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Electrodiagnostic Evaluation Of Acute Inflammatory Demyelinating Polyneuropathy

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Electrodiagnostic Evaluation Of Acute Inflammatory Demyelinating Polyneuropathy

Article Author:
Richard Huynh
Article Editor:
Franklyn Rocha Cabrero
Updated:
10/23/2020 4:23:35 PM
For CME on this topic:
Electrodiagnostic Evaluation Of Acute Inflammatory Demyelinating Polyneuropathy CME
PubMed Link:
Electrodiagnostic Evaluation Of Acute Inflammatory Demyelinating Polyneuropathy

Introduction

Demyelinating neuropathies can classify as hereditary, toxic, and immune-mediated. Immune-mediated polyneuropathies can be further classified in 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, AIDP some speculated to have 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 degrees of onset, progression, and recovery. Imaging may show hyperintense and hypertrophic nerves, especially in caudal nerve roots in the lumbar spine.

Further evaluation includes a lumbar puncture, which often shows albuminocytologic dissociation (0 cells and high cerebrospinal (CSF) protein without signs of infection), although a fair percentage of patients may not have positive CSF findings until three weeks into the disease course. A smaller percentage of patients may have unremarkable CSF results. In summary, the diagnosis of 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 serve for prognostication of the patient's course when an AIDP is suspected. They can help localize a lesion (e.g., bulbar, peripheral, neuromuscular junction, muscle), and discern the extent of the pathology and etiology (e.g., autoimmune, axonal, myopathic, etc.). They are thought of as an extension of the neurological exam, providing valuable information about the nerve conduction, muscle-nerve connections, and structural integrity of the myelinated sensory and motor fibers. In more severe cases, AIDP can affect axons, which may have a worse prognosis. This article will focus on the findings that are 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 body of neurons contains the euchromatic nucleus and organelles responsible for the production of 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 transmitter of 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 can vary in accordance to the effector organ.

Let us briefly review the physiology of nerve conduction for completion. 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 passive and active energy (ATP) expending receptors in the cells. During depolarization, there is an influx of Na+ ions (given higher concentration extracellularly), via partial voltage-gated sodium channels that, once they reach a positive voltage potential, open and lead to a propagating stimulation. 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/second. On the other hand, myelinated motor and sensory nerve axons have conduction velocities up to 150 meters/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 a decrease in 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 (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 will not pick these up (e.g., 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 measurements such as latency, duration, and amplitude. NCS is an electrodiagnostic study that measures the summated actions potentials of sensory (SNAPs) and motor muscle fibers (CMAPs) and has multiple measurements that are important to review.[5]

  • Conduction velocity: the speed of the fastest conducting motor axon and 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 a large number of fibers slowing conduction affecting the duration of action potentials. The measurement is the time from an initial deflection from baseline to the first crossing.

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 will evaluate the insertional, spontaneous, and exertional activity of motor units.

  • 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 to 10 days) denervation or muscle inflammation
    • Fasciculations: the 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 motor unit action potentials (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 be a sign of reinnervation from chronic neuropathic lesions.
    • Amplitude: similar to NCS definition
      • High amplitude can present in neuropathic lesions
    • Duration: similar NCS definition 
      • Increased duration can present in neuropathic/axonal injury

For AIDP, NCS, and EMG studies should take place no earlier than three 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/lumbar radiculopathies or myelopathies, myopathies, neuronopathies, small or large fiber peripheral neuropathy, motor neuron disease, and neuromuscular junction disorders. The categorical definition of these differentials follows as a refresher. 

  • 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 itself.

Equipment

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

Personnel

An adequately trained neurodiagnostic personnel is essential for proper evaluation. Familiarity with EMG/NCS hardware and software, electrode placement, and data interpretation of NCS and EMG measurements is indispensable. An interdisciplinary team that includes technicians, nurses, primary/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

Before performing any diagnostic study, a comprehensive review of the patient’s history and clinical course, as well as a complete physical exam, must be performed. The diagnostician will inform the patient bedside of the indications and 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 also get consent from the patient. One should ideally examine at least three extremities, performing both sensory and motor nerve conduction studies, as well as EMG needle testing in both proximal and distal muscles for comparison. A notch filter should be used to minimize the electrical interference, which can occur while doing the study bedside, and, if possible, all unnecessary machines 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, and/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 the Neurological Societies (EFNS) and Peripheral Nerve Societies (PNS) have specific electrodiagnostic criteria for diagnosing AIDP.

  • Prolonged distal latencies (2 or more nerves with > 115 to 125% of the upper limits of normal)[7]
  • Decreased conduction velocities (2 or more nerves with < 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 <0.50.
    • Possible conduction block- proximal/distal CMAP area ratio of <0.70
    • Temporal dispersion (1 or more nerves)- proximal/distal CMAP duration ratio > 1.15
  • Prolonged late responses (1 or more nerves, >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 length of the nerve, it can detect abnormalities that 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, positive sharp waves/fibrillation potentials, increased duration, increased amplitude, and fiber reinnervation signs.

Enhancing Healthcare Team Outcomes

An acute demyelinating polyneuropathy is a condition often seen in the inpatient setting and sometimes requires outpatient follow up. Patients frequently come with complaints 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, there could be a long and difficult recovery. A coordinated effort between the various medical disciplines and departments can provide the best outcomes for patients.


References

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[2] Walling AD,Dickson G, Guillain-Barré syndrome. American family physician. 2013 Feb 1;     [PubMed PMID: 23418763]
[3] Donofrio PD, Guillain-Barré Syndrome. Continuum (Minneapolis, Minn.). 2017 Oct;     [PubMed PMID: 28968363]
[4] Kaida K, Guillain-Barré Syndrome. Advances in experimental medicine and biology. 2019;     [PubMed PMID: 31760653]
[5] Tavee J, Nerve conduction studies: Basic concepts. Handbook of clinical neurology. 2019;     [PubMed PMID: 31277849]
[6] Gertken JT,Patel AT,Boon AJ, Electromyography and anticoagulation. PM     [PubMed PMID: 23523707]
[7] Chanson JB,Echaniz-Laguna A, Early electrodiagnostic abnormalities in acute inflammatory demyelinating polyneuropathy: a retrospective study of 58 patients. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2014 Sep;     [PubMed PMID: 24529487]
[8] Cornblath DR, Electrophysiology in Guillain-Barré syndrome. Annals of neurology. 1990;     [PubMed PMID: 2194420]
[9] Wali A,Kanwar D,Khan SA,Khan S, Early electrophysiological findings in acute inflammatory demyelinating polyradiculoneuropathy variant of Guillain-Barre syndrome in the Pakistani population - a comparison with global data. Journal of the peripheral nervous system : JPNS. 2017 Dec;     [PubMed PMID: 29091318]
[10] Khan F,Amatya B, Rehabilitation interventions in patients with acute demyelinating inflammatory polyneuropathy: a systematic review. European journal of physical and rehabilitation medicine. 2012 Sep;     [PubMed PMID: 22820829]