Paj 5103 clinical neuropahtophys ii hn10
Transcript of Paj 5103 clinical neuropahtophys ii hn10
Lecture IINg, Hoikee PA-C, MPASNova Southeastern University
Learning Objectives
Understand the mechanisms of brain injury Understand how the brain components affect
intracranial pressure Define different types of tramatic brain injury Understand different types of intracranial
hematomas Understand the epidemiology and etiology of
cerebrovascular disease Understand the epidemiology and etiology of
different type of central nervous system infections
Acute brain injury
Brain trauma Cerebrovascular disease Brain hemorrhage Central nervous infections
Mechanisms of Brain Injury
Primary brain injury occurs as a direct result of the initial insult (trauma, stroke)
Secondary injury refers to progressive damage resulting from the body’s physiologic response to the primary insult, (from days to weeks)
A critical factor in determining the neuronal cell fate after injury is the degree of adenosine triphosphate (ATP) depletion
Sequence of neuronal cell injury following acute ischemia
Ischemia
Cell hypoxia
Mitochondrial failure
Decreased ATP production
Decreased Ca++ pumping
Calcium overload
Increased Glutamate
release
Open NMDA
channelsFree-radical production Reperfusion
Immune cellsCell death
Mechanisms of Brain Injury (Cont.)Ischemia and Hypoxia Ischemia is a contributing factor as the
primary insult Ischemia results in immediate
neurologic dysfunction due to the inability of neurons to generate the ATP needed for energy-requiring processes
Ischemia sets the stage for secondary injury by oxygen free radicals, excitatory amino acids, and inflammatory cells.
Mechanisms of Brain Injury (Cont.)
Cellular Energy Failure Neuronal tissue is highly sensitive to oxygen
deprivation because it has great ATP requirement Lack of cellular oxygen results in mitochondrial
dysfunction; anaerobic glycotic pathways are initiated; pyruvate converted to lactate; hydrogen ions lead to cellular acidosis, which affects neuronal integrity; inadequate energy supply leads to deterioration of ion gradients (Calcium overload)
Calcium overload is thought to be a critical factor leading to activation of enzyme cascades, which disrupt function and cause irreversible damage to cell membranes
Mechanisms of Brain Injury (Cont.)
Excitatory Amino Acids Excessive glutamate may be released because of impaired
membrane integrity Reuptake mechanisms fail to remove excess glutamate
because they are energy-dependent processes Excess glutamate stimulates nearby neurons that then take
up large amounts of injurious calcium ions; calcium overload , which results in cytotoxic edema, a rapid swelling of neurons
Gluatmate binds to NMDA receptors, stimulates nitric oxide production in neurons; in excess it may increase the production of reactive nitrogen species that function as free radicals to damage cellular components
Mechanisms of Brain Injury (Cont.)Reperfusion Injury Is the secondary injury that occurs after re-
establishing blood flow When oxygen reenters cells, erratic transfer of
electrons to oxygen can produce reactive oxygen products that behave as free radicals (hydroxyl radicals, superoxide, peroxide)
Cell membranes may undergo lipid peroxidation in response to free radical damage with subsequent formation of arachidonic acid
Arachidonic acid cascade yields more oxygen free radicals and immune cells (interleukin, tumor necrosis factor, neurophils)
All this contributes to brain inflammation
Mechanisms of Brain Injury (Cont.)
Abnormal Autoregulation Autoregulation is normally influenced by
the partial pressures of carbon dioxide and oxygen in the arterial blood
PaCO2 decreased: cerebral vessels constrict
PaCO2 increased: cerebral vessels dilate Excessive cerebral blood volume can
exacebrate cerebral edema Hyperventilation low PaCO2
vasoconstriction reduction of ICP
Mechanisms of Brain Injury (Cont.) Injury can cause local or global
impairment of autoregulation Loss of matching between oxygen
supply and demand occurs when autoregulatory mechanisms fail
Sequence of neuronal cell injury following acute ischemia
Ischemia
Cell hypoxia
Mitochondrial failure
Decreased ATP production
Decreased Ca++ pumping
Calcium overload
Increased Glutamate
release
Open NMDA
channelsFree-radical production Reperfusion
Immune cellsCell death
Calcium overload is a key event in producing cellular damage
Mechanisms of Brain Injury (Cont.)
Consequence of the mechanisms of brain injury
A. Increased Intracranial Pressure (ICP)
Volume of cranium composed of three elements: brain tissue, cerebrospinal fluid (CSF), blood
Monro-Kellie hypothesis: compensatory responses to change in volume in any of these components
Increased ICP can occur with space-occupying lesions, vasogenic or cytotoxic edema, or with obstruction or excessive production of CSF
Mechanisms of Brain Injury (Cont.)
Cytotoxic edema (intracellular edema) Ischemic tissue swells because of cellular
energy (ATP) failure. Calcium overload, Na inflow to the cell, creating an osmotic force to draw in water
Vasogenic edema Increase capillary pressure damage to
the capillary endothelium extravasation of electrolytes, proteins and fluid into the intracellular space disrupt the blood brain barrier brain swells cerebral edema
Mechanisms of Brain Injury (Cont.)
Mechanisms of Brain Injury (Cont.)
Consequence of the mechanisms of brain injury
B. Brain Compression and Herniation• As intracranial pressure rises, it can compress
neural tissue and blood vessels• Herniation: the protrusion of brain tissue
through an opening in the supporting dura of the brain
• Types of herniation syndromes include:– Subfalcine – Tentorial– Uncal– Tonsillar
Mechanisms of Brain Injury (Cont.)
Mechanisms of Brain Injury (Cont.) From the ischemia injury, if not treat
promptly, will result in focal cell death, cascade event causes cerebral edema, increase ICP, brain herniation, result in permanent neurologic damage
Traumatic Brain Injury
TBI is a major cause of death and a leading cause of disability among young adults
Most head injuries are incurred in motor vehicle accidents, falls, and sports accidents
The severity of TBI is classified by the GCS (Glasgow Coma Scale) score as: Mild GCS score 13-15 Moderate GCS score 9-12 Severe GCS score 8 or below
Epidemiology
1.5 million cases of TBI diagnosed annually; 50,000 result in death
Males are more likely to sustain a TBI and have a higher risk of death from TBI than females
Those at lowest socioeconomic levels have the highest per capita rate of TBI
Types of Brain Injury
Tramatic brain injury: Primary injury Focal Polar Diffuse
Intracranial hematomas Epidural Subdural Subarachnoid
Primary Injury
Focal injuries localized to site of impact Polar injuries are due to acceleration-
deceleration movement of the brain within the skull, resulting in double injury
Diffuse injury is due to movement of the brain within the skull, resulting in widespread axonal injury
Types of Tramatic Brain Injury Concussion
Head injury produces an alternation on consciousness, but no evidence of brain damage is found on physical and radiologic exam
Common consequence of sports related head injury
Contusion When CT or MRI reveals an area of brain
tissue damage (necrosis, laceration, bruising)
Primary Injury (Cont.)
Intracranial Hematomas• Disruption of the vasculature can result
in intracranial hemorrhage• May expand slowly or rapidly,
progressively compressing brain structures and increasing ICP
• Three types of hematoma can develop:– Epidural– Subdural– Subarachnoid
Primary Injury (Cont.)
04/12/23
Primary Injury (Cont.)
Epidural Hematoma Collection of blood between dura and
skull Typically involves arterial injury thus
rapid onset of symptoms Often involves a fracture of the
temporal bone with disruption of the middle meningeal artery
Primary Injury (Cont.)
Subdural Hematoma Collection of blood between dura and
outer layer of the arachnoid membrane Typically involves bridging veins, thus
symptom onset may be slower Bridging veins drain venous blood from the
surface of the brain, crossing the arachnoid and subdural spaces before emptying into the venous sinuses
Chronic subdural hematomas may be prone to rebleeding
Primary Injury (Cont.)
Subarachnoid Hemorrhage Collection of blood between arachnoid
membrane and the pia mater Due to rupture of bridging veins
(tramatic brain injury) that pass through the subarachnoid space
Can also be caused by rupture of cerebral aneurysm, arteriovenous malformations
Blood spreads throughout CSF, causing meningeal irritation
Primary Injury (Cont.)
Cerebral Aneurysm and Arteriovenous Malformation Structural abnormalities of the cerebral
arteries predispose to intracerebral bleeding and hemorrhage
Cerebral aneurysms and AVMs are the most common causes of subarachnoid hemorrhage
Primary Injury (Cont.)
Cerebral Aneurysm Lesion of an artery that results in dilation and
ballooning of a segment of the vessel Congenital defect of the medial layer of the artery
weakens to arterial pressure, allowing the dilated portion to fill with blood and eventually burst causing SAH
90%of cerebral aneurysms are located in the circle of Willis
Typical presentation is severe HA with meningismus: worst headache in his/her life
Treatment involves surgical stabilization with aneurysm clipping or embolization
Primary Injury (Cont.)
Arteriovenous Malformation Capillary system fails to develop appropriately
with arterial blood shunted directly into the venous system; causes the vessels to progressively enlarge; becomes a congested mass of enlarged vessels that can burst
The majority of AVMs are diagnosed in 20-40 yrs of age
90% of AVMs are found in the cerebral hemispheres
Patients typically present with seizure and neurologic dysfunction
Secondary Injury
Ischemic and hypoxic events, subsequent vasogenic/ cytotoxic edema and other processes that lead to increased ICP, and altered vascular regulation may affect patient outcomes to a greater extent than the primary injury Vasogenic, cytotoxic edema may increase
for 48 to 72 hrs after injury
Cerebrovascular Disease and Stroke
Stroke is a sudden onset of neurologic dysfunction due to cardiovascular disease that results in an area of brain infarction
Stroke is the third leading cause of death in the United States
Most common form of stroke is ischemic
Epidemiology
Females affected more often than males
Most stroke victims are >65 years of age
Risk factors are similar to those for other atherosclerotic vascular diseases (hypertension, DM, hyperlipidemia, smoking)
Ischemic Stroke Result from sudden occlusion of cerebral artery
secondary to thrombus formation or emboli Thrombotic strokes associated with
atherosclerosis and coagulopathies Embolic strokes associated with cardiac
dysfunction or dysrhythmias (atrial fibrillation) Penumbra: a much larger area of ischemic but
viable cells that is surrounding the infarct. The penumbra receives some partial or collateral flow and may recover if the ischemia is mild or perfusion is restored in a timely manner.
Salvaging the penumbra is the aim of early thrombotic therapy; however, treatment must be instituted within 3 hours of symptom onset to be maximally effective
Ischemic Stroke Transient ischemic attack (TIA)
Neurologic symptoms typically last only minutes, but may last as long as 24 hrs. Symptoms resolve completely without evidence of neurologic dysunction
Lacunar infarcts Occlusion of the small penetrating
arterioles can produce small lesions. The basal ganglia, pons, cerebellum and internal capsule are common sites for lacunar infarcts
Hemorrhagic Stroke
Hemorrhage within the brain parenchyma
Usually occurs secondary to severe, chronic, hypertension
Most occur in basal ganglia or thalamus Degree of secondary injury and
associated morbidity and mortality is much higher in hemorrhagic stroke than ischemic stroke
Central Nervous System Infections
Organisms may gain access to the CNS through the bloodstream, direct extension from a primary site or along peripheral and cranial nerves, or through maternal-fetal exchange
Meningitis and cerebral abscess commonly associated with bacterial infections; encephalitis is usually viral
A frequent consequence of bacterial infections is hydrocephalus, as the bacterial, WBCs block CSF resorption in the arachnoid villi
Meningitis
Bacteria usually reach the CNS via the bloodstream or extension from cranial structures
Most common bacteria are Streptococcus pneumoniae and Neisseria meningitidis
Bacteria invade leptomeninges (pia mater & the arachnoid space) accumulation of inflammatory exudate can result in hydrocephalus
Encephalitis
Inflammation of the brain commonly caused by West Nile virus, western equine encephalitis, and herpes simplex
Typical presentation includes fever, HA, malaise, muscle pain, and/or rash
Brain Abscess
Localized collection of pus within the brain parenchyma
Pyogenic (pus-producing) pathogens reach the brain by Penetrating wounds Direct extension or retrograde
thrombophlebitis of an infected neighboring structure (mastoiditis)
Blood borne dissemination for a distant infected site (lungs)
Brain Abscess Most common infective organisms:
streptococci, staphylococci, and anaerobes The abscess has a focal infected core:
central portion contains neurtrophils and pus
The peripheral portion of the abscess: made up of inflammatory granulation tissue
Around the brain abscess is perifocal edema with proliferation of surviving astrocytes.
In chronic phase, the core is liquefied & the peripheral portion forms a collagenous capsule & is surrounded by fibrous gliosis
Brain Abscess
Chronic Disorders of Neurologic Function
Learning objectives Understand the etiology and
pathogenesis of cerebral and cerebellar disorder: Seizure disorder, Dementia, Parkinson disease, Cerebral Palsy, hydrocephalus, cerebellar disorders.
Understand the etiology and pathogenesis of certain spinal cord and peripheral nerve disorders: Multiple Sclerosis, Spina Bifida, Amyotrophic Lateral Sclerosis, Spinal Cord Injury, Guillain-Barre Syndrome
Brain and cerebellar disorders Seizure Disorder Dementia Parkinson Disease Cerebral Palsy Hydrocephalus Cerebellar Disorders
Seizure Disorder
Transient neurologic event of paroxysmal abnormal or excessive cortical electrical discharges that are manifested by disturbances of skeletal motor function, sensation, autonomic visceral function, behavior, or consciousness
Epilepsy or seizure disorder refers to recurrent seizures
Seizures are a component of many diseases
Seizure Disorder
Etiology Acquired event as a consequence of
cerebral injury or other pathologic process such as tumors, blood clots, infection, metabolic disorders, head injury, stroke, medication overdose, medication adverse effect, exposure to toxins
In some cases, no explanation for the seizure disorder: idiopathic seizures.
Seizure Disorder Pathogenesis
Due to an alteration in membrane potential that makes certain neurons abnormally hyperactive and hypersensitive to changes in their environment
Abnormal neurons form an epileptogenic focus. This focus functions autonomously, emitting excessively large numbers of paroxysmal electrical discharges. Nerve cells can recruit neurons in adjacent areas and synaptically related neurons in distant areas of the brain; thus, greatly increasing the number of neurons involved in seizure activity
Seizure Disorder
Seizure Disorder (Cont.)
Generalized seizures involve the entire brain from the onset of the seizure
Partial seizures are those in which abnormal electrical activity is restricted to one brain hemisphere
Status epilepticus is a continuing series of seizures without a period of recovery between seizure episodes and can be life-threatening
Dementia A syndrome associated with many
pathologic processes and characterized by progressive deterioration and continuing decline of memory and other cognitive changes
Patients may initially appear uninterested or lacking initiative, many have agnosia (lack of ability to interpret sensory stimulation) or lack of insight into their cognitive deficiencies
Important to first rule out manageable causes of dementia; often cause unknown
Dementia
Etiology 50-60% Alzhemier ‘sdisease 15-20% vascular dementia Dementia-causing illness:
alcoholism, intracranial tumor, normal pressure hydrocephalus, Parkinson disease, Lewy Body disease, Huntington disease, multiple sclerosis, Creutzfeldt-Jakob disease
Dementia
Delirium A global mental dysfunction includes
disturbed consciousness, decreased awareness of the environment, inability to maintain attention, disrupted sleep wake cycles, drowsiness, restlessness, emotional lability, incoherence, hallucinations
Abrupt onset, fluctuate often, worse at night Causes: polypharmacy, metabolic
abnormalities, nutritional deficiencies, infection
Dementia
Pathogenesis of Alzheimer’s disease 1. Intracellular neurofibrillary tangles 2. Extracellular amyloid (senile) plaques diffuse neuronal damage & brain
atrophy occurs The brain of Alzheimer disease often
weighs less than a normal person The temporoparietal and anterior frontal
regions of the brain are affected the most
Dementia
Pathogenesis of Alzheimer’s Disease 3. Neurotransmitter system:
abnormalities in cholinergic system Reduced activity of choline
acetyltransferase(the enzyme necessary for acetylcholine synthesis), and decreased ACH synthesis
Dementia
Conclusion: The dementia of Alzheimer disease is
characterized by degeneration of neurons in temporal and frontal lobes, brain atrophy, amyloid plaques, and neurofibrillary tangles
Cause remains unknown, although genetic and environmental triggers are suggested
Synthesis of brain acetylcholine is deficient and treatment is aimed at increasing acetylcholine levels by reducing acetylcholine reuptake
Parkinson’s disease
The basal ganglia includes the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, and substantia nigra.
Parkinson disease
The basal ganglia and the cerebellum transmit information via the thalamus to the cerebral cortex in order to regulate movement. In a healthy brain, the neurons based in the substantia nigra extend into the putamen and caudate (which both comprise the striatum). These cells release dopamine in the striatum, which modulates neuronal activity. As a result, this affects the performance of movement.
Basal Ganglia
Parkinson disease
In Parkinson’s disease, there is a breakdown in the connection between the neuron in the substantia nigra and the putamen portion of the striatum. Symptoms of Parkinson’s disease appear after 60-80% of these cells become impaired or die. It is not specifically the loss of the cells that causes the disease, but rather the decrease in the dopamine, which occurs with the decreased number of substantia nigra neurons.
Parkinson disease
Typically, symptoms appear after striatal dopamine levels have decreased by 20-50% of normal levels.
When Substantia nigra projections to the putamen have been impaired, the globus pallidus interna and subthalamic nucleus begin to function abnormally. The result is that the brain is no longer able to sufficiently control motor function.
Parkinson Disease (Cont.)
These signals could overly excite many of the muscles of the body, leading to rigidity. Symptoms include lead-pipe rigidity, tremor, pill-rolling movements, and reduced voluntary movement, loss of facial expression, drooling, propulsive gait, and absent arm swing
Parkinson Disease (Cont.)
Cerebral Palsy
Diverse group of crippling syndromes that appear during childhood and involve permanent, nonprogressive damage to motor control areas of the brain
Classified on the basis of neurologic signs and symptoms, with the major types involving spasticity, ataxia, dyskinesia, or a mix of one or more of the three
Cerebral Palsy (Cont.)
Etiology may include prenatal infections, or diseases of the mother; mechanical trauma to the head before, during, or after birth; exposure to nerve-damaging poisons or reduced oxygen supply to the brain
Hydrocephalus
Characterized by abnormal accumulation of fluid in the cerebroventricular system
1. Normal pressure hydrocephalus is due to an increased volume of CSF without change in ICP Ventricles become distended,
compressing brain tissue & cerebral vessels
NPH triad of symptoms: gait instability, urinary incontience, dementia
Hydrocephalus
2. Obstructive hydrocephalus is due to an obstruction to the flow of CSF There is an obstruction at some point in
either the intraventricular or extraventricular pathways of the ventricular system.
Usually congential abnormality, such as stenosis of the foramina of the 4th ventricle, aqueduct stenosis or spina bifida cystica
Hydrocephalus
3. Communicating hydrocephalus occurs due to abnormal absorption of CSF Also called acquired communicating
hydrocephalus Abnormality in CSF absorption from the
subarachnoid space. There is no obstruction to the flow of the fluid between the ventricles and subarachnoid space
Causes: Infections, trauma, tumors
Hydrocephalus (Cont.)
Hydrocephalus
Medical treatment is limited Obstructions may be corrected
surgically The most effective treatment for
management of hydrocephalus is surgical correction employing a shunt
Hydrocephalus (Cont.)
Cerebellar Disorders
Cerebellum is responsible for coordinated control of muscle action, excitation and inhibition of postural reflexes, and maintenance of balance
Etiology of cerebellar disorders includes abscess, hemorrhage, tumors, trauma, viral infection, or chronic alcoholism
Clinical manifestations include ataxia, hypotonia, intention tremors, and disturbances in gait and balance
Spinal cord & peripheral nerve disorders Multiple sclerosis Spina bifida Amyotrophic lateral sclerosis Spinal cord injury Guillain barre syndrome
Multiple Sclerosis
Chronic inflammation, demyelination, & gliosis (scarring) “Disseminated in time & space”
Affects 400,000 Americans Most frequent cause of neurologic disability
early/middle adulthood (excluding trauma) ? autoimmune etiology
environmental trigger in genetically susceptible
Name from plaques in white matter Occasionally - gray matter
Multiple Sclerosis
Epidemiology: Female:Male = 2:1 Onset of age: 20-50 yrs Orkney islands - Scandinavia - northern
European descent US - Caucasians > other races Rare in Japan; unknown in black Africans;
Japanese Americans/African Americans risk
Disease of temperate climates
Multiple Sclerosis
Etiology A viral infection or environmental toxin
intitates the autoimmune attack in a genetrically predisposed individual
Both humoral and cellular immune factors have been implicated in demyelination
T-cell lymphocyte-mediated damage to the myelin has also been implicated in causing the autoimmune damage and sustaining inflammation
Multiple Sclerosis
Pathogenosis Demyelination can occur throughout the
CNS but often affects the optic and oculomotor nerves, the corticospinal, cerebellar, and posterior column systems
Myelin facilitates nerve conduction, inflammation and scarring of the myelin slows or interrupts the conduction of nerves impulses
Spinal Cord and Peripheral Nerve Disorders
Spina Bifida
Developmental anomaly characterized by defective closure of the bony encasement of the spinal cord (neural tube) through which the spinal cord and meninges may or may not protrude
If anomaly not visible, condition is called spina bifida occulta
If there is an external protrusion of the saclike structure, the condition is called spina bifida cystica, and further classified according to the extent of neural involvement
Amyotrophic Lateral Sclerosis ALS is a progressive degenerative disease
affecting both the upper and lower motor neurons
Cause remains unknown, environmental factors, and genetic predisposition
Weakness and wasting of the upper extremities usually occur, followed by impaired speech, swallowing, and respiration
Typically occurs between the ages of 40-60 years and affects men more than women
Amyotrophic Lateral Sclerosis Pathologic changes in the spinal cord
include degeneration of the lateral columns where the corticospinal tracts are located
ALS is also known as Lou Gehrigh disease
Spinal Cord Injury
Etiology Usually traumatic, a result of motor vehicle
accidents, falls, penetrating wounds, or sports injuries
Spinal Cord Injury
Pathogenesis The major mechanisms of injury:
hyperflexion, hyperextension, and compression
Primary injury: The cord may be compressed, transected, or contused
Secondary injury: edema, ischemia, excitotoxicity, inflammation (neutrophils, macrophages, pro-inflammatory cytokines, T-lymphocytes), causing increased cell death, disruption of blood brain barrier, and demyelination
Spinal Cord Injury (Cont.)
Spinal Cord Injury (Cont.)
Spinal shock occurs immediately following SCI and is characterized by temporary loss of reflexes below the level of injury Muscles are flaccid; skeletal and autonomic
reflexes are lost Neurogenic shock may occur after SCI
due to peripheral vasodilation Hypotension and circulatory collapse can
occur; high spinal cord injuries can affect respiratory muscles, leading to ventilatory failure
Guillain-Barré Syndrome
Acute Inflammatory Demyelinating Polyneuropathy (AIDP) Axonal degeneration
Disease of the peripheral nervous system or a lower motor neuron disorder
Immune-mediated - ? immunopathogenesis
~ 75% - antecedent infection (prior 1-3 wks acute infection process) CMV& EBV, Campylobacter jejuni
gastroenteritis, herpesvirus, mycoplasma, surgical procedure
Guillain-Barré Syndrome (GBS) Occurs: 0.6-1.9 cases/100,000/yr All parts of world; all seasons;
children & adults; both sexes; all ages (d 50-81 yoa)
Life-threatening respiratory insufficiency, swallowing
difficulties, & autonomic dysregulation Mortality < 5% in optimal settings Ascending, primarily motor paralysis
References
Pathophysiology by Copstead & Banasik Ch 44, 45