Continuing Education Activity

Electrodiagnostic testing is an important tool for the diagnosis of acute inflammatory demyelinating polyneuropathy. This activity describes the electrodiagnostic findings of both nerve conduction tests and needle electromyography studies in acute inflammatory demyelinating polyneuropathy.

Objectives:

• Identify the anatomy and physiology of nerve conduction and its relevance to acute inflammatory demyelinating polyneuropathy.

• Determine the indications for electrodiagnostic testing in patients with symmetric distal weakness.

• Assess the nerve conduction study findings in patients with acute inflammatory demyelinating polyneuropathy.

• Improve communication and care coordination among the interprofessional team to better serve patients with acute inflammatory demyelinating polyneuropathy.

Introduction

Demyelinating neuropathies can be classified as hereditary, toxic, and immune-mediated. Immune-mediated polyneuropathies can be further classified as acute and chronic, depending on the onset. Guillain-Barre syndrome (GBS) is a syndrome with several variants, with acute inflammatory demyelinating polyneuropathy (AIDP) being the most common type of inflammatory neuropathy in North America. The pathophysiology of GBS and its variants appear to be secondary to an inflammatory process leading to molecular mimicry between central and peripheral nervous structural components and microbial/viral antigens. This condition leads to a lack of self-tolerance from the adaptive immune system and activation of neuroinflammatory processes affecting nerve conduction. The microbial and viral antigens may include Campylobacter jejuni, HIV infection, Epstein-Barr (mononucleosis), and Zika virus.[1] Previously, it was speculated that AIDP has links with vaccinations; however, further research has refuted this association.

Clinically, AIDP presents with an acute, symmetric, flaccid, and distal weakness that usually starts in the lower extremities and has an ascending pattern as time progresses.[2] The neurological examination may show facial paresis, cranial nerve/bulbar weakness, distal hyporeflexia without signs of upper motor neuron dysfunction, preserved muscle bulk, dysesthesias, allodynia, or neuropathic pain, and loss of light and vibratory sensation in the affected extremities. Motor symptoms and signs tend to predominate over sensory ones. Autonomic symptoms may be present, such as hypertension or hypotension, cardiac arrhythmias, and respiratory failure requiring mechanical ventilation. The latter can present in those with an advanced and severe disease course. It has a monophasic course with varying onset, progression, and recovery degrees. Imaging may show hyperintense and hypertrophic nerves, especially in caudal nerve roots in the lumbar spine.

Further evaluation includes a lumbar puncture, often showing albuminocytologic dissociation (0 cells and high cerebrospinal [CSF] protein without signs of infection). However, some patients may not have positive CSF findings until 3 weeks into the disease course. A smaller percentage of patients may have unremarkable CSF results. In summary, diagnosing AIDP requires a thorough history and physical exam, screening of risk factors, lumbar spine imaging, comprehensive CSF studies to discard alternate diagnoses, and ancillary electrodiagnostic studies.[3]

Electrodiagnostic studies can support the diagnosis and prognosticate the patient's course when an AIDP is suspected. They can help localize a lesion (eg, bulbar, peripheral, neuromuscular junction, muscle), and discern the extent of the pathology and etiology (eg, autoimmune, axonal, myopathic, etc). They are considered an extension of the neurological exam, providing valuable information about nerve conduction, muscle-nerve connections, and structural integrity of the myelinated sensory and motor fibers. AIDP can affect axons in more severe cases, which may have a worse prognosis. This topic focuses on the findings typical of acute demyelinating polyneuropathies. 

Anatomy and Physiology

Neurons are responsible for receiving, integrating, and propagating the summation of excitatory and inhibitory electrical potentials from other cells. Neurons are composed of dendrites, bodies, and axons. Dendrites receive information from other neurons and serve a critical role in neuroplasticity. The neurons contain the euchromatic nucleus and organelles responsible for producing proteins and chemicals essential for proper neurotransmission at the synapse. Polyribosomes are clustered and are visible under electron microscopy as Nissl bodies. Axons serve as the conductor and transmit information to other individuals or networks of neurons, glands, and muscles. The axonal fibers terminate at the synapse with the electrochemical activation of a complex and diverse quantity of ligand-gated or G-coupled receptors that vary according to the effector organ.

Physiology of Nerve Conduction

At rest, neurons have an intracellular resting membrane potential of -70 mV, which reflects a steady-state concentration of sodium (Na+) and potassium (K+) ions intracellularly and extracellularly. This state is maintained through the cells' passive and active energy (ATP) expending receptors. During depolarization, there is an influx of Na+ ions (given higher concentration extracellularly) via partial voltage-gated sodium channels that open and lead to a propagating stimulation once they reach a positive voltage potential. At the peak of the action potential, voltage-gated Na+ channels close, and voltage-gated potassium K+ channels open, leading to the exit of ions from inside to outside the cell through a concentration gradient, which leads to the hyperpolarization of cells. A Na+/K+-ATPase in the neurons brings the ion gradient back to baseline (to resting potential) by expending energy to expel 3 Na+ out of the cell for 2 K+ inside the cell. The nerve conduction is coordinated with directionality and propagation of depolarization throughout the entire axon, with ultimate activation or inhibition of neurotransmitters into the synaptic cleft. 

Unmyelinated fibers conduct in the range of 1 to 5 meters per second. On the other hand, myelinated motor and sensory nerve axons have conduction velocities up to 150 meters per second. This process is called saltatory conduction. Myelin production occurs via Schwann cells, which concentrically wrap around axons. These myelin sheaths have gaps called nodes of Ranvier, where action potentials occur and propagate quickly until encountering the next node. Therefore, current flows passively and jumps from node to node.

During AIDP, the autoimmune target can predict the electrodiagnostic findings, prognosis, and clinical presentation. The most common target is the myelinated sheaths across the axon and within Schwann cells, leading to decreased conduction velocity.[4] Although less common, nerve axon fibers can also be targets. This activity leads to axonal injuries that can decrease action potential amplitudes and lead to abnormal nerve-muscle connections. 

Indications

Electrodiagnostic studies can play a vital and ancillary role in the diagnosis and prognosis of AIDP.

Nerve conduction studies

Nerve conduction studies (NCS) can help to evaluate large myelinated sensory and motor fibers. Small myelinated fibers in the autonomic and spinothalamic tracts need specialized studies for neuropathy evaluation. The NCS does not pick these up (eg, quantitative sudomotor axon reflex test-QSART, useful to diagnose type II diabetes mellitus polyneuropathy). NCS should be performed in ideal conditions, including room temperature, as it can affect latency, duration, and amplitude measurements. NCS is an electrodiagnostic study that measures the summated action potentials of sensory (SNAPs) and motor muscle fibers (CMAPs). It has multiple important measurements to review:

• Conduction velocity: The speed of the fastest conducting motor axon, which tends to be prolonged in demyelinating disorders.
• Amplitude: Voltage difference from baseline to maximal negative peak with depolarization, a reflection of intact, non-diseased muscle fibers that can depolarize
• Latency: Reflects the speed of neurotransmission and is defined as the time from stimulus to initial CMAP deflection from baseline.
• Duration: Reflects the synchronous transmission of action potentials; it can give a global evaluation of the motor fiber conduction, with many fibers slowing conduction, affecting the duration of action potentials (measured by the time from an initial deflection from baseline to first crossing) [5]

Electromyogram 

An electromyogram (EMG) measures the integrity of the nerve-muscle connections when electrical stimulation is applied, with an anatomical evaluation of nerves, roots, and plexuses. It predominantly evaluates motor unit action potentials of type 1 muscle fibers and does not pick up type 2 fibers. EMG evaluates motor units' insertional, spontaneous, and exertional activity.

• Insertional activity: Muscle fiber action potentials burst, provoked by the irritation of the needle electrode
  • Increased activity: In neuropathy and myopathic processes
  • Decreased activity: In muscle necrosis
• Spontaneous activity: can be silent (in normal tissue) or show abnormal waves
  • Fibrillations and positive waves: Rhythmic firing of individual muscle fibers representing subacute (7-10 days) denervation or muscle inflammation
  • Fasciculations: Irregular popcorn-like firing of muscle fibers representing acute muscle-nerve denervation
  • Complex repetitive discharges: Rhythmic, frequent, complex, and rumbling running motor-like firing of MUAPs
  • Myotonic discharges: Waxing and waning diver bomber-like firing of muscle fibers
• Exertional activity: MUAP activity, recruitment, firing rate, etc, during muscle contraction 
  • Recruitment: Number of firing motor units firing x force applied during voluntary contraction
    • Early recruitment: In myopathy
    • Delayed recruitment: In neuropathic and axonal disorders
  • Firing rate: Frequency of discharges during voluntary contraction
  • Innervation of muscle fibers: Polyphasic versus single motor unit innervation
    • Single motor unit innervation can signal reinnervation from chronic neuropathic lesions.
  • Amplitude: Similar to the NCS definition
    • High amplitude can present in neuropathic lesions
  • Duration: Similar NCS definition 
    • Increased duration can present in neuropathic or axonal injury

For AIDP, NCS, and EMG, studies should occur no earlier than 3 weeks after the onset of clinical symptoms to avoid false negatives and increase the specificity of the studies. Electrodiagnostic testing can also rule out other superimposed or isolated neuromuscular disorders in the differential, which can include cervical or lumbar radiculopathies or myelopathies, myopathies, neuronopathies, small or large fiber peripheral neuropathy, motor neuron disease, and neuromuscular junction disorders. These differentials are defined as follows: 

• Myopathy: Diseased muscle fibers
• Motor neuron disease: Diseased motor neuron unit within the upper or lower motor spectrum.
• Neuromuscular junction disorder: Diseased connection or neurochemical process between the nerve and muscle at the synapse
• Myelopathy: Diseased or damaged spinal cord
• Neuronopathy: Diseased cell body; it can be sensory, motor, sensorimotor, or related to ganglions.
• Neuropathy: Diseased cell body, axon, or myelin

Contraindications

Performing electrodiagnostic studies in patients with suspected AIDP has few absolute contraindications. Needle EMG is contraindicated in those with severe bleeding disorders. [6] Needles should also never be inserted into areas of active soft tissue infection. Nerve conduction studies are contraindicated in patients with implanted cardiac defibrillators or if connected to external defibrillators. Patients should receive screening for pacemakers, and electrical stimulation should not be performed directly on or near the device.

Equipment

Electrodiagnostic studies for AIDP require EMG and NCS hardware and software, conduction gel, measuring tape, surface electrodes, needle electrodes, ring electrodes, and alcohol pads for skin sterilization.

Personnel

Adequately trained neurodiagnostic personnel are essential for proper evaluation. Familiarity with EMG and NCS hardware and software, electrode placement, and data interpretation of NCS and EMG measurements is indispensable. An interdisciplinary team that includes technicians, nurses, and primary or consultant physicians is essential to coordinate care and obtain the most accurate and precise data from the NCS and EMG.

Preparation

As with all nerve conduction studies, the temperature should be ideally between 32 and 33 degrees Celsius to avoid artifactual measurements. A warming lamp may help achieve proper limb temperature. Colder temperatures can cause mistakenly increased amplitudes, prolonged latencies, and slowed conduction velocities on NCS.

Technique or Treatment

Before performing any diagnostic study, a comprehensive review of the patient’s history, clinical course, and a complete physical exam must be performed. The diagnostician informs the patient's bedside of the indications and provides an overview of the studies needed to diagnose AIDP with proper electrodiagnostic testing.

The diagnostician must thoroughly explain the risks and benefits of the exam to the patient and get consent from the patient. For comparison, one should ideally examine at least 3 extremities, performing sensory and motor nerve conduction studies and EMG needle testing in both proximal and distal muscles. A notch filter should be used to minimize the electrical interference that can occur while doing the study bedside, and, if possible, all unnecessary machines should be turned off, including unplugging the clinic/hospital bed.

Complications

As with all electrodiagnostic studies in any setting and for any indication, the risk of complications is low. However, there is always a small risk of bleeding, infection, or nerve damage due to needle studies. 

Clinical Significance

Nerve conduction studies in AIDP may show signs of demyelination, such as delayed distal latencies, decreased conduction velocities, temporal dispersion, and conduction block (1 or more nerves) in SNAPs and CMAPs. The European Federation of Neurological Societies (EFNS) and Peripheral Nerve Societies (PNS) have specific electrodiagnostic criteria for diagnosing AIDP.

• Prolonged distal latencies: Two or more nerves with more than 115% to 125% of the upper limits of normal [7]
• Decreased conduction velocities: Two or more nerves with less than 80% to 90% of lower limits of normal; can be preserved if done too early in the disease course (<3 weeks)
  • Unequivocal conduction block: Proximal/distal CMAP area ratio of less than 0.50
  • Possible conduction block: Proximal/distal CMAP area ratio of less than 0.70
  • Temporal dispersion: One or more nerves; proximal/distal CMAP duration ratio more than 1.15
• Prolonged late responses: One or more nerves greater than 125% of upper limits of normal; F response and H reflex
  • Exception: If CMAP amplitude is too low, the absent F response may be normal [8]

NCS may show the sparing of the sural nerves. F-wave studies, while normally limited in their utility in many pathologies, are particularly useful in testing for AIDP. F-wave testing can detect early inflammation proximally at the nerve roots. Because the F-wave tests the entire nerve length, it can detect abnormalities clinicians would otherwise miss with standard segmental nerve conduction studies. Also, F-ratios may increase, suggesting greater proximal demyelination compared to distal.[9]

Needle electromyography is usually unremarkable in AIDP because most cases are demyelinating and not axonal. However, with axonal involvement, EMG studies may demonstrate signs of active denervation, PSWs/fibrillation potentials, increased duration, amplitude, and fiber reinnervation signs.

Enhancing Healthcare Team Outcomes

Acute demyelinating polyneuropathy is a condition often seen in the inpatient setting and sometimes requires outpatient follow-up. Patients frequently complain of pain, weakness, paresthesias, and weakness in the extremities. Imaging, cerebrospinal, and electrodiagnostic studies are routinely ordered. Physicians must be cautious, as imaging findings might not correlate with the patient's symptoms.

It is essential to take an interprofessional team including a team of physicians (general neurologists, neuromuscular neurologists, physical medicine and rehabilitation, pain management physicians), therapists (physical and occupational therapists), social workers, and case managers who can work together to coordinate mobilization with outpatient therapy and aggressive multifaceted rehabilitation so we can improve a patient's functional status.[10] If the axonal injury is severe and prolonged, a long and difficult recovery could occur. A coordinated effort between the various medical disciplines and departments can provide the best outcomes for patients.