|Year : 2013 | Volume
| Issue : 4 | Page : 388-391
A case of tuberculous meningitis presenting with cognitive defects
BH Shankaragouda, Amrut Savadkar, Harishchandra Barjatya, Utsav sahu
Department of Medicine, J. L. N, Medical College, Ajmer, Rajasthan, India
|Date of Submission||31-Mar-2013|
|Date of Acceptance||15-Jun-2013|
|Date of Web Publication||15-Oct-2013|
B H Shankaragouda
Room No. 211, Resident Doctors Hostel, JLN Medical College, Ajmer - 305 001, Rajasthan
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Tuberculosis (TB) affects one-third of the world's population and is the leading cause of human mortality and morbidity. Treating TB is the most efficient and cost-effective of all health interventions. A 22-year-old male patient presented with loss of appetite, on and off fever since a month, and past 4 days patient was irritable and in altered sensorium. There was no history of headache, nausea, and vomiting or neck pain. On examination he had signs of meningeal irritation with palsy of right sixth cranial nerve, resting tremors in hands, generalized rigidity and cognitive defects like apathy, psychomotor retardation, and impaired memory. Investigations revealed elevated ESR; Chest X-ray showed bilateral milliary shadows and MRI brain showed mildly dilated ventricles and hyperintense lesions. Patient was started on oral anti-tubercular treatment under category I intensive phase, parenteral dexamethasone and mannitol and patient made remarkable clinical improvement and was discharged after 2 weeks. Atypical presentation of TBM is not uncommon in developing nations like India. We report one such case presenting with unusual symptoms and signs. This report is intended to make physicians aware of the unusual clinical presentations of tuberculous meningitis.
Keywords: Cognitive defects, generalized rigidity, sixth nerve palsy, tuberculous meningitis
|How to cite this article:|
Shankaragouda B H, Savadkar A, Barjatya H, sahu U. A case of tuberculous meningitis presenting with cognitive defects. Int J Nutr Pharmacol Neurol Dis 2013;3:388-91
|How to cite this URL:|
Shankaragouda B H, Savadkar A, Barjatya H, sahu U. A case of tuberculous meningitis presenting with cognitive defects. Int J Nutr Pharmacol Neurol Dis [serial online] 2013 [cited 2019 Dec 14];3:388-91. Available from: http://www.ijnpnd.com/text.asp?2013/3/4/388/119856
| Introduction|| |
Tuberculosis (TB) affects one-third of the world's population and is the leading cause of human mortality and morbidity.  Treating tuberculosis is the most efficient and cost-effective of all health interventions. Factors contributing to an increased occurrence of TB are AIDS pandemic, poverty, unhygienic living conditions, malnutrition, drug abuse, and immigration. Tuberculosis results in two million deaths annually and 98% of these deaths occur in the developing countries, mostly Africa and Asia. About 50% of new cases are from Asia (WHO 2005). TB of central nervous system (CNS) constitutes 5% of extra pulmonary cases.  Late and atypical presentation of tuberculous meningitis (TBM) is common in developing nations like India which may lead to delay in diagnosis and to increased mortality and morbidity in as timing of treatment is crucial for the prognosis. We report a case of TBM presenting with unusual signs and symptoms. The purpose of the case report is to highlight the unusual clinical and laboratory features among the physician.
| Case Report|| |
A 22-year-old college student brought to our hospital with complaint of on and off fever, loss of appetite of 1-month duration. Patient recently became irritable and was in altered sensorium since 4 days. He had no history of headache, photophobia, nausea, and vomiting or neck pain. He had no seizures or blurring of vision. There was no history suggestive of respiratory, cardiac, or urinary abnormalities. There was no personal or family history of hypertension, diabetes mellitus, or TB. There was no history of blood transfusion. Evaluation for sexually transmitted disease was negative.
On examination patient was pale, febrile with toxic look, disoriented with Glasgow coma scale of 12/15. He was cachexic with low BMI (<18.5). Patient had signs of meningeal irritation along with right sixth nerve palsy, resting tremors in both hands, generalized rigidity of extra pyramidal type (lead pipe and cogwheel) but he did not had any weakness. Patient had cognitive defects like apathy, psychomotor retardation, and impaired memory. Patient's superficial reflexes were intact, deep reflexes were exaggerated, and plantar response was flexor bilaterally. Patient's chest was clear and rest of systemic examination was unimpressive.
Investigations revealed reduced hemoglobin (10 gm/dL), normal white blood cell count (8430/cumm) but elevated ESR (74). Na + (130 meq/L) was slightly reduced. Random blood sugar was 110 mg/dL, HIV I and II were negative by ELISA. Chest X-ray showed bilateral diffuse milliary infiltrates [Figure 1]. CSF analysis revealed normal ADA (<10 U/L), Low sugar (29.1 mg/dL), CSF to blood glucose ratio was low (<0.5), protein was elevated (164.9 mg/dL). No acid fast bacilli/Gram-reactive organism found. Cell count was 30 cells/mm 3 predominantly lymphocytes. His cranial MRI findings were mildly dilated ventricular system and hyperintense lesion along convexity sulci suggestive of chronic TBM [Figure 2].
|Figure 1: Chest X-ray PA view showing bilateral milliary shadows [Clearly visible in inset]|
Click here to view
|Figure 2: Cranial MRI, Axial section, of patient showing hyperintense lesions on T2 imaging|
Click here to view
A provisional diagnosis of disseminated tuberculosis was made and patient was started on oral anti-tubercular treatment under category I intensive phase along with parenteral dexamethasone and mannitol. Patient showed remarkable clinical recovery with improved conscious level and appetite. Patient was discharged on 14 th day of admission. Patient is on regular follow-up without any symptoms/signs of complications.
| Discussion|| |
Nearly all the CNS TB is due to the human tubercle bacillus Mycobacterium tuberculosis. TBM begins as a primary infection of the lungs (through inhalation of droplet infectious particles) or rarely following the ingestion of infected milk.  The bacteria may spread over several (usually 2-4) weeks to infect the regional lymph nodes from where bacteraemia may occur, and by hematogenous spread they invade the meninges or the brain parenchyma forming the rich focus where they remain dormant for many years. The reactivation of TB, if host immune vigilance decreases, occurs in the CNS. Most often the rupture of subependymal or subpial Rich focus or an intracerebral tubercle, which is formed during the initial silent hematogenous dissemination of M. tuberculosis, results in TBM. Rarely, the source of TBM is an adjacent extra neural infection, such as in vertebrae, ear, and mastoid sinuses. 
The clinical features of TBM can be influenced by one or more of the following pathophysiologies: 
In the prodrome phase symptoms are mainly constitutional like vague ill health, low-grade fever, apathy, lack of appetite, headache, vomiting, and pain in the abdomen. Later the patient may present with alteration in the level of consciousness (confusion to frank coma). The patient may also present with hemiparesis, aphasia, multiple cranial nerve palsies, visual loss, and seizures (focal or generalized) or with choreiform limb movement disorders. Usually the late symptoms develop with the onset of complications. Other unusual presentations such as generalized myoclonus, rigidity, hiccoughs, retention of urine, gait ataxia, and hearing impairment were documented in some patients. 
- Meningitis and meningeal exudates resulting in meningeal signs, cranial nerve palsies, and hydrocephalus
- Extension of inflammation to brain parenchyma, resulting in alteration of sensorium, seizure, hypothalamic, and brainstem signs
- Vasculitis and tuberculoma are responsible for focal neurological deficits
- Allergic and hypersensitivity responses resulting in massive brain edema and raised intracranial pressure in the absence of hydrocephalus.
Investigations that may help in the diagnosis of TBM include full blood count and ESR, which may typically show leucopoenia and/or normal WBC count. There may be anaemia with elevated ESR. Electrolyte urea and creatinine may show hyponatremia due to development of the syndrome of inappropriate ant diuretic hormone secretion. In about 10% of patients the urinalysis may show WBCs without significant bacteriuria, that is, sterile pyuria. 
Lumbar puncture is the cornerstone of diagnosis. In general, examination of cerebrospinal fluid (CSF) reveals a high leukocyte count (up to 1000/L), usually with a predominance of lymphocytes but sometimes with a predominance of neutrophils in the early stage; a protein content of 1-8 g/L (100-800 mg/dL); and a low glucose concentration. However, any of these three parameters can be within the normal range. AFB is seen on direct smear of CSF sediment in up to one-third of cases, but repeated lumbar punctures increase the yield. Culture of CSF is diagnostic in up to 80% of cases and remains the gold standard. Polymerase chain reaction has a sensitivity of up to 80%, but rates of false-positivity reach 10%. Imaging studies (CT and MRI) may show hydrocephalus and abnormal enhancement of basal cisterns or ependyma. If unrecognized, TBM is uniformly fatal. This disease responds to chemotherapy; however, neurological sequelae are documented in 25% of treated cases, in most of which the diagnosis has been delayed. Clinical trials have demonstrated that patients given adjunctive glucocorticoids may experience faster resolution of CSF abnormalities and elevated CSF pressure. 
The tuberculin skin test may be negative in some patients with comorbid immunosuppressive illness like in our patient. Electroencephalographic studies often show diffuse slowing. Meningeal calcification may be obvious on skull X-ray while chest X-ray may show pneumonic process, adenopathy, fibronodular changes, cavitations, and pleural effusion if there is associated tuberculous involvement of the lungs.
The patient should be screened for immunodeficiency states such as HIV, diabetes mellitus, Vitamin D deficiency,  and so on. The unusual clinical and laboratory features such as the presence of high grade fever, normal tuberculin test, the presence of normal CSF ADA level and normal CSF microscopy culture and sensitivity may lead to misdiagnosis or late diagnosis of TBM with the attendant high rate of morbidity and mortality.
Multiple drug treatment is required in the management of TBM and the drugs should adequately cross the blood-CSF barrier to achieve a therapeutic concentration in the CSF. Four major drugs are considered the first-line agents for the treatment of TB: Isoniazid, rifampin, pyrazinamide, and ethambutol. These drugs are well absorbed after oral administration, with peak serum levels at 2-4 h and nearly complete elimination within 24 h. These agents are recommended on the basis of their bactericidal activity (i.e., their ability to rapidly reduce the number of viable organisms and render patients non-infectious), their sterilizing activity (i.e., their ability to kill all bacilli and thus sterilize the affected tissues, measured in terms of the ability to prevent relapses), and their low rate of induction of drug resistance. 
Because of a lower degree of efficacy and a higher degree of intolerability and toxicity, six classes of second-line drugs are generally used only for the treatment of patients with TB resistant to first-line drugs. Included in this group are the injectable amino glycosides streptomycin (formerly a first-line agent), kanamycin, and amikacin; the injectable polypeptide capreomycin; the oral agents ethionamide, cycloserine, and P AS; and the fluoroquinolone antibiotics. Of the quinolones, third-generation agents are preferred: Levoflox acin, gatifloxacin (no longer marketed in the United States because of its severe toxicity), and moxifloxacin. Today amithiozone (thiacetazone) is used very rarely (mainly for MDR-TB) since it is associated with severe and sometimes even fatal skin reactions among HIV-infected patients. Other drugs of unproven efficacy that have been used in the treatment of patients with resistance to most of the first- and second-line agents include clofazimine, amox icillin/clavulanic acid, clarithromycin, imipenem, and linezolid.
Although comparative clinical trials of treatment for extra pulmonary TB are limited, the available evidence indicates that most forms of disease can be treated with the 6-month regimen recommended for patients with pulmonary disease. The American Academy of Paediatrics recommends that children with bone and joint TB, tuberculous meningitis, or miliary TB receive 9-12 months of treatment.  But this could be extended to 18-24 months if there is poor treatment response. If multidrug resistance occurs, second-line drugs should be used.
The adjunctive therapies include intravenous steroids, for example dexamethasone and oral steroids (prednisolone), usually given in the first 1-2 months of therapy to relieve the features of raised intracranial pressure while patients with hydrocephalus will benefit from surgical intervention (ventriculoperitoneal or ventriculoatrial shunt procedure).
The mortality in TBM is 20-30%. In the post-INH era, the neurological and psychiatric sequelae have been reported in 20-50% survivors. The neurological sequelae include spastic hemiparesis, seizures, ataxia, and cranial nerve palsies in decreasing order. 
Recent studies have shown that age, stage of disease, presence of cranial nerve deficit, presence of SIADH, abnormality of electroencephalography, abnormality of motor evoked potentials and low GCS were associated with poor clinical outcome. 
| Conclusions|| |
Atypical presentation of TBM is not uncommon in developing nations like India. Any patient with chronic fever not responding to routine antibiotics presenting with neurological deficits like multiple cranial nerve palsies, aphasia, hemiplegia, generalised rigidity, movement disorders, cognitive defects, and signs of meningeal irritation should raise the suspicion of TBM for Physician. Timely imaging and CSF studies helps in diagnosis since the timing of treatment is crucial for the prognosis.
| References|| |
|1.||Erhabor GE, Adewole OO, Ogunlade O. A five year review of tuberculosis mortality amongst hospitalized patients in Ile-Ife. Indian J Chest Dis Allied Sci 2006;48:253-6. |
|2.||Kalitha J, Misra UK. Tuberculous meningitis. Diagnosis and management of neurological disorders, 1 st ed. New Delhi: Lippincott Williams & Wilkins 2011. p.145-65. |
|3.||Davis LE. Tuberculous meningitis. In: Davis LE, Kennedy PG, editors. Infectious Diseases of the Nervous System. Oxford: Butterworth-Heinemann; 2000. p. 481-98. |
|4.||Ravighone MC, O'Brien RJ. Tuberculosis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, et al. Harrison's Principles of Internal Medicine, 18 th ed. New Delhi: McGraw-Hill; 2012. p. 1340-59. |
|5.||Osuntokun BO. Tuberculous meningitis in Nigerians; a study of 194 patients. Trop Geogr Med 1971;23:225-31. |
|6.||Merritt HH, Fremont-Smith F. Cerebrospinal fluid in tuberculous meningitis. Arch Neurol Psychiatry 1933;33:516-36. |
|7.||Afrozul haq. Global vitamin D deficiency and its role in health and disease, 1 st Abu Dhabi international conference on vitamin D deficiency. Int J Nutr Pharmac Neurol Dis 2013;3:58. |
|8.||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 multivariate analysis. J Neurol Neurosurg Psychiatry 2000;68:300-16. |
[Figure 1], [Figure 2]