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Navigator: Guillain-Barre Syndrome ˇ

Update April 2019

Nerve Conduction Velocity in Guillain-Barre

Physiology and Physics

 Guillain-Barre:  History and Physiologic Name

The disorder was first described by the French physician Jean Landry in 1859, who published a report on 10 patients with an ascending paralysis.

This was followed in 1916 by a report from three French physicians working in the Sixth Army camp during the First World War: Georges Guillain, Jean Alexandre Barré, and André Strohl.

They described 2 French soldiers who had motor weakness and areflexia, plus the key diagnostic abnormality of increased spinal fluid protein with normal white-cell count.

They carefully recorded the tendon reflexes of their patients, correctly interpreting the peripheral nature of the illness.

Historical Names

  • Landry's Ascending Paralysis
  • Landry-Guillain-Barré-Strohl Syndrome

Physiologic Name

  • Main variant is AIDP: Acute Inflammatory Demyelinating Polyradiculoneuropathy.

Name in Common Use, Even Among MDs

  • Guillain-Barre Syndrome

Gold-Standard Diagnostic Tests for Guillain-Barre

Guillain-Barre is an autoimmune disease, caused by anti-ganglioside antibodies, which act to destroy the myelin segments which wrap around, and insulate, the axons of peripheral nerves. There are two gold-standard tests to diagnose Guillain-Barre:

  • A spinal tap must show elevated protein in the cerebrospinal fluid, without any rise in white cells. It is termed albumin/white-cell dissociation or cytoalbuminologic dissociation. This represents an inflammatory process rather than an infection.
  • Electrodiagnostic testing, specifically Nerve Conduction Velocity tests, must show the changes characteristic of myelin damage, and in some cases axonal damage, to peripheral (Type A) nerves.

The Nerve Conduction Velocity Test

Nerve conduction velocity is sensitive to nerve injury. The NCV test measures the integrity of the conduction of electrical impulses as they travel down a nerve. Two patch electrodes are placed on a given limb, on the surface of the skin a few inches or a few feet apart. The distance between the electrodes is measured.

The first electrode (nearest the torso) emits a mild electric impulse to stimulate a nerve bundle. The resulting electrical activity is recorded by the second electrode which sits downstream from the first. The time for the impulse to travel between the electrodes is measured, and that along with distance allows a calculation of signal velocity.

The amplitude of the signal, and the temporal dispersal, are also important. One major nerve at a time is tested: in the upper limb these are typically the ulnar and median nerves, and in the lower limb the tibial and peroneal nerves.

On this page we cover:

The residual, long-term fatigue which appears so often after recovery from Guillain-Barre, in its relation to conduction velocity.

Appearance of Nerve Conduction Velocity graphs in a healthy nerve versus a case of Guillain-Barre.

Residual Fatigue After Guillain-Barre Syndrome

Gareth J. Parry wrote one of the first serious accounts of Residual Effects Following Guillain-Barre. From round the world, patients replied with letters saying they felt validated. Patients, if not their doctors, always knew there was a Post-GBS Syndrome, similar to Post-Polio Syndrome.

Parry's classic textbook, Guillain-Barre Syndrome, explains the physical causation of long-term fatigue in supposedly recovered patients. The section titled Mechanisms of Conduction Slowing and Temporal Dispersal states: After acute GBS, the myelin does gradually regenerate, but it builds an edifice less efficient than before. This impairs signal transmission, often for the patient's lifetime.

Several mechanisms contribute. In the chief one, the nodes of Ranvier are pivotal – in particular, the number of nodes. The physiology:

  • The conduction velocity along an axon is determined entirely by the delay that occurs at each node of Ranvier, and by the number of nodes.
  • Imagine a peripheral nerve as a string of beads. The axon core is the string. Wrapped around it are a series of myelin segments (also called internodes) which resemble beads. The gap between each bead is a node of Ranvier.
  • Conduction within a myelin segment (or internode) depends solely on the cable properties of the axon and is extremely rapid. The choke-point, even in a healthy nerve, is the node of Ranvier. The conduction velocity is governed by the delay at each node, multiplied by the number of nodes.
  • As an axon remyelinates, a number of factors combine to produce conduction slowing. First, there is an increase in the number of nodes of Ranvier.
  • The territory of the axon originally invested by a single myelin segment – which was derived from a single Schwann cell – if damaged, is remyelinated by several new Schwann cells, with a proportionate increase in the number of nodes.
  • As myelin thickness increases and nodal architecture matures, the conduction velocity increases, but the original conduction speed may never be restored.
  • Individual axons experience varied degrees of demyelination and remyelination. This increases the range of conduction velocities in a muscle, causing temporal dispersion of the compound action potential (CMAP). The pulse stretches out along the time axis of an NCV graph.

Video requires 320px screen width

Nodal Architecture in GBS Enlarge

The animation (left) shows this mechanism in action. At onset of GBS, anti-ganglioside antibodies denude long stretches of the peripheral nerves. When the myelin segments grow back, a single segment might be replaced by three short, thinner ones.

The gaps between myelin segments (called nodes of Ranvier) thus multiply by a factor of three in stricken areas. With 3 times as many gaps to jump, there are 3 times as many places for the signal to slow down.

The section below describes how Nerve Conduction Velocity tests can diagnose the characteristic features of Guillain-Barre Syndrome.

Appearance of Nerve Conduction Velocity Graphs

1.  Healthy Nerve / Narrow Smooth Pulse

On a Nerve Conduction Velocity graph, a normal healthy nerve has the appearance of a perfect sine-wave pulse: The profile is smooth and regularly-shaped – it resembles a narrow bell-curve. Such a pulse is fast and reaches the sensor with little delay.

Physiology:  The test stimulates a small localized bundle of healthy motor or sensory nerve fibers. These produce signals of approximately equal strength and speed. Because temporal dispersion is minimal, the signals all reach the sensor at nearly the same time (narrow profile). The amplitude of the signal does not attenuate (high peak).

Nerve Structure:  A peripheral nerve is insulated with myelin but, unlike a computer cable, the covering is not a straight tube. The architecture of a healthy nerve is best explained via the metaphor of beads on a string:

  • The core (or axon) of the nerve is the string, while myelin segments are the beads.
  • A Schwann cell forms an outer covering for each myelin segment. The Schwann cell (a type of glial cell) wraps around the axon like a crêpe, secreting a densely-packed cylinder of myelin inside, with the axon running through the core.
  • Each myelin segment and has a finite length of about 0.08-1.00 mm. The length is generally proportional to the size of the nerve. Large main nerves have longer (and thicker) myelin segments.
  • The myelin segments almost abut each other, with gaps between them called nodes of Ranvier. These gaps are narrow, on the order of 0.001 mm in length (which is one micron, or 1μm).

Physics of Myelin:  Myelin has the important job of preventing electrical signals from leaking or trickling away into surrounding tissue. When myelin is intact, the signal strength is preserved. But the myelin segments also act like little capacitors in physics. A capacitor is a device that stores electric charge. For this design in humans, we may quiz evolution, fate, or God for inefficiency.

Nerve Transmission: When a signal traverses a peripheral nerve, two phases alternate hundreds of times down the line. Inside a myelin segment, the signal travels along the axon at fair speed. But each time the signal reaches the end of a myelin segment, it must jump across to the next myelin segment. This jump across a node of Ranvier is called saltatoryFrom Latin saltatio, derived from saltare 'to dance', frequentative of salire 'to leap' conduction.

Signal Delay:  The actual jump is lightning-quick, but note the signal cannot begin to jump across until the next myelin segment has charged up. It is that charge differential which allows the signal to cross – similar to a spark-gap. In biology, a spark-gap is created by ion flow.

Axolemma:  Across a node of Ranvier, the axon is exposed to extracellular fluid. The axon here has only a thin covering called an axolemma which is rich in ion channels (in the form of channel-shaped protein molecules). When the signal reaches a node, the ion channels open.

  • Lay a nerve horizontally with the head (soma and dendrite receptors) at the left, and with signal transmission heading right. When the brain sends a stimulus to this nerve, potassium ions (K+) migrate from the extracellular fluid into the soma, while sodium ions (Na+) migrate out. Though both ions are positive, the gates designed for K+ ions are far more permeable than the gates for Na+ ions. The result is a net positive charge inside the neural cell.
  • When the soma reaches a threshold of positive charge, the ions seek an escape hatch. Electric repulsion drives the ions from the soma down the long axon.
  • First leg of the journey: through a myelin segment. The signal cannot penetrate the lipid content of the myelin sheath. Thus the signal, funneled forward, will propagate passively down the core axon. However, even in a single segment, the signal dissipates by some percent.
  • The signal encounters a node of Ranvier, which is laden with gated ion channels. The channels leftmost in the axolemma open, this starts a cascade, and channels open further and further to the right until the end of the node is reached.
  • Ion flow at the axolemma: Sodium ions (Na+) and potassium ions (K+) which have positive charge, and chloride ions (Cl-) which have negative charge, diffuse separately across the membrane. The direction of flow is perpendicular to the axon. The result is a voltage difference sufficient to boost the signal intensity, to regenerate it to its original strength.
  • Across the axolemma, when the cascade ends, the left myelin segment becomes depolarized, and the right segment becomes polarized. Voila, a spark gap. The signal jumps across.

Fatigue: Due to the prolonged ion movements, the signal suffers a delay at each separate node of Ranvier. People with normal physiology of course never notice this. But it is of crucial importance to recovered Guillain-Barre patients who endure life-long fatigue due to multiplication of the number of nodes of Ranvier.

2.  Myelin Damage / Ragged Wide Pulse

Turn now to a case of Guillain-Barre during its initial acute stage. The Nerve Conduction Velocity test excels as a diagnostic tool. What is its characteristic appearance? When myelin on peripheral nerves becomes sufficiently damaged, the NCV graph shows a pulse that is ragged, low-amplitude, and delayed along the time axis. The actual shape of this pulse is broad and stretched-out.

Physiology:  Each peripheral nerve fiber suffers myelin destruction to a greater or lesser degree, as anti-ganglioside antibodies attack at random locations. The NCV test applies one stimulus to a bundle of nerve fibers. The signals all launch with normal intensity, but on the way to the sensor they attenuate by varying amounts. The ragged profile is created by the mathematical sum of wave pulses of varying amplitude.

Louis Ranvier
Discovered Nodes of Ranvier in 1878

Nodes of Ranvier Are Still Key: The NCV test is done early in Guillain-Barre when the number of myelin segments may yet be normal. At this stage, the myelin cells are just beginning to disintegrate, yet the moth-eaten ravage interferes with saltatory conduction: Ion flow is impaired, thus polarization is inefficient. The signal gets delayed longer than normal at many individual nodes of Ranvier.

Thus on an NCV graph, the pulse will arrive late. The compound pulse, or compound muscle action potential (CMAP), is of course the sum of contributions from many individual nerve fibers. When the fibers vary greatly in their transmission speed, the pulse also stretches out along the time axis – this is called temporal dispersion.

3.  Axonal Damage / Signal Attenuates to Zero

Sometimes in Guillain-Barre the central axon of the nerve is also destroyed. This breaks entirely the path of the electrical signal. On the NCV graph, the amplitude of the pulse will attenuate to zero. The signal is physically blocked from getting through, akin to cutting a cable in half.

Signal Unobtainable:  An EMG report might contain phrases such as: The sensory responses were unobtainable or F Wave latencies were unobtainable. The word unobtainable here does not mean the patient withheld consent for the procedure. It means the test was performed, but the amplitude of the signal was zero: a pulse was sent from the first electrode, but no signal could be detected at the second electrode a few inches downstream on the same nerve. It represents a case of Guillain-Barre so severe that axonal damage has occurred.

Georgena S. Sil
Saskatoon, Canada
Physicist & Technical Writer
Alumnus: University of British Columbia
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I feel like I’m in a NASCAR race on a moped.

Former NFL player Danny Wuerffel

Seven months after GBS onset

Neuron Cell Body
10 μm

Neuron Cell Body / Electron Micrograph

Neuron: Cell Body, Myelin, Nodes of Ranvier

Peripheral Nerve / Full Architecture

Cell body, Myelin, Nodes of Ranvier

Node of Ranvier, Peripheral Nerve

Peripheral Nerve / Node of Ranvier

Electron Micrograph

Compound Action Potential: Normal Nerve, Speed Range

CMAP / Speed Range of Fibers

Temporal dispersion in normal nerve
(Pulse width-to-height ratio expanded)

Compound Action Potential: Normal Nerve, Phases

CMAP / Polarization Phases

Normal nerve: Biological spark-gap
Mechanism: Ion flow at Axolemma
(Pulse width-to-height ratio is normal)

NCV Graph: Acute Polyneuropathy, Median and Ulnar Nerves

NCV Test / Myelin Damage
Upper Limb, Median and Ulnar Nerves

Conduction is Slowed, and Distal Latencies are Markedly Prolonged
(Four weeks after GBS onset)

NCV Graph: Acute Polyneuropathy, Peroneal and Tibial Nerves

NCV Test / Myelin Damage
Lower Limb, Tibial and Peroneal Nerves

Conduction is Slowed, and Distal Latencies are Markedly Prolonged
(Four weeks after GBS onset)

Diagnostic Report: Acute Polyneuropathy

NCV Test / Axonal Damage
Complete Conduction Block

Diagnostic Report: F-Waves and Sensory Responses were unobtainable
(Four weeks after GBS onset)

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