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\begin{document}

\title{Encephalitis associated with cervical lymph nodes tuberculosis in a
patient with human immunodeficiency virus infection: A case report}



\author[1]{Rizaldy Pinzon}%
\author[1]{Hana Kristina}%
\affil[1]{Duta Wacana Christian University Faculty of Medicine}%


\vspace{-1em}



  
  \date{June 17, 2024}


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\selectlanguage{english}
\begin{abstract}
The risk of extrapulmonary tuberculosis increases in patients with human
immunodeficiency virus (HIV) infections. Encephalitis is a rare form of
extrapulmonary tuberculosis infection. We report a case of encephalitis
associated with cervical lymph nodes tuberculosis in a patient with
human immunodeficiency virus (HIV) infections.%
\end{abstract}%



\sloppy


\textbf{Encephalitis associated with cervical lymph nodes tuberculosis
in a patient with human immunodeficiency virus infection: A case report}

Rizaldy Taslim Pinzon\textsuperscript{1,2*}, Hana
Kristina\textsuperscript{1,2}

1 Duta Wacana Christian University School of Medicine, Yogyakarta,
Indonesia

2 Bethesda Hospital, Yogyakarta, Indonesia

* Corresponding author: Rizaldy Taslim Pinzon

Address: Duta Wacana Christian University School of Medicine, Wahidin
Sudirohusodo st 5-

25, Yogyakarta 55224, Indonesia. E-mail address: drpinzon17@gmail.com

\textbf{Key Clinical Message}

The risk of extrapulmonary tuberculosis increases in patients with human
immunodeficiency virus (HIV) infections. Encephalitis is a rare form of
extrapulmonary tuberculosis infection. We report a case of encephalitis
associated with cervical lymph nodes tuberculosis in a patient with
human immunodeficiency virus (HIV) infections.

\textbf{Keywords}

Encephalitis, Cervical lymph nodes tuberculosis, Human immunodeficiency
virus infection

\textbf{Introduction}

From 2003 to 2014, 27 countries of the EU/EEA have reported that 83\% of
tuberculosis patients had pulmonary infection only and 17\% of
tuberculosis patients had extrapulmonary infections\textsuperscript{1}.
The risk of extrapulmonary tuberculosis increases higher compared with
pulmonary tuberculosis in patients with HIV\textsuperscript{2}. It is
estimated a total of 208,000 deaths from tuberculosis among HIV-positive
individuals. In 2019, Indonesia had a tuberculosis burden of
8.5\%\textsuperscript{3}.

The most common location of head and neck tuberculosis is cervical lymph
nodes\textsuperscript{4}. Lymph nodes tuberculosis is common in children
and women. Tuberculous cervical lymphadenitis is often found along with
the increasing incidence of HIV infection\textsuperscript{5}.

Neurological involvement is reported in 3\% of extrapulmonary
tuberculosis infections\textsuperscript{1}. Central nervous system
tuberculosis usually appears as tuberculous meningitis, tuberculous
brain abscess, or intracranial tuberculoma\textsuperscript{6}. Its
manifestation as encephalopathy is rare and reported more common in
children\textsuperscript{7}. We report a case of encephalitis associated
with cervical lymph nodes tuberculosis in patients with HIV infection.

\textbf{Case Report}

A 50-year-old man visited the emergency unit with slurred speech,
difficulty swallowing, and involuntary movements of the right upper
extremity. Prior to complaints of involuntary movement of upper limb,
the patient complained of vomiting due to a hot and pressure-like
feeling on his throat. Then, he complained of slurred speech and
difficulty swallowing. These complaints appeared an hour and a half
before arriving at the hospital. All complaints disappeared as soon as
he arrived at the hospital. The patient also complained of numbness of
the right hand since one month before arrival. However, there were no
complaints of fever, headache, or cough. The patient had a history of
hospitalization 6 months before with dizziness. His next house neighbour
was reported having cough for months but the cause was unknown.

Based on physical examination, the patient was found to be compos
mentis. The patient has a temperature of 36.1\textsuperscript{o}C, pulse
of 112 beats/minute, respiratory rate of 22 breaths/minute, blood
pressure of 149/81 mm/Hg., and oxygen saturation of 96\%. The patient
had a fever with a temperature of 38.0\textsuperscript{o}C on the first
night of hospitalization, then the temperature immediately return to
normal after receiving paracetamol. He has no neck stiffness but has
bilateral cervical lymphadenitis. Based on neurological examination,
numbness was found in the patient's right palm. The result of cranial
nerves and motor examinations were normal.

Further, computed tomography (CT) scan of the head showed a hypodense
lesion in the left parietal lobe (Fig.1). The chest radiograph showed
peribronchial and parenchymal infiltrates (Fig. 2). Laboratory tests
showed a positive HIV antibody test. Cervical lymph node biopsy showed
the presence of cheese granulomatous inflammation and positive acid-fast
bacilli.\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

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Figure 1. Hypodense lesion in left parietal lobe on CT scan\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

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Figure 2. Peribronchial and parenchymal infiltrates on chest X-ray

The patient was given a fixed-dose combination of antituberculosis
therapy consisting of isoniazid (225 mg), rifampicin (450 mg),
ethambutol (825 mg), and pyrazinamide (1200 mg). The follow up showed
significant improvement.

\textbf{Discussion}

Encephalitis is caused by inflammation of the brain parenchyma causing
neurological dysfunction. The major criterion of encephalitis is an
altered mental status that remains for more than 24 hours without an
alternative diagnosis. Then, there are six minor criteria such as (1)
fever \textgreater{}38\textsuperscript{o}C within 72 hours before or
after symptom onset, (2) new onset of focal neurologic disorder, (3)
abnormality on electroencephalography consistent with encephalitis and
not secondary to another etiology, (4) CSF white blood cells count
\textgreater{} 5 mm\textsuperscript{2}, (5) acute onset of neuroimaging
abnormality consistent with encephalitis, (6) seizures not associated
with a pre-existing seizure disorder. The presence of 2 minor criteria
indicates possible encephalitis and the presence of more than 3 minor
criteria indicates probable or confirmed encephalitis (if the etiologic
agent is confirmed by polymerase chain reaction, serology, or brain
biopsy)\textsuperscript{8}. This case met 2 minor criteria of fever of
38\textsuperscript{o}C 24 hours after symptom onset and the presence of
new onset of focal neurologic disturbances of dysarthria, dysphagia, and
involuntary movements.

Clinical overlap between encephalitis and encephalopathy may occur in
which encephalopathy leads to a clinical condition of altered mental
status that can manifest as disorientation, confusion, or other
cognitive impairment, with or without evidence of brain tissue
inflammation. Encephalopathy can be triggered by some toxic or metabolic
conditions but sometimes occurs in response to infectious agents such as
the influenza virus and \emph{Bartonella henselae}
\textsuperscript{9,10}.

Patients with neurotuberculosis have few specific symptoms. Delay in
diagnosis must be considered, usually due to a mild initial neurologic
presentation in most cases, if compared with other infectious
encephalitis\textsuperscript{11}. Based on a report in France, only 20\%
of patients had a previous history of tuberculosis. Besides, only 20\%
of patients had respiratory symptoms\textsuperscript{12}. In this case,
the patient came with a mild initial neurologic presentation and had no
respiratory symptoms indicated by no history of cough.

Brain MRI is the best device for the diagnosis of encephalitis. CT scan
is used only when MRI is not possible\textsuperscript{13}. There are no
specific features for encephalitis except in brain abscess or
granulomatous lesions cases. A study in France revealed that CT scan and
MRI scan were normal in 8 of 17 patients. It means that there is a
possibility of a diagnosis of tuberculosis being ruled out in cases of
normal imaging\textsuperscript{12}.

There are no conventional lymphatics in the brain, but physiological
studies showed immunologically significant drainage from the brain to
cervical lymph nodes. Perivascular lymphatic drainage from the central
nervous system has an important role in neuroimmunological reactions on
autoimmune diseases and the same mechanism also plays a role in
infection of the central nervous system\textsuperscript{14--16}.

Specific antituberculosis therapy can be associated with the prolonged
onset of action, especially in patients with severe brain
damage\textsuperscript{17}. The standard recommended therapy is
fixed-dose combinations of 4 drugs (isoniazid, rifampicin, ethambutol,
and pyrazinamide) for 6 months intensively. Sudden discontinuation of
treatment is an independent risk factor for mortality in patients with
central nervous system tuberculosis\textsuperscript{11}.

\textbf{Conclusion}

The HIV risk factor has to be considered in extrapulmonary tuberculosis.
The physician has to observe for signs and symptoms that can be atypical
of tuberculous encephalitis. Delay in the initiation of antimicrobial
therapy in patients with encephalitis tuberculosis is associated with
increased mortality and risk of neurological
sequelae\textsuperscript{18}.

\textbf{Conflict of Interest}

None declared.

\textbf{Authorship}

RTP was responsible for the initial manuscript, data processing, imaging
report, and supervision. HK was involved in the manuscript's preparation
and editing.

\textbf{Funding}

This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors.

\textbf{References}

1. Sotgiu, G., D. Falzon, V. Hollo, et al. 2017. Determinants of site of
tuberculosis disease: An analysis of European surveillance data from
2003 to 2014. \emph{PLoS One} \textbf{12} : 1-14.

2. Shivakoti, R., D. Sharma, G. Mamoon, and K. Pham. 2017. Association
of HIV infection with extrapulmonary tuberculosis: a systematic
review.\emph{Infection} \textbf{45} : 11-21.

3. World Health Organization. Global Tuberculous Report 2020. Geneva:
World Health Organization; 2020.

4. Pang, P., W. Duan, S. Liu, et al. 2018. Clinical study of
tuberculosis in the head and neck region - 11 years' experience and a
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5. Rajasekaran, S., M. Gunasekaran, D. D. Jayakumar, D. Jeyaganesh, and
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6. Kim, H. J., K. W. Shim, M. K. Lee, et al. 2011. Tuberculous
encephalopathy without meningitis: Pathology and brain MRI
findings.\emph{Eur. Neurol} . \textbf{65} : 156-159.

7. Dev, N., M. Bhowmick, S. Chaudhary, and J. Kant. 2019. Tuberculous
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8. Venkatesan, A., A. R. Tunkel, K. C. Bloch, et al. 2013. Case
definitions, diagnostic algorithms, and priorities in encephalitis:
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9. Tunkel, A. R., C. A. Glaser, K. C. Bloch, et al. 2008. The management
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10. Weitkamp, J. H., M. D. Spring, T. Brogan, H. Moses, K. C. Bloch, and
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11. Stahl, J. P. 2019. Tuberculous Encephalitis. Pp. 121-130 in A Sener,
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12. Honnorat, E., T. De Broucker, A. Mailles, and J. P. Stahl. 2013.
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13. Stahl, J. P., P. Azouvi, F. Bruneel, et al. 2017. Guidelines on the
management of infectious encephalitis in adults. \emph{Med. Mal. Infect}
. \textbf{47} : 179-194.

14. Weller, R. O., E. Djuanda, H. Y. Yow, and R. O. Carare. 2009.
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disease. \emph{Acta Neuropathol} . \textbf{117} : 1-14.

15. van Zwam, M., R. Huizinga, N. Heijmans, et al. 2008. Surgical
excision of CNS-draining lymph nodes reduces relapse severity in
chronic-relapsing experimental autoimmune encephalomyelitis. \emph{J.
Pathol.} \textbf{217} : 543-551.

16. Thwaites, G. E., R. van Toorn, and J. Schoeman. 2013. Tuberculous
meningitis: More questions, still too few answers. \emph{Lancet Neurol}
.\textbf{12} : 999-1010.

17. Goulenok, T., R. Buzel\selectlanguage{ngerman}é, X. Duval, F. Bruneel, J.P. Stahl, and B.
Fantin. 2017. Management of adult infectious encephalitis in
metropolitan France. \emph{Med. Mal. Infect} . \textbf{47} : 206-220.\selectlanguage{english}
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