July 2, 2008
To the Editor:
A female, 34 years of age, was admitted to the hospital with a 5-day history of burning pain bilaterally in the legs, urinary retention, and leg weakness. Neurologic examination revealed abolished Achilles reflexes. She had been recovering from influenza, which she acquired ~4 weeks before admission. Four days before admission she noted some tingling in her left pinky finger that spread and traveled up her hand to the mid-forearm along the lateral aspect of the arm. The same day as the finger tingling she noticed some leg weakness that steadily worsened and ascended her legs. The day after the beginning of leg weakness she noticed bilateral burning neuropathic pain beginning in her toes and ascending to the back of her calves at the time of admission. Also, she had a week of urinary urgency, and the night before admission she had three episodes of urinary incontinence. However, at no point did she lose sensation with urination.
Before this episode, she had a history of transverse myelitis (TM) at 10 years of age, which left her with residual left upper extremity weakness, contractures in her left hand and absent temperature and pain sensation in her left leg at and below the L2–L3 distribution. At baseline, she had Wexler scale 3 hyperreflexic reflexes throughout her body based on previous admission notes.
Upon admission, she had flaccid paraparesis (strength 1–2/5 in the feet and lower legs and 3/5 to 4/5 in the gluteals and ileopsoas, Medical Research Council grade) with abolished Achilles reflexes, extensor plantar responses, and reduced sensory deficits bilaterally to the upper thigh, including light touch, vibration, pinprick, positional, and temperature modalities, in a stocking glove distribution. Rectal sphincter tone and sensation was intact. Lumbar puncture revealed a pleocytosis (188/mm3; 48% lymphocytes) and an elevated cerebrospinal fluid (CSF) protein of 83 mg/dL. No oligoclonal bands were detected, but there was an elevated immunoglobulin G (IgG) (17.4 mg/dL), IgG index (0.79), and IgG synthesis rate (34.5 mg/24 hours). Complete microbiological and virological investigations on CSF and blood specimens were negative. Testing for heavy-metal toxicities was negative as well.
Magnetic resonance imaging (MRI) of the whole spinal cord revealed no evidence of transverse myelitis or an inflammatory process. On MRIs of the brain, there were sparse scattered foci of T2 prolongation in the subcortical and deep white matter that was nonspecific. The pattern was not typical for a central demylinating disorder, but could not be excluded. Electrodiagnostic studies of the lower extremities indicated in the distal sites of the lower extremity 25% were absent (left peroneal motor [nerve]), 75% show profound decrease in amplitude (~100 μV) and abnormal morphology; it was difficult to estimate conduction velocity, and there was no obvious dispersion. More proximal recordings had increased, but still small amplitudes (300 μV average), appeared dispersed, and consistent with electromyographic signs of acute denervation. F waves were absent. Sensory action potentials and conduction velocities were absent. In the left arm, the ulnar nerve showed very low amplitude. In the right arm, the median nerve showed normal latency, amplitude, and conduction velocity, but delayed F wave (68 ms).
A diagnosis of acute combined encephalomyelopathy and demyelinating polyradiculoneuritis was made, a combined presentation of elements of Guillain Barre syndrome (GBS) and TM. The patient was treated with five sessions of plasmaphoresis, one every other day for a total of 9 days. Her muscle strength and sensation improved, and her neuropathic pain receded, and was well controlled with venlafaxine 75 mg/day and gabapentin 300 mg TID. Venlafaxine was also used to treat the patient’s depression and anxiety. Her urinary urgency improved as well.
One week after her last plasmaphoresis treatment, the patient could walk 100 feet with a walker and 10 feet without a walker. On examination, arm strength was at baseline, and there was no tingling in the left arm. Internal rotation of the hips, hip and knee flexors, and knee extensors were 5/5 on the right and 4/5 on the left; ankle flexors and extensors and toe dorsiflexors were 4/5 bilaterally. Ankle reflexes were 1 bilaterally. Her neuropathic pain was reduced to only her toes from the midcalf on admission, but still present. She also had full control of her bladder and no episodes of urinary incontinence since her fourth plasmapharesis treatment.
Our patient presented with an acute demyelinating disorder affecting the peripheral nervous system, but also with evidence of an inflammatory response in the central nervous system. The chronology of TM and GBS are similar, over the course of hours to days. In this setting, the polyneuropathy developed after infection with the influenza virus ~4 weeks before, which would be more indicative of GBS. Complicating the case is the patient had TM at 10 years of age, and while reoccurrence is rare, it has been reported. The EMG and spinal MRI results were consistent with a diagnosis of a demyelinating polyradiculoneuropathy such as GBS, and no evidence of TM. However, the CSF results showed increased protein, but also increased number of WBCs, indicative of GBS but potentially a central demyelinating inflammatory process as well.
GBS and TM are both uncommon neurologic disorders. GBS occurs world-wide with an incidence of 1–2 per 100,000/year. All age groups are affected, with peaks in young adults and the elderly.1 For TM approximate incidence is between 1–5 cases per million population annually.2 Most cases of TM are idiopathic, a central nervous system process and presumably result from an autoimmune process; up to half of these patients have a preceding infection.3,4 For GBS, the recurrence rate is 10%, while for TM it is rare. In the majority of cases, GBS results in a partial recovery in 1–2 months, with a full recovery taking anywhere from 6 months to a year. However, for TM most will have some residual deficits.
Early symptoms for both disorders include extremity weakness or sensory deficits, numbness or tingling; more often in the legs than the arms. The weakness and numbness ascends, to the proximal leg muscles, and proximal arm muscles. TM typically develops rapidly over several hours; ~37% of patients worsen maximally within 24 hours, while GBS usually progresses over a period of ~2 weeks.5 Also, one of the most common symptoms in addition to muscle weakness is pain, up to 88% in pediatric cases compared to 40% to 50% in GBS.6 At 4 weeks from the initial symptoms, 90% of GBS patients have reached the nadir of the disease. However, both disorders can progress quickly, and compromise respiratory function, resulting in respiratory failure, up to 30% in GBS. For this reason, it is important to have intensive care unit support, to be able to maintain mechanical ventilation. Diagnostic confirmation for TM is an MRI of the spine, while for GBS it is CSF analysis and nerve conduction studies.
There are a few treatment recommendations for each disorder, but a common treatment is plasmapharesis. Treatment typically consists of one plasma exchange daily for 5–7 days. Patients should begin to improve with treatment, more rapidly with milder disease, longer with more severe symptoms such as respiratory failure.7 Other treatments include high dose steroids for TM, and intravenous IgG antibodies for GBS.
Recovery is variable based on whether the disorder is TM or GBS. Most patients with TM have at least a partial recovery, which usually begins within 1–3 months.6 Some degree of persistent disability is common, occurring in ~40%.6 Significant recovery is unlikely if there is no improvement by 3 months. A very rapid onset with complete paraplegia and spinal shock have been associated with poorer outcomes.4,6,8 TM is generally a monophasic illness. However, a small percentage of patients may suffer a recurrence.9,10
Documented overlap of acquired acute central and peripheral system demyelination is very rare. Cases of combined demyelinating disorders include both adult and pediatric cases.11-13
Amit and colleagues12 coined the entity of acute severe combined demyelination for cases in which central and peripheral nervous system pathology equally contributed to the overall clinical picture. An acute or subacute combined central and peripheral myelinopathy has been rarely reported in adults with successful treatment with plasmaphoresis and IV IgG or IV corticosteroids being documented.11,14,15
We have presented a case of a young female fulfilling clinical, electrophysiological, and neuroradiological criteria for both TM and GBS in the context of an acute influenza viremia. We believe that this case demonstrates the importance of considering influenza infection in the adult as predisposing to severe neurological sequelae and also illustrates the close overlap that may exist between TM and GBS, both in etiology and clinical presentation.
Adam Tripp, MD, PhD
1. Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barre syndrome. Ann Neurol. 1990;27(suppl):S21-S24.
2. Jeffery DR, Mandler RN, Davis LE. Transverse myelitis. Retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events. Arch Neurol. 1993;50:532-535.
3. Kaplin AI, Krishnan C, Deshpande DM, et al. Diagnosis and management of acute myelopathies. Neurologist. 2005;11:2-18.
4. de Seze J, Lanctin C, Lebrun C, et al. Idiopathic acute transverse myelitis: application of the recent diagnostic criteria. Neurology. 2005;65:1950-1953.
5. Knebusch M, Strassburg HM, Reiners K. Acute transverse myelitis in childhood: nine cases and review of the literature. Dev Med Child Neurol. 1998;40:631-639.
6. Defresne P, Hollenberg H, Husson B, et al. Acute transverse myelitis in children: clinical course and prognostic factors. J Child Neurol. 2003;18:401-406.
7. Raphael JC, Chevret S, Hughes RA, et al. Plasma exchange for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2002(2):CD001798.
8. Bruna J, Martinez-Yelamos S, Martinez-Yelamos A, et al. Idiopathic acute transverse myelitis: a clinical study and prognostic markers in 45 cases. Mult Scler. 2006;12:169-173.
9. Seifert T, Enzinger C, Ropele S, et al. Relapsing acute transverse myelitis: a specific entity. Eur J Neurol. 2005;12:681-684.
10. Kim KK. Idiopathic recurrent transverse myelitis. Arch Neurol. 2003;60(9):1290-1294.
11. Schulze Beerhorst K, Klein B, Oelerich M, et al. The rare coincidence of Guillain-Barre syndrome and myelitis. Nervenarzt. 2007;78:445-450.
12. Amit R, Glick B, Itzchak Y, et al. Acute severe combined demyelination. Childs Nerv Syst. 1992;8:354-356.
13. Ropper AH. Unusual clinical variants and signs in Guillain-Barre syndrome. Arch Neurol. 1986;43:1150-1152.
14. Katchanov J, Lunemann JD, Masuhr F, et al. Acute combined central and peripheral inflammatory demyelination. J Neurol Neurosurg Psychiatry. 2004;75(12):1784-1786.
15. Bajaj NP, Rose P, Clifford-Jones R, et al. Acute transverse myelitis and Guillain-Barre overlap syndrome with serological evidence for mumps viraemia. Acta Neurol Scand. 2001;104:239-242.