Non-compressive myelopathy : clinical and radiological study.
Fifty seven patients (42 males and 15 females) with non-compressive myelopathy were studied from 1997 to 1999. Acute transverse myelitis (ATM) was the commonest (31) followed by Vit B12 deficiency myelopathy (8), primary progressive multiple sclerosis (5), hereditary spastic paraplegia (3), tropical spastic paraplegia (2), subacute necrotising myelitis (1), radiation myelitis (1), syphilitic myelitis (1) and herpes zoster myelitis (1). 4 cases remained unclassified. In the ATM group, mean age was 30.35 years, antecedent event was observed in 41.9% case, 25 cases had symmetrical involvement and most of the cases had severe deficit at onset. CSF study carried out in 23 patients of ATM revealed rise in proteins (mean 147.95mg%, range 20-1200 mg/dL) and pleocytosis (mean 20.78/cumm, range 0-200 mm3). Oligoclonal band (OCB) was present in 28% of cases of ATM. The most common abnormality detected was a multisegment hyperintense lesion on T2W images, that occupied the central area on cross section. In 6 patients hyperintense signal was eccentric in location. MRI was normal in 4 cases of ATM. Thus ATM is the leading cause of non-compressive myelopathy. Clinical features combined with MRI findings are helpful in defining the cause of ATM.
Non-compressive myelopathy encompasses a large range of disease entities ranging from demyelination, infection, nutritional, toxic, heredo-familial to degenerative conditions. The disease spectrum is somewhat different in India as compared to the western countries, where infections and nutritional causes are less common and demyelinating and familial causes are the leading causes. Various studies on non-compressive myelopathy from India have been in the pre magnetic resonance imaging (MRI) era.,,, With the advent of MRI which is a very sensitive modality for the intramedullary spinal lesions it has become pertinent to have a relook at the profile of non-compressive myelopathies in India. Acute transverse myelitis (ATM), is an acute or sub-acute spinal cord dysfunction characterized by paraplegia, horizontal level of sensory impairment and sphincteric disturbances in which secondary causes like compression, infections, arteriovenous malformation, trauma and malignant infiltration have been excluded.
This disease has particularly invoked great interest amongst neurologists as it strikes apparently healthy individuals in the prime of their lives, who are left with variable degree of sequelae. There are a number of studies covering various aspects of this illness including prognostic factors and differentiation of ATM from the first attack of myelopathic form of multiple sclerosis.,,,,, In this paper we want to present our experience with various non-compressive myelopathies with particular reference to ATM encountered during the last two years.
57 cases of non-compressive myelopathy admitted in the Neurology ward of Postgraduate Institute of Medical Education and Research, Chandigarh or attending Neurology OPD during 1997-1999 were included in the study. They were examined clinically and followed up by laboratory investigations and neuroimaging studies. Region of interest was determined after clinical examination. MRI study of the spinal cord was done in all the 31 cases of ATM and in 22 out of 26 rest of the cases. Details of onset of illness, antecedent events and grade of power (Medical Research Council) at admission and discharge, symmetry/asymmetry of symptoms, type of treatment given and complications were particularly recorded. CSF was done in 24 out of 31 cases of ATM. Oligoclonal band (OCB) was tested in 14 cases of ATM and 5 cases of primary progressive multiple sclerosis (PPMS). Estimation of rheumatoid factor, ANF and VDRL was done wherever suspected. Vitamin-B12 levels were done in 6 patients suspected of B12 deficiency myelopathy. Upper gastrointestinal endoscopy was done in 3 cases of B12 deficiency.
Criterion for diagnosis of acute transverse myelitis modified from Berman et al were as follows : (1) acutely or subacutely developing motor, sensory and sphincteric disturbance, (2) sensory level, (3) no clinical or laboratory evidence of spinal cord compression, (4) absence of other known neurological illness and (5) lack of progression over 4 weeks.
Out of 57 patients included in this study there were 42 males and 15 females. Mean age at presentation was 34.45 (range 14-82) years. The mean age in the ATM group was 30.35 (range 14-65) years. The patients were subdivided into groups based on their clinical symptomatology as shown in [Table I].
Out of 31 cases of ATM, antecedent event was observed in 13 cases (41.9%). Febrile illness with or without upper respiratory illness was the most common, being present in 10 cases; whereas chickenpox, tetanus toxoid injection and semple vaccination for rabies was present in one case each. Antecedent events observed in other myelopathies were radiation, herpes zoster and rhinoseptoplasty.
Majority of myelopathies were symmetrical 46 (81 %). Out of the 11 cases in which myelopathy was asymmetrical, 6 cases were of ATM, 4 cases of progressive MS and 1 of zoster myelitis. Two patients had Brown - Sequard like manifestation, out of which one case was of ATM and the other was of zoster myelitis. All types of atypical presentations associated with ATM were seen including Brown-Sequard involvement of only posterior columns and a presentation mimicking anterior spinal artery involvement. The distribution of the various tracts involved was as shown in [Table II].
Most of the cases of ATM were severely dirabled with the power in lower limbs at presentation being grade 0-1 in 14 cases, grade 2-3 in 11 cases and grade 4 or more in 6 cases. Two cases of ATM had respiratory involvement requiring ventilatory support. Out of 23 patients of ATM admitted, 15 had shown improvement at the time of discharge.
One of the patients on ventilator died due to concurrent illnesses. Two of the patients had reported recurrence of symptoms on follow up and both of them had asymmetrical myelitis. Out of 23 patients of ATM who were admitted, 11 patients received intravenous methylprednisolone, 1 gm daily for 3 days followed by oral steroids, 5 patients received oral steroids while no treatment was offered in 7 cases. Mean improvement at discharge was 1.36 grade (MRC) with i/v methylprednisolone followed by tapering steroids, 1.80 grade (MRC) with oral steroids and 1.00 grade if no treatment was used.
In the B12 deficiency group nerve conduction study was suggestive of neuropathy in 5 out of 7 cases. In 6 patients serum vit B12 levels were found to be low. The remaining two cases had hypersegmented polymorphs and macrocytosis on the peripheral smear. In addition antiparietal cell antibodies and atrophic gastritis was present on gastric fundal biopsy.
CSF was studied in 23 patients out of 31 cases of ATM. CSF analysis revealed presence of WBCs with a mean of 20.78 (range 0-200)/mm3. Lymphocyte was the predominant cell type except in one, where neutrophils were present. Mean protein level was 147.95 (range 20-1200) mg/dl whereas mean sugar level was 65.65 (range 22-103) mg/dl. OCB was present in 4 out of 14 patients (28 %) in the ATM group. In the PPMS group, OCB was present in one case and increased gamma globulins were present in two cases.
MRI was done in all cases of ATM. It was normal in 4 cases. The abnormality involved dorsal spine in 10 cases (32 %), cervical spine in 8 cases (26 %), cervico-dorsal in 7 cases (22 %), lumbosacral spine in 1 case (3 %) and involvement of entire cord was present in 1 case (3 %). In three patients there was streak like hyperintensity on T2W images whereas myelomalacia was seen in one patient in whom MRI was done 9 months after the episode. In 15 patients hyperintinsity on T2W images involved multiple segments, was central and occupied more than 2/3rd of cross-section [Figure. 1A] and [Figure. 1b]. 7 of these also showed cord swelling, there was evidence of haemorrhage as inferred from hyperintensity on both T1 and T2 weighted images in two cases of ATM. Spinal angiogram done in one patient was found to be normal. The hyperintense lesion was central, multisegmental and less than 2/3rd in two patients. However, in one patient MRI was done one month after onset of disease. In 6 patients hyperintense lesion was eccentric, less than half of cross section and multisegment, excepting for one case in which it extended over 2 segments [Figure. 2] and [Figure. 3]. In patients with asymmetrical clinical presentation, hyperintense signal was eccentric in 3 patients, central in 2 and myelomalacia was present in one case.
In the present study, acute transverse myelitis formed the major bulk of non-compressive myelopathies comprising 54.38% of all cases. Vit. B12 deficiency myelopathy was the next common cause. Rest of the conditions producing myelopathies formed a small percentage and included 5 cases of primary progressive MS, 3 cases of hereditary spastic paraplegia, 2 cases of tropical spastic paraplegia, 1 case of syphilitic myelitis, 1 case of radiation myelitis, 1 case of zoster myelitis, 1 case of subacute necrotising myelitis and 4 were grouped as unclassified.
Syphilitic myelitis, now a days, is becoming a rare entity because of widespread use of antibiotics. We were, however, able to pick up one case because of routine testing for VDRL in the CSF of all cases of ATM. 3 cases were classified in TSP on the basis of their clinical presentation. In a previous study from PGIMER, the authors did not find HTLV-1 positivity in their patients clinically diagnosed as tropical spastic paraplegia, except in one patient. Recent studies from Africa, however, have shown a very high incidence of HTLV-1 positivity in a group of patients with unexplained myelopathy.
Primary progressive multiple sclerosis is a clinical conundrum. We diagnosed 5 cases on the basis of clinical examination, history and course of disease. However, OCB positivity was found in only 1 case. Gama globulins were raised in CSF in 2 patients. Dissemination of lesions was not detected as cranial MRI was not done. OCB positivity is known to be low in Indian patients with multiple sclerosis. Weinshenker described 4 patients with progressive demyelinating myelopathy with symptoms spanning 6-25 yrs with no clinical evidence of dissemination. Radiological evidence was present in 2 cases only, and in 1 case, it appeared later in the course of illness. 3 out of 4 had OCB positivity. At least some of these cases are known to remain localized.
Some of the interesting MRI findings were noted in other cases as well including hyperintense signal on T2W images in cases of radiation myelopathy and syphilitic myelitis. In a MRI study of radiation myelopathy, Wang et al found low intensity signal over a long segment of the cord on T1W images and high signal intensity on T2W images 1-4 months after the onset of symptoms. Focal contrast enhancement and oedema were also seen in their cases. Subacute necrotising myelopathy is distinguished from ATM by its prolonged course. In one patient the course was suggestive of subacute necrotising myelitis. The MR image resembled intramedullary tumour. However, rim like enhancement and clinical as well as radiological stability after 6 months helped to diagnose this case. Two patients with B12 deficiency myelopathy had shown hyperintense lesions on T2 in axial cuts involving posterior and lateral columns [Figure. 4]. Myelopathies associated with toxin intake, portasystemic encephalopathy and subacute myeloptic neuropathy (SMON) though observed previously were not seen during this period. Myelopathies associated with MND were also not included in this study.
ATM is a monophasic illness and represents a localized form of post infectious encephalomyelitis. Amongst the 31 cases of ATM, 23 were males and 8 females. In the previous studies too, there has been male predominance.,, The mean age was 30.35 (range 14-65) years which is, consistent with previous studies (20-45 years). Antecedent event in the form of febrile illness was seen 41.9% of cases, which is also consistent with findings in previous studies.,,,, ATM following vaccination has been reported but was not documented by us.,
One of the important questions to be addressed, while confronted with a case of ATM, is to differentiate between a post-infectious from an initial presentation of a case of MS as there are different prognostic and possibly treatment ramifications. Brain MRI and CSF- OCB have the highest negative predictive value for subsequent development of MS. The clinical features which possibly help in differentiating ATM (post infectious) and myelopathic MS are symmetrical, rapidly evolving symptoms, back pain, ascending myelitis and a more severe deficit favouring the former.,,, High incidence of ATM as presenting features of MS is only seen in patients with acute partial spinal cord syndrome, where all components are not involved. Scott delineated clinical features that can help to distinguish acute myelopathic multiple sclerosis (MMS) from ATM. In general, all ATM patients have symmetrical features as compared to myelopathic MS, which have asymmetrical motor and sensory symptoms. In our study, out of 31 cases of ATM, 6 had asymmetrical signs and symptoms. 2 cases out of them have already reported with recurrence of symptoms strengthening the view that asymmetrical ATM are more likely to progress to MS.
There are reports showing beneficial effects of steroids in ATM,, although in the series by Saleh et al no benefit was found with steroids. Our patients at the time of discharge, faired better, if they were given steroids. It is difficult to draw any definite conclusion; therefore, a long term study evaluating affect of oral steroids vs I/V methyl prednisolone along with other clinical and electrophysiological variables is being planned. Other prognostic variables which determine the outcome of ATM are severity of deficit, EMG of the muscles showing denervation pattern and spinal somato sensory evoked potentials. Abnormal neuroimaging was found to be another bad prognostic factor. Altrocchi as early as in 1963 reported that approximately 1/3rd of cases had good recovery, 1/3rd had fair and 1/3rd had little or no recovery. Jain et al in a study conducted in early eighties found age above 40 years, interval between onset of first symptom to greatest neurological deficit of 24 hrs or less, spinal shock and absence of any change in the cerebrospinal fluid to be associated with poor prognosis. In their series, poor prognosis was present in 22.2% cases and death occurred in 5.5% cases. In other series good out come was noted in 48-58% cases., Myelopathic MS has a much better prognosis in the short term. Another entity noted is recurrent myelitis which according to some possibly represents a distinct form of MS.,
In previous studies no OCB's were seen in the ATM group whereas there was high incidence in the myelopathic form of M.S.,, In our series OCB was present in 4 out of 14 cases (28%), out of which only 2 had asymmetrical myelitis, whereas 2 patients had symptoms and signs that were suggestive of ATM (non-MS). However, OCB is known to be present in other neurological diseases as well. It remains to be seen whether some of myelopathic type of MS can present like ATM (postinfectious) or whether the presence of OCB is only a transitory phenomenon. Glial fibrillary acidic protein (GFAP) specific IgG oligoclonal bands in CSF of patients with acute myelitis have recently been described.
In our series, the MRI lesions were in dorsal spine (32%), cervical spine (26%), cervicodorsal (23%), entire cord (3%) and in the conus in (3%). It was normal in 13% of cases. Pradhan et al described 12 cases of para infectious conus myelitis. It was suggested by them that this entity be suspected in all cases of unexplained acute and subacute urinary symptoms in the adolescent and adult patients.
The MRI findings in ATM and myelopathic MS have been described by various workers. Normal MRI has previously been reported in 7-50% of cases., MRI is likely to be normal if done early in the course i.e. within 5 days. Tartaglino et al found that on MR imaging, the MS plaques in spinal cord are characteristically less than 2 vertebral segments in length, peripherally located and occupy less than 2/3rd of cross section. Bakshi et al described ATM as a longitudinal myelitis involving multiple segments, whereas MS plaques are more focal and involve only 1-2 segments. However, both the lesions are equally likely to expand the cord. Likewise cranial MRI was more likely to be normal in ATM (78%) than MS myelitis patients (15%).10 In ATM, the centrally located high signal intensity was more likely to occupy more than 2/3rd of cross section. Cord swelling in myelopathic MS has been described by other workers as well. In our series 17 patients had central, multisegment hyperintense lesion on T2W images and in all except 2 the lesion occupied more than 2/3rd of cross section. Haemorrhagic conversion was noted in 2 patients. Thus it is possible to classify and predict the prognosis of ATM after MRI to a great extent.