GBS

Case 1 / NBSS Bunga Diela
Guillain-Barré syndrome 130110120114
GENERAL CONCEPT OF NERVOUS SYSTEM

The nervous system is composed of specialized cells:
- Afferent nerve fibers : to receive sensory stimuli.
- Efferent nerve fibers : to transmit stimuli to effector organs, whether muscular or glandular.
The nervous system is divided into two main parts:

- The central nervous system (CNS) : consists of the brain and spinal cord
= are the main centers where correlation and integration of nervous information occur.
= are covered with a system of membranes (meninges) and are suspended in the cerebrospinal fluid and
further protected by the bones of the skull and the vertebral column.
= composed of large numbers of neurons (excitable nerve cells) and their processes (long axons and short
dendrites), which are supported by neuroglia (specialized tissue).
= are organized into gray matter (consists of nerve cells / cell body embedded in neuroglia) and white matter
(consists of nerve fibers / myelinated axons embedded in neuroglia)
- The peripheral nervous system (PNS) : consists of the cranial and spinal nerves and their associated ganglia.
= consist of bundles of nerve fibers or axons, conduct information to and from the central nervous system.
***Autonomic Nervous System***

= The part of the nervous system (distributed both through CNS and PNS) concerned with the innervation of
involuntary structures, such as the heart, smooth muscle, and glands within the body.
= Divided into two parts (with afferent and efferent nerve fibers in both parts) :
- The sympathetic : to prepare the body for an emergency.
- The parasympathetic : to conserve and restore energy
1. Major Divisions of the Central Nervous System
CEREBRUM
FOREBRAIN DIENCEPHALON
BRAIN MIDBRAIN MEDULA OBLONGATA
HINDBRAIN PONS
CEREBELLUM
CNS
CERVICAL SEGMENT
THORACIC SEGMENT
SPINAL CORD LUMBAR SEGMENT
SACRAL SEGMENT
COCCYGEAL SEGMENT
A. Brain
- Lies in the cranial cavity and is continuous with the spinal cord through the foramen magnum.
- It is surrounded by three meninges : the dura mater, the arachnoid mater, and the pia mater.
- The cerebrospinal fluid surrounds the brain in the subarachnoid space.
B. Spinal Cord
- Situated within the vertebral canal of the vertebral column. Begins superiorly at the foramen magnum in the
skull, and terminates inferiorly in the lumbar region.
- Surrounded by three meninges: the dura mater, the arachnoid mater, and the pia mater.
- Further protection is provided by the cerebrospinal fluid, which surrounds the spinal cord in the
subarachnoid space.
- Are attached 31 pairs of spinal nerves by the anterior or motor roots and the posterior or sensory roots.
Each posterior nerve root possesses a posterior root ganglion, the cells of which give rise to peripheral
and central nerve fibers.
- Composed of an inner core of gray matter (an H-shaped pillar with anterior and posterior gray horns
united by a thin gray commissure), which is surrounded by an outer covering of white matter (which is
divided into anterior, lateral, and posterior white horns).
2. Major Divisions of the Peripheral Nervous System (GENERAL CONCEPT OF PNS)
CRANIAL NERVES (and their ganglia) : 12 pairs that exit the skull through the foramina
I. Olfactory (A) VII. Facial (A/E)

II. Optic (A) VIII. Vestibulocochlear (A)
III. Oculomotor (A/E) IX. Cochlear (A/E)
IV. Trochlear (E) X. Vagus (A)
V. Trigeminal (A/E) XI. Accessory (E)
VI. Abducent (E) XII. Hypoglossal (E)
PNS
SPINAL NERVES (and their ganglia) : 31 pairs that exit the vertebral column through
the intervertebral foramina
CERVICAL (8)
THORACIC (12)
LUMBAR (5)
SACRAL (5)
COCCYGEAL (1) based on origin
SENSORY (AFFERENT) based on function

PNS SOMATIC
MOTOR (EFFERENT) AUTONOMIC SYMPHATETIC
PARASYMPHATETIC
Roots (1):
- The anterior root : consists of bundles of efferent nerve fibers / motor fibers carrying nerve impulses away from
the central nervous system (at anterior gray horn of the spinal cord) to go to skeletal muscles (by neuromuscular
junction).
- The posterior root : consists of bundles of afferent nerve fibers / sensory fibers carrying nerve impulses (such as
sensations of touch, pain, temperature, and vibration) to the central nervous system (at posterior gray horn).
SPINAL → P. root of SN → SPINAL P. rami of spinal nerve (smaller) EMERGED back side of body
CORD ← A. root of SN ← NERVE A. rami of spinal nerve (larger) PLEXUS front side and limbs
Contains motor and sensory fibers; located at level of intervertebral foramina emerged of rami from some levels
- In the upper cervical region, the spinal nerve roots are short and run almost horizontally.
- In the lower level of the first lumbar vertebra, the roots of the lumbar and sacral nerves form cauda equina
(a long vertical leash of nerves around the filum terminale).
Vertebrae Spinal Segment
Cervical vertebrae Add 1
Upper thoracic vertebrae Add 2
Lower thoracic vertebrae (7–9) Add 3
10th thoracic vertebra L1-2 cord segments
11th thoracic vertebra L3-4 cord segments
12th thoracic vertebra L5 cord segment
1st lumbar vertebra Sacral and coccygeal cord segments
Ganglia (2)
Are the ovoid structures containing many of neuronal cell bodies and glial cells supported by connective tissues.
It serves as relay stations to transmit nerve impulses, one nerve enters and another exits from each ganglion.
The direction of the nerve impulse determines whether the ganglion will be a sensory or an autonomic ganglion.
a. Sensory Ganglia: fusiform swellings on posterior root of each spinal nerve and cranial nerves V, VII, VIII, IX, X.
- Sensory ganglia receive afferent impulses that go to the CNS
- Each ganglion is surrounded by a layer of connective tissue, continuous with the epineurium and perineurium
of the peripheral nerve.
- Neurons are UNIPOLAR, possessing cell bodies that tend to be separated by nerve fibers bundles, which allow
the nerve impulse passes directly from the peripheral axon to the central axon when reaching the T junction.
- A single nonmyelinated process leaves cell body and, after a convoluted course, bifurcates at a T junction into:
*Peripheral branches, where the former axon terminates in a series of dendrites.
*Central branches, where the latter axon enters the central nervous system.
- Each nerve cell body is COMPLETELY surrounded by capsular cells or satellite cells (flattened sheet-like
extensions of small glial cells derived from neural crest cells), which is create the microenvironments of the
nerve cell body, allowing the production of membrane action potentials and regulating metabolic exchange.
b. Autonomic ganglia (sympathetic and parasympathetic ganglia): fusiform swellings on along the course of
efferent nerve fibers of the autonomic nervous system, at a distance from the brain and spinal cord.
- Effect the activity of smooth muscle, the secretion of some glands, modulate cardiac rhythm and other
involuntary activities by which the body maintains a constant internal environment (homeostasis).
- Found in the sympathetic trunks, in prevertebral autonomic plexuses (e.g., in the cardiac, celiac, and
mesenteric plexuses), and as ganglia in or close to viscera.
- Each ganglion is surrounded by a layer of connective tissue, continuous with the epineurium and perineurium
of the peripheral nerve.
- Neurons are MULTIPOLAR, possessing cell bodies that are irregular in shape.
- The dendrites of the neurons make synaptic connections with the myelinated axons of preganglionic neurons.
- The axons of the neurons are small diameter (C fibers) and unmyelinated nerve fibers, and pass to viscera,
blood vessels, and sweat glands.
- Each nerve cell body is INCOMPLETELY surrounded by capsular cells or satellite cells (a layer of flattened cells),
which is similar in structure to Schwann cells.
- Autonomic nerves comprise an autonomic nervous system with two parts (symphatetic and parasymphatetic):
* Preganglionic sympathetic division : in the thoracic and lumbar segments of the spinal cord
* Preganglionic parasympathetic division : in the medulla & midbrain, and in the sacral segment of spinal cord.
** Postganglionic symphatetic division : in small ganglia along the vertebral column.
** Postganglionic parasymphatetic division : in very small ganglia located near or within the effector organs.
Plexuses (3)
- A network of nerves composed of nerve fiber bundles, as result from joining some of peripheral nerve branches
that allows individual nerve fibers to pass from one peripheral nerve to another, thus permits a redistribution of
the nerve fibers within the different peripheral nerves.
- At the root of the limbs, the anterior rami of the spinal nerves form complicated plexuses:
* The cervical and brachial plexuses are at the root of the upper limbs.
* The lumbar and sacral plexuses are at the root of the lower limbs.
- Cutaneous nerves form fine plexuses before they reach their terminal sensory endings.
- The autonomic nervous system forms numerous nerve plexuses that consist of preganglionic and postganglionic
nerve fibers and ganglia.
DEVELOPMENT OF PERIPHERAL NERVE
Diagrams showing some derivatives of the neural crest. Neural crest cells also differentiate into the cells in the
afferent ganglia of cranial nerves and many other structures. The formation of a spinal nerve is also illustrated.
A to D, Diagrams of successive stages in the differentiation of a neural crest cell into a unipolar afferent neuron in a spinal ganglion.
BASIC DEVELOPMENT OF NEUROEPITHELIAL CELL

- Thick walls and thin roof- and floor-plates produced from proliferation and differentiation of
neuroepithelial cells in the developing spinal cord.
- Differential thickening of the lateral walls of the spinal cord produces the sulcus limitans, a shallow
longitudinal groove on each side of the walls that is separates the dorsal part (alar plate) from the
ventral part (basal plate). Later, alar and basal plates associated with afferent and efferent functions.
- The neural crest cells is a group of cells that originated from ectodermal and extend throughout the
length of the neural tube, which are formed during elevation of the neural plate.
- The cells of the neural crest soon differentiate into dorsal root ganglia, sympathetic neuroblasts,
Schwann cells, pigment cells, odontoblasts, meninges, and mesenchyme of the pharyngeal arches.
DEVELOPMENT OF DORSAL AND VENTRAL HORNS

- Cell bodies in the basal plates form the ventral gray horns and lateral gray horns, that its axons grow
out of the spinal cord as a ventral nerve rootlets in the ventrolateral side of spinal cord and become
arranged in a bundle forming a ventral nerve root.
- Cell bodies in the alar plates form the dorsal gray horns, that its neurons constitute afferent nuclei.
And migration of the neural crest cells to this horn occurs that is emerged as dorsal nerve root that
will differentiate into the cells of the dorsal root ganglion.
DEVELOPMENT OF DORSAL ROOT GANGLIA

- The unipolar neurons in the dorsal root ganglia are derived from neural crest cells.
- First, axons are bipolar but the central and peripheral processes soon unite in a T-shaped fashion.
- But dendrite only did the peripheral process that causes conduction of dendrite toward the cell body.
* The peripheral processes pass in the spinal nerves to sensory endings in somatic structures.
* The central processes enter the spinal cord and constitute the dorsal roots of spinal nerves.
DEVELOPMENT OF SPINAL NERVES

- Spinal nerve formed by joining of ventral nerve root and the result of distal processes of spinal
ganglion cells.
- Immediately after being formed, a mixed spinal nerve divides into dorsal and ventral primary rami.
* The dorsal primary ramus, the smaller division, innervates the dorsal axial musculature, vertebrae,
posterior intervertebral joints, and part of the skin of the back.
* The ventral primary ramus, the major division, innervates the limbs and ventrolateral parts of the
body wall. This rami also forms the major nerve plexuses (cervical, brachial, and lumbosacral)
DEVELOPMENT OF NERVE PLEXUS

- The nerves from the spinal cord segments elongate and grow into the limb, that are distributed to its
muscles (dermatome innervations) and the skin of the developing limbs is also innervated in a
segmental manner (cutaneous innervations).
- Ventral primary rami are joined by connecting loops of nerve fibers, especially those supplying the
limbs (e.g., the brachial plexus).
* The dorsal division of the trunks supply the extensor muscles and the extensor surface of the limbs.
* The ventral divisions of the trunks supply the flexor muscles and the flexor surface of the limbs.
HISTOLOGY OF PERIPHERAL NERVE
INTODUCTION : Neurons
Neurons are the functional units in nervous system, consist of three parts:
1. Cell body or perikaryon : trophic center for the entire nerve cell and is receptive to stimuli.
- Has a spherical large and euchromatic nucleus with a well-developed nucleolus, surrounded by cytoplasm.
- Has Nissl bodies, are large masses of highly developed RER and free polyribosomes surround it.
- Has golgi apparatus, mitochondria, neurofilaments (intermediate filaments), microtubules.
- Has inclusions of pigmented material (e.g: lipofuscin), consists of residual bodies left from lysosomal digestion.
- In the CNS nerve cell bodies are present only in the gray matter.
- In the PNS cell bodies are found in ganglia and in some sensory regions, such as the olfactory mucosa.
2. Dendrites : processes from the cell body specialized to receive stimuli from the environment, or other neurons.
- Numerous, short, and, often covered with many synapses.
- The diameter of dendrites is inconstant : become much thinner as they subdivide into branches.
- The cytoplasmic composition of the dendrite base is similar to at the perikaryon, but without Golgi complexes.
- Dendritic spines : short blunt structures 1 to 3 m long projecting from dendrites where most synapses come.
→ participates in the constant changes that make up neuronal plasticity for adaptation, learning, memory.
3. Axon : a single process specialized in generating and conducting stimuli to other cells.
- Originate from axon hillock, a pyramid-shaped region arising from the cell body.
- Axolemma is the plasma membrane of the axon, and its contents are known as
- Axoplasm is the content of axolemma that contains mitochondria, microtubules, neurofilaments, and some
cisternae of smooth ER. While the polyribosomes and rough ER are absent.
- Initial segment located close to the axon hillock, is the site where various excitatory and inhibitory stimuli are
collected, resulting in the decision to a nerve impulse. Here, there are several types of ion channels that are
important in generating the action potential.
- Have a constant diameter and do not branch profusely.
- The distal portion of the axon is usually branched as the terminal arborization. Each branch terminates on the
next cell in swollen end bulbs (boutons), which interact with other neurons or nonnerve cells at synapses,
which then initiate impulses in the next cell of the circuit.
- Collateral branches : returns to the area of the nerve cell body to connect to other groups of cells.
Morphologic types of neurons
1. Multipolar neurons : has 1 axon and ≥2 dendrites

→In most neurons
2. Bipolar neurons : has 1 axon and 1 dendrite

→In the retina, olfactory mucosa, and the (inner ear) cochlear and vestibular ganglia, where they serve the
senses of sight, smell and balance respectively.
3. Unipolar or pseudounipolar neurons : has a single short process close to the perikaryon that bifurcates into
2 branches : A long branch extending to a peripheral ending and A shorter branch toward the CNS
→Both of these processes have terminal arborizations.
→Those of the peripheral process serve as dendrites, receiving stimuli that travel directly to the terminals at the
other end of the axon without passing through the cell body.
→The cell body does not to be involved in impulse conduction but remains as the synthetic center for entire cell.
→In the sensory ganglia and in most cranial ganglia.
Peripheral nervous system
Nerves : bundles of nerve fibers (axons) surrounded by glial cells and connective tissue.
The nerve fibers may be myelinated or nonmyelinated.
A.MYELINATED FIBERS
- Are types of axons that are engulfed and wrapped around by Schwann cell* or neurolemmocytes, and allow
for their myelination (one neurolemmocyte forms myelin around a segment of one axon).
- The external surface of Schwann cell is surrounded by external lamina (contains type IV collagen, produced
by its cell) which is continuous with the endoneurium (surrounding connective tissue rich in reticular fibers).
- Myelin sheaths is multiple layers of Schwann cell which is very rich in lipid (in its cell membrane) and
provide insulation and facilitate action potentials along the axolemma.
- Internodal segment is about 1 millimeter in length of axon covered by one Schwann cell.
- Nodes of Ranvier are small nodal gaps along axon between adjacent intermodal segment, so axon is naked.
- Myelin clefts (Schmidt-Lanterman clefts) contain Schwann cell cytoplasm that was not displaced to the cell
body during myelination. This cytoplasm moves slowly along the myelin sheath, opening temporary spaces
(the clefts) between the membrane layers, which allows renewal of some membrane components as
needed and maintenance of the sheath.
*MYELINATION
A process of myelin sheaths formation, that begin before birth and during the first year postnatally.
- Axon first indents the side of a Schwann cell.
- As axon farther sinks into the Schwann cell, the plasma membrane of the Schwann cell forms a mesaxon.
- The schwann cell rotates (clockwise in some segments and counterclockwise in others) and wrapped around
the axon in a spiral that makes the myelinated axon become thicker.
- Gradually, most of cytoplasm disappears, leaving cytoplasm in the region of the nucleus.
- In the mature form, myelin is seen to be laminated :
* Dark major dense line : consists of the fused form of two inner protein layers of the plasma membrane.
* Lighter minor dense line : formed by the outer surfaces of adjacent plasma membranes (made by lipid).
- At the node of Ranvier, the axolemma (axon plasma membrane) is exposed because of two adjacent
Schwann cells terminate and the myelin sheaths become thinner by the turning off of the lamellae.
- The incisures of Schmidt-Lanterman : the continuous spiral of cytoplasm as result of the localized
persistence of Schwann cell cytoplasm involves all the layers of the myelin, that may provide a pathway for
the conduction of metabolites from the surface region of the Schwann cell to the axon.
A–D: Cross sections showing the stages in the formation of Schmidt-Lanterman incisures in the myelin sheath of a
the myelin sheath. peripheral nerve.
E: A longitudinal section of a mature myelinated nerve fiber A: Transverse section of a myelinated nerve fiber.
showing a node of Ranvier. B: Schematic diagram of a myelinated nerve fiber in which the
Note the presence of a basement membrane. myelin sheath has been unrolled.
B. Nonmyelinated Nerve Fibers

- ≥ 15 axons may share a single Schwann cell, each lying within its own trough.
- The axons are separated and each becomes enclosed within its own fold or
pocket of Schwann cell surface.
- No myelin is formed.
- In some situations, the troughs are deep and the axons are embedded deep
in the Schwann cells, forming a mesaxon.
- The Schwann cells lie close to one another along the length of the axons,
and the nodes of Ranvier is absent.
Connective tissue of nerve fibers

Axons and Schwann cells of nerves are enclosed within three connective tissue layers.
1. Epineurium is a dense and irregular fibrous external coat, that contains large blood vessels (arteries and veins)
and fascicles or nerve fibers bundle.
2. Perineurium is a few layers of unusual epithelial-like fibroblastic cells which are all joined at the peripheries by
tight junctions to form a blood-nerve barrier that protects the fascicle from most macromolecules and helps
regulate the microenvironment inside the fascicle
3. Endoneurium is a sparse layer of loose connective tissue which surrounds capillaries (C) and is continuous with
an external lamina of type IV collagen, laminin, and other proteins produced by the Schwann cells.
CLASSIFICATION OF NERVE FIBERS

1. BASED ON STRUCTURE, nerve fibers classified to:
a. Myelinated Nerve Fibers : surrounded by a myelin sheath*
b. Nonmyelinated Nerve Fibers : does not surrounded by a myelin sheath
2. BASED ON STIMULATION, nerve fibers classified to:

a. Somatic : response to conscious / voluntary stimulation
Controls voluntary movement and communication with the sense organ (e.g: skeletal muscle).
b. Autonomic : response to unconscious / involuntary stimulation
Controls involuntary movement and communication with the sense organ (e.g: smooth or cardiac muscle)
→ Symphatetic : acts to prepare the body in emergency situation (fight or flight response)
Neurotransmitter : Norepinephrine
→ Parasymphatetic : acts to calm the body after symphatetic nerve worked to reserve energy
Neurotransmitter : Acethylcholine
* Each pathway has 2 neurons : preganglionic and postganglionic, differ in neuroanatomy & neurochemistry.
3. BASED ON FUNCTION, nerve fibers classified to:

a. Motoric (efferent) : transfer impulse from interneuron in spinal cord to the skeletal muscle.
b. Sensoric (afferent) : transfer impulse from receptors to interneuron in spinal cord.
* 3 types of motor fibers:

- Large alpha myelinated fibers: supply the extrafusal fibers that form the main mass of the muscle.
- Small gamma myelinated fibers: supply the intrafusal fibers of the neuromuscular spindles.
- Fine unmyelinated C fibers / postganglionic autonomic efferents: supply the smooth muscle in blood vessels wall.
* 3 types of sensory fibers:

- The myelinated fibers which originate in the annulospiral and flower-spray endings of the neuromuscular spindles
- The myelinated fibers which originate in the neurotendinous spindles.
- The myelinated and nonmyelinated fibers which originate from sensory endings in the muscle connective tissue.
4. BASED ON CONDUCTION VELOCITY, SIZE, AND FUNCTION, nerve fibers classified to:
Conduction Velocity Fiber Diameter
Fiber Type Functions
(m/s) (µm)
A Fibers
70–120 12–20 Motor: Alpha motor neuron
Alpha (Ia)
(faster) (larger) Sensory: Skeletal muscle spindle
Alpha (Ib) 70–120 12–20 Sensory : Golgi tendon organ, touch, pressure
Motor: intrafusal and extrafusal muscle fibers
Beta (II) 40–70 5–12
Sensory: muscle spindle, touch, pressure, vibration
Gamma
10–50 3–6 Motor : gamma motor neurons, muscle spindle
(III)
Sensory: pain, temperature, touch
Delta (III) 6–30 2–5
B Fibers
3–15 <3 Motor: Preganglionic autonomic fibers
(IV)
C Fibers Motor: Postganglionic autonomic fibers
0.5–2.0 0.4–1.2
(IV) Sensory: pain, temperature
Conduction in Peripheral Nerves

In the polarization (resting) state:
- Polarization is occur in a nerve fiber, so that the interior is negative to the exterior.
- The resting membrane potential has -80 mV potential difference across the axolemma (axon plasma membran).
- Here, 3 Na+ ions are pumped to the outside for each 2 K+ ions to the inside, through the channels of the plasma
membrane that is maintained by the sodium-potassium pump by using an adenosine triphosphate (ATP).
In the depolarization (action) state:

- A nerve impulse (action potential) starts at axon hillocks and passes rapidly along the axolemma.
+
- The action potential alters the permeability of the membrane to Na ions at the point of stimulation, that cause
+
Na ions rapidly enter the axon, results in the membrane potential is reduced to zero (depolarization)
- The depolarized membrane potential is about +40 mV, with the outside of the membrane negative to the inside.
- The negatively charged point on the outside of the axolemma acts as a stimulus to the adjacent positively
charged axolemma, and in less than 1 msec, the polarity of the adjacent resting potential is reversed.
- The action potential then travels along the full length of a nerve fiber (axolemma) to its end.
In the repolarization (restoration) state:

a+
- As the action potential moves along the nerve fiber, the entry of the N ions into the axon stops, and the
permeability of the axolemma to K+ ions increases, cause K+ ions rapidly diffuse outside the axon.
- The permeability of the axolemma now decreases and cause restoration, by doing active transport of the N+ ions
out of the axon and the K+ ions into the axon using an adenosine triphosphate (ATP).
In the absolute refractory period:

- This is the period of time when after the passage of a nerve impulse along a nerve fiber (while the axolemma is
still depolarized), however strong the second stimulus comes to the axolemma is unable to excite the nerve.
- This condition is due to Na+ channels inactivation, so that no stimulation will open the Na+ gates.
In the relative refractory period:

- This is the period of time when after the absolute refractory period occur, a further short interval during which
the excitability* of the nerve gradually returns to normal.
Creation of the action potential by the arrival of a stimulus

from a single presynaptic terminal. Note that the action
Ionic and electrical changes that occur in a nerve fiber potential generated at the initial segment will only occur if
when it is conducting an impulse. the threshold for excitation is reached at the initial segment.
* Conduction velocity of a nerve fiber:

- The thicker fibers conducting more rapidly than those of smaller diameter.
- The myelinated fibers conducting more rapidly than those of nonmyelinated fibers.
- In nonmyelinated fibers, the action potential passes continuously along the axolemma, progressively exciting
neighboring areas of membrane.
- In myelinated fibers, the presence of a myelin sheath serves as an insulator, cause the axolemma can be
stimulated only at the nodes of Ranvier (a region where the axon is naked). In these fibers, the saltatory
conduction is occur, so that the action potential jumps from one node to the next node quickly.
A. Electrical changes that occur in

stimulated myelinated axon (saltatory
conduction)
B. Electrical changes that occur in stimulated

nonmyelinated axon
NEUROMUSCULAR JUNCTION
Neuromuscular Junctions in Skeletal Muscle
- Skeletal muscle fibers are innervated by large alpha myelinated nerve fibers derived from large motor neurons
in the anterior gray horns of the spinal cord or from the motor nuclei of cranial nerves.
* Motor Unit is the single alpha motor neuron and the muscle fibers that it innervates.
- The motor units possess only a few muscle fibers, such as in the the small muscles of the hand.
- The motor units may innervate many hundreds of muscle fibers, such as in a large limb muscle.
- Each myelinated fiber enters a skeletal muscle at the neurovascular hilus and then branches many times. Then,
a single branch, referred as Neuromuscular junction or motor end-plate, terminates on a muscle fiber.
- On reaching the muscle fiber, the nerve loses its myelin sheath and breaks up into a number of fine branches.
Each branch ends as a naked axon and forms the neural element of the neuromuscular junction.
- At the site of the neuromuscular juction, it forms the sole plate (the muscular element of the plate) with local
accumulation of granular sarcoplasm beneath the sarcolemma and the presence of numerous nuclei and
mitochondria to provides ATP as the energy source for the synthesis of the transmitter acetylcholine (ACh).
- The expanded naked axon lies in a groove on the surface of the muscle fiber that is formed by the infolding of
sarcolemma (the plasma membrane of muscle fiber), which is thrown into numerous junctional folds that serve
to increase the surface area of the plasma membrane that lies close to the naked axon.
- Synaptic cleft separate the axolemma (presynaptic membrane) from the sarcolemma (postsynaptic membrane)..
- Endomysium (the connective tissue sheath of the muscle fiber) is a continuous form of the connective tissue
sheath of the nerve fiber (endoneurium), which strengthens the neuromuscular junction.
A skeletal neuromuscular junction. The terminal naked axon lying in the surface groove of the muscle fiber.
Skeletal contraction
- A nerve impulse (action potential) reaches the presynaptic membrane of the neuromuscular junction
- Voltage-gated Ca2+ channels open and allow Ca2+ ions to enter the axon
- Some of the synaptic vesicles fused with the presynaptic membrane
- Acetylcholine release into the synaptic cleft by exocytosis (the amount of acetylcholine released will depend on
the number of nerve impulses arriving at the nerve terminal)
- Acetylcholine diffuses rapidly across the cleft to reach the nicotinic type of ACh-gated channels on the
postsynaptic membrane of the junctional folds.
- ACh-gated channels are opened
+ +
- The end-plate potential is created, when Na influx and K efflux from the postsynaptic membrane.
+
- If the end-plate potential is large enough, the voltage-gated channels for Na ions are opened, and an action
potential will be initiated and will spread along the surface of sarcolemma.
- T tubules system carries the wave of depolarization into the muscle fiber to the contractile myofibrils.
- Ca2+ ions release from the sarcoplasmic reticulum causes the muscle to contract.
- The acetylcholine is rapidly undergoes hydrolysis by acetylcholinesterase (AChE), cause the concentration of
Acetylcholine in the cleft decreases.
- The ionic channels close and remain closed until the arrival of more acetylcholine, cause the prevention of the
muscle fiber reexcitation.
ACh → Nicotinic type of ACh receptor, ACh-gated channels opened → Na+ influx → End-plate potential created.
End-plate potential (if large enough) → Na+-gated channels opened → Na+ influx → Action potential created.
2+
Action potential → Increased release of Ca → Muscle fiber contraction.
Immediate hydrolysis of ACh by AChE → ACh-gated channels closed → Muscle fiber repolarization.
Topography of Sensoric Distribution in Peripheral Nerve

Dermatome is the area of skin that is supplied by a single spinal nerve.
- On the trunk, the dermatomes extend round the body from the posterior to the anterior median plane.
- The area of tactile loss is always greater than the area of loss of painful and thermal sensations, because the
degree of overlap of fibers carrying pain and thermal sensations is much more extensive than the overlap of
fibers carrying tactile sensations.
- In the limbs, the arrangement of the dermatomes is more complicated because of the embryologic rotation of
the limbs as they grow out from the trunk.
- In the face, the divisions of the trigeminal nerve (Cranial Nerve V) supply a precise area of skin, and there is little
or no overlap to the cutaneous area of another division.
Topography of Motoric Distribution in Peripheral Nerve
Myotome is the area of skeletal muscle that supplied by more than one spinal nerve
The segmental innervation of the following muscles should be known because it is possible to test them by eliciting
simple muscle reflexes in the patient :
- Biceps brachii tendon reflex C5-6 (flexion of the elbow joint by tapping the biceps tendon).
- Triceps tendon reflex C6-7 and C8 (extension of the elbow joint by tapping the triceps tendon).
- Brachioradialis tendon reflex C5-6 and C7 (supination of the radioulnar joints by tapping the insertion of the
brachioradialis tendon).
- Abdominal superficial reflexes (contraction of underlying abdominal muscles by stroking the skin). Upper
abdominal skin T6-7; middle abdominal skin T8-9; lower abdominal skin T10-12.
- Patellar tendon reflex (knee jerk) L2, L3, and L4 (extension of knee joint on tapping the patellar tendon).
- Achilles tendon reflex (ankle jerk) S1 and 2 (plantar flexion of ankle joint on tapping the Achilles tendon).
GENERAL CONCEPT OF LOWER MOTOR NEURON

Motor neuron merupakan neuron efferent yang mengantarkan impulse dari sistem syaraf pusat ke efektor
sehingga menyebabkan bagian tubuh dapat bergerak.
Motor Neuron dibagi menjadi 3 jenis, yaitu :

1. Upper Motor Neuron : mengantarkan impuls dari nukleus di cerebral cortex ke nukleus di ventral gray horns
pada spinal cord.
2. Peripheral Motor neuron : terletak di peripheral reflex arc, mengantarkan impuls dari interneuron ke otot
skeletal atau otot rangka.
3. Lower Motor Neuron : mengantarkan impuls dari ventral gray horns pada spinal cord ke otot skeletal atau
otot rangka.
Descending pathway yang berasal dari cerebral cortex ke otot skeletal tersusun dari 3 macam neuron :
1. First order neuron : badan sel terletak di cerebral cortex, axon menuju ke sinaps pada second order neuron
2. Second order neuron : badan sel tertelak di anterior gray horn spinal cord, axon pendek menuju ke sinaps
pada third order neuron.
3. Third order neuron : badan sel masih berada di anterior gray horn spinal cord, axon mempersarafi otot rangka
melalui anterior root dan spinal nerve.
Lower Motor Neuron dibagi menjadi 3 kategori, yaitu :

1. Alpha motor neuron : neuron motorik besar yang terletak pada pada anterior gray horn, yang mendapat
input dari dorsal root ganglion cells dari muscle spindle, upper motor neuron dari motor cortex dan brain
stem, serta spinal interneurons.
2. Beta motor neuron : neuron yang berperan dalam kontraksi pada spindle dan non spindle fibers.
3. Gamma motor neuron : neuron yang terletak di anterior gray horn, dgn axon yang berakhir di muscle fibers.
Manifestation of Syndrome Upper Motor Neuron Syndrome Lower Motor Neuron Syndrome
Type of Paralysis Spastic / Rigid / Kaku Flaccid / Lemas
Athropy Karena jarang digunakan Karena pengurangan volume otot
Physiological Reflex √ X
Superficial Reflex X √
Pathological Reflex Babinski Sign (+) X
Fasciculation X √
Reflex Arc
An involuntary pathway in response a stimulus
A reflex arc consists of:

- A receptor organ, situated in the skin, muscle, or tendon
- An afferent neuron, its cell body is situated in the posterior
root ganglion
- An effector neuron, is the termination of afferent neuron
- An effector organ, situated in the muscle spindle
Figure A: Multiple branching of afferent fibers entering

the spinal cord and the presence of many internuncial
neurons that synapse with the effector neuron
Figure B: The law of reciprocal innervation

- The flexor and extensor reflexes of the same limb
cannot be made to contract simultaneously.
- The afferent nerve fibers responsible for flexor
reflex muscle action must have branches that
synapse with the extensor motor neurons of the
same limb, causing them to be inhibited.
- A reflex on one side of the body causes opposite
effects on the limb of the other body side, this
crossed extensor reflex may be demonstrated.
- Afferent stimulation of the reflex arc that causes
the ipsilateral limb to flex results in the
contralateral limb being extended.
A monosynaptic reflex arc: a reflex arc involving only one synapse (and occur in very short time).
Criteria: - The afferent fibers has large diameter
- The afferent fibers are rapidly conducting
- The afferent fibers entering the spinal cord frequently branch
- The afferent fibers synapse with many internuncial neurons, which ultimately
synapse with the effector neuron.
The spinal segmental reflex arc involving motor activity is greatly influenced by higher centers
in the brain, which are mediated through the corticospinal, reticulospinal, tectospinal,
rubrospinal, and vestibulospinal tracts.
Lower motor neuron axons give off collateral branches as they pass through the white matter
to reach the anterior roots of the spinal nerve. These collaterals synapse on neurons described
by Renshaw, which, synapse on the lower motor neurons. These internuncial neurons are
believed to provide feedback on the lower motor neurons, inhibiting their activity.
A: A monosynaptic reflex arc.

B: Multiple neurons synapsing with the lower motor neuron.
SUMMARY
Cerebral cortex
↓
Thalamus
↓
Brainstem Corticonuclear tract Cranial Nerve
↓
Corticospinal tract Upper
Motor
Neuron
Anterior Lateral
↓ ↓
Tidak menyilang Menyilang di decussition of pyramid
↓ ↓
Postular muscle tone Gray matter of spinal cord
↓
Anterior gray horn
↓
Anterior root
↓
Spinal nerve
Reflex ↓ Lower
Arc Anterior rami Motor
↓ Neuron
Nerve plexus
↓
Neuromuscular junction
↓
Skeletal muscle
PERIPHERAL NERVE DISEASE
Classification
1. Radiculopathy
Caused by compression, infection, inflammation, ischemia, or direct trauma to the radix (nerve roots that enter
or exit the spinal cord).
→cause presence of weakness in asymmetric distribution (at proximal part in one limb and distal part in others)
→cause presence of local pain and decreasing sensoric, motoric, and reflex in the innervated area
→cause presence of fasciculation and mild fatigue
2. Plexopathy
Caused by trauma, compression, infiltration, or iatrogenic (positioning during surgery or intramuscular injection)
that involve the nerve plexus distal to the spinal roots but proximal to the formation of the peripheral nerves.
→cause motor weakness, muscle atrophy, and sensory loss in affected areas.
→cause paralysis with complete plexus lesions.
3. Mononeuropathy
Generalized neuropathy that affecting only one type of peripheral neuron
a. Sensory neuronopathy : mostly affecting dorsal root ganglion cells
→cause sensory loss in both proximal and distal distribution (scalp, thorax, abdomen, buttocks)
→cause sensory ataxia (awkward movement)
b. Motor neuronopathy : disorder that affecting anterior horn cells.
→cause weakness, fasciculation, atrophy in widespread distribution
4. Mononeuropathy multiplex
Focal or multifocal neuropathy affecting sensory and motor fibers in two or more peripheral nerves in separate
area in the body
→cause paralysis in the whole muscle (lower limb are affected first)
→cause decreasing of tone and deep tendon reflexes in affected muscle
→cause decreasing of primary sensation (may be paresthesias or dysesthesias)
→cause atrophy, fasciculation, mild fatigue, and alteration of reflexes
5. Polyneuropathy
Generalized symmetric neuropathy that characterized by involvement of sensory, motor, and autonomic fibers,
although one type of fiber may predominate.
a. Distal axonal polyneuropathy
→cause sensory and motor impairment in the longest nerve of the body that going to loer limb first
→small damage cause decreased pain and temperature sensation, tingling, and numbness of the feet
→large damage cause decreased light touch, vibration, and position sense
b. Autonomic neuropathy
→involve any symphatetic or parasymphatetic nerve fiber with impairment of cardiovascular, gastrointestinal,
urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic function
c. Demyelinating polyneuropathy
→cause symmetrical weakness in the beginning and progress bilaterally
→cause lost reflex in affected parts, particularly at the ankles
→cause loss of sensation, mostly at distal area (lower limbs at first, then upper limbs)
Pathomechanism
a. Axonal Degeneration : result in glove-stocking distribution of sensory loss
Caused by slowly evolving neuronopathies or axonopathies

↓
Only a few fibers degenerated (myelin breakdown is scant)
↓
The proximal portion of the severed nerve shows degenerative changes
↓
It undergoes regenerative activity (1-2mm/day): develop new growth cones as axon regrows
(Guided by degenerated axons)
↓
Forms multiple closely aggregated thinly myelinated small-caliber axons (regenerating clusters)
b. Wallerian Degeneration : may cause muscle atrophy
Caused by focal lesion (such as chronic or severe traumatic transaction of a nerve)

↓
The distal portion of the lesion shows degenerative changes
↓
Schwann cells begin to degrade the myelin and then engulf axon fragments, results in formation of myelin ovoid
(fragment of the axons that often contain large amounts of myelin debris)
↓
Macrophages recruited into that area and phagocytes the axonal and myelin-derived debris
↓
May cause changes of neuronal body (central chromatolysis: neuronal body balloons, smoothened cytoplasm,
disaggregation of neuronal body rough ER, and displaced nucleus toward to peripheral)
c. Segmental demyelination : result in decreasing conduction velocity
Caused by disease primarily affects the Schwann cell that may lead to a loss of myelin
↓
Dysfunction of the Schwann cell or damage of myelin sheath
↓
Affects some Schwann cells and their corresponding internodes randomly
↓
Result in myelin engulfment that cause axon denuded or thinning of myelin sheath layer
↓
Provide a stimulus for remyelination
↓
Population of cells within the endoneurium differentiating to replace injured Schwann cells
↓
It proliferates and encircles the axon, and remyelinate the denuded axon portion
↓
This repetitive cycles of demyelination and remyelination cause the formation of “onion bulbs”: concentric layers
of Schwann cell cytoplasm and redundant basement membrane that surround a thinly myelinated axon)
↓
But if this demyelinating neuropathies become chronic, it cause axonal injury (as mentioned before)
d. Remyelination
Pathophysiology
1. Neurapraxia :
Usually temporary failure of nerve conduction in the absence of structural changes, due to blunt injury,
compression, or ischemia.
Does not involve loss of nerve continuity, but causes transient functional loss due to a local ion-induced
conduction block at the injury site, although subtle alteration in myelin structure.
2. Axonotmesis :
Nerve injury characterized by disruption of the axon and myelin sheath but with preservation of the connective
tissue fragments, resulting in degeneration of the axon distal to the injury site; regeneration of axon is
spontaneous and of good quality.
3. Neurotmesis :
Partial or complete severance of a nerve with disruption of the
axon and its myelin sheath and the connective tissue elements.
Involves disconnection of a nerve and irreversible complete
functional loss, so grafting is required to restore its function.
And the results of grafting are good to moderate to failures.
* SUNDERLAND’S CLASSIFICATION, based on severity :

Etiology, Clinical Characteristic and Diagnostic
Etiology Clinical Characteristic Laboratory Tests

Vitamin Deficiencies
B1,B6,B12 Deficiencies S, SM, SYM Vitamins B12, B6, B1
Infectious
Lyme disease S, SM, SYM, MF, CN Serology, PCR
HIV-1 S, SM, SYM, MF, CN Serology, PCR
Hepatitis C S. SM, SYM, MF, CN Serology, PCR
Herpes zoster S, radicular Serology, PCR
Cytomegalovirus SM, M, SYM, MF Serology, PCR, culture
Immune Mediated
Guillain-Barr and SM, S, M, SYM, MF, CN IgG antiganglioside antibodies (GM1,GD1a,GQ1b,
variants GD1b), urine porphyrins
IgM antibody associated M, MF S, SM, SYM IgM anti-GM1, GD1a IgM anti-MAG, sulfatide, GD1b
Monoclonal M, S, SM, SYM, MF Serum immunofixation electrophoresis,
gammopathy quantitative immunoglobulins
Autonomic neuropathy Autonomic dysfunction Antinicotinic acetylcholine receptor antibodies
Vasculitis SM, S, MF, SYM ESR, cryoglobulins, hepatitis C serology, or PCR
Sacroid SM, S, MF, SYM ACE, chest radiograph
Celiac disease S, SM, MF, SYM Antigliadin, endomysial, transglutaminase
antibodies
Rheumatological SM, S, MF, SYM SSA-Ro, SSB-La antibodies ANA, ANCA (PR3,
diseases myeloperoxidase), dsDNA Ab, rheumatoid factor
Paraneoplastic
Lung cancer S, SYM Anti-Hu Ab, Chest radiograph
Myeloma SM, M, SYM, MF Serum and urine immunofixation electrophoresis,
skeletal survey
Hereditary
CMT1-1 Demyelinating, SM, SYM, MF DNA tests for PMP-22, MPZ, EGR2, Cx32
CMT-2 Axonal, SM, SYM DNA tests for NF-L, Cx32, MPZ
Mitochondrial NARP, SM, MF Serum lactate, thymidine phosphorylase, DNA
testing
Other Axonal S, SM, amyloid, DNA tests for transthyretin, periaxin; urine
porphyria porphyrins
Metabolic/Toxic
Diabetes S, SM, SYM, MF, CN Chem 7, HgbA1c, glucose tolerance test
Renal failure S, SM, SYM Chem 7
Thyroid disease S, SM, SYM, MF TSH, T4
Heavy metal toxicity S, SM, SYM Urine lead, mercury, arsenic
S : Sensory
M : Motor
SYM : Symmetry
MF :
CN : Cranial Nerve
Sign and Symptoms
1. Persistent impairment of motor function over days, weeks, or months

- Generalized paralysis : caused by toxic polyneuropathy and respiratory failure
- Bibrachial paralysis : caused by inflammatory demyelinating polyneuropathy
2. Loss of tendon reflexes
3. Loss of sensory function (impaired sensation of touch-pressure, pain, temperature)
4. Paresthesias, dysesthesias, and pain that mostly marked in hands and feet
- Paresthesias : sensation of tingling and tickling
- Dysesthesias : abnormal sensation (mostly in response of touch)
5. Sensory ataxia and tremor

- Ataxia : decreasing voluntary coordination of muscle involvement, balance and speech impairment due to
dysfunction of cerebellum
- Tremor : involuntary movement of body
6. Deformity and tropic changes

- The feet, hands, and spine become deformed (appear to be talipes equmus / the foot will be rotated internally
at the ankle, mostly in childhood)
- Denervation atrophy of muscle (is the main trophic disturbances from interrupted motor nerve)
7. Autonomic dysfunction
- Anhydrosis : inability to sweat normally, leads to overheating
- Orthostatic hypotension : an extreme drop of blood pressure when a person stands up suddenly due to
accumulation of the blood to the legs area (that cause blood carried to the heart decreased)
- Decreasing amount of tears and saliva
- Weak bowel and bladder sphincter with urinary retention
8. Fasciculation, cramps, and spasm in the innervated muscle is due to chronic root compression.
TREATMENT
Treatment of patients with peripheral nerve disorders can be divided into two phases:
a. Removal or treatment of the condition responsible for the disorder
b. Symptomatic therapy, that consists of :
- General supportive measures
- Physiotherapy: massage of all weak muscles and passive movement of all joints. When voluntary movement
begins to return, muscle training exercises are done daily.
- Tracheal intubation and respiratory support (especially for GBS patients).
- Paralyzed limbs are splinted to prevent contractures.
- Dietary salt supplementation or mineralocorticoid therapy to expand blood volume (for postural hypotension)
PROGNOSIS
- Prognosis is affected by the extent of nerves destruction before treatment. If the treatment not been
interrupted, recovery is more rapid. But if axons are destroyed, recovery may be delayed for months.
- In axonal regeneration: proceeds at a rate of 1-2 mm/day, but may be delayed for months.
- In wallerian degeneration: may be permanent weakness, diminution of reflexes, and sensory loss.
- In demyelinating neuropathies, recovery may sometimes be more rapid and complete.
Neuromuscular Junction Disease
Myasthenia Gravis: postsynaptic disorder

Pathophysiology:
Antibody-mediated autoimmune attack
↓
Decrease in number of available acetylcholine receptors (AChRs) at post-synaptic muscle membrane of
neuromuscular junctions and the post-synaptic folds are also flattened or simplified
↓
Although ACh is released normally, but it produces small end-plate potentials
↓
Fail to trigger muscle action potentials and results in decreased efficiency of neuromuscular transmission
↓
Cause these clinical manifestation :
- Weakness and fatigability of skeletal muscle (can be seen in muscle contraction)
- Facial weakness produce “snarling” expression when the patient attempts to smile
- Cranial nerve findings, including ptosis of eyelids and diplopia
- Difficulty in speech, chewing, and swallowing
- Presence of deep tendon reflex
- There is clinical improvement after administration of ACHase agents
Lambert-Eaton Myasthenic Syndrome (LEMS): Presynaptic disorder

Pathophysiology:
In most patients with small cell carcinoma of the lung, the malignancy can express calcium channels
↓
Stimulate the autoantibodies directed against P/Q-type calcium channels at the presynaptic nerve terminals
↓
Impaired release of Ach vesicle from the presynaptic nerve terminals
↓
Although the content of AChase is normal and the postsynaptic membrane is normally responsive to AChase, but
fewer ACh vesicles are released in response to each presynaptic action potential
↓
- Weakness, mostly in the proximal muscle of the lower limbs.
- Cranial nerve findings, including ptosis of eyelids and diplopia
- Absence of deep tendon reflex
- Presence of autonomic changes (such as dry mouth and impotence)
- No clinical improvement after administration of ACHase agents
Botulism
Pathophysiology:
Any of seven different strains of Clostridium botulinum produces potent bacterial toxins (enter human body by
Ingestion of improperly prepared food containing toxin or germination of C.botulinum spores in wounds or GIT)
↓
The toxins enzimatically cleave specific proteins essential for the release of ACh from presynaptic nerve terminal
↓
Neuromuscular transmission become interrupted
↓
- Presence of myasthenia-like bulbar weakness (e.g: diplopia, dysarthria, dysphagia) and sensory loss
- Presence of weakness generalized to the limbs and may result in respiratory failure
- Reflexes are present early, but diminished as the disease progresses.
- Presence of autonomic findings, include paralytic ileus, constipation, urinary retention, unreactive pupils, etc
Guillain-Barre’ Syndrome (GBS)
Definition
Guillain-Barré syndrome (GBS) is a collection of clinical syndromes that manifests as an acute inflammatory
polyradiculoneuropathy with resultant weakness, diminished reflexes, and acute flaccid paralysis.
Classification
a. Acute inflammatory demyelinating polyneuropathy (AIDP)
- By a bacterial or viral infection (±40% of patients are seropositive for Campylobacter jejuni).
- Presence of lymphocytic infiltration and macrophage-mediated peripheral nerve demyelination.
- Symptoms generally resolve with remyelination.
2. Acute motor axonal neuropathy (AMAN)

- A purely motor disorder that more prevalent in pediatric age groups.
- By a bacterial or viral infection (±70-75% of patients are seropositive for C jejuni).
- Presence of wallerian-like degeneration without significant lymphocytic inflammation.
- Patients typically have high titers of antibodies to gangliosides (e.g: GM1, GD1a, GD1b).
- Characterized by rapidly progressive symmetric weakness, ensuing respiratory failure, and may be
hyperreflexic (due to the presence of anti-GM1 antibodies)
- Prognosis is often good. But severely disabled AMAN patients may show improvement over a period of years.
3. Acute motor-sensory axonal neuropathy (AMSAN)

- An acute severe illness that affects motor sensory nerves and roots that more prevalent in adults.
- By a bacterial or viral infection (associated with preceding C jejuni diarrhea)
- Presence of severe axonal degeneration of motor and sensory nerve fibers with little demyelination.
- Presents as rapid and severe motor and sensory dysfunction, characterized by muscle wasting
- Recovery is poorer than from electrophysiologically similar AMAN cases.
4. Miller-Fisher syndrome (MFS)

- Presents as the triad of ataxia, areflexia, and ophthalmoplegia.
- Patients may also have mild limb weakness, ptosis, facial or bulbar palsy, reduced or absence of sensory nerve
action potentials and absence of tibial H reflex.
- Anti-GQ1b antibodies have a relatively high specificity and sensitivity MFS, and dense concentrations of GQ1b
ganglioside are found in the oculomotor, trochlear, and abducens nerves, which may explain the relationship
between anti-GQ1b antibodies and ophthalmoplegia.
- Recovery generally occurs within 1-3 months.
5. Acute panautonomic neuropathy

- Disorder that affects both the sympathetic and parasympathetic nervous systems with lack of motor or
sensory involvement.
- Patients have severe postural hypotension, bowel and bladder retention, anhidrosis, decreased salivation and
lacrimation, pupillary abnormalities, cardiovascular involvement, and dysrhythmias.
- Recovery is gradual and often incomplete.
6. Pure sensory Guillain-Barré syndrome

- A pure sensory variant of GBS.
- Characterized by a rapid onset of sensory loss and areflexia in a symmetric and widespread pattern.
- Lumbar puncture show albuminocytologic dissociation in the CSF.
- Electromyography (EMG) shows characteristic signs of a demyelinating process in the peripheral nerves.
- Prognosis is generally good.
- Recovery by Immunotherapies (plasma exchange and administration of IVIGs / intravenous immunoglobulins).
Etiology
a. Campylobacter jejuni
2. Cytomegalovirus (CMV)
3. Mycoplasma pneumonia
4. Epstein-Barr virus (EBV), Varicella-zoster virus, Human Immunodeficiency Virus (HIV)
5. Haemophilus influenza, Para-influenza virus type 1, Influenza A virus, Influenza B virus
6. Adenovirus and Herpes simplex virus
Precipitating Factors
- Administration of certain vaccinations, with no definite cause-effect relationship.
- Administration of certain drugs: penicillin, antimotility drug, oral contraceptive drug, tumor necrosis factor
antagonist agents (used in rheumatoid arthritis), streptokinase, isotretinoin, danazol, captopril, and heroin. It is
believed that they increases the autoimmune response.
- Administration of certain medical procedures: gastric surgeries, renal transplantation, and epidural anesthesia.
- Certain illness : Trauma, systemic lupus erythematosus, sarcoidosis, lymphoma, and snakebite.
Pathogenesis and pathophysiology

Campylobacter jejuni infection occur
↓
Increased body immune response and activating macrophage (lymphocyte) recruited
↓
Immune responses (IgG antibodies) directed against lipopolysaccharide antigens in the capsule of C jejuni
(which is mimic to the receptor in the ganglioside of peripheral nerves : GM1)
↓
IgG antibodies cross-react with ganglioside GM1 in myelin site
↓
Resulting in the immunologic damage to the peripheral nervous system (local demyelination)
↓
Electrical conduction blocked (neurapraxia)
↓
Peripheral nerve damage (GBS)
↓
Nerve impulse slowing down and disrupt signal between the brain and other parts of body
↓
Results in clinical manifestation
Clinical Manifestation
- Ascending and symmetrical weakness:
Lower limbs involved earlier than upper limbs, and Proximal muscle involved earlier than distal ones
- Impairment of sensory function:
Numbness, hypesthesias (abnormally decreased sensation mostly in lower limb), loss of vibration sensation,
proprioception, touch, and pain distally
- Impairment of motor function:
Physiological reflex negative, paralysis, paresis, unable to stand or walk
- Impairment of autonomic nerves:
Tachycardia, bradycardia, facial flushing, orthostatic hypotension, anhidrosis, and severe weakness and
respiratory failure (dyspnea, shortness of breath, difficulty swallowing, slurred speech)
- Impairment of cranial nerve :
Diplopias, dysarthria, dysphagia, ophthalmoplegia, pupillary disturbances.
Diagnosis
a. History taking
b. Vital sign :
- Blood pressure, Pulse rate, Respiration rate, and Temperature
c. Neurologic examination :
- Cranial nerve impairment (mostly in facial/CN VII)
- Sensory impairment (hypesthesia)
- Motor impairment (paresis)
- Physiological and Pathological reflex
d. Laboratory studies :
- Complete blood count and hemoglobin A1C
- Random blood glucose
- Acid-base balance (electrolyte levels)
- Rheumatology profiles
- Vitamin B12 and folic acid
e. Lumbar puncture :
- GBS (+) if there are elevation in CSF protein (>0.55 g/L) without an elevation in white blood cells.
- Elevated CSF protein level (>400 mg/L), with normal CSF cell counts. (But, a normal CSF protein level does not
rule out GBS, however, as the level may remain normal in 10% of patients)
- Elevated or rising protein levels on serial lumbar punctures and ≤10 mononuclear cells/mm3. (Normal CSF cell
counts may not be a feature of GBS in HIV-infected patients)
f. Imaging studies (MRI or CT SCAN) of the spine :

- To exclude other diagnoses, such as mechanical causes of myelopathy.
- Spinal nerve root enhancement with gadolinium is a nonspecific feature seen in inflammatory conditions and
is caused by disruption of the blood-nerve barrier.
- Selective anterior nerve root enhancement appears to be strongly suggestive of GBS.
g. Serologic studies (assays for antibodies to the following infectious agents) :

- Campylobacter jejuni
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Herpes simplex virus (HSV)
- Human Immunodeficiency Virus (HIV)
- Mycoplasma pneumonia
h. Nerve Conduction Studies (NCS)

- Abnormalities in NCS shows axonal neuropathy, demyelination, or even severe demyelination with distal
conduction block results and represent specific findings for classic GBS.
- Nerve motor action potentials and compound muscle action potential (CMAP) amplitude may be decreased.
- Demyelination is characterized by nerve conduction slowing, prolongation of the distal latencies, prolongation
of the F-waves, conduction block, and/or temporal dispersion. Changes on NCS should be present in at least 2
nerves in regions that are not typical for those associated with compressive mononeuropathies.
- On needle examination, axonal injury showed by profuse and early denervation potentials.
i. Histologic Finding
- Lymphocyte and macrophage infiltration as responsible for the multifocal demyelination observed on
microscopic examination of peripheral nerves in patient with GBS.
- A variable degree of wallerian degeneration also can be observed with severe inflammatory changes.
Differential diagnosis
1. Myasthenia Gravis
A postsynaptic disorder that is characterized by muscular weakness and fatigability
2. Poliomyelitis
A predominantly motor paralysis that caused by the West Nile virus and enterovirusother than the polio agent. It
is characterized by fever, meningioencephalitic symptoms, early pleocytosis in the spinal fluid, and assymetrical
flaccid motor paralysis.
3. Radicular syndrome
A combination of changes usually seen with compromise of a spinal root within the intraspinal canal (includes
neck or back pain) and in the affected root distribution (includes dermatomal pain and paresthesias), decreased
deep tendon reflexes, and occasionally myotomal weakness
4. Hereditary Neuropathy
A group of heterogenous, typically progressive and often disabling syndromes that affect peripheral nerves. The
genetic and molecular basis of many of hereditary peripheral neuropathies is being elucidated.
Management
1. The patient will initially be treated in hospital as an emergency and the respiratory, autonomic, and motor
function will be carefully monitored. Depending on the condition, they can be treated in:
- a general ward
- a neurology ward  a ward specialising in neurological conditions
- an ICU  for people who are in a critically ill or unstable condition
- a high-dependency unit  one step down from an ICU
2. If have breathing problems, patient will be put on a ventilator (a machine that helps to breathe).
3. There are two main treatments to reduce the severity of Guillain-Barré syndrome:
- Intravenous immunoglobulin: 5 infusions daily for total dose 2gr/kgBW IV IG.
* The healthy antibodies given IV and will block and destroy the harmful antibodies that are attacking nerve
- Plasma exchange (plasmapheresis): 4 times over a week.
* The plasma is separated and removed by machine.
* The blood cells are then put back into your body without the harmful plasma cells that attack the nerves.
4. Monitoring your condition
- Patient with GBS may need to spend several weeks in hospital
- During this time you will be closely monitored to check your breathing, heart rate and blood pressure.
- Also do physical therapy : passive movement and positioning of limbs to prevent pressure palsies and mild
resistance exercise. It should begin once the patients can be comfortably undertaken.
- You may be given painkillers if you are in pain, and any other necessary medication.
- Once you start to recover, you may be moved to a general ward in the hospital before being discharged.
Complication
1. Bronchopneumonia
Completely paralyzed lung and need a respirator to keep breathing.
2. Bladder infection
May be due to bladder catherization as the treatment of bladder dysfunction (weakness of bladde muscle)
3. Decubitus ulcer
Areas of breakdown skin that cannot absorb high pressure caused by lying down on bed for a long time. It is
occur in patients who are unable to stand (bed-bound patients)
4. Thrombophlebitis
Deep vein thrombosis that formed when someone is inactive or confined to bed
5. Others
Cardiac arrhythmias, electrolyte imbalance, gastrointestinal hemorrhage, and pulmonary embolism
Prognosis
- 3 to 5 percent of patients do not survive the illness. In the early stages, death is most often due to cardiac arrest,
related to dysautonomia, adult respiratory distress syndrome, pneumo- or hemothorax, or some type of
accidental machine failure. But later in the illness, pulmonary embolism and bacterial complications of
prolonged immobilization and respiratory failure are the main causes.
- The majority of patients recover nearly completely (with mild motor deficits or sensory complaints in the legs).
The speed of recovery varies but its pace is steady. Often it occurs within a few weeks or months; however, if
axons have degenerated, their regeneration may require 6 to 18 months or longer.
- 10 percent of patients, the residual disability is pronounced. Such as weakness of the lower leg muscles,
numbness of the feet and toes, and mild bifacial weakness. A few patients are left with a sensory ataxia, distal
neuropathic pain and persistent autonomic problems.
- Some 5 to 10 percent of patients suffer one or more recurrences of the acute polyneuropathy.
BHP
Patients with GBS and their families should be educated on the illness, disease process, and the anticipated course.
PHOP
Family education and training also is recommended to prevent complications during the early stages of the disease
and to assist in the recovery of function during the rehabilitation stages.
CRP
- GBS has been reported throughout the world.
- GBS has a male-to-female ratio of 1.5:1; male preponderance is seen especially in older patients.
- GBS occurring at any time between infancy and old age.
- Infants appear to have the lowest risk of developing GBS.

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Case 1 / NBSS Bunga Diela

Guillain-Barré syndrome 130110120114

GENERAL CONCEPT OF NERVOUS SYSTEM

The nervous system is divided into two main parts:

***Autonomic Nervous System***

1. Major Divisions of the Central Nervous System

2. Major Divisions of the Peripheral Nervous System (GENERAL CONCEPT OF PNS)

I. Olfactory (A) VII. Facial (A/E)

SENSORY (AFFERENT) based on function

DEVELOPMENT OF PERIPHERAL NERVE

BASIC DEVELOPMENT OF NEUROEPITHELIAL CELL

DEVELOPMENT OF DORSAL AND VENTRAL HORNS

DEVELOPMENT OF DORSAL ROOT GANGLIA

DEVELOPMENT OF SPINAL NERVES

DEVELOPMENT OF NERVE PLEXUS

HISTOLOGY OF PERIPHERAL NERVE

Morphologic types of neurons

1. Multipolar neurons : has 1 axon and ≥2 dendrites

2. Bipolar neurons : has 1 axon and 1 dendrite

Peripheral nervous system

B. Nonmyelinated Nerve Fibers

Connective tissue of nerve fibers

CLASSIFICATION OF NERVE FIBERS

2. BASED ON STIMULATION, nerve fibers classified to:

3. BASED ON FUNCTION, nerve fibers classified to:

* 3 types of motor fibers:

* 3 types of sensory fibers:

Conduction in Peripheral Nerves

In the depolarization (action) state:

In the repolarization (restoration) state:

In the absolute refractory period:

In the relative refractory period:

Creation of the action potential by the arrival of a stimulus

* Conduction velocity of a nerve fiber:

A. Electrical changes that occur in

B. Electrical changes that occur in stimulated

Topography of Sensoric Distribution in Peripheral Nerve

Topography of Motoric Distribution in Peripheral Nerve

GENERAL CONCEPT OF LOWER MOTOR NEURON

Motor Neuron dibagi menjadi 3 jenis, yaitu :

Lower Motor Neuron dibagi menjadi 3 kategori, yaitu :

A reflex arc consists of:

Figure A: Multiple branching of afferent fibers entering

Figure B: The law of reciprocal innervation

A: A monosynaptic reflex arc.

PERIPHERAL NERVE DISEASE

a. Axonal Degeneration : result in glove-stocking distribution of sensory loss

Caused by slowly evolving neuronopathies or axonopathies

b. Wallerian Degeneration : may cause muscle atrophy

Caused by focal lesion (such as chronic or severe traumatic transaction of a nerve)

c. Segmental demyelination : result in decreasing conduction velocity

* SUNDERLAND’S CLASSIFICATION, based on severity :

Etiology, Clinical Characteristic and Diagnostic

Etiology Clinical Characteristic Laboratory Tests

Sign and Symptoms

1. Persistent impairment of motor function over days, weeks, or months

2. Loss of tendon reflexes

3. Loss of sensory function (impaired sensation of touch-pressure, pain, temperature)

5. Sensory ataxia and tremor

6. Deformity and tropic changes

Neuromuscular Junction Disease

Myasthenia Gravis: postsynaptic disorder

Lambert-Eaton Myasthenic Syndrome (LEMS): Presynaptic disorder

Guillain-Barre’ Syndrome (GBS)

Autonomic Nervous System