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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 6  |  Page : 1802-1804

New Onset Refractory Status Epilepticus as a Manifestation of Tuberculosis of the Central Nervous System

1 Harrogate District Hospital, Harrogate, United Kingdom; Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
2 Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
3 Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India

Date of Submission16-Oct-2018
Date of Decision13-Jul-2019
Date of Acceptance24-Sep-2020
Date of Web Publication23-Dec-2021

Correspondence Address:
Dr. Preet Mukesh Shah
21 Rajvi Building, Flat 102, K.A.S. Road, Matunga, Mumbai - 400 019, Maharashtra

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.333528

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 » Abstract 

A 28-year-old male presented to us with new onset refractory status epilepticus. Prior to his seizures, he had a history of fever, headache and blurring of vision, for which he was admitted elsewhere. No cause was found; he was treated symptomatically and was discharged as his symptoms had abated. Post-discharge, he started having multiple seizures. Neuro-imaging suggested encephalitis. He progressed to status epilepticus and was referred to our center. We intensified the anti-epileptic medications but owing to no response, he had to be put under coma with thiopental, yet the seizures persisted. Workup for the etiology of his seizures was negative except for CSF TB-PCR (Gene Xpert) being positive and hence anti-tuberculous therapy was initiated. By this time, he developed rhabdomyolysis, and thereafter renal failure with dyselectrolytemia, and thus there was a plan to initiate dialysis. But before this could be done, he succumbed to a cardiac arrest secondary to ventricular tachyarrhythmias. We believe this to be the first reported case of new onset refractory status epilepticus secondary to tuberculosis of the central nervous system.

Keywords: Central nervous system, meningoencephalitis, status epilepticus, tuberculosis
Key Message: Tuberculosis may affect the central nervous system in various ways and because it is so prevalent in a country such as India, it should always be considered as a possible etiology in a case of new onset refractory status epilepticus. Tuberculosis of the central nervous system may also present in an acute and rapidly progressive manner, deviating from its usual insidious onset and slowly progressive course. CSF TB-PCR (Gene Xpert) is an important tool in the diagnosis of CNS tuberculosis which provides rapid results, and owing to its high specificity, it should always be performed whenever an infection of the central nervous system is suspected. It is possible to diagnose CNS tuberculosis solely on the basis of TB-PCR (Gene Xpert), even when neuro-imaging, and other CSF studies fail to do so.

How to cite this article:
Shah PM, Deshmukh V, Poncha F, Dhakre V. New Onset Refractory Status Epilepticus as a Manifestation of Tuberculosis of the Central Nervous System. Neurol India 2021;69:1802-4

How to cite this URL:
Shah PM, Deshmukh V, Poncha F, Dhakre V. New Onset Refractory Status Epilepticus as a Manifestation of Tuberculosis of the Central Nervous System. Neurol India [serial online] 2021 [cited 2022 Jan 20];69:1802-4. Available from:

The most common form of tuberculosis of the central nervous system (CNS) is tuberculous meningitis.[1] New onset refractory status epilepticus (NORSE) is mostly secondary to a viral etiology, with tuberculosis not being described as a cause.

Although seizures may occur in a case of CNS tuberculosis usually secondary to tuberculomas or interactions between anti-convulsants and anti-tuberculous drugs,[2] here we have described NORSE being a manifestation of the condition, in the absence of the above two factors.

 » Case History Top

A 28-year-old gentleman who was an officer in the merchant navy, a resident of the northern part of Maharashtra, with no prior history of tuberculosis, presented with continuous fever since 6 days and headache since 3 days. The headache was associated with blurring of vision which spontaneously recovered within 4 hours.

He was first hospitalized at another hospital in view of the fever where his complete blood count was within normal limits, and tests for malaria, dengue, enteric fever, HIV were negative. He received symptomatic therapy, and was discharged after 2 days. Immediately a few hours after discharge, he started having altered behavior, irrelevant talking, blurring of vision and vomiting. He was re-hospitalized, where he had multiple seizures at the time of admission.

Magnetic Resonance Imaging (MRI) Brain (FLAIR sequence) showed bilaterally symmetrical hyper-intense areas in the caudate and lentiform nuclei which were suggestive of encephalitis [Figure 1].
Figure 1: MRI Brain (FLAIR sequence) showing bilaterally symmetrical hyperintense areas in the caudate and lentiform nuclei (yellow arrows), suggesting of encephalitis

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He had to be intubated and put on the ventilator as he was in status epilepticus, and was given anti-epileptics in the form of levetiracetam, lacosamide, phenytoin and propofol; all of which were added in a step-wise manner. As per the history given by the relatives and the transfer summary, there was no preceding respiratory event at the previous center which could have caused hypoxia, and the moment he went into status epilepticus, he was promptly intubated.

CSF analysis showed 18 cells (6 neutrophils and 12 lymphocytes), 75 mg/dL protein, 108 mg/dL sugar, with absence of any organisms on microscopy; cryptococcal antigen and VDRL were negative.

He was empirically started on ceftriaxone, artesunate and acyclovir over there. Since the condition of the patient didn't improve, he was shifted to our center after 1 day.

At the time of presentation to our center, he was sedated with fentanyl and propofol, but despite this he was having continuous seizures. His complete blood count, renal and liver function tests were normal. Lorazepam, valproate, topiramate, midazolam, phenobarbitone and finally thiopental were added, one after the other, for further anti-epileptic coverage.

The patient came to us in an intubated state, and because he was continuously seizing it was not possible to get any neuro-imaging done at our center. Electroencephalogram (EEG) was suggestive of generalized epileptiform activity. After coming to us, his ventilator settings and parameters were optimal, and being monitored, so he was definitely not hypoxic with us.

Repeat lumbar puncture was performed and the CSF was sent for investigations to look for possible viral, mycobacterial or autoimmune etiology. Initial analysis of the CSF showed 16 cells (6 neutrophils and 10 lymphocytes), 68 mg/dL protein, 100 mg/dL sugar, with again no presence of any organisms on microscopy; and cryptococcal antigen and VDRL were again negative.

Two differential diagnoses were considered: the first being viral encephalitis, namely secondary to Japanese encephalitis virus, since it commonly has bilateral involvement of the basal ganglia on neuroimaging. It may also manifest as status epilepticus, especially new onset refractory status epilepticus. The second one was auto-immune encephalitis, which may also present in the form of status epilepticus, with basal ganglia involvement being present on neuroimaging.

Methylprednisolone was empirically added to cover possible auto-immune encephalitis. Continuous EEG monitoring still showed persistent epileptiform activity, hence he received a single dose of IVIg empirically, to cover any possible auto-immune etiology, but was unsuccessful. The CSF (tested using PCR, as part of the “Xcyton Acute Encephalitis Panel”) was negative for viruses such as herpes simplex virus, enterovirus (including polio, coxsackie, echovirus and enteroviruses 70-72), measles virus, mumps virus, rubella virus, Japanese encephalitis virus, dengue virus, west nile virus, rabies virus, nipah virus, chikungunya virus and chandipura virus. CSF was also negative for NMDA receptor antibody, VGKC antibody, anti-CASPR, anti-GABA, anti-LGI, anti-AMPAR, and anti-GAD which were also negative, thus ruling out any auto-immune cause. CSF culture was negative as well. However, CSF TB-PCR (Gene Xpert) was positive for Mycobacterium tuberculosis with no evidence of resistance to rifampicin. Hence he was started on anti-tuberculous therapy which included isoniazid, rifampicin, pyrazinamide and ethambutol (as per the RNTCP protocol).

Rhabdomyolysis due to repeated seizure activity led to acute kidney injury. Dialysis was being planned for him but before it could be initiated, he developed a cardiac arrest, and resuscitation failed.

 » Discussion Top

Meningitis, the commonest form of tuberculosis (TB) of the central nervous system (CNS), accounts for 10% cases of tuberculosis.[1] Encephalitis in TB patients is uncommon.[3] Patients develop meningitis secondary to direct seeding of bacilli during bacteraemia, or due to rupture of an old lesion present in the parameningeal regions.[4] Symptoms are headache, altered sensorium and features of meningeal irritation. Focal neurological signs may be attributable to cranial nerve involvement/vasculitis.[5]

Our patient had new onset refractory status epilepticus (NORSE), which is defined as clinical presentation of new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause, occurring in a patient without active epilepsy or other pre-existing relevant neurologic disorder.[6] This is often secondary to a viral etiology. We found several cases of CNS tuberculosis with seizures in adult patients in medical literature but couldn't find NORSE in a CNS tuberculosis case.

In almost half of cases of CNS tuberculosis, there is a positive chest x-ray finding, which wasn't the case with our patient. Sputum cultures are positive in nearly 40-50% cases,[5] but even this was not a feature seen with our patient. The diagnosis of tubercular meningitis generally depends on CSF examination and imaging. Acid fast bacilli are seen on smear of CSF in only 10 to 20% cases. Rates of positive CSF culture are low as well (approximately 25%).[7] Our patient's CSF culture was negative. In many cases, Mycobacterium tuberculosis is isolated from other sources along with typical CSF findings such as high opening pressure, 100-1000 cells per microliter (with a predominance of lymphocytes), elevated proteins and low sugar.[5] In our case the first CSF showed only 18 cells with merely 12 lymphocytes. These findings did not clearly point towards tuberculosis.

Based on WHO guidelines, nucleic acid amplification test (Gene Xpert) has specificity of around 98%.[7] The CSF Gene Xpert of our patient was positive, thus confirming tuberculosis. We would like to report this case and document the association of NORSE with tubercular involvement of the CNS.

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Conflicts of interest

There are no conflicts of interest.

 » References Top

Kumar K, Giribhattanavar P, Chandrashekar N, Patil S. Correlation of clinical, laboratory and drug susceptibility profiles in 176 patients with culture positive TBM in a tertiary neurocare centre. Diagn Microbiol Infect Dis 2016;86:372-6.  Back to cited text no. 1
Danciu FA, Bistriceanu C. Cerebral tuberculosis and secondary epilepsy-Interactions between antiepileptic and antituberculous treatment. Arch Clin Cases 2015;2:2015.  Back to cited text no. 2
Christie LJ, Loeffler AM, Honarmand S, Flood J, Baxter R, Jacobson S, et al. Diagnostic challenges of central nervous system tuberculosis. Emerg Infect Dis 2008;14:1473-5.  Back to cited text no. 3
Auerbach O. Tuberculous meningitis: Correlation of therapeutic results with the pathogenesis and pathologic changes. I. General considerations and pathogenesis. Am Rev Tuberc 1951;64:408-18.  Back to cited text no. 4
Hopewell P, Kato-Maeda M, Ernst J. Tuberculosis, Murray and Nadel's textbook of respiratory medicine. 2016.  Back to cited text no. 5
Hirsch LJ, Gaspard N, van Baalen A, Nabbout R, Demeret S, Loddenkemper T, et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018;59:739-44.  Back to cited text no. 6
Organization W. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children: Policy update [Internet]. 2018 [cited 6 October 2018]. Available from:  Back to cited text no. 7


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