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Definition:

1. Neuropathy -Neuropathy is a term that refers to general diseases or malfunctions of the


nerves. Nerves at any location in the body can be damaged from injury or disease.
Neuropathy is often classified according to the types or location of nerves that are affected.
Neuropathy can also be classified according to the disease causing it
2. Alcohol - In chemistry, an alcohol is any organic compound in which the hydroxyl functional
group is bound to a saturated carbon atom. The term alcohol originally referred to the primary
alcohol ethyl alcohol, the predominant alcohol in alcoholic beverages

a.
3. Chronic Alcoholism
-a pathological condition resulting from the habitual use of alcohol in excessive amounts. The syn
drome involves complex cultural, psychological, social, and physiological factors and usually imp
airs an individual's health and ability tofunction normally in society.

Pathologic condition, affecting chiefly the nervous and gastroenteric systems, associated with
impairment in social and occupational functioning, caused by the habitual use of alcoholic be
verages in toxic amounts.

Effects of Alcohol
1. Skeletal Muscle
- Myopathy
- Reduce muscle strength and muscle function
- Myalgia (pain in a muscle or group of muscles.)
- Loss of proprioception
- Progressive weakness in the proximal muscle
- Osteopenia (reduced bone mass of lesser severity than osteoporosis.)
- Easy fatigability
- Delayed bone healing
2. CNS
- Decrease excitability of nerves and cerebral activity
- Increase blood pressure
- Changes in cognition
- Amnesia (anterograde)
- Alodynia (experience of pain from a non-painful stimulation of the skin,
such as light touch)
- Hyperalgesia (abnormally heightened sensitivity to pain)
- Paresthesia (an abnormal sensation, typically tingling or pricking (pins
and needles), caused chiefly by pressure on or damage to peripheral
nerves.)
- LE>UE
- Thiamine deficiency (B1)
- Memory impairment
- Loss of higher brain function (recognition, memory, judgment, abstract,
accuracy in fine motor skills)
- Disturbance of balance

Epidemiology:
Mortality/Morbidity
Chronic consumption of alcohol has been implicated in end-organ damage to
multiple systems. Damaged structures include the brain (exhibited by development
of Wernicke encephalopathy, Korsakoff psychosis, and cerebellar ataxia), heart (as
in cardiac myopathy and autonomic neuropathy), pancreas, gallbladder, and liver
(cirrhosis), as well as the peripheral nerves. Patients with multisystem damage as a
result of alcohol consumption often die of cardiac or liver failure.
Children exposed to greater than 2 oz of alcohol per day in utero exhibit nerve
conduction slowing and decreased compound muscle action potential (CMAP)
amplitude in comparison with children with no prenatal exposure to alcohol.
Race
Cultural and racial factors involved in the consumption of alcoholic beverages are
beyond the scope of this article. The subject has not been well studied in terms of
the development of alcoholic neuropathy. However, one noteworthy study
suggested that the risk of developing peripheral neuropathy is higher in alcoholic
patients whose parents had a history of alcoholism.
Sex
Ammendola and colleagues conducted a study to assess differences between men
and women in the development of alcoholic neuropathy. [18] This study used the sural
sensory nerve action potential (SNAP) amplitude (ie, nerve conduction study) as the
variable measure to detect significant neuropathy in a population of males and
females with chronic alcoholism. Although the study provided control for nutritional
deficiencies, the female group with chronic alcoholism had a significantly lower
sural SNAP amplitude compared with the male group with similar total lifetime dose
of ethanol consumption (TLDEC). This study suggested that females may
demonstrate increased sensitivity to the toxic effects of alcohol on peripheral
nerves.
- Drinking four or more drinks on any given day OR drinking eight or more drinks in
a typical week increases a womans risk of developing alcohol abuse or
dependence.
- "moderate drinking." It's no more than 3-4 standard drinks per drinking episode,
no more than 9 drinks per week for women and 12-14 for men.
A standard drink is equal to

a 12 oz (355 ml.) beer with 5% alcohol (average for most U.S. beers).

A 5 oz. (150 ml.) glass of wine (12.5% alcohol).

1.5 oz. (45 ml.) of 80 proof liquor (40% alcohol).

Age
Most patients diagnosed with alcoholic neuropathy are aged 40-60 years. As
mentioned previously, development of alcoholic neuropathy is associated with the
duration and extent of total lifetime consumption of alcohol. Elderly persons,
because of the natural diminution of postural reflexes and the nerve cell
degeneration that occurs with advanced age, may be more at risk for the clinical
problems associated with a peripheral neuropathy, such as frequent falls and loss of
balance.
Anatomy and Physiology:
Peripheral Nervous System (PNS)
Includes all nervous tissue outside the CNS
Components:
1. Cranial nerves and their branches
2. Spinal nerves and their branches
3. Ganglia
4. Sensory receptors
Division:
1. Somatic Nervous System (SNS)
2. Autonomic Nervous System (ANS)
3. Enteric Nervous System (ENS)
Divisions:
A. Somatic Nervous System
Voluntary
Components:
a. Sensory neurons Convey information from somatic receptors in the head,
body wall, and limbs and from receptors for the special senses of vision, hearing,
taste, and smell to the CNS.
b. Motor neurons Conduct impulses from the CNS to skeletal muscles only.
Because these motor responses can be consciously controlled, the action of this
part of the PNS is voluntary.
B. Autonomic Nervous System
Involuntary

Components:
a. Sensory Neurons Convey information from autonomic sensory receptors,
located primarily in visceral organs such as the stomach and lungs, to the CNS.
b. Motor Neurons Conduct nerve impulses from the CNS to smooth muscle,
cardiac muscle, and glands.
Branches of Motor Part:
a. Sympathetic Division Helps support exercise or emergency
actions, so-called fight-or-flight responses.
b. Parasympathetic Division Takes care of rest-and-digest
activities.
C. Enteric Nervous System
Involuntary
The brain of the gut.
Once considered part of the ANS.
Consists of approximately 00 million neurons in enteric plexuses that extend most of the
length of the gastrointestinal tract.
Many of the neurons of the enteric plexuses function independently of the ANS and CNS
to some extent, although they also communicate with the CNS via sympathetic and
parasympathetic neurons.
Components:
a. Sensory Neurons Monitor chemical changes within the GI tract as well as the
stretching of its walls.
b. Motor Neurons Govern contraction of GI tract smooth muscle to propel food
through the GI tract, secretions of the GI tract organs such as acid from the
stomach, and activity of GI tract endocrine cells, which secrete hormones
Cell Body
This is the cell body (or soma) of the motor or sensory nerve.
Motor Neuron It is located in the anterior (ventral) horn region of the spinal cord and projects
an axon distally. It regulates the characteristics of the entire motor unit.
Sensory Neurons Are bipolar cells with 2 axons (1 axon projects proximally and the other
distally). They are found in the dorsal root ganglion, which is located outside the spinal cord in
the proximity of the intervertebral foramen.

Axon
This is the projection from the sensory or motor nerve cell body that propagates current flow and
transports cell nutrition (axonal transport).
It can be unmyelinated or myelinated by Schwann cells.
Motor axons project from their cell bodies to become motor roots.
Sensory axons project proximally to the spinal cord and distally to become sensory roots.
At each spinal level, motor and sensory nerve roots combine to become a mixed spinal nerve.
Each spinal nerve then branches off to a dorsal and ventral ramus.
Peripheral Nerve
Motor and sensory nerve fibers combine at various levels in the body (spinal nerve, ventral
ramus, plexus) and ultimately terminate as peripheral nerves.
A peripheral motor nerve consists of multiple neural branches from the distal portion of the axon.
They innervate individual muscle fibers.
Neuromuscular Junction (NMJ)
Motor nerves synapse with muscle fibers at sites known as neuromuscular junctions. These sites
are where the electric impulse propagated along the axon is converted into a chemical reaction.
The signal is then translated back into an electrical impulse at the postsynaptic membrane to
initiate muscle fiber action potentials.
Muscle Fibers
These extrafusal fibers are the final components of the motor unit.
Here, the electrical signal from the postsynaptic NMJ membrane stimulates fiber depolarization
and muscle fiber action potentials. Muscle fiber characteristics, including twitch response, depend
upon the type of alpha motor neuron by which it is innervated.
Nerve Connective Tissue
1. Endoneurium

This is the connective tissue surrounding each individual axon and its myelin sheath.
2. Perineurium
This is the strong, protective, connective tissue surrounding bundles or fascicles of
myelinated and unmyelinated nerve fibers.
It helps strengthen the nerve and acts as a diffusion barrier. Individual axons may cross
from one bundle to another along the course of the nerve.
3. Epineurium
This is the loose connective tissue the entire nerve that holds the fascicles together and
protects it from compression.

Motor Unit
This motor unit is the basic functional element of the neuromuscular system.
It consists of the following components:
1. Anterior horn cell (motor nerve cell body)
2. Motor nerve axons
3. Peripheral nerve
4. Neuromuscular junction
5. Muscle fibers

Motor Neurons
Motor Neuron
Alpha Motor Neuron
(Somatic Efferent Fibers)
Gamma Motor Neuron
(Efferent Fibers)
Beta Motor Neuron

Location of Cell Body


Anterior column of spinal
cord.
Lateral column of spinal cord.

Innervations
Intrafusal fibers Skeletal muscle
Intrafusal fibers Muscle spindle
Intrafusal and extrafusal fibers

Muscle Fibers
Fiber Type
Type I

Type II

Innervation Characteristic
Smaller cell body
Thinner diameter axon
Lower innervations ratio
Slower twitch muscle fibers
Larger cell body
Thicker diameter axon
Higher innervations ratio
Faster twitch muscle fibers

Nerve Fiber Classification


Nerve fibers vary in their function based on their physiologic characteristics. Their classification
is based on their diameter, conduction velocity, and function.

Resting Membrane Potential (RMP)


This is the voltage of the axons cell membrane at rest.
Normal RMP is -70 to -90 mV.
Leak Channels

These are openings in the cell membrane that allow sodium (Na +) and potassium (K+) to move
passively in and out of the cell membrane.

Na+K+ ATP-Dependent Pumps


A negative potential is maintained inside the cell by actively exporting 3 Na + ions while
importing 2 K+ ions through Na+K+ ATP-dependent pumps located within the cells
semipermeable membrane.
This keeps each ion against a concentration gradient with a deficit of positive ions inside the cell.
The RMP of the nerve would otherwise dissipate from the ions diffusing through the ion leak
channels.
Depolarization
When an outside current is applied to a nerve by a stimulator consisting of a cathode (negative
pole) and an anode (positive pole), positive charges on the axon become attracted under the
cathode and lower the membrane potential. The membrane becomes increasingly permeable to
Na+, which rushes into the cell through the opened voltage-gated channels toward an equilibrium.
This process of sodium conductance is the most important event in generating an action potential.
Action Potential
This is a voltage change occurring from an excited cell.
The electric impulse propagates along an axon or muscle membrane. It can also be
evoked by a stimulator.
The all-or-none response travels in both directions along the axon.
All-or-None Response
A stimulus must be strong enough to reach a certain threshold of activation. Once
reached, the AP generated remains at a constant size and configuration.
If it is below this threshold, no potential will occur. Any stimulus intensity greater than
the threshold will not generate a larger potential.
Na+ Voltage Gated Channels
These are protein channels used for ion exchange.
They have activation and inactivation gates that undergo conformational changes from a
depolarization. They allow increased Na+ influx into the cell when activated.
Absolute Refractory Period
This may vary in certain disease states.
This pertains to the time after closure of the inactivation gates. They will not immediately
reopen. No action potential can be formed at this time, no matter how strong a repeated
stimulus is used.
Relative Refractory Period

This pertains to the period of time after the absolute refractory period. At this time an
action potential can be elicited with more intense stimulation. This may also be increased
or decreased in certain disease states.

Temperature Effects
The Na+ channels will remain open for approximately 25 microseconds.
A decrease in temperature affects the protein configuration and causes a delay in opening
and closing of the gates. This typically changes the waveform appearance.
However, the amplitude can drop due to an increase in temporal dispersion or phase
cancellation.
Also, note the difference in focal cooling compared to generalized limb cooling.
Waveform Appearance Due to a Decrease in Temperature
Parameters
Change
Latency
Prolonged
Amplitude
Increased
Duration
Increased
Conduction velocity
Decreased
Propagation
As Na+ goes into the cell from a depolarization, it moves away from the membrane and
spreads the current down a path of least resistance along the length of the axon.
The affinity to flow back out through the membrane is low due to the myelin sheath
covering. Thus, the potential jumps to the next group of Na + channels, located between
the myelin, to areas called the nodes of Ranvier. This process of propagating a current
from one node to another is known as saltatory conduction.

Directional Recording

a. Orthodromic Recording
The action potential is recorded traveling in the direction of its typical
physiologic conduction. Normal physiologic conduction along motor fibers
travels away from the spinal cord, whereas nerve impulses from sensory fibers
travel toward the spinal cord.
b. Antidromic Recording
The action potential is recorded traveling in the opposite direction of its typical
physiologic conduction. The action potential from a recording of an antidromic
motor nerve study travel toward the spinal cord, whereas impulses from sensory
fibers travel away from the spinal cord.
Repolarization
The process of bringing the depolarized membrane back to its resting state, it is dependent on Na +
channel inactivation and K+ channel activation.
K+ Voltage-Gated Channels
These are protein channels, which, after a slight delay, open from a depolarization. This
allows K+ to move out of the cell to establish charge equilibrium. A delay exists in
channel closure, which results in a membrane with a hyperpolarized state called an
overshoot phenomenon.
This process of potassium conductance eventually returns the waveform to its baseline
due to the K+ leak channels restoring the RMP.
Neuromuscular Junction (NMJ)
The distal portion of a motor axon has small twig-like terminal branches that innervate individual
muscle fibers.
This portion of the nerve and single muscle fiber forms the motor endplate. The axon terminal,
containing various neural structures, including mitochondria and synaptic vesicles with
acetylcholine (ACh), does not make direct contact with the muscle fiber. Rather, it remains
separate from it by primary and secondary synaptic clefts.
NMJ Components
1. Presynaptic Region
This is the bulbous area at the axons terminal zone.
It is comprised of 3 storage compartments containing acetylcholine.
They are contained in packets called quanta consisting of approximately 5,00010,000
molecules. The acetylcholine migrates from the main and mobilization storage
compartments to replenish the immediate storage compartment, which is depleted in the
process of generating each action potential. This migration of acetylcholine takes
approximately 45 seconds.
2. Synaptic Cleft
This is a space 200500 angstroms wide where acetylcholine crosses from the
presynaptic region toward receptors on the postsynaptic region.

It contains an enzyme called acetylcholinesterase, which degrades acetylcholine into


acetate and choline as it crosses the cleft.

3. Postsynaptic Region
This is a membrane lined with acetylcholine receptors. It has convolutions to increase its
surface area by approximately 10 times the surface of the presynaptic membrane. At the
crests of each fold, receptors are located across from the presynaptic active zones, which
are the sites of acetylcholine release. Each postsynaptic acetylcholine receptor requires
two molecules of acetylcholine to become activated.

ETIOLOGY
Alcoholism
Many alcoholics develop peripheral nerve injuries because they make poor dietary
choices, leading to vitamin deficiencies.
2. Autoimmune diseases
These diseases include Sjogren's syndrome, lupus, rheumatoid arthritis, Guillain-Barre
syndrome, chronic inflammatory demyelinating polyneuropathy and necrotizing
vasculitis.
3. Diabetes
When damage occurs to several nerves, the cause frequently is diabetes. At least half of
all people with diabetes develop some type of neuropathy. Multiple forms of diabetic
neuropathy exist. Some occur due to diabetes and others are associated with it.
4. Exposure to poisons
Exposure to poisons may include some toxic substances, such as heavy metals or
chemicals.
1.

a. Heavy Metals

Antimony

Arsenic
Gold
Lead
Mercury
Thallium
b. Organic Compounds
Carbon disulfide
Ethyl alcohol
Ethylene oxide
Methyl butyl ketone
5.

Medications
Certain medications, especially those used to treat cancer (chemotherapy), may cause
peripheral nerve injuries.

Drugs
Amiodarone
Corticosteroids
Heroin
Tetanus toxoid
Dapsone
Disulfiram
Isoniazid
6. Infections
Certain viral or bacterial infections can cause peripheral neuropathy, including Lyme
disease, shingles (varicella-zoster), Epstein-Barr virus, hepatitis C, leprosy, diphtheria
and HIV.
7. Inherited disorders
Disorders such as Charcot-Marie-Tooth disease are hereditary types of neuropathy.
8. Trauma or pressure on the nerve
Traumas, such as motor vehicle accidents, falls or sports injuries, can sever or damage
peripheral nerves.
Nerve pressure can result from using a cast or crutches, spending a long time in an
unnatural position, or repeating a motion many times, such as typing.
9. Tumors
Growths can form directly on the nerves themselves, or tumors can put pressure on
surrounding nerves. Both cancerous (malignant) and noncancerous (benign) tumors.
10. Vitamin deficiencies
B vitamins, including B-1, B-6 and B-12, are particularly important to nerve health.
Vitamin E and niacin also are crucial to nerve health. Not having enough of these
vitamins in your system may cause peripheral nerve injuries.
11. Other diseases
Kidney disease, liver disease, connective tissue disorders, an underactive thyroid (hypothyroidism) and
amyloidosis.

Pathophysiology:
Alcohol

Increase oxidative stress

Increase free radicals which results neurotoxic effect in nerve

Reduction in myelination
Of neural fibers

Impairs axonal transport

Neuropathy
DDX:
Desease:
Sign/Symptoms:

Multiple Sclerosis
- Sensory loss (ie,
paresthesias):
Usually an early
complaint
- Spinal cord
symptoms (motor):
Muscle cramping
secondary to
spasticity
- Spinal cord
symptoms
(autonomic):
Bladder, bowel,
and sexual
dysfunction
- Cerebellar
symptoms: Charcot
triad of dysarthria,
ataxia, and tremor
- Optic neuritis
- Trigeminal
neuralgia: Bilateral
facial weakness or
trigeminal

Peripheral Neuropathy
-

Gradual onset of
numbness and
tingling in your feet
or hands, which
may spread
upward into your
legs and arms

Sharp, jabbing or
burning pain

Extreme sensitivity
to touch

Lack of
coordination and
falling

Muscle weakness

Causes

neuralgia
Facial myokymia
(irregular twitching
of the facial
muscles): May also
be a presenting
symptom
Eye symptoms:
Including diplopia
on lateral gaze
(33% of patients)
Heat intolerance
Constitutional
symptoms:
Especially fatigue
(70% of cases) and
dizziness
Pain: Occurs in 3050% of patients at
some point in their
illness
Subjective
cognitive
difficulties: With
regard to attention
span,
concentration,
memory, and
judgment
is an immunemediated
inflammatory
disease that
attacks myelinated
axons in the
central nervous
system, destroying
the myelin and the
axon in variable
degrees and
producing
significant physical
disability within
20-25 years in
more than 30% of
patients

or paralysis if
motor nerves are
affected

Alcoholism. Poor
dietary choices
made by alcoholics
can lead to vitamin
deficiencies.

Autoimmune
diseases.These
include Sjogren's
syndrome, lupus,
rheumatoid
arthritis, GuillainBarre syndrome,

chronic
inflammatory
demyelinating
polyneuropathy
and necrotizing
vasculitis.
Coarses:

Most of the time


the problem starts
in the fingers and
toes. As it gets
worse, it moves
into the limbs,
causing pain and
loss of feeling in
the feet, legs, and
hands.

Hallmark of MS is
symptomatic
episodes that
occur months or
years apart and
affect different
anatomic
locations.

Clinical Manifestation:

Gradual onset of numbness and tingling in your feet or hands, which may
spread upward into your legs and arms

Sharp, jabbing or burning pain

Extreme sensitivity to touch

Lack of coordination and falling

Muscle weakness or paralysis if motor nerves are affected

If autonomic nerves are affected, signs and symptoms may include:

Heat intolerance and altered sweating

Bowel, bladder or digestive problems

Changes in blood pressure, causing dizziness or lightheadedness

Peripheral neuropathy may affect one nerve (mononeuropathy), two or more nerves
in different areas (multiple mononeuropathy) or many nerves (polyneuropathy).

Test and Measurement:


nerve conduction - study (NCS), also called a nerve conduction
velocity (NCV) test--is a measurement of the speed of conduction of an electrical
impulse through a nerve. NCS can determine nerve damage and destruction. During
the test, the nerve is stimulated, usually with surface electrode patches attached to
the skin.
Electromyography (EMG) - is a diagnostic procedure to assess the health of muscles
and the nerve cells that control them (motor neurons).

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