Introduction

Transverse myelitis is an acute or subacute inflammatory disorder of the spinal cord, from diverse causes, resulting in loss or impairment of motor, sensory and autonomic disturbances below the level of the lesion.1 Recently, the term ‘longitudinally extensive transverse myelitis’ has been proposed to refer to myelitis with the involvement of more than three vertebral levels in the spinal cord, as is commonly seen with NMO.2 LM, with extensive contiguous involvement of the spinal cord, is rare and is described in the literature almost exclusively in the context of SLE.3, 4, 5, 6, 7 We describe six cases of isolated monophasic (follow-up 9 months to 4 years) LM, involving the entire length of the spinal cord.

Methods

Case records of patients treated for myelitis at the Vanderbilt Multiple Sclerosis Center were reviewed. Of the 339 patients who had been treated for myelitis since 2005, the vast majority had transverse myelitis secondary to either MS or NMO. These, and patients with another diagnosis, such as systemic inflammatory disorder or neurosarcoidosis, were excluded from review. Six patients who had LM not attributable to other diagnoses were reviewed in detail.

Results

Clinical presentation

All six patients presented with acute or subacute progressive loss of motor, sensory and bladder and bowel functions (Table 1). None of the patients had cognitive or visual problems, or symptoms referable to brainstem dysfunction. None had a history of antecedent infections. None of the patients had features of systemic inflammatory autoimmune diseases. Neurological examinations at the time of maximum deficits are shown in Table 1. Mental function, vision, cranial nerve examinations and ocular funduscopy were normal in all patients.

Table 1 Clinical features of patients with isolated LM
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Imaging and evoked potentials

Magnetic resonance imaging (MRI) of the brain and spinal cord was performed on presentation in all patients and consisted of T1, T2, T2-FLAIR and T1 post-contrast sequences. Brain MRIs were normal in five patients and showed a solitary white matter lesion, possibly ischemic in one (patient 4). Spinal cord MRIs in all patients showed swelling and patchy T2 hyperintense lesions, extending from the cervicomedullary junction to the conus medullaris, with foci of T1 contrast enhancement (Figure 1). In patient 1, there was diffuse thickening of the spinal cord, raising concerns for an infiltrative tumor (Figure 2), but biopsy showed only inflammation. Visual evoked potential studies were available in four patients (1,2,4,6), and in patients 2 and 4, showed unilateral prolongation of P100.

Figure 1
figure 1

Spinal cord magnetic resonance imaging (MRI) in longitudinal myelitis (patient 2). Sagittal T2-weighted images of cervical and upper thoracic (a), thoracic (d) and lumbar (g) demonstrate a contiguous T2 hyperintense lesion extending from C1 to the conus medullaris. Sagittal T1 pre-contrast (b, e and h) and T1 post-contrast (c, f and i ) images of these regions of spinal cord show swelling and foci of contrast enhancement (arrows).

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Figure 2
figure 2

Spinal cord magnetic resonance imaging (MRI) in longitudinal myelitis (patient 1). (a) Sagittal T2-weighted image of thoracic spinal cord demonstrates a contiguous T2 hyperintense lesion extending down to the conus medullaris. (b) Pre-contrast and (c) post-contrast sagittal T1-weighted images of thoracic spinal cord demonstrate diffuse thickening and contrast enhancement of the thoracic spine down to the conus medullaris.

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Laboratory studies

Cerebrospinal fluid studies (Table 2) in all patients reflected a sterile inflammatory response within the central nervous system. Routine bacterial and viral cultures and PCRs (herpes simplex virus types 1 and 2, cytomegalovirus, varicella-zoster virus) were negative. Oligoclonal bands were absent in all patients except patient 5, who also had an elevated IgG index of 2.13. Other laboratory studies are shown in Table 2.

Table 2 Laboratory findings in patients with isolated LM
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Treatment and outcomes

All patients received high-dose intravenous methylprednisolone, 1 g daily for 5–7 days, followed in patients 2, 3, 4 and 6 by plasma exchange (Table 1). Patients 4, 5 and 6 received rituximab at a dose of 375 mg m−2. Patient 4 developed an allergic reaction (skin rash) and received no further doses. Her lower extremity strength improved from BMRC scale 0/5–4/5, and after 5 months, she is ambulatory with the help of a cane. The others received additional doses at 3-month intervals (Table 1). Patient 6 received six doses of rituximab over 18 months, along with mycophenolate mofetil at a dose of 2000 mg daily, followed by mycophenolate mofetil alone. After a further 12 months, he has normal strength in all extremities, but uses a cane for walking because of persistent proprioceptive loss in the lower extremities. Patient 5, who was started on rituximab several months after the onset of her symptoms but whose symptoms were still evolving, has received three doses of rituximab so far. She recovered from being wheelchair-confined to being ambulatory with the help of a cane. In patient 3, rituximab was started after several months during which she received rehabilitation and mycophenolate mofetil 2000 mg daily, when there were no signs of further evolution of symptoms. She made only a minimal motor recovery. She has had a return of sensation in the lower extremities. Patients 1 and 2, who did not receive rituximab, made no appreciable recovery from their maximum disability (Table 1).

MRI of the spinal cord after treatment was available in all patients except patient 4, who was the most recently diagnosed and has not yet had a follow-up scan. There was resolution of swelling and contrast enhancement, with residual areas of T2 hyperintensities, and variable atrophy in all patients. Figure 3 shows serial MRIs of patient 6, at presentation, 8 and 20 months later.

Figure 3
figure 3

Spinal cord MRIs before and after treatment (patient 6). (a–d) The cervical and thoracolumbar spinal cord at presentation; (e–h) 8 months later and (i–l) 20 months later. Initial MRIs show extensive T2 hyperintense signal and swelling of the entire spinal cord (a and c) with extensive contrast enhancement (b and d). In the second set of MRIs, the corresponding sequences show lower T2 abnormality and contrast enhancement, and resolution of the swelling. The third set of MRIs show the absence of contrast enhancement (j and l) and atrophy of spinal cord with patchy T2 hyperintense abnormality (i and k).

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Discussion

The six cases of LM had a varied presentation (Table 1). The features common to all cases included a monophasic course, lack of visual symptoms suggestive of NMO, lack of inflammatory brain lesions and absent laboratory or clinical evidence of systemic inflammatory autoimmune diseases.

Several cases of longitudinal myelitis have been described in the literature, all in the context of SLE except for one case with Sjogren's syndrome.8 Extensive workup in our series could not point to a specific cause for the myelitis. Isolated longitudinal myelitis may therefore represent a new clinical syndrome. NMO, however, cannot be fully excluded, although longitudinally extensive transverse myelitis seen in NMO usually involves three to four segments of the spinal cord, rather than the entire cord.2 Because of the reported efficacy of B-cell depletion therapy in NMO, we decided to treat our patients using rituximab.9, 10, 11 Rituximab use appeared to facilitate recovery. Insurance authorization could not be obtained in patients 1 and 2, and they appeared to have made no appreciable recovery. There was a delay of several months in patient 3, and she too made a minimal recovery. The remaining patients received rituximab when their symptoms were still evolving, and they showed recovery. The response to rituximab may indicate that the inflammation in LM is mediated by a B-lymphocyte-mediated process, similar to that seen in NMO,12 but may also reflect SLE or another process mediated by B cells. NMO also cannot be fully excluded, as the positivity of the NMO antibody is only present in 12.5% of patients with the monophasic variant of NMO.13 Finally, given the short follow-up period in these patients (9 months to 4 years), it is possible that they may experience recurrent episodes of myelitis, or optic neuritis, in the future.