An Atypical Presentation of Antibody Negative Axonal Guillain Barré Syndrome

doi:10.21203/rs.3.rs-1953445/v1

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Case Report

An Atypical Presentation of Antibody Negative Axonal Guillain Barré Syndrome

https://doi.org/10.21203/rs.3.rs-1953445/v1

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Guillain Barré Syndrome (GBS) is an antibody mediated peripheral nerve disorder that commonly presents after infection, usually campylobacter jejuni.8 Guillain Barré can be broken down into two different forms: axonal and demyelinating. The demyelinating form is termed acute inflammatory demyelinating polyneuropathy. The axonal form can further be categorized into acute motor neuropathy and acute motor and sensory neuropathy. In typical cases of GBS, patients present with acute, progressive, symmetrical, ascending flaccid paralysis reaching peak severity within 5-9 days of symptom onset. All forms of GBS are diagnosed clinically. Patients who present with the progression of symptoms as mentioned above are thought to have GBS unless a better diagnosis is available.7 However, diagnosing GBS can become difficult when patients present with atypical symptoms. The case discussed in this article focuses on the complexity of diagnosing and treating patients who present with atypical GBS symptoms.

Guillain Barré Syndrome is an antibody mediated peripheral nerve disorder that commonly presents after infection, usually campylobacter jejuni.⁸ GBS can be broken down into two different forms: axonal and demyelinating. The demyelinating form is termed acute inflammatory demyelinating polyneuropathy. The axonal form can further be categorized into acute motor neuropathy and acute motor and sensory neuropathy. The axonal and demyelinating forms can be differentiated via electrodiagnostic methods that measure the electrical activity of a muscle in response to stimulation of the corresponding nerve, termed electromyogram.⁹

In typical cases of GBS, patients present with acute, progressive, symmetrical, ascending flaccid paralysis reaching peak severity within 5–9 days of symptom onset. Patients with axonal GBS show a more rapid progression of these symptoms reaching an earlier peak severity than others.⁸ As the syndrome progresses, deep tendon reflexes including the Achilles, patellar, biceps, brachioradialis, and triceps become absent. The patient’s symptoms often progressively worsen for the first 2 weeks followed by a plateau 4 weeks after onset and then recovery of symptoms begins.⁶

All forms of GBS are diagnosed clinically. Patients who present with the progression of symptoms as mentioned above are thought to have GBS unless a better diagnosis is available.⁷ However, there are laboratory tests that can be helpful in confirming the clinical diagnosis of GBS. One test is the EMG as discussed previously. Second is obtaining a lumbar puncture to test the patient’s cerebral spinal fluid paying specific attention to the protein and anti-ganglioside antibody levels as these would typically be increased in a patient with GBS.⁸ It can also be confirmed with results of a brain MRI with gadolinium displaying high-signal intensity in various areas of the brain or spinal cord.⁸

A right-handed female in her early 60s with a history of hypothyroidism, R eye glaucoma, osteopenia, ventricular tachycardia s/p ablation in 2019, and bilateral breast cysts s/p bilateral biopsies presented to the ED for progressive weakness of all extremities and associated generalized pain.

The patient had recently been admitted to the ED 5 days prior for the weakness which at the time, was limited to the proximal RUE. During this visit, a brain and cervical MRI was obtained which showed multilevel degenerative changes but nothing that would explain the patient’s RUE weakness. A lumbar puncture was also performed showing significant findings of RBC 2, TNC 3, 100% lymphocyte dominance, protein 39, and glucose 68. The patient also received an EMG which showed widespread myopathic process affecting mostly the proximal muscles. The patient was diagnosed with unspecified myopathy and discharged with an appointment for a muscle biopsy with neurosurgery outpatient.

However, the patient returned to the ED just 5 days later due to the progression of her symptoms. The patient’s extremity weakness started 10 days prior to her most recent admission after returning from a trip to Dallas, TX. The progression of weakness was as follows; proximal RUE, then proximal LLE, then proximal LUE, followed lastly by the proximal RLE. She denied recent fever, illness or injury, SOB, CP, extremity numbness or tingling, headache, dizziness, and vision or hearing changes. She did, however, endorse experiencing trouble with climbing stairs and standing from a seated position and generalized muscle pain.

Upon physical examination the patient was noted to have significant weakness of all extremities, only able to move them against gravity. The patient also had diminished deep tendon reflexes (1/4) bilaterally except at the Achilles tendon which was absent bilaterally.

Initially the patient’s diagnosis was unclear due to her atypical presentation of symptoms. As a result, the patient received a series of tests to rule out potential causes including regular lab tests in addition to a HIV and hepatitis panel, autoimmune testing of both the serum and CSF, West Nile antibody and GM1 and GM2 test of the CSF, CJD (14-3-3 protein) testing, syphilis screening, MG screening, CT chest, abdomen and pelvis, and CSF testing for viral, bacterial, and fungal infections. All these tests were nonsignificant except the autoimmune CSF studies which displayed elevated levels of IgG (4.4), CNS IgG synthesis (15), and IgG index (1.78), as seen in inflammatory disorders. Additionally, the patient also obtained an MRI lumbar/thoracic for back pain which showed mild enhancement of the conus medullaris and cauda equina nerve roots.

Treatment with plasmapheresis was discussed and initiated due to a high likelihood of an inflammatory process as the cause of the patient's symptoms. However, the patient’s symptoms continued to progress and alternative treatment with IVIG was discussed. The patient was hesitant to start IVIG as she was displeased with having two working diagnoses (myopathy vs GBS) at the time. The patient received a muscle biopsy at this time which indicated a diagnosis of an acute motor axonal neuropathy or axonal variant of GBS. The patient then agreed to initiate IVIG but developed a DVT in her LLE shortly after. The patient was treated appropriately and completed her IVIG regimen which appeared to halt the progression of her symptoms. She was then cleared from neurology for discharge to an acute rehab facility.

However, the patient developed a significant hematoma at the side of the muscle biopsy and was held in the hospital until this could be addressed. The patient continued to remain stable during this time and was then later discharged to the acute rehab facility for PT after her hematoma resolved.

While the axonal GBS variant is less common in North America (3–20% of all GBS cases vs 65–76% in Northern China)⁸, it is important to keep in mind when developing a list of differential diagnoses in patients with myopathic symptoms with no sensory deficits. Differentiating between the different forms of GBS and diagnosing GBS can be a difficult task when the patient presents with atypical symptoms as the case above. Occasionally, serial EMG exams may be used to distinguish between the different forms of GBS.⁹ It can be helpful to obtain CSF GM1 and GM2 or CSF inflammatory markers such as the IgG index as axonal GBS is an inflammatory process and commonly presents with detectable levels of GM1 and GM2 in the CSF. A lumbar/thoracic MRI with/without contrast can also be obtained as cauda equina nerve root enhancement can be present in up to 95% of patients with typical cases of GBS.² However, GBS is a clinical diagnosis and therefore cannot be diagnosed based strictly on these results and instead requires a detailed history from the patient.³

Treatment of GBS is not for rapid or complete resolution of symptoms but rather to decrease progression of symptoms and to decrease symptom duration and severity.⁶ Treatment includes IVIG or plasmapheresis in addition to supportive therapy.⁸ Commonly plasmapheresis is the preferred treatment as it appears to have better outcomes for length of recovery, relapse rates, and adverse effects.¹ However, for those who do not have significant improvement with plasmapheresis, IVIG can be utilized. Patients are also advised to engage in physical therapy and occupational therapy as many patients experience significant muscular atrophy and deconditioning.

The recovery phase of GBS commonly lasts anywhere between 6–12 months with few patients making a full recovery, some patients with some long-term deficits, and a few patients with severe long-term deficits.⁶ The prognosis of individuals at 1 month, 3 months, and 6 months with the axonal variant of GBS is significantly poorer than individuals with a different variant of GBS.⁸ These patients experienced long-term poor conditioning and loss of strength, dysautonomia, infection, DVT, PE, hypercalcemia, and more. The recovery time and permanence of symptoms in axonal GBS varies on the severity of the injury which may be assessed by an EMG of the involved muscle. Those with injury confined to distal motor axons recover faster than those with injury to the spinal roots or proximal nerve trunks. Recovery is also dependent on whether these patients are antibody positive or negative. Those with positive antibody titers of GM1 or GM2 in the CSF have better outcomes regarding the degree of recovery and duration of the recovery period.⁸

CT: Computed tomography
CP: Chest pain
CJD: Creutzfeldt-Jakob disease
CNS: Central nervous system
CSF: Cerebral spinal fluid
DVT: Deep vein thrombosis
ED: Emergency department
EMG: Electromyogram
IVIG: Intravenous immunoglobulins
GBS: Guillain Barré Syndrome
L: Left
LLE: Left lower extremity
LUE: Left upper extremity
MG: Myasthenia gravis
MRI: Magnetic resonance imaging
PE: Pulmonary embolism
PT: Physical therapy
R: Right
RBC: Red blood cells
RLE: Right lower extremity
RUE: Right upper extremity
S/p: Status post
SOB: Shortness of breath
TNC: Total nucleated cell count

Ethical Approval and Consent to participate

Approval was obtained from the facility at which the patient was seen; Cleveland Clinic – Florida from Dr. Ross, the internal medicine chair and student coordinator. Consent was obtained from the patient to write a case report and share details of the case while maintaining privacy for patient identifying factors.

Consent for publication

I declare that this case report is an original report of my research, has been written by me and has not been submitted for any previous publication. The work is almost entirely my own work; the collaborative contributions have been indicated clearly and acknowledged. I consent to allow Journal of Neuroinflammation via Springer Nature to publish my work publicly. Consent was also obtained from the patient allowing for public publication of the case report.

Availability of supporting data

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

Competing interests

The authors declare that they have no competing interests.
Funding

Not applicable
Authors' contributions

Full manuscript and additional documents were written by JG. DR reviewed and edited the manuscript.

Acknowledgements

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No competing interests reported.

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An Atypical Presentation of Antibody Negative Axonal Guillain Barré Syndrome

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