Abstract
Tuberculous meningitis (TBM) remains a common serious neurological emergency—especially in the developing world. Elevated intracranial pressure (ICP) is often a feature of severe TBM and is associated with high morbidity and mortality. The pathology associated with TBM, such as cerebral edema, hydrocephalus, tuberculoma(s), and infarcts related to arthritis, contribute to increase in intracranial volume and, therefore, elevated ICP. The three types of edema (vasogenic, cytotoxic, and interstitial) may contribute to cerebral edema. The molecular mechanisms underlying the events that ultimately lead to brain damage and cerebral edema during infection are complex. Similarly to bacterial meningitis, cerebral blood flow autoregulation is probably impaired in TBM, and the mechanisms are unclear. Although no universal guidelines are available to institute ICP monitoring in patients with severe TBM, it is be prudent to monitor patients at risk for increases in ICP. Such an approach helps to detect the secondary brain insults, allowing for a more informed approach to treatment. Treatment of elevated ICP involves a multipronged approach. The first step should be to identify focal brain lesions and hydrocephalus (which require surgical intervention) by brain imaging. Cerebral edema is treated with hyperosmolar agents. Mannitol is currently the most commonly used agent. It appears that use of hypertonic saline as an osmotic agent in infection-related cerebral edema has certain advantages. However, this needs to be established by well-designed trials. Use of steroids reduces not only cerebral edema but also the production of cytokines and other chemicals involved in the immunopathogenesis of TBM. Fever associated with TBM should be aggressively treated, because fever can worsen the impact of elevated ICP. Hyponatremia may complicate TBM and requires appropriate correction because it can aggravate cerebral edema.
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References
World Health Organization. The world health report. Geneva: WHO, 1998.
Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999;282:677–686.
Selwyn PA, Haitel D, Lewis VA, et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 1989;320:345–350.
Bishburg E, Sunderam G, Reichman LB, et al. Central nervous system tuberculosis with the acquired immunodeficiency syndrome and its related complex. Ann Intern Med 1986;105:21–23.
British Medical Research Council. Streptomycin treatment of tuberculous meningitis. Lancet 1948;1:582.
Misra UK, Kalita J, Srivastava M, et al. Prognosis of tuberculous meningitis: a multivariate analysis. J Neurol Sci 1996;137:57–61.
Misra UK, Kalita J, Roy AK, Mandal SK, Srivastava M. Role of clinical, radiological, and neurophysiological changes in predicting the outcome of tuberculous meningitis: a multivariable analysis. J Neurol Neurosurg Psychiatry 2000;68:300–303.
Bhargava S, Gupta AK, Tandon PN. Tuberculous meningitis: a CT scan study. Br J Radiol 1982;55:189–196.
Kingsley DPE, Hendrickse WA, Kendall BE, et al. Tuberculous meningitis: role of CT scan in management and prognosis. J Neurol Neurosurg Psychiatry 1987;50:32–36.
Dastur DK, Manghani DK, Udani PM. Pathology and pathogenetic mechanisms in neurotuberculosis. Radiol Clin North Am 1995;33:733–752.
Shankar SK, Santosh V, Mahadevan A, Yasha TC, Satishchandra P. Pathology of cerebral vasculature in neurotuberculosis—some observations. In: Mehta VS, Misra UK, eds. Progress in Neurosciences, New Delhi: Neurological Society of India. 2001, pp. 134–141.
Yaramis A, Gurkan F, Elevli M, et al. Central nervous system tuberculosis in children: a review of 214 cases. Pediatrics 1998;102:E49
Oxates M, Kemaloglu S, Gurkan F, Ozkan U, Hosoglu S, Simsek MM. CT of the brain in tuberculous meningitis. A review of 289 patients. Acta Radiol 2000;41:13–17.
Kilani B, Ammari L, Tiouiri H, et al. Neuroradiologic manifestations of central nervous system tuberculosis in 122 adults. Rev Med Intern 2003;24:86–96.
Ranjan P, Kalita J, Misra UK. Serial study of clinical and CT changes in tuberculous meningitis. Neuroradiology. 2003;45:277–282.
Hsich FY, Chia LG, Shen WC. Locations of cerebral infarction in tuberculous meningitis. Neuroradiology 1992;34:197–199.
Dastur DK, Udani PM. Pathology and pathogenesis of tuberculous encephalopathy. Act Neuropathol 1966;6:311–326.
Tsenova L, Sokol K, Freedman VH, Kaplan G. A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death. J Infect Dis 1998;177:1563–1572.
Tsenova L, Bergtold A, Freedman VH, Young RA, Kaplan G. Tumor necrosis factor a is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system. Proc Natl Acd Sci 1999;96:5657–5662.
Kinder V, Sappino AP, Grau GE, et al. The inducing role of tumor necrosis factor in the development of bactericidal granuloma during BCG infection. Cell 1989;56:731–740.
Donald PR, Schoeman JF, Beyers N, et al. Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis. Clin Infect Dis 1995;21:924–929.
Mastroianni CM, Paoletti F, Lichtner M, D’Agostino C, Vullo V, Delia S. Cerebrospinal fluid cytokines in patients with tuberculous meningitis. Clin Immunol Immunopathol 1997;84:171–176.
Yaramis A, Colpan L, Tas MA. Diagnostic value of cytokine measurement in cerebrospinal fluid in children with central nervous system tuberculosis. Pediatrics 2001;107:1236.
Thwaites GE, Simmons CP, Than Ha Quyen N, et al. Pathophysiology and prognosis in Vietnamese adults with tuberculous meningitis. J Infect Dis 2003;188:1105–1115.
Chen L, Jiang H, Wei C. Nitric oxide, TNF-alpha and IL-8 in cerebrospinal fluids of tuberculous and cryptococcus meningitis. Hunan Yi Ke Da Xue Xue Bao 1997;22:514–516.
Paul R, Lorenzl S, Koedel U, et al. Matrix metalloproteinases contribution to the blood-brain-barrier disruption during bacterial meningitis. Ann Neurol 1998;44:592–600.
Leppert D, Leib SL, Grygar C, Miller KM, Schaad UB, Hollander GA. Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: Association with blood-brain-barrier damage and neurological sequelae. Clin Infect Dis 2000;31:80–84.
Price NM, Farrar J, Tran TT, Nguyen TH, Tran TH, Friedland JS. Identification of a matrix-degrading phenotype in human tuberculosis in vitro and in vivo. J Immunol 2001;166:4223–4230.
Moller K, Larsen FS, Qvist J, et al. Dependency of cerebral blood flow on mean arterial pressure in patients with acute bacterial meningitis. Crit Care Med 2000;28:1027–1032.
Moller K, Skinhoj P, Knudsen GM, Larsen FS. Effect of short-term hyperventilation on cerebral blood flow autoregulation in patients with acute bacterial meningitis. Stroke 2000;31:1116–1122.
McKnight AA, Keyes WG, Hudak ML, Jones MD Jr. Oxygen free radicals and the cerebral arteriolar response to group B streptococci. Pediatr Res 1992;31:40–44.
Andersen NEO, Gyring J, Hansen AJ, Laursen H, Siesjo BK. Brain acidosis in experimental pneumococcal meningitis. J Cerebr Blood Flow Metab 1989;9:381–387.
Koedel U, Bematowicz A, Pal R, Frei K, Fontana A, Pfister HW. Experimental pneumococcal meningitis: cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitiric oxide. Ann Neurol 1995;37:319–327.
Tunkel AR, Scheld WM. Pathogenesis and pathophysiology of acute bacterial meningitis. Clin Microbiol Rev 1993;6:118–136.
Jeren T, Beus I. Characteristics of cerebrospinal fluid in tuberculous meningitis. Acta Cytol 1982;26:678–680.
Karstaedr AS, Vltchanova S, Barriere R, et al. Tuberculous meningitis in South African urban adults. Q J Med 1988;91:743–747.
Hopewell PC. Overview of clinical tuberculosis. In: Bloom BR, ed., Tuberculosis, Pathogenesis, Protection, and Control. Washington, DC: ASM, 1994.
Kennedy DH, Gallon RJ. Tuberculous meningitis. JAMA 1979;241:264–268.
Sinclair S, Prabhamani VS, Ghai OP, et al. Evaluation of diagnostic criteria in tuberculous meningitis in children including the hemagglutination test of CSF. Ind Pediatr 1977;14:967–972.
Thwaites GE, Chau TT, Farrar JJ. Improving the bacteriological diagnosis of tuberculous meningitis. J Clin Microbiol 2004;42:378–379.
Radhakrishnan VV, Mathai A. Correlation between isolation of M. tuberculosis and estimation of mycobacterial antigen in cisternal, ventricular, and lumbar CSF in patients with tuberculous meningitis. Ind J Pathol Microbiol 1993;36:341–347.
Hooker JA, Muhindi DW, Amayo EO, Mc’ligeyo SO, Bhatt KM, Odhiambo JA. Diagnostic utility of cerebrospinal fluid studies in patients with clinically suspected tuberculous meningitis. Int J Tuber Lung Dis 2003;7:787–796.
Gambhir JS, Mehta M, Singh DS, et al. Evaluation of CSF-ADA activity intuberculous meningitis. J Assoc Phys Ind 1999;47:192–194.
Ribera E, Marinez-Vazuez JM, Ocana I, et al. Activity of adenosine deaminase in cerebrospinal fluid for the diagnosis and follow-up of tuberculous meningitis in adults. J Infect Dis 1987;155:603–607.
Thwaites G, Chau TTH, Mai NTH, Drobniewski F, McAdam K, Farrar J. Tuberculous meningitis. J Neurol Neurosurg Psychiatry 2000;68:289–299.
Kox LFF, Der SK, Kolls AHJ. Early diagnosis of tuberculous meningitis by polymerase chain reaction. Neurology 1995;45:2228–2232.
Seth P, Ahuja GK, Vijaya Bhanu N, et al. Evaluation of polymerase chain reaction for rapid diagnosis of clinically suspected tuberculous meningitis. Tubercle Lung Dis 1996;77:353–357.
Shankar P, Manjunath N, Mohan KK, et al. Rapid diagnosis of tuberculous meningitis by polymerase chain reaction. Lancet 1991;337:5–7.
Nguyen LN, Kox LFF, Pham LD, et al. The potential contribution of polymerase chain reaction to the diagnosis of tuberculous meningitis. Arch Neurol 1996;53:771–776.
Rafi A, Naghily B. Efficiency of polymerase chain reaction for the diagnosis of tuberculous meningitis. Southeast Asian J Trop Med Public Health. 2003;34:357–360.
Schoeman JF, Laubscher JA, Donald PR. Serial lumbar CSF pressure measurements and cranial computed tomographic findings in childhood tuberculous meningitis. Childs Nerv Syst 2000;16:203–208.
Goitein KJ, Tamir I. Cerebral perfusion pressure in central nervous system infections of infancy and childhood. J Pediatr 1983;103:40–43.
Rebaud P, Berthier JC, Hartemann E, Floret D. Intracranial pressure in childhood central nervous system infections. Intensive Care Med 1988;14:522–525.
Dennis LJ, Mayer SA. Diagnosis and management of increased intracranial pressure. Neurology India 2001;49 (Suppl 1):S37-S50.
Battistella FD, Wisner DH. Combined hemorrhagic shock and head injury: effects of hypertonc saline (7.5%) resuscitation. J Trauma 1991;31:182–188.
Prough DS, Johnson JC, Poole GV Jr., Stullken EH, Johnston WE Jr., Royster R. Effects on intracranial pressure of resuscitation from hemorrhagic shock with hypertonic saline versus lactated Ringer’s solution. Crit Care Med 1985;13:407–411.
Suarrz JI. Hypertonic saline for cerebral edema and elevated intracranial pressure. Cleveland Clin J Med 2004;71 (Suppl 1):S9-S12.
Messeter K, Nordstrom CH, Sundbarg G, Algotsson L, Ryding E. Cerebral hemodynamics in patients with acute severe head trauma. J Neurosurg 1986;64:231–237.
Amtrop O. Estimation of capillary permeability of inulin, sucrose and mannitol in rat brain cortex. Act Physiol Scan 1980;110:337–342.
Mizoi K, Suzuki J, Imaizumi S, Yoshimoto T. Development of new cerebral protective agents: the free radical scavengers. Neurol Res 1986;8:75–80.
Rhee P, Wang D, Ruff P, Austin B, et al. Human neutrophil activation and increased adhesion by various resuscitation fluids. Crit Care Med 2000;28:74–78.
Angle N, Hoyt DB, Cabello-Passini R, Herdon-Remelius C, Loomis W, Junger WG. Hypertonic saline resuscitation reduces neurotphil migration by suppressing neurophil L selectin expression. J Trauma 1998;45:7–12.
Angle N, Hoyt DB, Coimbra R, et al. Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock. Shock 1998;9:164–170.
Angle N, Cabello-Passini R, Hoyt DB, et al. Hypertonic saline infusion: can it regulate human neurtophil function? Shock 2000;14:503–508.
Rizoli SB, Kapus A, Fan J, Li YH, Marshall JC, Rotstein OD. Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock. J Immunol 1998;161:6288–6296.
Qureshi AI, Wilson DA, Traystman RJ. Treatment of elevated intracranial pressure in experimental intracerebral hemorrhage: comparison between mannitol and hypertonic saline. Neurosurgery 1999;44:1055–1063.
Schatzmann C, Heissler HE, Konig K, et al. Treatment of elevated intracranial pressure by infusions of 10% saline in severely head injured patients. Act Neurochir Suppl (Wien) 1998;71:31–33.
Simma B, Burger R, Falk M, Sacher P, Fanconi S. A prospective, randomized, and controlled of fluid management in children with severe head injury: lactated Ringer;s solution versus hypertonic saline. Crit Care Med 1998;26:1265–1270.
Christopher R, Gourie-Devi M. The syndrome of inappropriate antidiuretic hormone secretion in tuberculous meningitis. J Assoc Phys Ind 1997;45:933–935.
Singh BS, Patwari AK, Deb M. Serum sodium and osmolal changes in tuberculous meningitis. Indian Pediatr 1994;31:1345–1350.
Narotam PK, Kemp M, Buck R, Gouws E, van Dellen JR, Bhoola KD. Hyponatremic natriuretic syndrome in tuberculous meningitis: the probable role of atrial natriuretic peptide. Neurosurgery 1994;34:982–988.
Ostensen J, Stokke ES, Bugge JF, Langberg H, Kiil F. Difference between hypertonic NaCl and NaHCO3 as osmotic diuretics in dog kidneys. Act Physiol Scand 1989;137:177–187.
Maxwell RE, Long DM, French LA. The effects of glucosteroids on experimental cold-induced brain edema. Grossmorphological alterations and vascular permeability changes. J Neurosurg 1971;34:477–487.
Weiss MH, Nulsen FE. The effect of glucocorticoids on CSF flow in dogs. J Neurosurg 1970;32:451–458.
Hall ED, Yonkers PA, Mccall JM, Braughler JM. Effects of the 21-aminosteroid U74006F on experimental head injury in mice. J Neurosurg 1988;68:456–461.
Coyle PK. Glucocorticoids in central nervous system bacterial infection. Arch Neurol 1999;56:796–801.
Mcintyre PB, Berkey CS, King SM, et al. Dexamethasone as adjunctive therapy in bacterial meningitis: a meta-analysis of randomized clinical trials since 1988. JAMA 1997;278:925–931.
Prasad K, Volmink J, Menon GR. Steroids for treating tuberculous meningitis. Cochrane Database Sys Rev 2000(3):CD002244.
Schoeman JF, Van Zyl LE, Laubscher JA, Donald PR. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Pediatrics 1997;99:226–231.
Garg RK. Tuberculosis of the central nervous system. Postgrad Med J 1999;75:133–140.
Hajat H, Hajat S, Sharma P. Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke 2000;31:410–414.
Schwartz S, Hafner K, Aschoff A, et al. Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology 2000;54:354–361.
Ginsberg BR. The influence of altered brain temperature in cerebral ischemia. In: Ginsberg MD, Bogousslavsky J, eds., Cerebrovascular Disease: Pathophysiology, Diagnosis, and Management. Malden, MA: Blackwell Science, 1998, pp. 287–307.
Diringer MN, Reaven NL, Funk S. The influence of fever on length of stay in neuro-ICU patients [abstract]. Neurology 2003;60(Suppl):A425.
Rosomoff HL, Holaday DA. Cerebral blood flow and cerebral oxygenconsumption during hypothermia. Am J Physiol 1954;179:85–88.
Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001;344:556–563.
Smith J, Godwin-Austen R. Hypersecretion of anti-diuretic hormone due to tuberculous meningitis. Postgrad Med J 1980;56:41–44.
Arunodaya GR. Sodium dysregulation and infections of central nervous system. Ann Ind Acad Neurol 2003;6:253–258.
Loo KL, Ramachandran R, Abdullah BJ, Chow SK, Goh EM, Yeap SS. Cerebral infarction and cerebral salt wasting syndrome in a patient with tuberculous meningoencephalitis. Southeast Asian J Trop Med Public Health 2003;34:636–640.
Ti LK, Kang SC, Cheong KF. Acute hyponatraemia secondary to cerebral salt wasting syndrome in a patient with tuberculous meningitis. Anaesth Intensive Care 1998;26:420–423.
Dass R, Nagaraj R, Murlidharan J, Singhi S. Hyponatraemia and hypovolemic shock with tuberculous meningitis. Indian J Pediatr 2003;70:995–997.
Huang SM, Chen CC, Chiu PC, Cheng MF, Chiu CL, Hsieh KS. Tuberculous meningitis complicated with hydrocephalus and cerebral salt wasting syndrome in a three-year-old boy. Pediatr Infect Dis J 2004;23:884–886.
Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med 2000;342:1681–1689.
Bhagwati SN. Ventriculoatrial shunt in tuberculous meningitis with hydrocephalus. J Neurosurg 1971;35:309–313.
Roy TK, Sircar PK, Chander V. Ventriculo-peritoneal shunt in the management of tuberculous meningitis. Indian J Pediatr 1979;16:1023–1027.
Singhal BS, Bhagwati SN, Syed AH, et al. Raised intracranial pressure in tuberculous meningitis. Neurology India 1975;23:32–39.
Palur R, Rajshekhar V, Chandy MJ, et al. Shunt surgery for hydrocephalus in tuberculous meningitis: a long term follow up study. J Neurosurg 1991;74:64–60.
Lamprecht D, Schoeman J, Donald P, Hartzenberg H. Ventriculoperitoneal shunting in childhood tuberculous meningitis. Br J Neurosurg 2001;15:119–125.
Mathew J, Rajshekhar V, Chandy MJ. Shunt surgery in poor grade patients with tuberculous meningitis and hydrocephalus: effects of response to external ventricular drainage and other variables on long-term outcome. J Neurol Neurosurg Psychiatry 1998;65:115–118.
Wasay M, Moolani MK, Zaheer J, Kheleani BA, Smego AR, Sarwari RA. Prognostic indicators in patients with intracranial tuberculoma: a review of 102 cases. J Pak Med Assoc 2004;54:83–87.
Tandon PN, Bhargava S. Effect of medical treatment on intracranial tuberculoma: a CT study. Tubercle 1985;66:85–97.
Traub M, Colchester AC, Kingsley DP, et al. Tuberculosis of the central nervous system. Quart J Med 1984;53:81–100.
Bhagwati SN, Parulekar GD. Management of intracranial tuberculoma in children. Childs Nerv Syst 1986;2:32–34.
Choudhury AR. Non-surgical treatment of tuberculomas of the brain. Br J Neurosurg 1989;3:643–653.
Bouchama A, al-Kawi MZ, Kanaan I, Coates R, Jallu A, Rahm B, Siqueira EB. Brain biopsy in tuberculoma: the risks and benefits. Neurosurgery 1991;30:405–409.
Ravenscroft A, Schoeman JF, Donald PR. Tuberculous granulomas in childhood tuberculous meningitis: radiological features and course. J Trop Pediatr 2001;47:5–12.
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Murthy, J.M.K. Management of intracranial pressure in tuberculous meningitis. Neurocrit Care 2, 306–312 (2005). https://doi.org/10.1385/NCC:2:3:306
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DOI: https://doi.org/10.1385/NCC:2:3:306