Circulation CNS and Acute ND and Neurodevelopmental disorders

Patho Final

CNS components

Brain and spinal cord

CNS function

Detect, transmit, and analyze sensory info

Generate signals to autonomic and motor pathways that orchestrate visceral and endocrine functions, coordination, movement

Major CNS disorders

Transient Ischemic Attack

Stroke

Subdural and spinal hemorrhage

Transient Ischemic Attack (TIA)

Temporary episode of neurologic dysfunction

Caused by focal brain, spinal cord, or retinal ischemia without acute infarction

TIA cause and patho

Same as ischemia stroke

Clot blocking blood supply to region of brain

Atherosclerosis

TIA risk factors

Age, history, sickle cell disease

Cardiovascular disease, Diabetes, high cholesterol

TIA clinical man

Facial drooping

Arm or leg weakness on one side

Speech difficulty

Lack of balance

Trouble seeing

TIA diagnosis

BG and other blood tests

Electrocardiography

Noncontract CT

Carotid doppler

Stroke

Brain attack - interruption in blood supply to region of brain or bleeding of vessel resulting in brain tissue damage or infarction

Enduring disruption of speech, motor, communication accompanied by cognitive deficits

Ischemic: 87%      Hemorrhagic: 13%

Ischemia

Obstructed blood vessels

Drop in blood flow to brain

Increased pressure within skull

Hematoma

Excessive production of cerebral spinal fluid

Blockage of duct system conveying cerebral spinal fluid

Brain

2.5% of total body mass, receives 15% of cardiac output, and uses 20% of body’s oxygen consumption

White matter

60% of brain mass, uses 6% of cerebral oxygen

Gray matter

Uses 94% of cerebral oxygen

Maintain cerebral circulation

R and L internal carotid arteries

R and L vertebral arteries

CSF

Produced by choroid plexi of ventricles

Flows through ventricular system of brain and through subarachnoid space around brain and spinal cord

Hydrocephalus blockage

Blockage in flow of CSF through ventricles of brain or when cannot be reabsorbed by arachnoid villi

Blood brain barrier

Specialized endothelium present in brain capillaries

Permits selective entry of substances

• Tight junctions and active transport

Substances that cross barrier

• High lipophilic substances cross directly- most need facilitated diffusion

Regions in brain lacking BBB

Subfornical organ and area postrema of brainstem

Infundibulum of hypothalamus and pituitary gland

Cerebral Autoregulation

Mechanism that maintains steady flow of blood to brain and spinal cord

Cerebral blood flow

Is closely matched to metabolic needs

• Arteries respond to pH, carbon dioxide, oxygen

• Increased blood pressure = constricted cerebral capillaries

• Decreased blood pressure = dilated capillaries

• Decreased PaCO2 levels = constricted cerebral

vessels

• Increased PaCO2 levels rise = dilated vessels

Autoregulatory mechanisms fail

Loss of match between oxygen supply and demand of tissues

Intracranial pressure

Pressure exerted by contents of cranium

Monro-Kellie hypothesis

Compensatory relationship maintaining cerebral compliance in response to changes in volume

Injured brain tissue

• Cytotoxic edema

• Vasogenic edema

• Clearance of brain tissue swelling

Hydrocephalus

Excessive accumulation of CSF in cranial vault

Compresses surrounding structures

Cause:

• Lesions that obstruct flow of CSF

• Problems with resorption

Cerebral blood flow (CBF)

Autoregulation

Blood viscosity

Cerebral vascular resistance (CVR)

Cerebral perfusion pressure (CPP)

• CBF = CPP/CVR

Mitochondrial dysfunction due to hypoxia

Leads to infarction and tissue death

Anaerobic glycolytic pathways initiated

Energy deprivation and loss of ion homeostasis from hypoxia

Cells unable to maintain negative membrane potential

Excitatory amino acids in extracellular space

Glutamate and influx of calcium ions

Apoptosis

Cerebral hemorrhage in sepsis

▪Immune cells activated

▪Leukocytes enter brain

▪Inflammatory agents contribute to brain

inflammation

▪Nitric oxide/nitric oxide synthetase pathway

▪Mitochondrial dysfunction and apoptosis

Ischemic Stroke Cause and patho

Partial or complete occlusion of cerebral blood flow due to thrombus or embolus

Atherosclerosis

Cardiac disorders

Thrombotic strokes

Hemorrhagic stroke cause and patho

Bleeding into brain from blood vessel

• intracerebral, intraventricular, or extracerebral

Subarachnoid hemorrhage Cerebral aneurysm

Arteriovenous malformation (AVMs)

Ischemic and hemorrhagic stroke clinical man

Sudden onset of focal neurologic deficit persisting for at least 24 hours due to reduction or occlusion of cerebral circulation or rupture of blood vessels

Depends on affected area

Ischemic stroke treatment

Restoration of blood flow and reducing area of infarction

Supplemental oxygen

Aspirin

Antihypertensive therapy

Hypothermia

Penumbra

Tissue surrounding infarction

Hemorrhagic stroke treatment

Osmotic diuretics

Surgical evacuation

Craniotomy with aneurysm clipping

Subdural hematoma

Bleeding from bridging veins btw dura mater and arachnoid membrane

Subdural hematoma cause and patho

Trauma from high speed impact to skull

Spontaneous

Acute subdural hematoma

• bleeding identified immediately after an injury

Chronic subdural hematoma

• brain atrophy

Subdural hematoma clinical man

Headache

Confusion and change in behavior

Apathy

Seizures

Subdural hematoma treatment

Surgery

Spinal cord Hemorrhage cause and patho

Rare

Trauma, vascular malformation, bleeding disorders

Epidural, subdural, subarachnoid or intramedullary

• Intramedullary hemorrhage

• Epidural and subdural spinal cord hemorrhage

Spinal cord Hemorrhage clinical man

Sudden, severe back pain

Neurodevelopmental disorders

Impairments of brain function occurring as brain develops

• language, coordination, attention, behavior

Brain tumors

Space-occupying lesions that cause increase in ICP

Benign and malignant tumors can be life-threatening

• unless accessible and removable

Gliomas form the largest category of primary malignant tumor

Primary malignant tumors

Rarely metastasize outside the CNS (BBB)

Secondary brain tumor

Metastasizing from breast or lung tumor

Brain tumors patho

Usually not well defined

Invasive and have irregular projections into adjacent tissue

• usually inflammation around the tumor

Brain tumor etiology

Brainstem and cerebellar tumors common in young children

Adults; more frequently in the cerebral hemispheres

Brain tumor signs and symptoms

Seizures often a sign

Headaches, vomiting, unilateral faial paralysis

Do not cause systemic signs of malignancy

Brain tumor treatment

Surgery if accessible 

Chemotherapy and radiation

Meningitis

Inflammation of the meninges

Different age groups are susceptible to different causative organisms

• may be secondary to other infections

Meningitis in young adults

Most often due to haemophiles influenza bacteria (more often in the fall or winter)

Meningitis in children and young adults

Neisseria meningitides or meningococci

• Classic meningitis pathogen

• Frequently carried in the nasopharynx of asymptomatic carriers

• Spread by respiratory droplets (late winter/early spring)

Meningitis in older adults

Strept pneumonia is the major cause

Meningitis signs and symptoms

Sudden onset

Back pain

Photophobia 

Nuchal rigidity

Kerning sign

Brudzinski sign

Meningitis diagnosis

Examination of CSF (lumbar puncture)

Identify causative organism

Meningitis treatment

Aggressive antimicrobial therapy

Specific treatment for ICP and seizures

Glucocorticoids (that stop inflammation)

Vaccines are available

Brain Abscess

Pus-filled swelling in the brain, caused by bacteria/fungi entering brain tissue after infection/injury

Localized infection

Necrosis of brain tissue and surrounding edema

Can spread

Treatment: Surgical drainage and antimicrobial therapy

Encephalitis

Infection of the parenchymal (nerve or glial cells) or connective tissue of the brain/spinal cord

• necrosis and inflammation development in brain tissue 

  • Viral, bacterial, autoimmune, or allergic rxns

Encephalitis early signs

Severe headache, stiff neck, lethargy, vomiting, seizures, fever

Encephalitis diagnosis

Imaging tests (CT, MRI) CSF analyses

Tetanus

Caused by Clostridium tetani

Spores can survive in soil (years)

Wound

Exotoxin enters nervous system

• jaw spasms and stiffness

• Difficult swallowing

Herpes Zosters (shingles)

Caused by varicella-zoster virus in adults

Years after infection of varicella

Affect a CN or dermatome

Pain, paresthesia, vesicular rash

Lesions and pain persist for a few weeks - could even be months/years

Concussion

Minimal brain trauma

Reversible interference with brain function

Results of mild blow to the head or whiplash type injury

Amnesia and headaches

recovery usually 24 hours without permanent damage

Contusion

Bruising of brain tissue, rupture of small blood vessel (inflammation and edema)

Blunt blow to head-possible residual damage

Closed head injury

Skull is not fractured in injury

Brain tissue is injured and blood vessel may be ruptured

Extensive damage may occur when head is rotated

Open head injury

Involved fractures or penetration of the brain

Depressed skull fracture

Involve displacement of a piece of bone below the levels of the skull

Compression of brain tissue

Blood supply to area often impaired - pressure to brain

Basilar fractures

Occur at the base of the skull

Leakage of CSF through ears or nose is possible

May occur when forehead hits the windshield

Contrecoup injury

Area of the brain contralateral to the site of the direct damage is injured

May be secondary to acceleration or deceleration injuries

Think rebound injury

Head injury

Trauma to brain tissue

Causes loss of function in part of body controlled by the area of the brain

Cell damage and bleeding lead to inflammation and vasospasm around injury site

Hematoma

Classified by their location in relation to the meninges

ADD IN DIF TYPES OF DURAL BLEEDS slide 26

Head injury signs

Focal signs (neurological symptoms that affect a specific area of the brain or nervous system)

General signs of increased ICP

Seizures

Cranial nerve impairment may occur

Otorrhea or rhinorrhea

Fever

Head injury treatment and diagnosis

MRI and CT

Glucocorticoids agents (decrease edema)

Antibiotics (reduce infections)

Surgery (to reduce ICP)

Oxygen (to protect remaining brain tissue)

Spinal cord injury

Damage can be temp or permanent

1. Laceration of nerve tissue by bone fragments or complete transection or crushing of cord

2. Partial transection or crushing of the cord or bruising

3. Prolonged ischemia and necrosis

Spinal cord injury treatment

PT/OT

Hydrocephalus patho

Excess CSF accumulates at skull

• more production than reabsorption

If cranial sutures have not closed, head enlarges (infant)

Damage depends on the rate of the pressure

Non-communicating/obstructive Hydrocephalus

Flow is blocked

Communicating Hydrocephalus

Problem on absorption on CSF through subarachnoid villi

Hydrocephalus signs

Increase in CSF

Scalp veins look dilated

Hydrocephalus diagnosis

Diagnostic test

CT or MRI

Hydrocephalus treatment

Surgery or shunt

Dementia

Chronic (persistent) disorder of mental processes

Caused by brain disease or injury

Memory disorders, personality changes, impaired reasoning

Slow, progressive onset with impairments in abstract thinking and memory loss

Dementia causes

Illnesses

Head trauma

Alzheimer disease (AD)

• more than 50% of cases

Vascular dementia

• Changes in thinking following series of small strokes

Dementia clinical man

Slow decline of cognitive function

Increasing cognitive impairments over years

Progressive changes in mobility

Dementia diagnosis

Compete physical and neurologic exam

Dementia treatment

regular monitoring of health and cognitive status

Reinforcing orientation to person, place, time

Encouraging establishment of advance directives

CAN ONLY DELAY

Multiple Sclerosis

Progressive demyelination of the neurons in the brain spinal cord and cranial nerves

• autoimmune

Loss of myelin interferes with conduction of impulses in affected fibers

• may effect motor, sensory, and autonomic system

Multiple Sclerosis lesions

Inflammatory response

Loss of myelin in white matter of brain or spinal cord

Multiple Sclerosis plaques

Larger areas of inflammation and demyelination

Develop later, become visible in X-Ray

Multiple Sclerosis Recurrence

Initial inflammation may subside

Neural fct may return to normal for short period of time

Each recurrence causes additional areas of the CNS to become affected

Multiple Sclerosis treatment

No known treatment

Parkinson Disease

Idiopathic, chronic, progressive degenerative disorder of CNS

Has motor, nonmotor, neuropsychiatric manifestations

Affected indvs over 50 years

Parkinson Disease symptoms

Tremors

Bradykinesia

Rigidity

Postural instability

Parkinson Disease decreased risk

Cigarette smoking, caffeine intake

High blood urate levels

Parkinson Disease pathogenic mechanisms

Proteolytic stress

• accumulation and aggregation of proteins

• Lewy bodies

Oxidative stress

• Generation of ROS

• Depletion of glutathione, increase of iron

Mitochondrial dysfunction

• Decreased mitochondrial activity

Inflammation

• Overactivation of microglia

Parkinson Disease clinical man (motor/nonmotor)

Insidious onset

Motor features

• tremors

• Rigidity

• Cogwheeling

nonmotor

• Fatigue, pain, autonomic dysfunction

Parkinson Disease treatment

Pharmacologic replenishment with dopaminergic drugs

Deep brain stimulation

Supportive therapies

Huntington Disease

Progressive, incurable, neurodegenerative disease of brain, autosomal dominant inherited

Causes uncontrolled involuntary movements, dementia, and behavior changes

Onset of symptoms: 35-44 yrs

• duration: 19yrs avg

Primary cause of death:

• Pneumonia, CVD