We had only one response to this most recent edition of Case of the Month, and Dr. Birnbaum hit the nail right on the head.
Check here for the complete vignette.
The patient is a 28-year-old man with a history of systemic lupus erythematous with numerous complications, and recent medication non-compliance who presented to the ED with non-traumatic back pain refractory to over the counter medications, and during his ED course, developed rapidly ascending paralysis with concurrent urinary retention. His exam was notable for absent sensory, motor function, and reflexes below his xiphoid process; imaging studies indicated an inflammatory or demyelinating process within his spinal cord.
What is your differential diagnosis for this patient?
The patient’s clinical presentation is consistent with neuromuscular weakness, which is either due to pathology affecting the upper motor neuron, lower motor neuron, neuro-muscular junction, or the muscles themselves. His symptoms are not related to frequency of muscle use, eliminating neuromuscular junction disorders such as myasthenia gravis from the differential diagnosis. The presence of sensory symptoms eliminates pure a muscular disorder from the differential. Thus, his pathology can be attributed to dysfunction with his lower motor neurons and/or his upper motor neurons. The sensory and motor deficits, the lack of reflexes, and autonomic dysfunction generate a broad differential, including an inflammatory polyneuropathy like Guillain-Barre syndrome (GBS), transverse myelitis, multiple sclerosis, malignancy, cord compression, or infection [Ganti, 2016]
The constellation of symptoms, ascending paralysis with numbness, is most consistent with classical Guillain-Barre syndrome (as opposed to the Miller-Fisher variant which progresses in a proximal to distal direction) [Ganti, 2016]. By contrast, transverse myelitis usually causes hyperreflexia and a positive Babinski sign along with neurologic symptoms depending on the involved spinal cord level, though atypical cases may be characterized by areflexia, rapid ascending paralysis, and sensory deficits, with symptom progression occurring between 4 hours and 21 days [Frohman, 2010]. This confusion between GBS and transverse myelitis has implications for therapy (more on this later).
What, if any, further tests would you perform on this patient?
MRI is the most important immediate diagnostic test to order as it can evaluate for cord compression and help with determining disposition. The lack of cord compression on MRI eliminates any indication for neurosurgical intervention, and points towards a demyelinating (like GBS), inflammatory (like an autoimmune disorder like MS or transverse myelitis), or less likely, malignancy.
A close second is measurement of the pulmonary function tests, including his negative inspiratory force (NIF) and forced vital capacity (FVC) because they can indicate the severity of the patient’s presentation, and point you towards his or her ultimate disposition. The general rule is a NIF (which measures the maximum negative pressure the patient can generate when inhaling) greater than -30 cm H20 (e.g. a NIF of -15 cm H2O) or a FVC (which measures the largest volume that a patient can exhale) less than 20 mL/kg correlate with an increased risk of respiratory failure [Lawn, 2011].
That said, these parameters should be serially measured, and used in conjunction with the patient’s overall presentation, including work of breathing, vital signs, and overall clinical picture [Ibid; Farkas, 2015]. In short: if the clinical gestalt gives you any concern for impending respiratory failure, then you should strongly consider intubating the patient and consulting the ICU.
While a lumbar puncture would help with diagnostic differentiation between GBS and other inflammatory myelopathies, it will not determine this patient’s disposition, and could be performed after patient disposition. Though the classic USMLE Step 1 buzzword for Guillain-Barre is “albuminocytologic dissociation,” or elevated protein without elevated cell count, this may not be the case during the first week of the illness, let alone the first few hours like with our patient. Unfortunately, transverse myelitis can have similar LP findings of elevated protein and immunoglobulins [Ganti, 2016].
How would you manage this patient?
The first step is the same as with every patient: assess the ABCs! If there is any concern about respiratory compromise, then consider intubating the patient and mechanical ventilation. If the clinical gestalt is suggestive of neurogenic shock, then pursue the appropriate supportive care with vasopressors.
In general, non-invasive positive pressure ventilation should be avoided in patients with concern for or impending neurogenic respiratory failure, as patients who have decompensated to the point where their diaphragms are too weak to expand the lungs will likely be afflicted for days to weeks. Additionally, the possibility of concomitant neurogenic autonomic dysfunction will make that crash intubation, when the patient has failed NIPPV, much more dicey [Rubinstein, 2016].
Treatment of the underlying primary process depends on what you think the primary process is. If the clinical presentation is more suggestive of Guillain Barre syndrome (based on the symptomatology described above, the classic LP findings of albuminocytologic dissociation), then the gold standard treatments are intravenous immunoglobulin (IVIG), and plasmapheresis, as demonstrated by two recent Cochrane reviews, with similar efficacy [Chevret, 2017; Hughes 2014]. A separate Cochrane review demonstrated that corticosteroid monotherapy did not demonstrate any improvement with the rate of recovery [Hughes, 2016].
For transverse myelitis, the primary goal is to halt and reverse the acute inflammation. The first line therapy is high dose corticosteroids, either oral or intravenous methylprednisolone, oral prednisone, or oral dexamethasone. Plasmapheresis can be considered for those cases refractory to corticosteroids [Frohman, 2010].
What is the ultimate disposition for this patient?
Again, the key decision-making tool is the patient’s performance on pulmonary function tests. If there is any concern for impending respiratory compromise, then the patient should go straight to the ICU for close monitoring and intervention.
Back to our patient…
Based on the rapid progression of his symptoms, a NIF was measured and the ICU was consulted. Though he was able to generate a NIF of -50, he was accepted to the ICU for close monitoring, where he consistently demonstrated NIFs of -50 or greater and thus never required intubation. Subsequent to his admission, an LP was performed, with a protein of 795 mg/dL and 1160 WBCs. He received stress dose steroids, and received broad spectrum antimicrobials based on his initial LP results, though these were discontinued when the cultures were negative. His labs were notable for significantly elevated anti-NMO titers, and on that basis he was diagnosed with NMO transverse myelitis in his C6-L1 spinal cord. He experienced no improvement with corticosteroids, and underwent several days of plasmapheresis with gradual regaining of sensation in his T4-L1 dermatomes, though he never regained urinary or fecal continence. He was eventually discharged to a subacute rehab facility, with mild improvement noted in his last follow-up appointment with Neurology about 1 month ago.
Stay tuned for our next edition of Case of the Month!
Ganti, Latha, and Vaibhav Rastogi. “Acute Generalized Weakness.” Emergency Medicine Clinics of North America, Nov. 2017, pp. 233–249
Frohman, Elliot M., and Dean M. Wingerchuk. “Transverse Myelitis.” New England Journal of Medicine, vol. 363, no. 6, May 2010, pp. 564–572.
Farkas, Josh. “Five pearls for the dyspneic patient with Guillain-Barre Syndrome or Myasthenia Gravis.” EMCrit Project, 3 June 2017, emcrit.org/pulmcrit/five-pearls-for-the-dyspneic-patient-with-guillain-barre-syndrome-or-myasthenia-gravis
Hughes RAC, Brassington R, Gunn A, van Doorn PA. Corticosteroids for Guillain-Barré syndrome | Cochrane, www.cochrane.org/CD001446/NEUROMUSC_corticosteroids-guillain-barre-syndrome
Chevret S, Hughes RAC, Annane D. Plasma exchange for Guillain-Barré syndrome | Cochrane, www.cochrane.org/CD001798/NEUROMUSC_plasma-exchange-guillain-barre-syndrome.
Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome | Cochrane, www.cochrane.org/CD002063/NEUROMUSC_intravenous-immunoglobulin-guillain-barre-syndrome.
Lawn ND, Fletcher DD, Henderson RD, Wolter TD, Wijdicks EF. Anticipating mechanical ventilation in Guillain-Barre syndrome. Archives of Neurology. June 2001, 58(6) 893-898