Hypoxia and Ischemic Injury
Focal cerebral ischemia
Global ischemia
Focal Cerebral Ischemia
Short term
Typical causes - thrombus/embolism
“Zone of penumbra” without infarction
Global Ischemia
Loss of Consciousness
Release of “excitatory” amino acid neurotransmitters
Disruption of calcium balance
Formation of free radicals
Mitochondrial injury
ATP malfunction = “power failure” = edema
Vulnerable Areas in the Brain
“Water-shed” areas
- At limits of cerebral blood flow
- Fragile, vulnerable
- Result in focal defects
Segments of short arteries supplying cerebral cortex = Laminar necrosis
Excitatory Amino Acid Injury
Neuron injury results in release and activation of mediators that overstimulate cell receptors
- Amino acids (glutamate), catecholamines, free radicals etc
Glutamate attaches and opens calcium channels leading to “calcium cascade” into cells
- Protein breakdown
- Free radical formation
- DNA fragmentation
- Mitochondrial injury
- Cell death
Cerebral Edema
Vasogenic (vessel)
Cytotoxic
Vasogenic cerebral edema
Leaking of water/proteins into ISS (interstitial space)
Causes: hemorrhage, meningitis, injury, tumours
White matter more so (not as dense as gray – more blood vessels)
Result: herniation, focal defects, increased ICP (intracranial pressure), altered LOC
Cytotoxic cerebral edema
Increased ICF (intracellular fluid) Causes: water intoxication, impaired K/Na pump Result: cell rupture with damage to surrounding tissue, increased ICP
Monro-Kellie Hypothesis
Tissue - 80% (most stable) Blood - 10% (less stable) CSF - 10% (less stable) Compliance! An increase in one will cause a decrease in the other
Increased Intracranial Pressure (ICP)
Compartment syndrome in the skull
- Intracranial pressure greater than arterial blood pressure
- Arteries collapse; blood flow to brain cut off
Compliance = change in volume (divided by) change in pressure
Tissue: tumour, edema, bleed
Blood: vasodilation, obstruction of outflow
CSF: increased production, decreased absorption, obstruction
Results in hypoperfusion, hypoxia, cell damage = decreased LOC, coma
Cushing Reflex – late signs of ICP
- Hypertension
- Widening pulse pressure
- Reflex bradycardia
Treatment - decreasing CO2 levels (vasodilator)
Increased Intracranial Pressure (ICP) manifestations
Changes in LOC Papilledema Impaired eye movement Decreased sensory/motor function Vomiting Headache Pupillary changes Changes in VS (increased BP, decreased P, changes in reap pattern) Infants - bulging fontanels, cranial suture separation, increased head circumference, high pitched cry
Brain Herniation
Increased intracranial pressure pushes the brain out of position
Brain tissue is compressed into the center of the brain, against bone or against rigid folds of the dura mater
Compression of the oculomotor nerve is an early sign
Hydrocephalus
Increased CSF volume enlarges ventricles and compresses brain tissue
Non-communicating/Obstructive
- Congenital malformations, tumors, inflammation, hemorrhage = CSF blockage
Communicating
- Impaired reabsorption of CSF via arachnoid villi d/t infection, scarring, blockage by lyzed RBCs post repair of bleed
- Increased production of CSF (rare)
Manifestations
- Fontanel bulging fetus/newborn
- Signs of increased ICP in all ages
- Optic nerve atrophy/blindness
Traumatic Brain Injury
Primary/Direct injuries
- D/t impact
- Microscopic damage: diffuse axonal injury
- Contusions (coup - brain hits front of skull, countercoup - brain hits back of skull)
Secondary injuries - D/t: Ischemia (most common) Hemorrhage Infection Increased intracranial pressure
Traumatic Brain Injury types
- Mild
Concussion (immediate & possible post-concussion syndrome)
Limited symptoms to momentary LOC, residual amnesia - Moderate
Small hemorrhages, edema
LOC, cognitive/motor deficits, hemiparesis, nerve palsies - Severe
Shearing, pressure = axon/vessel/tissue damage
Extensive damage with secondary manifestations (Hemiplegia, signs of elevated ICP, coma)
Hematoma - Epidural
Meningeal artery tear
- Rapid bleeding; unconsciousness may be followed by brief lucid period
- Ipsilateral pupil dilation, contralateral hemiparesis d/t uncal herniation (push down to brain stem)
- Treatment prior to LOC has good prognosis
Hematoma - Subdural
Venous tear between dura & arachnoid
Slower bleeding
1. Acute (within 24 hours)
Increased ICP, decerebrate posturing, LOC, high mortality rate
2. Subacute (2-10 days)
Periods of improvement prior to rapid deterioration
3. Chronic (weeks)
Slow bleed, decreased LOC, drowsiness, confusion, apathy, headache
Hematoma – Intracerebral (Traumatic)
Usually frontal or temporal lobes Risk: age, alcoholism Symptoms dependent on size and location Increased ICP Herniation
Diffuse Brain Injury Signs
- Doll’s eye response (vestibulo-ocular reflex)
- Indicates brain stem damage
- Possible tentorial herniation
Abnormal posturing
- Decorticate posturing
- Damage to one or both corticospinal tracts involving the “red nucleus” (motor movement) in midbrain
- Arms flexed
- Legs extend with feet turned inward - Decerebrate posturing
- Indicates brain stem damage bwloe level of red nucleus
- Upper and lower extremity extension
- Head arched back
- Can be one side or both or just arms - Cheyne-Stokes
Brain Attack (CVS/Stroke) Risk Factors
- Ischemic Stroke (interruption in blood flow)
- Age, gender, race, familial, HTN, smoking, DM, sickle cell disease, atrial fibrillation, CAD
- Obesity, physical inactivity, alcohol, drug use, hypercoagulability disorders, oral contraceptives, hormone replacement therapy - Hemorrhagic Stroke (bleed into brain tissue)
- Htn, aneurysms, AV malformations, head injury, blood dyscrasias
Transient Ischemic Attack (TIA)
Focal cerebral ischemia “zone of penumbra” without infarction Reverses prior to ischemia Similar risk factors and symptoms as stroke but symptoms last < 1 hour with fully recovery Increases risk of stroke
Manifestations of Acute Stroke
Usually unilateral and focal Always sudden Weakness/numbness (face, arm, leg) Vision loss Aphasia (language disorder) Dysarthria (motor speech disorder) Ataxia (muscle coordination disorder)
Aneurysmal Subarachnoid Hemorrhage
- Pre-rupture
- Sudden-onset headache with nausea and vomiting, dizziness - Hemorrhage
- Sudden severe headache, N/V, nuchal rigidity (neck), photophobia, vision and motor problems, LOC - Complications post-op
- Rebleeding, vasospasm, hydrocephalus
Risk factors of rupture
Age Smoking HTN Alcoholism Size of aneurysm Conditions that increase ICP
Arteriovenous Malformations
Tangle of abnormal arteries and veins linked by fistulas
- Possibly due to lack of capillary formation
- Structurally unstable with high pressure flow from arteries to veins
- Ischemic symptoms
Symptoms may not show until > 40 years of age
Hemorrhage usually slower process
Surgical removal
Acute Bacterial Meningitis
Inflammation of pia, arachnoid and subarachnoid
Contagious (direct contact – blood/mucous)
Carriers
10% permanent damage (ear, sight)
10% fatal
Neisseria meningitidis or Streptococcus pneumoniae
Group B streptococci (neonates)
Acute Bacterial Meningitis risk factors
Basilar skull fracture Otitis media Sinusitis/mastoiditis Neurosurgery Sepsis Living in close quarters/aged/infants
Acute Bacterial Meningitis patho
Bacteria replicate and lyze in CSF
Endotoxins/debris result in inflammatory process
Neutrophils/albumin allowed in CSF
Thrombi, scarring, blockage
Acute Bacterial Meningitis manifestations
Headache, fever, nuchal rigidity
N/V, photophobia, altered mentation
Petechial rash/palpable purpura (N. meningitides)
Acute Bacterial Meningitis manifestations
Headache, fever, nuchal rigidity
N/V, photophobia, altered mentation
Petechial rash/palpable purpura (N. meningitides)
Seizures, cranial nerve palsies, focal cerebral signs
Acute Bacterial Meningitis diagnosis
Lumbar puncture - cloudy, purulent
Kernig sign
- Resistance to extension of knee while lying with hip flexed
Brudzinski sign
- Flexion of neck induces flex of hip/knees
Acute Bacterial Meningitis treatment
Antibiotics
Viral Meningitis
Acute lymphocytic
Enteroviruses, Epstein-Barr virus, mumps virus, HSV, West Nile
Similar to bacterial but less severe
CSF has lymphocytes and small amounts of protein only, normal sugar
Self-limiting unless herpes simplex virus type 2 (HSV-2) which requires acyclovir
Encephalitis
Parenchymal infection of brain or spinal cord
Usually viral
- HSV
- West Nile
Encephalitis manifestations
Lethargy, disorientation
Fever, headache, nuchal rigidity
Seizures, paralysis, delirium, coma
Encephalitis diagnosis
Lumbar puncture
CSF investigation
Brain Tumors
Most often secondary site of metastasis
Primary more common in children (mortality rate 45%)
Risks:
Rarely benign, but if so, still dangerous
- Pressure
- Attachment = difficult to excise
Neurogliomas of astrocytic origin most common in adults
Medulloblastomas most common in children
Neuroglial Tumors
Most common primary tumor
Graded I to IV
Astrocytes: protective neurons, supply nutrients/oxygen
Oligodendrocytes: supportive cells in brain, ex form myelin
Ependyomal: line ventricles & spinal cord
Astrocyte
- Infiltrating (middle adult)
Usually cerebral hemispheres
Focal deficits, headache, seizures - Non-infiltrating (children)
Usually cerebellum, 3rd ventricle
Slow growth, minimal symptoms, easily resected
Oligodendroglioma
Middle adult
Usually cerebral hemispheres white matter
Unpredictable, prone to hemorrhage
Ependymoma
Young adult
Epithelial lining of 4th ventricle/spinal canal
Hydrocephalus, increased ICP
Medulloblastoma
Originates in neurons of cerebullum, posterior fossa
Fast growing, spreads via CSF to brain/spine
Appears in infants, young children
Manifestations include signs of increased ICP
Highly malignant, but radiosensitive and excisable
Meningiomas
Outside brain, grows slowly
Older adult
Usually benign and excisable
Primary central nervous system lymphomas
Increased incidence of late
Common in immunocompromised
B-cell origin (lymphocytic)
Invasive, diffuse, aggressive
Metastatic tumors
Melanomas to frontal & temporal lobes
Breast cancer to cerebellum and basal ganglia
NSC (non small cell) lung cancer to occipital lobe
Brain Tumor Manifestations
Dependent on location and size Vasogenic edema/papilledema/increased ICP Headache - distinctive characteristics - In morning - Improves with elevation of head - Worse with sudden head movements - Doesn’t respond to usual medications - Accompanied by N/V
Diagnosis of Brain Tumors
MRI as CT unreliable
EEG
Cerebral angiogram
Treatment of brain tumours
Surgery
Irradiation
Chemotherapy
Seizure Disorders
Temporary alterations in cerebral activity
Causes are numerous
1. Provoked = seizure Fever (children) Metabolic condition (adults) Structural changes Cellular changes
- Unprovoked/idiopathic = epilepsy
Genetic
Partial Seizures
Simple Partial/Elementary
Complex Partial
Secondarily Generalized Partial
Simple Partial/Elementary seizures
One hemisphere only No LOC Symptoms dependent on area involved May cause “Jacksonian march” Sensory symptoms may be only sign No observable symptoms Prodrome/aura is not just a warning! ANS involvement (tachycardia, diaphoresis, hypo/hypertension, pupil changes)
Complex Partial
Often temporal lobe Altered consciousness Hallucinations, déjà vu, idea flood, fear, etc. Automatisms Repetitive non-purposeful movements Confusion after is common
Secondarily Generalized Partial
Focal onset but generalized
Tonic/clonic activity, may have aura
Generalized Seizures
Absence (“petit mal”) Atonic (“drop attacks”) Myoclonic Tonic-Clonic (“grand mal”) Status Epilepticus
Absence seizure
Generalized disturbance of consciousness
Blank stare, often motionless or automatisms
Lasts only seconds so can be overlooked
“Atypical” type has slow onset/end
Atonic seizures
Sudden loss of muscle tone
Myoclonic seizures
Brief muscle contractions bilaterally Face, trunk or one or more extremities Tonic - Rigid, violent contractions or Clonic - Repeated contraction/relaxation
Tonic-Clonic seizures
- Tonic Phase
- Extension of extremities, LOC, incontinence, cyanosis - Clonic Phase
- Rhythmic contraction/relaxation - Postictal Phase
- Return to consciousness once RAS (wake/sleep center) function
Status Epilepticus
Seizure activity that doesn’t cease on own or occurs successively
High mortality rate
Must treat cause
Dementia
Permanent brain damage resulting in impaired memory and cognition - Short and long-term memory - Abstract thinking - Judgement - Personality changes Alzheimer Disease Vascular Dementia Frontotemporal Dementia Creutzfeldt Jakob Disease Wenicke-Korsakoff Syndreom Huntington Disease
Alzheimer Disease
40% of 85 year olds Genetic, familial or sporadic Death in 8 years (average) Diffuse degeneration/atrophy of cerebral cortex Enlargement of ventricles
Alzheimer Disease – pathological processes
- Neuritic (senile) plaques
- Accumulation of amyloid peptide
- Degenerative nerve terminals with an amyloid core - Neurofibrillary tangles
- Helical fibrous proteins - Decreased enzyme that synthesizes acetylcholine
- Neurotransmitter associated with memory
Manifestations of Alzheimer’s
- Initial: subtle
Loss of memory and denial of shame
Mild personality change – withdrawal/loss of sense of humour
2. Moderate stage Loss of higher cortical functions (problem solving) Depression if aware of changes Hostility Sundown syndrome
- Late stage
Loss of ability to respond to environment/family
Incontinence
Vascular Dementia
Ischemic or hemorrhagic damage (MI, arrhythymias, DM, PVD, infection, smoking)
Slow psychomotor functioning
Depression is common
Frontotemporal Dementia (Pick)
Atrophy of frontal and temporal lobes
- Progressive syndrome
Behavioral changes common
- Impulsiveness, loss of inhibitions (social behaviour), apathy
Language/understanding issues are less common but do happen
Death d/t infection in 2-10 years
Diagnosis: Neuroimaging
Creutzfeldt Jakob Disease (mad cow)
Rapid, infective protein “prion” (protein)
Bovine spongiform encephalopathy (BSE)
- “Mad cow disease”
Dementia within 6 months of infection
Results in degeneration of pyramidal and extrapyramidal systems
Personality changes Visual/spatial coordination issues Impaired memory and judgement Extreme dementia Insomnia Ataxia Death in months
Wernicke-Korsakoff Syndrome
Cause is typically thiamine deficiency as a result of chronic alcoholism Manifestations: - Weakness of eye muscles - Delirium, confusion, hallucinations - Memory loss with confabulation - Polyneuritis
Physical symptoms are somewhat reversible with nutrition, thiamine, but not “psychosis”
Huntington Disease
Cause is hereditary
Emerges in 40-50’s
Cell death in basal ganglia motor control
Manifestations
- Chronic progressive chorea (rhythmic movement)/ dyskinesia (inability to control movement)
- Psychological changes
- Cognitive decline, dementia