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 »  Introduction
 »  Material and methods
 »  Results
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Year : 2001  |  Volume : 49  |  Issue : 3  |  Page : 267-71

Effect of methyl prednisolone on sensory motor functions in tuberculous meningitis.

Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226 014, India.

Correspondence Address:
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226 014, India.
[email protected]

  »  Abstract

A prospective hospital based study was undertaken to study the effect of methyl prednisolone therapy on sensory and motor functions in tuberculous meningitis (TBM). The patients with TB meningitis seen during 1994-1998 were studied. CT scan, motor evoked potential (MEP) to upper and lower limbs; and median and tibial somatosensory evoked potentials (SEP) were carried out in all the patients. Outcome was defined at the end of 3 months into poor, partial or complete recovery on the basis of Barthel index score. Inj methyl prednisolone (MPS) 500 mg IV was given to 21 patients followed by oral tapering dose of prednisolone over one month in addition to 4 drug anti-tubercular treatment. The control group comprised of 16 patients who received 4 drugs anti-tubercular therapy without any corticosteroid. These groups were comparable with respect to their age, stage of meningitis, Glasgow coma scale score and radiological findings. In MPS group, CMCT was abnormal in 9 and SEPs in 7 patients. In the control group, these were abnormal in 9 and 5 patients respectively. Three months after the therapy the frequency of improvement, deterioration and stationary evoked potential (EP) changes were also noted in both the groups. Diversity of evoked potential changes were also noted. Evoked potential changes were neither significantly different between the groups nor there was any beneficial effect shown in MPS group at 3 months. On the contrary, the control group fared significantly better than the MPS group. Initial MEP and SEP abnormalities were however related to 3 months outcome (p<0.01).

How to cite this article:
Kalita J, Misra U K. Effect of methyl prednisolone on sensory motor functions in tuberculous meningitis. Neurol India 2001;49:267

How to cite this URL:
Kalita J, Misra U K. Effect of methyl prednisolone on sensory motor functions in tuberculous meningitis. Neurol India [serial online] 2001 [cited 2023 Mar 21];49:267. Available from: https://www.neurologyindia.com/text.asp?2001/49/3/267/1242

   »   Introduction Top

Sensory and motor functions can be affected in tuberculous meningitis due to associated infarction, granuloma formation, hydrocephalus and/or arachnoiditis. Corticosteroids have been reported to reduce adhesion formation,[1] reduction of mortality and sequelae[2],[3],[4] and improvement in cerebrospinal fluid.[5] There are, however, a number of reports in which corticosteroids have not been associated with any benefit.[6],[7],[8] High dose corticosteroids have an established role in the management of a number of CNS vasculitides. The role of methyl prednisolone (MPS) has not been investigated in TBM so far. The sensory motor functions are difficult to assess in a patient with altered sensorium which is common in TBM. Motor and somatosensory evoked potentials have an established role in objective documentation of integration of motor sensory pathways. These techniques have been used to monitor the effect of corticosteroids in multiple sclerosis[9] and cervical spondylotic myelopathy.[10] In the present study, we have compared the sensory and motor functions in TBM patients, receiving a short course of methyl prednisolone with those not receiving any form of corticosteroids.

   »   Material and methods Top

All patients with TBM managed by us during 1994 and 1998 were included in the present study. All the patients underwent a detailed neurological evaluation. Consciousness was assessed by Glasgow coma scale (GCS), muscle power by Medical Research Council (MRC) scale and tone by Ashworth scale. Reflexes were graded into normal, reduced or exaggerated. Pinprick, joint position and movement sense were tested in the patients who were co-operative for these tests. The activities of daily living were evaluated by Barthel index (BI) score. Plain and contrast cranial CT scan was carried out in all the patients employing a third generation CT scanner. Cranial MRI was carried out on 2T scanner operating at 1.5T (Magnetom SP Siemens Germany). T1, proton density and T2, weighted spin echo sequences were obtained. Presence of hydrocephalus, infarction, exudate and tuberculoma were noted. The diagnosis of TBM was based on clinical, CT scan and CSF criteria.[11] The clinical criteria included fever, headache and neck stiffness. Supporting evidences were obtained from CSF (cells 0.2x109/L or more with lymphocytic predominance, protein more than 1 gm/L, sterile bacterial and fungal culture) and presence of hydrocephalus and exudation on CT scan. Evidence of tuberculosis outside CNS and response to antitubercular therapy was also noted. The diagnostic categories included highly probable (clinical and 3 supportive criteria), probable (clinical and 2 supportive criteria) and possible (clinical and 1 supportive criteria). Presence of acid fast bacilli (AFB) in the CSF was regarded as definite evidence of TBM which was present in one patient only. The remaining patients were in highly probable category. The severity of meningitis was graded into stage Ipresence of meningitis only, stage II - meningitis with neurological signs and stage III - meningitis, neurological signs and altered sensorium.
Evoked potential studies : The evoked potential studies included bilateral median and tibial somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) to upper and lower limbs.
Motor evoked potentials (MEPs) : Motor evoked potentials were recorded from both upper and lower limbs bilaterally following transcranial electrical stimulation of cerebral cortex and spinal cord. A digitimer D180 stimulator delivering electrical shock upto 750 V with a time constant of 50-100 µS was used. Motor evoked potentials were recorded by surface electrodes placed on abductor [digiti] minimi (ADM) or tibialis anterior (TA) in a belly tendon montage. Central motor conduction time was calculated for the upper limb (CMCT-ADM) by subtracting the latency on C7 stimulation from that on cortical stimulation. The lower limb CMCT-TA was calculated by subtracting the latency on L1 stimulation from that on vertex stimulation.[12]
Somatosensory evoked potentials (SEP) : Median SEPs were obtained by stimulating the median nerve at the wrist. For tibial SEP, posterior tibial nerve was stimulated below the medial malleolus. 512 responses were twice averaged at a gain of 1-2 µV/division to ensure reproducibility. Median SEPs were analysed for the latency of N9, N20 and interpeak latency of N9-N20. For tibial SEPs latencies of N21, P40 and N21-P40 central sensory conduction time (CSCT) were measured.[12] The results of evoked potentials were compared with the normal values of our laboratory, which were obtained from 32 healthy adult volunteers. Their age ranged between 15-60 years. The upper limit of CMCT-ADM (mean+SD) was 8.1 (5.1+1.2) ms, CMCT-TA 16.1 (12.1+1.6) ms, median N9-N19 conduction time was 11.3 (8.3+1.2) ms and tibial N21-P40 conduction time 27.1 (20.1+2.8) ms.
Treatment and follow-up : All the patients were prescribed 4 antitubercular drug comprising of isoniazide, ethambutol, rifampicin and pyrazinamide. In children below 12 years, ethambutol was substituted by streptomycin. During initial two years of our study, the corticosteroids were not used whereas in the later part i.e. since 1996 the patients received inj. methyl prednisolone (MPS) 500 mg IV slowly over 6 hours for 5 days followed by oral prednisolone over 1 month. The patients with septicaemia, bedsore and diabetes were not prescribed MPS. Ventriculoperitoneal shunt was carried out as and when indicated. The clinical and neurophysiological examination was repeated at 3 months followup. The outcome was defined on the basis of Barthel index (BI) score at 3 months into complete (BI=20), partial (BI=12-19) or poor (BI<12) recovery.[13] The changes in evoked potential parameters were evaluated by paired `t' test and comparison between MPS and non MPS group by Mann Whitney U test. The effect of clinical and evoked potential parameters on the outcome was evaluated by x2 test.

   »   Results Top

Out of 37 patients with TBM, 21 received a short course of IV methyl prednisolone therapy, followed by oral tapering dose, whereas 16 patients did not receive any form of corticosteroids and served as controls. MRI was carried out in 16 patients. In 9 patients whose CT scan was normal, MRI revealed hydrocephalus in 8, infarction in 9 and tuberculoma in 8 patients. Two of these patients who had multiple tuberculoma had miliary shadows in their chest radiographs. The infarctions were located in basal ganglionic region in all except in 3 patients in whom the infarctions were located in brainstem (midbrain in 2, lateral medulla in 1).
Evoked potential studies : There were 21 patients who received IV methyl prednisolone therapy. In the MPS group, the CMCT was abnormal in 9 patients. CMCT-ADM was prolonged in 2 and unrecordable in 3 sides. CMCT-TA was prolonged in 5 and unrecordable on 6 sides. Similarly, SEPs were abnormal in 7 out of 21 patients receiving MPS therapy. Median SEPs were unrecordable in 3, tibial in 5 and tibial CSCT was prolonged in 3 sides. In the control group, MEP was abnormal in 9 patients and SEP in 5. CMCT-ADM was prolonged and unrecordable in 4 sides each and CMCT-TA was prolonged in 4 and unrecordable in 3 sides. Median SEP was prolonged in 3 and unrecordable in 5 sides. Tibial CSCT was prolonged in 3 and unrecordable in 4 sides.
In the followup study, MEP revealed more changes compared to SEP. The results of evoked potential studies on the initial and final evaluation are shown in table II. In the MPS group, at 3 month followup, the prolonged CMCT-ADM returned to normal in both the patients whereas in one patient there was deterioration of CMCT-ADM which became prolonged from the earlier normal values. In 3 patients in whom CMCT-ADM was unrecordable, it become normal in 2. The prolonged CMCT-TA deteriorated to unrecordable in 2 and continued to be prolonged, although showed improvement on 3 sides. In one patient, CMCT-TA deteriorated in one side, becoming prolonged from normal. Out of 6 sides with unrecordable CMCT-TA, it became recordable in 3 (prolonged in 2 and normal in 1 side). In the followup, SEPs were more stable than MEP. In all the patients with unrecordable median SEP, the same remained unrecordable whereas prolonged CSCT improved to normal in 2 sides and in another it improved, although remained prolonged. In another patient, normal tibial SEP became prolonged and in 2 patients (3 sides) normal tibial SEP deteriorated to become unrecordable at 3 month. In the control group, similar changes were noted. Prolonged CMCT-ADM improved to normal on one side and unrecordable CMCT-ADM improved to normal in one side. Deterioration was noted in CMCT-TA in 5 sides. Median SEP improved in 2 patients (4 sides); unrecordable to prolonged in one, unrecordable to normal in one and prolonged to normal in 2 sides. Tibial SEPs improved in 2 patients (2 sides). At the end of 3 months, all the patients were clinically evaluated. In the non MPS group 5 had poor, 3 partial and 8 complete recovery. In the MPS group 7 patients had poor, 3 partial and 11 complete recovery. Evoked potential study was possible in all the MPS patients but 3 patients in the control group could not be repeated due to lack of consent or financial reasons.
In the treated group comparing initial and 3 month EP findings CMCT-ADM (t=1.74, p=0.05, NS), CMCT-TA(t=0.40, NS), median SEP (t=0.26, NS), tibial SEP (t=2.01, NS); and in the control group CMCT-ADM (t=1.96, p<0.03), CMCT-TA (t=-1.79, NS), median SEP (t=1.66, NS) and tibial SEP (t=1.23, NS), were generally not significant. On comparing the evoked potential changes in the control and treated group employing Mann Whitney U test; the findings included CMCT-ADM to right side (Z=4.87, p<0.01), CMCT-TA to left side (Z=4.17, p<0.01), CMCT-TA to right side (Z=3.79, p<0.01) CMCT-TA to left side (Z=3.79, p<0.01), right median SEP (Z=5.24, p<0.01), left median SEP (Z=-4.89, p<0.01), right tibial SEP (Z=1.96, p<0.01) and left tibial SEP (Z=2.08, p<0.01). These results do not suggest any benefit of MPS therapy over control group. The outcome of TBM at 3 months was related to initial MEP (x[2]=8.85, df=2, p<0.01) and SEP (x[2]=10.21, df=2, p<0.01) abnormalities but not on stage of meningitis (x[2]=8.03, df=4, NS) and MPS (x[2]=0.13,
df=2, NS) therapy.

   »   Discussion Top

In our study, the motor evoked potentials were more frequently abnormal compared to somatosensory evoked potentials. The MEPs were abnormal in 18 patients and SEPs in 12. The abnormalities included unrecordable evoked potential and mild to moderate prolongation of central motor or sensory conduction time. During followup, MEP and SEP changed to a variable extent in both MPS and control groups. Some patients improved, some deteriorated and in some there was no change. The evoked potential changes were patchy and focal. Even in the same patient, the improvement in EPs occurred in one and deterioration in the other limb. The patchy and focal distribution of evoked potential changes can be explained by multiplicity and diversity of pathophysiological mechanisms. In TBM there may be occurrence of hydrocephalus, infarction, tuberculoma and arachnoiditis in various permutations and combinations.[14],[15],[16] The changes in evoked potential parameters in both the groups may be due to resolution of above mentioned pathological processes following antitubercular therapy. Deterioration in evoked potential parameters may occur inspite of recovery from meningitis because of arachnoiditis and infarction, following strangulation of vessels at the base of brain.[16] In some patients following antitubercular therapy, the worsening occurs which has been attributed to paradoxical response.[17] In two of these patients, the healing process resulted in disabling paraplegia due to arachnoiditis in 1 and stroke in another in the present study.
The improvement and deterioration have occurred in both MPS and control groups; however the later fared better than the MPS group. Corticosteroids have been used in TBM for long. The basis of popularity of corticosteroids in TBM is their role in reducing meningeal inflammation, decrease in liberation of interleukin, tumour necrosis factor and different cytokines, thus minimising tissue injury.[18] Methyl prednisolone, however, has not been found to be significantly related to clinical outcome and evoked potential improvement in our study. In severe infection the endogenous production of corticosteroids is increased; hence further addition of corticosteroids may not be advantageous.[19] During a severe illness, the cortisol correlated with the severity of illness.[20] Most of our patients were in stage II or III meningitis, suggesting a severe meningitis; therefore, further addition of MPS may not be beneficial. In a double blind placebo control study, on the role of oral prednisolone, it was not found to be beneficial in patients with severe brain lesion, increased intracranial pressure and cranial nerve palsies.[8]
The outcome of TBM was dependent on initial MEP and SEP abnormalities but not on stage of meningitis and MPS therapy. This may be due to more patients with stage III meningitis in our study compared to less severe meningitis. In these patients, the clinical assessment of sensory and motor functions is not reliable and EP studies are valuable for documenting the respective deficit and predicting the outcome.
From this study, it can be concluded that methyl prednisolone in TBM does not alter outcome at 3 months. Initial MEP and SEP abnormalities however are related to poor outcome at 3 months.

  »   References Top

1.Feldman S, Behar AJ, Weber D : Experimental tuberculous meningitis in rabbits. Results of treatment with antituberculous drugs separately and in combination with cortisone. Arch Pathol 1958; 65 : 343-354.   Back to cited text no. 1    
2.Kendig EL, Choy SH, Johnson WH : Abbreviation in the effect of cortisone in the treatment of tuberculous meningitis. Am Rev Tuber 1956; 73 : 99-109.   Back to cited text no. 2    
3.Johnson JR, Furstenberg NE, Patternson et al : Corticotropin and adrenal steroid adjunct to treatment of tuberculous meningitis. Ann Int Med 1957; 46 : 631.   Back to cited text no. 3    
4.Ashby M, Grant H : Tubercular meningitis treated with cortisone. Lancet 1955; 1 : 65-66.   Back to cited text no. 4    
5.Girgis NI, Farid Z, Hanna LS et al : The use of dexamethasone in preventing ocular complications in tuberculous meningitis. Trans Roy Soc Trop Med1983; 77 : 658-659.   Back to cited text no. 5    
6.Weiss W, Flippin HF : The prognosis of tuberculous meningitis in the isoniazide. Am J Med 1961; 242 : 423-430.   Back to cited text no. 6    
7.Lepper MH, Spies HW : The present status of treatment of tuberculosis of the central nervous system. Ann NY Acad Sci 1963; 106 : 106-123.   Back to cited text no. 7    
8.Chotmongkol V, Jitpimolmard S, Thavornpitak Y : Corticosteroid in tuberculous meningitis. J Med Assoc Thai 1996; 79 : 83-90.   Back to cited text no. 8    
9.Smith T, Zeeberg I, Sjo O : Evoked potential in multiple sclerosis before and after high dose methylprednisolone infusion. Eur Neurol 1986; 25 : 67-73.   Back to cited text no. 9    
10.Misra UK, Kalita J : Motor evoked potentials are useful for monitoring the effect of collar therapy in cervical spondylotic myelopathy. J Neurol Sci 1998; 154 : 222-228.   Back to cited text no. 10    
11.Shankar P, Manjunath N, Mohan KK et al : Rapid diagnosis of tuberculosis meningitis by polymerase chain reaction. Lancet1991; 337 : 5-7.   Back to cited text no. 11    
12.Misra UK, Kalita J, Kumar S : Clinical, MRI and neurophysiological study of acute transverse myelitis. J Neurol Sci 1996; 150-156.   Back to cited text no. 12    
13.Misra UK, Kalita J, Srivastava M et al : Prognosis of tuberculous meningitis : A multivariate analysis. J Neurol Sci 1996; 137 : 57-61.   Back to cited text no. 13    
14.Gupta RK, Gupta S, Singh D et al : MR imaging and angiography in tuberculous meniingitis. Neuroradiology 1994; 36 : 87-92.   Back to cited text no. 14    
15.Bhargava S, Gupta AK, Tandon PN : Tuberculous meningitis : A CT scan study. Brit J Radiol 1982; 55 : 189-196.   Back to cited text no. 15    
16.Dastur DK, Lailtha VS, Udani PM et al : The brain and meningitis in TBM : gross pathology in 100 cases and pathogenesis. Neurol India1970; 18 : 86-100.   Back to cited text no. 16    
17.Lees AJ, McLeod AF, Marshall J : Cerebral tuberculoma developing during treatment of tuberculous meningitis Lancet1980; 1 : 1208-1211.   Back to cited text no. 17    
18.Abraham E, Anzueto A, Guitierrez G et al : Double blind randomised controlled trial of monoclonal antibody to human tumor necrosis factor in treatment of septic shock. Lancet 1998; 358 : 929-933.   Back to cited text no. 18    
19.Lamberts SJW, Brunning HA, Jong FH : Corticosteroids therapy in severe illness. N Engl J Med 1997; 347 : 12851295.   Back to cited text no. 19    
20.Jurney TH, Cockrell JR, Lindberg JS et al : Spectrum of serum cortisol response to ACTH in ICU patients : correlation with degree of illness and mortality. Chest1987;92 : 290-295.   Back to cited text no. 20    


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