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Neuro Pathophysiology

Terms

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Functions of the Nervous System
Controls skeletal muscle movement
Helps regulate cardiac and visceral smooth muscle activity
Enables reception, integration, and perception of sensory information
Functions of the Nervous System (cont.)
Provides substratum necessary for intelligence, anticipation, and judgment
Facilitates adjustment to ever-changing external environment
Components of the Nervous System
CNS
PNS
CNS
Consists of the brain and spinal cord, which are protected by the skull and vertebral column
Concentration of computational and control functions
PNS
Found outside structures of CNS
Functions as input-output system for relaying information to CNS and transmitting output messages to control effector organs
Structures of the Brain
Hindbrain
Midbrain
Forebrain
Hindbrain
(Brain Stem)
medulla oblongata
pons
cerebellum
Midbrain
Include two pairs of dorsal enlargements
- superior coliculi
- inferior colliculi
Forebrain
Consists of two hemispheres covered by cerebral cortex
Contains central masses of gray matter, basal ganglia, diencephalon with its derivatives—thalamus and hypothalamus
Lobes of the Brain
frontal lobe
parietal lobe
temporal lobe
occipital lobe
Frontal lobe
extends from frontal pole to central sulcus (fissure)
- separated from temporal lobe by lateral sulcus
Parietal lobe
lies behind central sulcus (postcentral gyrus); above lateral sulcus
Temporal lobe
lies below the lateral sulcus and merges with the parietal and occipital lobes
Occipital lobe
- lies posterior to temporal and parietal lobes
- arbitrarily separated from them
Levels of the Spinal Cord
- spinal cord is shorter than spinal column in adult

Cauda Equina
- collection of spinal nerves that travel down spinal canal below termination of spinal cord
Spinal Nerves
Each exits at a vertebral level that corresponds to its level in the cord
Horns of the Spinal Cord
- extensions of gray matter that form the letter “H”
- White matter of the cord is composed of myelinated axons traveling up cord to the brain (sensory) or down cord from brain (motor).
- dorsal horns
- ventral horns
Dorsal Horns
Contain neurons that receive afferent impulses through dorsal roots
Ventral Horns
Contain neurons and the efferent lower motor neurons that leave the cord through the ventral roots
Information Flow
- cranial and spinal nerves come out from the CNS
BUT
- information flowing through may be coming out (efferent; motor information)
- OR coming in (afferent; sensory information) to the CNS
Afferent Nerve
- carries information from sensory receptors in skin to brain
Efferent Nerve
- carries information from brain to neurons controlling leg muscle, causing response
Nerves

Cranial or Spinal
- collections of nerve fibers (individual axons or dendrites of individual neurons)

Individual fibers within nerve may be transmitting motor information out to periphery or sensory information in to CNS
Major Cells of the Nervous System
- neurons
- glia
Neurons
(Functioning Cells)
- Afferent (sensory) neurons carry information to CNS
- Efferent (motor neurons) carry information from CNS to effector organs
Neurons
(Functioning Cells)
cont.
- gray matter: nerve cell bodies in CNS
- white matter: myelinated axons forming tracts in CNS
Glia
- protect nervous system; supply metabolic support
- astrocytes contribute to blood-brain barrier; also give metabolic support
- oligodendrocytes in brain and Schwann cells in periphery make myelin to insulate nerve fibers
- microglia: immune cells in brain
Sensory Component of Nervous System

Function
Provides awareness of body sensations (i.e. body position in space, sight, hearing, touch, temperature, limb position, pain)
Sensory Component of Nervous System

Composition
- sensory receptors: consist of discrete nerve endings in skin and other body tissues
- dermatomes: areas of skin supplied by discrete levels of spinal nerves
Major Modalities of Sensory Experience
Discriminative Touch
Temperature Sensation
Body Position
Nociception (Pain sense)
Discriminative Touch
Location, Sharp, Dull, Soft, Fuzzy, Scratchy
Temperature Sensation
Hot, Warm, Cool, Cold
Body Position
Flexion, Extension, Position in Space, Balance
Nociception (Pain sense)
Sharp, Dull, stabbing, Aching, Burning
Neurons Found in Sensory Systems
First-order neurons
Second-order neurons
Third-order neurons
First-Order Neurons
Transmit sensory information from periphery to spinal cord.
Second-Order Neurons
Relay sensory information up spinal cord to thalamus.
Third-order neurons
Relay information from the thalamus to the cerebral cortex
Pathways from Spinal Cord to Thalamic Level of Sensation
- anterolateral pathways (spinothalamic tracts)
- discriminative pathway (posterior columns)
Anterolateral Pathways (Spinothalamic Tracts)
- bilateral multisynaptic slow-conducting tracts
- provide for transmission of sensory information that does not require discrete localization of signal source or fine discrimination of intensity
Discriminative Pathway (Posterior Columns)
- crosses at base of medulla
- relays information to brain for perception, arousal, and motor control
Corticospinal (Pyramidal) Tracts
-Nerve cell bodies: pyramid-shaped neurons in motor cortex
-myelinated axons pass down through brain in bundle called internal capsule.
- In brain stem, axons cross to opposite side: decussation of pyramids
- axons then course down ventral lateral spinal cord
- individual axons peel off from rest at particular levels; then synapse with primary motor neurons
- important in gross motor movement
Extrapyramidal Tracts
Additional synapses may be present in midbrain and pons and finally at the lower motor neurons at each level of cord.

Serves to smooth and integrate movement
Requirements of Motor Systems
Functioning neuromuscular junction that links nervous system activity with muscle contraction
Motor Systems
Pyramidal motor system
Extrapyramidal system
Pyramidal Motor System
Originates in motor cortex
Provides control of delicate muscle movement
Extrapyramidal System
Originates in basal ganglia
Provides background for more crude, supportive movement patterns
Motor Unit
Excitatory & inhibitory influences come from higher centers.

Excitatory influences may come from sensory input at same level.
Neuromuscular Junction
Acetylcholine binds to receptors in the endplate region of the muscle fiber surface to cause muscle contraction
Mechanisms Controlling Coordinated Movement
Antagonists
- Oppose movement
Synergists
- Assist agonist muscles by stabilizing a joint or contributing additional force to movement
Spinal Cord Injury (SCI)
Definition
Damage to neural elements of spinal cord
Spinal Cord Injury (SCI)
Causes
Motor vehicle crashes, falls, violence and sporting activities
Spinal Cord Injury (SCI)
Involvement
Most SCIs involve damage to vertebral column and/or supporting ligaments as well as spinal cord
Commonly involve both sensory and motor function
Types of Injuries to Vertebral Column
Fractures
Dislocations
Subluxations
Incomplete Spinal Cord Injuries
Central Cord Syndrome
Brown-Séquard Syndrome
Anterior Cord Syndrome
Types of Paralysis
Monoplegia
Hemiplegia
Tetraplegia or quadriplegia
Paraplegia
Areas Affected by SCI
Pain Transmission
Bladder and bowel function
Sexual function
Disorders of Motor Function
Upper motoneuron lesions
Lower motoneuron lesions
Upper Motoneuron Lesions
Can involve motor cortex, internal capsule, or other brain structures through which corticospinal or corticobulbar tracts descend, or spinal cord
Lower Motoneuron Lesions
Disrupt communication between muscle and all neural input from spinal cord reflexes, including stretch reflex, which maintains muscle tone
Muscle Spasm
Sudden violent involuntary contraction of a muscle or group of muscles
Spasticity
Certain muscles are continuously contracted leads to
- muscle stiffness/tightness
-may interfere with gait, movement, or speech:
= Damage to the portion of brain or spinal cord that controls voluntary movement usually causes spasticity
Diseases Associated with Spasticity
Brain damage due to lack of oxygen
Brain trauma
Severe head injury
Metabolic disease (adrenoleukodystrophy
Spastic Contractions
- often triggered by sensory stimuli that normally elicit motor reflex
- sensory stimulus that evokes contraction much smaller than normal
- contraction evoked much stronger than normal
Spasticity (cont.)
when chronic can result in contractures
Basal Ganglia
function in inherited & highly learned & rather automatic
- involved in cognitive and perception functions
Dopamine pathway & effects
Mesocortical - Cognition
Mesolimbic - Emotions
Nigrastriatal - Extra-pyramidal system that modulate movement
Cholinergic pathway & effects

Cortex and Limbic System
-Learning and memory;
-Wakefulness and attention
Cholinergic pathway & effects

PNS
Useful throughout the body
- Regulation of Parasympathetic Nervous System
- Excitatory transmission at neuromuscular junction
Disorders of the Basal Ganglia
Characteristics
Involuntary movements
Alterations in muscle tone
Disturbances in body posture
Involuntary Movement Disorders Types
Tremor
Tics
Chorea
Athetosis
Ballismus
Dystonia
Dyskinesias
Parkinson Disease

Definition
degenerative disorder of basal ganglia function that results in variable combinations of tremor, rigidity, and bradykinesia
Parkinson Disease

Characteristics
- progressive destruction of nigrostriatal pathway
- subsequent reduction in striatal concentrations of dopamine
Multiple Sclerosis (MS)
- most common non-traumatic cause of neurologic disability among young & middle-aged adults
Multiple Sclerosis (MS)

Characteristics
- exacerbations and remissions over many years in several different sites in CNS
- starts with normal or near-normal neurologic function between exacerbations
- during progression, less improvement between exacerbations, neurologic dysfunction increases
Brain Injury Causes
Trauma
Tumors
Stroke
Metabolic derangements
Degenerative disorders
Brain Injury Manifestations
Alterations in sensory and motor function
Changes in the level of consciousness
Levels of Consciousness
Confusion
Delirium
Obtundation
Stupor
Coma
Signs of Decreased LOC
Earliest
- Inattention, mild confusion, disorientation, and blunted responsiveness

Later
- marked inattention; variable lethargic or agitated
- may progress to obtunded; may respond only to vigorous or painful stimuli
Common Pathways of Brain Damage
Effects of ischemia
Excitatory amino acid injury
Cerebral edema
Injury due to increased intracranial pressure (ICP)
Hypoxia
deprivation of oxygen with maintained blood flow
Ischemia
- greatly reduced or interrupted blood flow
- interferes with O2 and glucose delivery, and metabolic waste removal
Injury From Excitatory Amino Acids

Definition
Injury to neurons caused by overstimulation of receptors for specific amino acids that act as excitatory neurotransmitters
Injury From Excitatory Amino Acids

Causes
Stroke
Hypoglycemic injury
Trauma
Chronic degenerative disorders (Huntington’s disease,Alzheimer’s dementia)
Cerebral Edema
Vasogenic Edema

Cytotoxic Edema
Vasogenic Edema
- occurs with conditions that impair the function of blood-brain barrier
- allows transfer of water and protein from vascular into interstitial space
Cytotoxic Edema
- increase in intracellular fluid
Brain Injury Types
Primary or Direct

Secondary Injuries
Primary or Direct Brain Injuries
Damage is caused by impact
Include diffuse axonal injury and focal lesions of laceration, contusion, and hemorrhage
Secondary Brain Injuries
Damage results from subsequent brain swelling, infection, cerebral hypoxia
Often diffuse or multi-focal, including concussion, infection, and hypoxic brain injury
Epidural Hematoma
- Usually caused by head injury with skull fracture
- between inner table of bones of skull and dura
Subdural Hematoma
- Usually result of tear in small bridging veins that connect veins on surface of cortex to dural sinuses
- Develops in area between dura and arachnoid (subdural space)
Blood Supply to Brain
Anterior
- two internal carotid arteries

Posterior
- vertebral arteries
Cerebral Blood Flow

Metabolic Factors
Carbon dioxide
Hydrogen ion
Oxygen concentration
Ischemic Strokes
- interruption of blood flow in cerebral vessel
- most common type of stroke (70%-80%)
Hemorraghic Strokes
- bleeding into brain tissue
- blood vessel rupture
-- HTN, aneurysms, AVM, head injury, blood dyscrasias
Stroke Risk Factors
Age, sex, race
Family history
Hypertension
Smoking
Diabetes mellitus
Asymptomatic carotid stenosis
Sickle cell disease
Hyperlipidemia
Atrial fibrillation
Stroke Related Deficits
Motor deficits
Dysarthria and Aphasia
Cognitive and Other Deficits
Seizure
- uncontrolled, chaotic activity in brain
- produces muscular activity
-- tonus (muscle contraction)
-- clonus (alternate contraction and relaxation
-- complete relaxation/ paralysis
Seizure Risk Factors
Lifetime risk - 10%
Epilepsy at some point: 3-4%
Epilepsy at any given time: 0.5-1%
Acute reaction seizure: 3-4%
Single unprovoked seizure: 1%
Active epilepsy >55 yrs: 0.9%
Seizure Activity Risk Factors

Specific Populations
Acute stroke – ~ 25%
Brain tumor – 30% as first symptom
-- 18% with brain metastasis
Infection
-- Bacterial meningitis – 25%
-- Herpes encephalitis – 50%
Dialysis encephalopthy – 50%
Alzheimer's – 16%
Seizure Classification
Partial

Generalized
Partial Seizures
Simple - no impairment of consciousness
Complex - impairment of consciousness
Partial seizures evolving to secondarily generalized seizures
Generalized Seizures
Absence seizures (typical or atypical)
Atonic seizures
Myotonic seizures
Clonic seizures
Tonic seizures
Tonic-clonic seizures
Status Epilepticus
Definition
- Rapid succession of epileptic seizures
Sudden withdrawal of AEDs may precipitate seizures or status epilepticus
First drug of choice
- IV diazepam (benzodiazepine)
Status Epilepticus

(cont.)
- possible intubation, ventilation
- after IV benzo, give loading dose of phenytoin (long-acting anticonvulsant)
- Possible complications: lactic acidosis, hyperthermia
Bacterial Meningitis
“Meningococcal meningitis” = Neisseria meningitides.

“Pneumococcal meningitis” = Streptococcus pneumonae.

Other bacterial causes:
- Haemophilus influenza
- Mycobacterium tuberculosis.
Bacterial Meningitis

(cont.)
- after infecting meninges, rapidly destroy capillary structure and invade brain
- can be rapidly fatal (hours)
- prophylactic abx w/exposure
Viral Meningitis
- caused by various viruses
- usually mild
Immunosuppressed patients (HIV, chemotherapy) can get fulminant, fatal viral meningitis caused by
- Epstein Barr virus
- herpes simplex virus
- West Nile virus
Alzheimer's Disease Stages
- progressive, unrelenting
- NO KNOWN CURE
- few therapeutic options
- > 4 million Americans
- by 2010, Medicare/Medicaid costs will be >$79 billion
- other costs include informal caregiving (can cost businesses $61 billion/yr in lost work days
Clinical Hallmarks/Major Symptoms Of Alzheimer’s Disease
Progressive cognitive impairment, particularly memory loss.

Impaired judgment and decision-making ability.

Difficulty orienting to physical surroundings.

Language problems
Neuropathological Hallmarks of Alzheimer’s Disease
Neuron Death

Neurofibrillary Tangles

Amyloid Plaques

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