Mechanism, spectrum, consequences and management of hyponatremia in tuberculous meningitis

Hyponatremia is the commonest electrolyte abnormality in hospitalized patients and is associated with poor outcome. Hyponatremia is categorized on the basis of serum sodium into severe (< 120 mEq/L), moderate (120-129 mEq/L) and mild (130-134mEq/L) groups. Serum sodium has an important role in maintaining serum osmolality, which is maintained by the action of antidiuretic hormone (ADH) secreted from the posterior pituitary, and natriuretic peptides such as atrial natriuretic peptide and brain natriuretic peptide. These peptides act on kidney tubules via the renin angiotensin aldosterone system. Hyponatremia <120mEq/L or a rapid decline in serum sodium can result in neurological manifestations, ranging from confusion to coma and seizure. Cerebral salt wasting (CSW) and syndrome of inappropriate secretion of ADH (SIADH) are important causes of hyponatremia in tuberculosis meningitis (TBM). CSW is more common than SIADH. The differentiation between CSW and SIADH is important because treatment of one may be detrimental for the other; evidence of hypovolemia in CSW and euvolemia or hypervolemia in SIADH is used for differentiation. In addition, evidence of dehydration, polyuria, negative fluid balance as assessed by intake output chart, weight loss, laboratory evidence and sometimes central venous pressure are helpful in the diagnosis of these disorders. Volume contraction in CSW may be more protracted than hyponatremia and may contribute to border zone infarctions in TBM. Hyponatremia should be promptly and carefully treated by saline and oral salt, while 3% saline should be used in severe hyponatremia with coma and seizure. In refractory patients with hyponatremia, fludrocortisone helps in early normalization of serum sodium without affecting polyuria or functional outcome. In SIADH, V2 receptor antagonist conivaptan or tolvaptan may be used if the patient is not responding to fluid restriction. Fluid restriction in SIADH has not been found to be beneficial in TBM and should be avoided

Management of intracranial tuberculous mass lesions: how long should we treat for? [version 3; peer review: 3 approved]

Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment response is unpredictable, with lesions frequently enlarging paradoxically or persisting for many years despite appropriate TB treatment and corticosteroid therapy. Most international guidelines recommend a 9-12 month course of TB treatment for central nervous system TB when the infecting Mycobacterium tuberculosis (M.tb) strain is sensitive to first-line drugs. However, there is variation in opinion and practice with respect to the duration of TB treatment in patients with tuberculomas or tuberculous abscesses. A major reason for this is the lack of prospective clinical trial evidence. Some experts suggest continuing treatment until radiological resolution of enhancing lesions has been achieved, but this may unnecessarily expose patients to prolonged periods of potentially toxic drugs. It is currently unknown whether persistent radiological enhancement of intracranial tuberculomas after 9-12 months of treatment represents active disease, inflammatory response in a sterilized lesion or merely revascularization. The consequences of stopping TB treatment prior to resolution of lesional enhancement have rarely been explored. These important issues were discussed at the 3rd International Tuberculous Meningitis Consortium meeting. Most clinicians were of the opinion that continued enhancement does not necessarily represent treatment failure and that prolonged TB therapy was not warranted in patients presumably infected with M.tb strains susceptible to first-line drugs. In this manuscript we highlight current medical treatment practices, benefits and disadvantages of different TB treatment durations and the need for evidence-based guidelines regarding the treatment duration of patients with intracranial tuberculous mass lesions

Etiology and clinical management of adult meningitis in Indonesia

Contains fulltext : 106968.pdf (publisher's version ) (Open Access)This thesis consists of 8 chapters and addresses the etiology, diagnosis, outcome and treatment of adult meningitis in Indonesia. The studies were conducted in Hasan Sadikin Hospital, Bandung, the referral hospital for West Java province, Indonesia between December 2006 and August 2012. In a cohort of adult patients presenting with meningitis, we found that the vast majority of patients present with subacute meningitis, with high HIV prevalence. The most common diagnosis was TB meningitis, and cryptococcal meningitis was found in one-third of HIV patients. Bacterial meningitis was rare. The outcome was bad, approximately half of patients died during follow up, with HIV infection being the strongest risk factor for death. Bacteriological confirmation of TB cases was found in 50% of cases. In-house real-time PCR (rt-PCR) targeting insertion sequence IS6110 had a higher sensitivity than microscopy and culture. In the search of other possible cause, we found that CSF PCR for Toxoplasma gondii was positive in one third of the HIV-infected population tested. In the field of treatment, we examined if intensified antibiotic treatment containing a higher dose rifampicin intravenously and/or moxifloxacin may improve outcome. Intensified treatment regimens result in higher exposure in blood and CSF, did not result in increased toxicity, and high dose rifampicin was associated with a significant mortality reduction. In the field of prevention, we investigated the prevalence and clinical significance of cryptococcal antigenemia in a cohort of HIV outpatient clinic. We found that 7.1% of ART-naïve patients with low CD4 count had a positive cryptococcal antigen. This cryptococcal antigenemia at baseline was strongly associated with the development of cryptococcal meningitis, early dropout, and early death. General lack of awareness of meningitis signs and symptoms was found both in laypeople and health providers. Measures to deal with this situation need to be formulated.Radboud Universiteit Nijmegen, 8 april 2013Promotor : Ven, A.J.A.M. van der Co-promotores : Crevel, R. van, Ruslami, R

Rifampicin and moxifloxacin for tuberculous meningitis--authors' reply

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Is laparoscopy useful in the diagnosis of primary hepatic carcinoid?

Meningitis is the most severe manifestation of tuberculosis. It is largely unknown why some people develop pulmonary TB (PTB) and others TB meningitis (TBM); we examined if the genetic background of infecting M. tuberculosis strains may be relevant

Cerebral toxoplasmosis presenting as subacute meningitis in HIV-infected patients; a cohort study from Indonesia.

Contains fulltext : 118116.pdf (publisher's version ) (Open Access

Characteristics of patients according to microbiological diagnosis.

<p>Patients with combined TB-toxoplasmosis (n = 5), combined TB-Cryptococcus (n = 2), and no definite diagnosis (n = 14) were excluded from the table. Data are presented as no. of patients/no. evaluated (%) unless stated otherwise.</p><p>GCS = Glasgow Coma Scale.</p>*<p>significantly different: TB vs. toxoplasmosis (p = .01); cryptococcosis vs. toxoplasmosis (p = .02).</p>**<p>significantly different: TB vs. toxoplasmosis (p = .03), cryptococcosis vs. toxoplasmosis (p = .02).</p>***<p>CD4 cell counts were only available for 16 patients with definite diagnoses.</p