Central sleep apnea in a patient with dengue encephalitis

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Case Report

Central sleep apnea in a patient with dengueencephalitis

Suresh Ramasubban a,*, Lawni Goswami a, Narayan Banerjee b

a Department of Sleep Medicine & Critical Care Medicine AGHL, Kolkata, Indiab Department of Internal Medicine AGHL, Kolkata, India

a r t i c l e i n f o

Article history:

Received 30 January 2015

Accepted 9 February 2015

Available online xxx

Keywords:

Encephalitis

Leucopenia

Mild thrombocytopenia

Polysomnographic evaluation

* Corresponding author.E-mail address: drsuresh@hotmail.com (S

Please cite this article in press as: RamaMedicine (2015), http://dx.doi.org/10.1016

http://dx.doi.org/10.1016/j.apme.2015.02.0150976-0016/Copyright © 2015, Indraprastha M

a b s t r a c t

We report for the first time a case of Central sleep apnea in a patient with dengue en-

cephalopathy. This is a case report of a 50 year old male who had presented with fever,

body ache, headache and altered mental status. A diagnosis of dengue fever was made on

the basis of IgM antibodies in serum and encephalopathy was attributed to dengue en-

cephalitis in the absence of another etiological cause of encephalopathy. Persistent hyper

somnolence and desaturation despite resolution of fever led to a polysomnographic eval-

uation, which revealed significant central sleep apnea. Hypersomnia, a primary complaint

of excessive sleepiness is frequently seen in neurological conditions like neurodegenera-

tive and genetic disorders, stroke, head trauma, encephalitis, and brain tumors. Some

encephalitis such as bulbar poliomyelitis, Western equine encephalitis, listeria mono-

cytogenes brainstem encephalitis, and paraneoplastic brainstem encephalitis & Japanese

encephalitis have been reported to cause central apnea. This is the first reported case of

Central sleep apnea associated with Dengue infection.

Copyright © 2015, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Introduction

Central apnea is characterized by a lack of central drive to

breathe and is identified by cessation of airflowwith cessation

of respiratory efforts.1 Dengue encephalitis is itself a rare

complication of Dengue fever and incidence of respiratory

disturbance in this encephalitis is not well reported as

compared to other arboviral encephalitis. To our knowledge

there are no reports of central sleep apnea due to Dengue

encephalitis as proven by polysomnography. In this case

report we present a patient with Dengue encephalitis who

. Ramasubban).

subban S, et al., Centra/j.apme.2015.02.015

edical Corporation Ltd. A

developed Central sleep apnea confirmed by a full laboratory

based polysomnography.

2. Case report

A 59-year-old obese male (BMI 25.4) was admitted to the hos-

pital with complaints of high-grade fever, and altered mental

status. Patient was well about five days prior to admission

whenhe developed fever associatedwith body aches, lowback

pain and anorexia. Fever was not associated with cough,

l sleep apnea in a patient with dengue encephalitis, Apollo

ll rights reserved.

a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) 1e42

coryzaoranyother respiratory symptoms.Healsodidnothave

any urinary symptoms. Over the next couple of days contin-

uous high-grade fever was present and subsequently he was

noted to be lethargic and drowsy necessitating an emergent

admission via the emergency department (ED).

Review of his past medical history revealed the presence of

a well-controlled Diabetes Mellitus on Metformin. He had no

history of hypertension, coronary artery disease or hypothy-

roidism. He did not consume alcohol on a regular basis and

was a half pack per day smoker. He did not have history of

loud snoring, witnessed apneas or excessive daytime

somnolence.

On arrival in the ED, he appeared ill and assessment

revealed a temperature of 101F, tachycardia, tachypnea and

blood pressure of 150/80. There was a diffuse erythematous

rash, blanching with pressure prominent on the trunk and

mild petechiae over the lower extremity. Auscultation of the

chest was normal and oxygen saturationwas 95% on room air.

He was drowsy, easily arousable with no neck stiffness or any

cranial nerve or focal motor deficit. Pupillary response to light

was normal and consensual reflex was also normal. Sensory

examination was limited due to drowsiness and the plantar

response was flexor bilaterally.

His initial laboratory evaluation revealed a normal he-

matocrit, leucopenia, mild thrombocytopenia, elevated

transaminitis and normal renal parameters. Chest radiolog-

ical examination was normal with no focal consolidation.

Computerized tomographic evaluation of the brain also was

normal and there was no infarcts or hemorrhage. A rapid

diagnostic test for dengue was positive for both IgM and IgG

antibodies and patient was admitted to the wards with a

working diagnosis of Dengue fever.

He was managed in the ward with closely monitored fluid

resuscitation, resulting in a restoration of hemodynamics very

rapidly over the first 6e8 h itself. Over the next 72 h his blood

parameters also stabilized. He did not have hypotension,

altered renal function, liver function and any electrolyte ab-

normality. However his fever and drowsiness persisted. On day

5 of admission, he became delirious and agitated and was

shifted to the intensive care unit (ICU). A lumbar Puncture was

performed and cerebrospinal fluid (CSF) analysis revealed

normal cell count withmildly elevated protein of 60mg/dl. EEG

evaluation did not reveal any seizure activity. Fever and

headache did not resolve over next 7 days and in view of

persistent alteredmental status amagnetic resonance imaging

of the brain was obtained which did not reveal any infarcts,

hemorrhage or focal hyper intensities. A repeat CSF analysis

revealed a lymphocytic pleocytosis (60 cells) with elevated

protein of 60 mg/dl, normal adenosine deaminase levels, with

negative polymerase chain reaction to TB and herpes Simplex

virus type 1 (HSV). A diagnosis of dengue encephalitis was

made on the basis of encephalopathy in a patient with sero-

logically confirmed dengue fever with absence of an alternative

explanation i.e. absence of shock/renal/liver failure. Fever

finally resolved after 15 days, however patient remained

drowsy. Repeat CSF on day 20 revealed decreasing CSF pleo-

cytosis (cell count 3) and decreasing protein concentration in

CSF (58 mg/dl) with repeatedly normal ADA and TB& HSV PCR.

Despite resolution of fever, his drowsiness persisted and

during sleep he was observed to have episodes of

Please cite this article in press as: Ramasubban S, et al., CentraMedicine (2015), http://dx.doi.org/10.1016/j.apme.2015.02.015

desaturation. In view of presence of desaturation only during

sleep a diagnosis of sleep-disordered breathing was enter-

tained. The presence of drowsiness, mild obesity and desa-

turation prompted a full polysomnographic evaluation.

He underwent a standard overnight polysomnography

with multichannel electroencephalographic (EEG), electro-

myographic (EMG) and electrooculographic (EOG) recording

and respiratory monitoring using a nasal thermistor. The

sleep study was supervised and performed with the Alice 5

recording system (Respironics, Carlsbad, CA, USA). A single

sleep technologist recorded and reported the study according

to the criteria of Rechtschaffen and Kales, after which an

accredited sleep physician reviewed and reported the study

findings, scored the sleep study. His polysomnographic find-

ings revealed a total sleep time of 358 min, Sleep latency of

1 min, fragmented sleep with predominant slow wave sleep

and absence of REM sleep. Respiratory monitoring revealed

mild snoring and a predominant central apnea pattern with

the apnea-hypopnea index (AHI) was 19, the average duration

of apnea was 12 s, and the longest duration of apnea was 34 s.

Significant oxygen desaturation was noted with a desatura-

tion index of 18/hour, with lowest level of 80%.

3. Discussion

40% of the world's population is at risk for dengue due to its

endemicity.2 Infection can range from asymptomatic infec-

tion to severe infection. Encephalopathy and neurologic

complications like transverse myelitis, Gullian barre syn-

drome, acute disseminated encephalomyelitis are well re-

ported. Encephalopathy usually occurs as a result of an

indirect insult in the form of liver failure, shock, cerebral

edema and deranged electrolytes. Very rarely there is a direct

neurotopism of the virus causing encephalitis. Since the other

arboviruses like west Nile and Japanese encepahalitis cause

direct neural invasion, it is not surprising than dengue also

can result in infection of the central nervous system. Thus

encephalitis is a distinct clinical entity. The largest evidence

for dengue encephalitis comes fromMisra et al,3 they describe

11 encephalopathic patients with confirmed dengue infection,

who had extensive evaluation to exclude nonencephalitic

cases and 8 of them had CSF pleocytosis suggesting a viral

meningoencephalitis process. Similar cases from Solomon

et al4 from Vietnam suggest that in case of dengue encepha-

litis, all patients had CSF pleocytosis, focal neurologic signs or

seizure and dengue confirmed in serum. A case definition of

dengue encephalitis as proposed by Varatharaj5 includes

fever, headache, reduced consciousness which is not

explained by liver failure, shock, electrolyte derangements

and intracranial hemorrhage and which is corroborated with

dengue virus or IgM in serum or CSF. In this patient a diag-

nosis of Dengue encephalitis was based on the case definition

proposed by Varatharaj.

Encephalitis per se rarely leads to respiratory disturbance.

Some encephalitis such as bulbar poliomyelitis, Western

equine encephalitis, listeria monocytogenes brainstem en-

cephalitis, paraneoplastic brainstem encephalitis and Japanese

encephalitis have been reported to cause central apnea.6 There

is even a case of transient obstructive apneaswith encephalitis.

l sleep apnea in a patient with dengue encephalitis, Apollo

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In Dengue encephalitis there have been no case reports of res-

piratory disturbance so far. This is the first reported case of

dengue encephalitiswith sleep disordered breathing suggestive

of central sleep apnea. In our patient, a full PSG revealed a

diagnosis of central sleep apnea, as both thoracic and abdom-

inal movements were not seen with cessation of airflow.

Many neurological conditions like stroke, dementia, en-

cephalitis have been associated with sleep apnea especially

when they cause injury to the brainstem. Spontaneous

respiration is initiated by the medullary respiratory center,

which is composed of the dorsal respiratory group (DRG) (the

nucleus solitarius) and the ventral respiratory group (VRG)

Please cite this article in press as: Ramasubban S, et al., CentraMedicine (2015), http://dx.doi.org/10.1016/j.apme.2015.02.015

(includes the nucleus ambiguus).7 In our patient there was no

MRI evidence of injury to the VRG, so it is possible that the

central sleep apnea is the result of damage to the VRGwhich is

not visible with the present MRI technology. During sleep,

most behavioral influences on breathing are lost and respi-

ration is largely dependent on chemical control mechanisms;

therefore, central sleep apnea arises.

In conclusion physicians should be aware of the possibility

of Dengue encephalitis and the presence of sleep disordered

breathing in this group of patients. This also stresses the

importance of polysomnography for the diagnosis of sleep-

disordered breathing.

l sleep apnea in a patient with dengue encephalitis, Apollo

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Conflicts of interest

All authors have none to declare.

r e f e r e n c e s

1. Eckert DJ, Jordan AS, Merchia P, Malhotra A. Central sleepapnea: pathophysiology and treatment. Chest.2007;131:595e607.

2. Guzman MG, Halstead SB, Artsob H, et al. Dengue: a continuingglobal threat. Nat Rev Microbiol. 2010;8(suppl l):S7eS16.

Please cite this article in press as: Ramasubban S, et al., CentraMedicine (2015), http://dx.doi.org/10.1016/j.apme.2015.02.015

3. Misra IK, Kalita J, Syam UK, Dhole TN. Neurologicalmanifestation of dengue virus infection. J Neurol Sci.2006;244:117e122.

4. Solomon T, Nm Dung, Vaughn DW, Kneen R, Thao LT, et al.Neurological manifestations of dengue infection. Lancet.2000;355:1053e1059.

5. Varatharaj A. Encephalitis in the clinical spectrum of dengueinfection. Neurol India. 2010;58.

6. Miura S, Noda K, Kusumoto M, Tomioka R, et al. Central sleepapnea in a patient with Japanese encephalitis. Neurol Asia.2008;13:77e81.

7. Dyken ME, Afifi AK, Lin-Dyken DC. Sleep-related problems inneurologic diseases. Chest. 2012;141:528e544.

l sleep apnea in a patient with dengue encephalitis, Apollo

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