Background

• any acute or subacute focal, inflammatory, non-compressive spinal cord myelopathy, often with sensory dysfunction that is limited to a clearly defined rostral border.

• neurological dysfunction occurs in motor, sensory and autonomic nerves and nerve tracts of the spinal cord.

• spinal MRI and lumbar puncture often show evidence of acute inflammation.

• Other known neurologic diseases such as compressive myelopathy, syphilis, malignant neoplasm, or spinal AVM should be excluded before the diagnosis of TM is given.

Clinical

• Symptoms may progress rapidly over minutes to hours in some TM patients, or may progress over days to weeks in others. When the maximal level of deficit is reached, approximately 50% of patients have lost all movements of their legs, virtually all patients have some degree of bladder dysfunction, and 80-94% of patients have numbness, paresthesias or band like dysesthesias.

• Autonomic symptoms consist variably of increased urge to urinate, bowel or bladder incontinence, difficulty or inability to void, a sensation of incomplete evacuation or bowel constipation.

Epidemiology

• TM is a rare disorder with an incidence of between 1-4 new cases per million people per year and. TM

• can affect people of all ages (range six month old to 88 years old) with peak incidences between the ages of 10-19 and 30-39 years of age.

• There is no gender or familial predisposition to TM.

Prognosis

• Approximately 1/3 of patients recover with little to no sequelae following the initial attack, 1/3 are left with moderate degree of permanent disability, and 1/3 have virtually no recovery and are left severely functionally disabled.

• Several clinical features such as rapid progression of symptoms, the presence of back pain and the presence of spinal shock may serve as poor prognostic indicators for ultimate recovery.

• Paraclinical evidence such as absent central conduction on evoked potential testing and the presence of 14-3-3 protein in the CSF during the acute phase also predict poor outcomes.

ETIOLOGIES OF TM

• may be a result of damage to neural tissue by an infectious agent or by the immune system or both.

• Many cases are likely parainfectious, often following a respiratory infection or GI illness.

• In many fewer cases has TM been shown to be caused by direct microbial infection of the CNS. 30-60% of patients with TM report a preceding infection within 3-8 weeks, and serologic evidence for acute infections with rubella, measles, infectious mononucleosis, influenza, enteroviruses, mycoplasma or hepatitis A, B and C has been demonstrated.

• Other pathogens such as herpes viruses (CMV, VZV, HSV1 HSV2, HHV6, EBV), HTLV-1, HIV-1directly infect the spinal cord and can cause the clinical syndrome of TM.

• Borrelia burgdorferi (Lyme neuroborreliosis) and Treptonema pallidum (syphilis) have also been associated with direct CNS infection and TM.

• TM has been associated with systemic autoimmune diseases such as SLE. Several patients were shown to have a focal spinal vasculitis associated with active SLE symptoms, while other patients were shown to have antiphospholipid antibody or the related antibody to beta-2- glycoprotein I. Both antibodies are associated with a pro-thrombotic state, and microvascular thrombosis may underly the clinical syndrome in these patients.

• Finally, patients with transverse myelopathy will often be ultimately diagnosed with multiple sclerosis.

DDX

• spinal cord ischemia; arterial, venous and watershed infarcts have been described in patients initially diagnosed with transverse myelitis.

• Spinal cord infarcts due to arterial occlusion are most common in the anterior spinal artery territory,  causing damage to the corticospinal tract, descending micturition/defecation fiber tracts, and the spinothalamic tract with sparing of posterior column function. In the rostrocaudal axis, most arterial infarcts occur in the T4-T10 region due to the limited collateral blood supply in this watershed area. Venous infarction also may occur with progressive neurologic deficits, often with hemorrhagic transformation reflective of persistent venous hypertension. Further, dural AV fistulas cause a stuttering or intermittently progressive myelopathy usually in men between the ages of 40 and 70. This is a diagnosis that should be considered in any patient with recurrent myelopathy since surgical or endovascular embolization therapy may restore neurologic function in some individuals.

• Any patient suspected of having acute spinal cord dysfunction warrants emergent evaluation.

• Since relatively few patients have the full triad of motor, sensory and autonomic dysfunction at the outset, physicians must have a low threshold for recommending further evaluation.

• Unfortunately, back pain with a radicular quality is a common and non-specific early symptom of many patients with TM.

• However, a patient’s complaints of difficulty urinating or new onset incontinence and a transverse sensory complaint (band like pressure, pain or numbness) should prompt the physician to recommend urgent further evaluation.

• Similarly, bilateral acute progressive leg weakness with any of the above symptoms should prompt rapid evaluation.

• Many patients, presenting with a rapidly progressive paraparesis, are incorrectly diagnosed with Guillain-Barre Syndrome (GBS). However, in contrast to GBS, TM does not present with cranial nerve palsies, and GBS rarely presents with bladder dysfunction and a band like sensory complaint.

• Initial evaluation of a patient with an evolving myelopathy should determine whether a structural cause (e.g. herniated disk, pathologic vertebral fracture, tumor metastasis or spondylolisthesis) can be identified (see acute TM algorithm).

• Ideally an MRI with gadolinium contrast should be obtained within several hours of presentation. If, however, one cannot be obtained in a short time period, CT-myelography or CT of the spine is a reasonable alternative. These latter two studies have the distinct disadvantage of being unable to assess intramedullary pathology, and all patients diagnosed with TM should have an MRI as soon as possible in the acute phase.

• If there is a delay in obtaining any imaging study and a patient clinically has a rapidly evolving myelopathy, then methylprednisolone should be empirically administered as follows: <3 hours from symptom onset- 30 mg/kg bolus over one hour followed by 5.4 mg/kg/hour for 23 additional hours; between 3-8 hours from symptom onset- 30 mg/kg bolus followed by 5.4 mg/kg/hour for an additional 47 hours. If a structural cause is identified for the myelopathy, urgent neurosurgical evaluation is mandatory.

• If no structural cause is identified for the patient with an acutely or subacutely evolving transverse myelopathy, then treatment is highly dependent on the potential cause.

• A lumbar puncture should be performed and CSF should be evaluated for routine studies as well as oligoclonal bands, IgG index, viral PCRs, lyme and mycoplasma antibodies, and VDRL. Though this list of studies is not comprehensive, it does identify potentially treatable causes of acute transverse myelopathy. Additional serologic studies may be warranted depending on the clinical scenario.

• While awaiting the return of serologic and PCR studies, we will often initiate treatment with acyclovir empirically (10 m/kg IV TID for 14-21 days), especially if there is a history of burning, radicular pain or zoster radiculitis preceding the myelitis. If the patient has clinical or radiologic evidence for mycoplasma pneumonia, treatment of the TM should include doxycycline (100 mg PO BID) or azithromycin (500 mg times one, then 250 mg PO qD ). Similarly, in the appropriate clinical setting, one needs to consider adding IV ceftriaxone empirically for the diagnosis of neuroborreliosis (Lyme). Immunosuppressed patients with a history of CMV retinopathy or polyradiculopathy should receive gancyclovir (5 mg/kg IV q12). Consideration of a microbiologic etiology for the TM should not dissuade aggressive use of intravenous corticosteroids.

• The administration of high dose intravenous steroids is often given once the diagnosis of TM is made, and several small studies have suggested that it improves time to independent ambulation and ultimate motor recovery. Many physicians initiate treatment with methylprednisolone 1000mg IV qD for 5 days, and this regimen should be started in most patients as soon as the diagnosis of TM is considered. Weinshenker and colleagues have shown that a subset of steroid-refractory patients with idiopathic inflammatory demyelinating disorders respond to plasmapheresis. Therefore, at our institution, patients with acute TM are given a five-day course of IV solumedrol followed by plasmapheresis at 1.1 plasma volumes QOD for two weeks. It is unclear presently when to initiate plasmapheresis, but we wait for one week following the completion of the steroids to initiate plasmapheresis.

• In TM patients with known or suspected connective tissue disorder such as SLE, investigation should attempt to elicit evidence for a systemic vasculitis, or alternatively, evidence for a pro-thrombotic predisposition on the basis of anti-phospholipid antibodies. Vasculitic etiology may be suspected with lowered complement levels, high ANA titer, hematuria, high ESR or other systemic manifestations of active SLE. Such patients should receive high dose IV corticosteroids and consideration for pulse IV cyclophosphamide (500-1000 mg/m2). Subsequent pulses of cyclophosphamide should be given monthly at a dose designed to give a nadir WBC count of 3,000-4,000/mm3. SLE patients with antiphospholipid antibodies often report previous arterial or venous thrombotic events, fetal loss, or exhibit livedo reticularis. These patients will often require intensive anticoagulation to prevent recurrent TM and potentially as acute therapy.

Excerpted from: “Transverse Myelitis” chapter in Current Therapy in Neurologic Disease, Sixth edition, Author-Douglas Kerr MD/PhD editors, Johnson, R.T, Griffin, J.W., & McArthur, J.C. Mosby Press, 2001