm location of hematoma : basal ganglia,

internal capsule, thalamus, cerebellum and pons

• Other cause: tumor, vascular malformation, vasculitis, coagulative disorder

Spontaneous Intracerebral Hemorrhage

CNS INFECTION

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Route of entry for organisms 1. Hematogenous spreading: most common

route 2. Direct implantation 3. Local extension 4. Spread via peripheral nervous system

Meningitis

• Bacteria: most common origin adult Streptococcus, Neiseria children Hemophilus newborn E.coli, Group B Streptococci • Virus • Fungus • Parasite

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• Reach the CNS by hematogenous route or extension from adjacent site

• Headche, fever, stiff neck and signs of cerebral dysfunction

• Diagnosis lumbar puncture • ↑ neutrophils • ↓ glucose level • ↑ protein level

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• An inflammation of the brain parenchyma • Virus are the most often pathogen

Arbovius encephalitis Japanese B encephalitis Western equine encephalitis animal normal host human accidental host

Encephalitis

Herpes simplex encephalitis type 1 adult infected by direct contact

nerve ganglion encephalitis type 2 newborn acquire the organisms

from birth canal encephalitis • Bacteria, fungus, parasite

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Brain Abscess

• Localized collection of pus within the brain parenchyma

• Most common organism bacteria streptococci staphylococci anaerobes

DEGENERATIVE DISEASES

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• Cerebral cortex – Alzheimer disease – Pick disease

• Basal ganglia and brain stem – Parkinson disease – Huntington disease

• Motor neurons – Amyotrophic lateral sclerosis (motor neuron

disease)

• Most common cause of dementia • Aβ critical molecule in the pathogenesis of the

disease • Aβ peptide are derived from amyloid precursor

protein (APP) on the cell surface • APP are cleaved by secretase Aβ peptide

endocytosis aggregate Aβ fibrils • Aβ neurotoxic cellular response

oxidative damage

Alzheimer Disease

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Clinical findings • Symptomatic cause running more than 10

year • Forgetfullness • Dementia : gradual loss of memory and

cognitive function • Incontinent, mute, unable to walk • Bedridden • Pneumonia death

Parkinson Disease

• Second most common neurodegenerative disease

• Degeneration of dopaminergic neurons in substantia nigra

• Cause idiopathic • Movement disorders

– ↓ voluntary movement – ↑ involuntary movement

• 10-15% dementia

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BRAIN TUMORS

• Incidence 10-17:100,000 • Unique characteristic

– Distinction between benign and malignant is less evidence : benign tumor may be poor prognosis

– Limitation of surgical resection without neurologic deficit

– Anatomic site of the tumor can have lethal consequence

– Pathway for spread is subarachnoid space, rarely metastasize outsize the CNS

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Clinical signs and symptoms • Primary effect

– Location – Size increase intracranial pressure

• Secondary effect – Edema – Disturb cerebrospinal fluid drainage

hydrocephalus – Herniation

WHO classification 1999 • Tumors of the neuroepithelial tissue

– Astrocytic tumors astrocytoma glioblastoma (multiforme) – Oligodendroglial tumors oligodendroglioma – Ependymal tumors ependymoma

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• Tumor of cranial and peripheral nerve – Schwannoma – Neurofibroma

• Tumors of the mininges – Meningioma

• Tumors of the sellar region – craniopharyngioma

• Metastasic tumor

Glioblastoma (multiforme) : GBM • Most severe glial cell tumor • Most frequent brain tumor • Peak incidence between 45-70 yrs • Cerebral hemispheres • Seizure, headache, neurological deficit

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Metastasic Tumors • 50% of intracranial tumors • Five most common primary site:

– Lung – Breast – Skin (maligant melanoma) – Kidney – Gastrointestinal tract

• Extensive cerebral edema increased intracranial pressure

Neurocutaneous syndromes

• Group of inherited disease • Autosomal dominant • Multiple harmatomas or neoplasms,

particular CNS and skin Neurofibromatosis type I, type II Tuberous sclerosis von Hippel-Lindau disease

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Neurofibromatosis type I • 1:3,000 • Neurofibromas • Gliomas of optic nerve • Pigmented nodule of iris (Lisch nodules) • Cutaneous hyperpigmented macules (café

au lait spots)

Peripheral Nervous System

• Inflammatory (immune-mediated) neuropathies

• Traumatic neuropathies

• Tumors of the peripheral nervous system

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INFLAMMATORY NEUROPATHIES

Acute inflammatory demyelinating poly-radiculoneuropathy (Guillain-Barré syndrome)

• Acute and subacute paralytic illness • Ascending paresthesia and paralysis (from leg to

arm) bedridden respiratory failure • Autoimmune diseases • Associated with viral infection or another

immunologic stimulus

TRAUMATIC NEUROPATHY

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• Laceration • Avulsion • Compression neuropathy (Entrapment

neuropathy) – Carpal tunnel syndrome Predisposing factor Inflammatory arthritis Excessive use of wrist joint Amyloidosis Pregnancy Hypothyroidism

TUMORS OF THE PNS

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• Neuronal origin neuroblastoma • Nerve sheath origin neurofibroma schwannoma (neurilemmoma) malignant peripheral nerve sheath

tumor (malignant schwannoma)

Schwannoma • Arise from Schwan cell • Associated with neurofibromatosis II • In cranial cavity cerebellopontine angle

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Neurofibroma • Solitary neurofibroma

• Peripheral nerve • Skin cutaneous neurofibroma • Associated with NFI

• Plexiform neurofibroma • Associtaed with NFI