Lp 8 neurology 2008

Neurology

VTT 235/245 Anatomy & Pathology

The Nervous System

A complex communication and control system.

It monitors the animal’s internal and external environments and directs activities to maintain the well-being of the body.

2 Main Divisions

Central Nervous System- Composed of the brain and spinal cord.

Peripheral Nervous System- Consists of cord-like nerves that link

the CNS with the rest of the body.

Functions

Sensory Functions- The nervous system senses changes

from inside/outside the body and conveys this information to the spinal cord or brain.

Integrating Functions- In the brain and spinal cord, the sensory

information is received, analyzed, stored, and integrated to produce a response.

Functions…

Motor Response Functions- Instructs the body to do something,

such as contract a muscle or cause a gland to secrete its product(s).

Neurons & Supporting Cells

Neuroglia

“Glial cells”, glia- greek for glue! Structurally and functionally supports

and protects neurons. Outnumbers neurons 10:1. Not directly involved in the

transmission of information or impulses.

Neurons

Nerve cells. The basic

functional units of the nervous system.

Has a high requirement for oxygen.

Neuron Structure

Central cell body- “stoma” Dendrites-

Receive stimuli, or impulses, from other neurons and conduct the stimulation to the cell body.

May also be modified into sensory receptors that receive, or sense, stimuli such as heat, cold, touch, pressure…

Short, numerous, multi-branched projections extending from the cell body.

Neuron Structure…

Axons- Conduct nerve impulses away from the

cell body toward another neuron or effecter cell. A cell that does something when stimulated.

A single process can be very long. Often covered by a fatty substance

called myelin (white matter).

Neuron Structure…

Myelin sheath- Actually cell membranes of specialized

glial cells called oligodendrocytes in the brain & spinal cord, and Schwann cells in nerves outside of the brain and spinal cord.

These special glial cells are wrapped around the axon.

Neuron Structure…

Nodes of Ranvier- Small gaps in the

myelin sheath between adjacent glial cells.

Works with the myelin sheath to enhance the speed of conduction of nerve impulses along the axon.

Organization of the Nervous System

CNS vs. PNS

CNS- anatomically composed of the brain and spinal cord.

PNS- made up of components of the nervous system that extend away from the CNS, towards the periphery of the body.

Cranial nerves- nerves of the PNS that originate directly from the brain.

Spinal Nerves- nerves of the PNS that originate from the spinal cord.

Afferent vs. Efferent

Afferent nerves- Conduct nerve impulses towards the

CNS. Conducts sensations from the sensory

receptors in the skin and other locations in the body to the CNS.

Also called sensory nerves.

Afferent vs. Efferent…

Efferent nerves- Conduct impulses from the CNS out

toward muscles and other organs. They cause skeletal muscle contractions

and movement.

Neuron Function

Resting State

When a neuron is not being stimulated, it is in a resting state.

The cell membranes of neurons are electronically polarized when at rest (like tiny, charged batteries).

Specially charged molecules located in the neuron’s cell membrane pump sodium (Na+) ions from inside the neuron to the outside.

They also pump potassium (K+) ions from the outside to the inside.

Resting State…

This specialized molecule is called the sodium-potassium pump.

The action of the sodium-potassium pump causes a higher concentration of Na+ to accumulate outside the cell.

The pump’s actions and the negative charges inside the cell cause a higher concentration of K+ to accumulate inside the cell.

Resting State…

This keeps the cellular membrane between Na+ and K+ polarized.

The distribution of positive and negative charges creates a difference in electrical charge across the membrane. Inside the cell- negative

This electrical difference in charges is called the resting membrane potential.

Depolarization

When an impulse from an adjoining neuron stimulates another neuron, a set of specific steps occurs, resulting in the nerve “firing” or depolarizing.

The Na+ channel opens and allows only Na+ ions to pass through it by passive diffusion into the cell.

Depolarization refers to this opening of the Na+ channels and the sudden influx of many Na+ ions.

Depolarization…

The inside of the neuron goes from a negative charge to a positive charge.

The significant change in electrical charge is also referred to as the action potential.

Repolarization

Within a fraction of a second, the Na+ channels snap shut, halting the influx.

At the same time, potassium channels open and only allow K+ ions to pass through them.

K+ ions passively diffuse out of the cell by a concentration gradient and positive cell charge.

Repolarization…

The outflow of K+ ions continues until the channels close a split-second after they have opened.

This causes the charge inside the cell to swing back in the negative direction.

The change of the cell’s charge back to negative is called repolarization.

All-or-Nothing Principle

Not every depolarization stimulus results in a complete depolarization-repolarization cycle.

The initial stimulus must be sufficient enough to make the neuron respond.

When the stimulus is strong enough to cause complete depolarization, it is said to have reached the threshold.

All-or-Nothing Principle…

Regardless of how strong the initial stimulus was, if it was sufficient enough to achieve threshold, the action potential would be generated and conducted along the entire length of the neuron with a uniform strength.

All-or-Nothing Principle…

This phenomenon is called the all-or-nothing principle, because either the neuron completes a depolarization to the maximum strength, or it does not depolarize at all.

Refractory Period

If a second threshold stimulus arrives at the dendrites while the Na+ channels are open or while K+ molecules are moving through their open channels, the stimulus is incapable of a second depolarization.

The Synapse

How Neurons Communicate

The Synapse…

Once the action potential has been successfully conducted to the end of the axon, the nerve impulse must be transmitted to the next neuron or to the cells of the target organ or tissue.

Because two neurons do not physically touch, the depolarization wave is unable to continue to the next neuron.

Instead, the neuron must release a chemical that stimulates the next neuron or cell.

The Synapse…

This perpetuation is called a synaptic transmission.

The synapse is the junction between two neurons or a neuron and a target cell.

The synapse consists of a physical gap between the two cells called the synaptic cleft.

The Synapse…

Presynaptic neuron- the neuron bringing the depolarization wave to the synapse and releasing the chemical to stimulate the next cell.

Neurotransmitter- the chemical released from the presynaptic neuron.

Postsynaptic neuron- the neuron that contains the receptors that receive the neurotransmitter.

The Synapse…

On the postsynaptic membrane are specialized proteins called receptors.

The neurotransmitter binds with these receptors and trigger a change in the postsynaptic cell.

The postsynaptic membrane receptors are very specific about which neurotransmitters they will allow to bind.

Neurotransmitters

Can be classified into 2 categories- Excitory- usually

causes an influx of Na+ so that the postsynaptic membrane moves toward the threshold.

Inhibitory- moves the charge away from the threshold.

Neurotransmitters…

Acetylcholine- Excitory or inhibitory, depending on its

location in the body. Excitory- at the junction between somatic

motor neurons that stimulates muscle fibers to contract.

Inhibitory at the site where nerves synapse with the heart and slows the heart rate.

Neurotransmitters…

Catacholamines- Norepinepherine- associated with the “fight-

or-flight” reactions of the sympathetic nervous system.

Epinepherine- released primarily from the adrenal medulla to participate in the “fight-or-flight” response.

Dopamine- Found in the brain. Involved in autonomic functions and muscle control. Low dopamine= Parkinson’s disease.

Neurotransmitters…

GABA & Glycine- GABA- gamma-aminobutyric acid. GABA is found in the brain, glycine is

found in the spinal cord.

Neurotransmitters…

One postsynaptic membrane may have multiple types of presynaptic neurons across the synaptic cleft.

By having both, the nervous system can selectively increase or decrease the activity of specific parts of the brain or spinal cord.

Stopping & Recycling Neurotransmitters

The body needs a way to stop the neurotransmitter or the excitory or inhibitory effect would continue.

In the case of acetylcholine, it is broken down into the enzyme acetylcholinesterase. “-ase”- enzyme

Stopping Neurotransmitters

If nothing breaks down neurotransmitters, the effect would continue indefinitely.

Ex.- This is what happens with organophosphate toxicity: The insecticide combines with

acetylcholinesterase and inactivates it. Overstimulation of acetylcholine

receptors results in vomiting, diarrhea, difficulty breathing, and constricted pupils.

THE BRAIN

CerebrumCerebellum

DiencephalonBrainstem

The Brain

Cerebrum

Made up of gray and white matter fibers.

The largest part of the brain. Responsible for higher-order

behaviors: Learning Intelligence

Cerebrum…

Receives and interprets sensory information- Initiates nerve impulses to skeletal

muscles. Integrates neuron activity normally

associated with: Communication Emotional expression Memory

Cerebrum…

The wrinkled appearance is due to folds called gyri, separated by deep grooves called fissures and more shallow grooves called sulci.

The most prominent groove is the longitudinal fissure which divides the cerebrum into the right and left cerebral hemispheres.

Each hemisphere is divided by sulci into lobes.

Different lobes specialize in certain functions.

Cerebellum

Located caudal to the cerebrum. The second largest component of the

brain. Allows the body to have coordinated

movement: Balance Posture Complex reflexes

Diencephalon

Serves as a nervous system passageway between the primitive brainstem and the cerebrum.

Pituitary- the endocrine “master gland” that regulates hormone production and release.

Thalamus- acts as a relay station for regulating sensory inputs to the cerebrum.

Diencephalon…

Hypothalamus- and interface between the nervous and endocrine systems. Plays a major role in:

Temperature regulation Hunger Thirst

Brainstem

The connection between the brain and spinal cord.

The most primitive part of the brain. Composed of: the medulla oblongata,

pons, and midbrain. Maintains basic body support

functions.

Brainstem…

Heavily involved in autonomic control functions related to: The heart Respiration- including coughing,

sneezing, and hiccuping. Blood vessel diameter Swallowing Vomiting

Meninges

A set of connective tissue layers that surround the brain and spinal cord.

They contain a rich network of blood vessels that supply oxygen and nutrients to the superficial tissues of the brain and spinal cord.

Cerebrospinal Fluid

The brain and spinal cord are bathed and protected from the hard inner surfaces of the skull and spinal column by CSF.

It circulates between layers of meninges and through cavities inside the brain and spinal cord.

The chemical composition may be involved in the regulation of certain autonomic function, such as respiration and vomiting.

Blood-Brain Barrier

A functional barrier separating the capillaries in the brain from the nervous tissue itself.

The composition results in a cellular barrier that prevents many drugs, proteins, ions, and other molecules from readily passing from the blood into the brain.

In this way, the BBB protects the brain from many poisons circulating in the bloodstream. Ex.- Ivermectin Parasites and insects don’t have a BBB so the drug kills

them by allowing it to reach target receptors in the brain.

Cranial Nerves

A special set of 12 nerve pairs in the peripheral nervous system that originate directly from the brain.

Cranial NervesColville p. 155

Nerve Type Function

I Olefactory Sensory Smell

II Optic Sensory Vision

III Occulomotor MotorEye movement,

pupil size, focusing lens

IV Trochlear Motor Eye movement

V Trigeminal MixedS: eye & faceM: chewing

VI Abducens Motor Eye movement

VII Facial Mixed

Face and scalp movement, salivation,

tears, & taste

VIIIVestibulocochlea

rSensory Balance/hearing

IX Glossopharyngeal Mixed

S: 1/3 caudal tongue taste

M: swallowing & salivation

X Vagus Mixed

S: GI tract, resp., M: larynx, pharynx,

parasympathetic motor to the

abdominal viscera & thoracic organs

XI Spinal Accessory MotorSkeletal muscles of the

neck and shoulderAccessory with vagus

XII Hypoglossal MotorSkeletal muscles of the

tongue

I

II

III

IVV

VI

VIIVIII

IXXXI

XII

Pyramid

Pons

Cerebralpeduncle

Pituitary gland

Optic chiasma

Olfactory bulb

Cranialnerves

Spinal Cord

The caudal continuation of the brain stem outside the skull.

It conducts sensory information and motor instructions between the brain and the periphery of the body.

Autonomic Nervous System

Autonomic Nervous System

Controls many functions of the body on a subconscious level.

These autonomic functions are performed by two divisions: Sympathetic nervous system Parasympathetic nervous system

These two systems generally have opposite effects on eachother.

IV. Pathology

By: Dr. Tuya Buchanan, DVM

Cerebral Pathology

Cerebral Trauma/ Hemorrhage

Severe bruising of the brain causes capillary rupture & bleeding of the brain resulting in increased ICP (intracranial pressure)

Cerebellar Hypoplasia

The cerebellum does not grow properly

Due to in utero viral infections or injury, or just bad genetics Panleukopenia in cats Herpesvirus infections in dogs Vaccinating pregnant animals w/ MLV

Problems are first noticed when the young animal starts to ambulate

Cerebellar Hypoplasia (cont)

Signs include: Ataxia

(incoordination) Hypermetria

(over reaching when walking)

Intention tremors

Broad-based stance

Hydrocephalus

Commonly referred to as “water on the brain”

Characterized by a dome-shaped head

Either too much CSF is produced or there is inadequate drainage

Cerebral Hypoxia

Lack of oxygen to the brain

Numerous causes- clots (“stroke”), heart disease, renal disease, hyperthyroidism in cats, parasites, etc.

Brain Tumors

Can arise from any type of neuro cells

Clinical signs depend on the location, size, and degree of pressure they are putting on the brain

Glial tumors include astrocytomas & oligodendrogliomas

Meningiomas are another type of tumor

Brain Tumor in a Boxer

Strychnine Poisoning

Strychnine blocks an inhibitory neurotransmitter (glycine) in the medulla & spinal cord

So you end up with excitation of neurons which results in muscle rigidity & seizures

Animals die from lack of oxygen to vital body parts and exhaustion

Some Infectious Agents which cause Cerebral Pathology

Rabies

Rhabdovirus Furious Rabies- aggressive, snarling,

seizuring, drooling animal Dumb Rabies- depression, dementia,

hind-end weakness, & drooling Some animals will show obsessive

licking/self mutilation of an old wound No ante-mortem tests- need the brain

Rabies (cont)

Rabies (cont)

Bad Raccoon! A Negri Body inside a neuron. When seen this viral inclusion body can mean only Rabies!

Distemper

Caused by a Paramyxovirus The virus depletes the immune

system so the puppy is very prone to secondary infections

Starts out respiratory, then GI signs, then neurological signs

“hard pads” usually occur end-stage

Distemper (cont)

Difficult to diagnose ante-mortem

Serology can be very unrewarding

Can do immunoflourescent assays for the virus in conjunctival scrapings (or wait for necropsy)

Equine Encephalitis

Caused by a virus

3 forms: Eastern, Western, & Venezuelan

Horses have a fever, appear sleepy, and may show incoordination of the rear-end; it can progress to full paralysis and death

Seizures

A seizure is an episode of abnormal electrical activity in the brain resulting in: loss or altered consciousness increased muscle tone involuntary urination & defecation

Most seizures are grand mal but some may be petit mal where there is not a complete loss of consciousness and may only involve a limb shaking or small body tremors

Seizures (cont)

Seizures have either an intracranial or an extracranial cause

Intracranial seizures are caused by primary CNS disease (problem is inside the brain itself)

Extracranial seizures are caused by organ dysfunctions or toxins which have secondary effects on the brain (problem is outside the brain)

Intracranial Causes of Seizures

Brain tumors- primary or those that metastasize to the brain

Bacteria (abscesses) Viruses (distemper) Protozoa (toxoplasmosis) Fungal Hydrocephalus Idiopathic epilepsy

Extracranial Causes of Seizures

Hypoglycemia Liver disease Renal disease Hypocalcemia Toxins- strychnine, lead,

organophosphates

Spinal Cord Pathology

Wobbler Syndrome

In horses, known as Cervical Stenotic Myelopathy

In dogs, known as Caudal Cervical Spondylomyelopthy

Either way, it’s a malformation of the cervical spine causing cord compression

Wobbler (cont)

Breeds of dogs include Dobermans, Great Danes, & Basset Hounds

Affected dogs are mostly young adults

Signs range from hind-end weakness to tetraplegia, neck pain, & the neck is flexed ventrally

Wobbler (cont)

Seen in young, rapidly growing horses, especially Thoroughbreds

Over nutrition is a big contributing factor

Signs consist of limb weakness and incoordination

Vertebral Fractures

Usually secondary to trauma (HBC) or bone pathology (osteomyelitis)

Spinous process fractures do not usually cause problems

Problems arise when the spinal cord becomes compressed or is also fractured

Fractures (cont)

Spinal Cord Concussion

Usually secondary to trauma, such as HBC

Due to severe bruising of the cord, the motor nerves do not function properly

These dogs can look completely paralyzed but radiographs +/- CT scan will show no abnormalities

With time and steroids, there will be improvement

Intervertebral Disc Disease (IVDD)

Affects dogs, rarely cats Disease can occur anywhere in the

spinal tract but the lumbosacral and cervical regions are most common

Can have partial or complete herniation of the disc up into the spinal cord

Typically a degenerative process Dachshunds, Beagles, Pekingese, etc.

IVDD (cont)

Clinical signs can be acute or chronic Severity of signs depends on the degree

of spinal cord compression Signs progress from ataxia/incoordination

& loss of conscious proprioception >> paresis (muscle weakness) >> paralysis >> loss of deep pain sensation

Animals with acutely compressed cords can be very painful while there may be little to no pain with chronic compression

IVDD (cont)

IVDD (cont)

Degenerative Myelopathy

Most common in German Shepherds & Welsh Corgis

A progressive degeneration of the axons & myelin of the white matter of the SC

Dogs are usually > 5 yrs old and develop a gradual onset of non painful ataxia & weakness in the pelvic limbs

Poor prognosis; most are euthanized within 1-3 yrs

Spinal Neoplasia

Relatively common in dogs & cats Tumors are classified according to their

relationship with the spinal cord & meninges Extradural: outside the dura mater; compress

SC; most common SC tumor in dogs/cats Intradural-extramedullary: in the

subarachnoid space; compress SC Intramedullary: inside the SC itself; least

common type

SC Neoplasia (cont)

Laboratory

CSF Analysis

Evaluation

Evaluation is important to patients with neurologic disease.

Helpful in evaluating patients with unexplained fever.

Collection Sites

Atlantooccipital Lumbosacral

Analysis

Examination of CSF should consist of: Physical characteristics-

Color Turbidity

Total nucleated cell count (TNCC) Erythrocyte count Protein concentration Cytologic examination

Analysis…

Analysis of CSF should be done as quickly as possible. The low protein concentration of CSF

cause the cells to degenerate rapidly.

Dissection