Early Guillain-Barré Syndrome Complicating Dengue Fever: Two Cases from Myanmar

Abstract

Dengue fever is a mosquito-borne flavivirus which creates a heavy burden of clinical illness in tropical and subtropical countries, including Myanmar. Although it has very wide clinical presentations, neurological manifestations are quite rare. Here we report two cases of Guillain-Barré syndrome complicating dengue fever. In both cases Guillain-Barré syndrome occurred in the first week of fever, which is unusual compared with other case reports and literature review14. Motor weakness of case 1 patient was severe and the patient underwent plasma exchange for 10 days. Case2 had mild motor weakness and needed only conservative treatment. Nerve conduction study of both cases revealed variant types of Guillain-Barré syndrome which are more common in Asian countries, specifically acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN).^6,8 Both cases ended with complete recovery. Awareness of early Guillain-Barré syndrome in patients with dengue fever is important in order to potentially reduce morbidity and mortality from this serious complication.

Introduction

Dengue is an important global public health problem. The World Health Organization reports that dengue incidence has grown dramatically in recent decades and about half of the world’s population is at risk.³ According to a Ministry of Health and Sports report from Myanmar, the incidence of dengue cases is rising annually. Reported number of dengue cases increased from 1,654 in 1970 to 42,913 in 2015. The case fatality rate decreased from 5.50% in 1970 to 0.33% in 2015.¹⁰ Dengue infection is one of the highest morbidity diseases in Myanmar. Most dengue infections are mild and end with complete recovery. But dengue can be very severe and have fatal outcomes. Atypical presentations including neurological manifestations (1-5%) are one of the recognized complications of dengue virus and can be fatal if not treated properly.¹² Encephalitis, myelitis and meningitis are the most common neurological presentation of dengue and 30% of those with neurological complications present with Guillain-Barré syndrome.¹⁶

Case report

Case 1 was a 20-year-old man who presented with 4 days of fever with myalgia and joint pain. On the 3rd day of fever, he developed bilateral lower limb weakness with are flexia, motor power 3/5 which was ascending in nature with sensory impairment up to mid-thigh but without sphincter and cranial nerve involvement. His vital signs were stable with no respiratory distress despite motor weakness. Investigations on 3rd day of fever revealed dengue NS1 Ag positive, IgM and Ig G negative. But dengue infection was confirmed by dengue ELISA test which showed IgM positive and IgG negative. On the day of admission, Hgb 12, Hct41, WBC 3.2, Plt 140. Serial monitoring of full blood counts revealed WBC nadir was 1.9 and Plt nadir was 76 on 6^th day. Both WBC and Plt count returned to normal on 8^th day of fever. His hepatic and renal function, serum calcium and albumin level were normal. Hepatitis B, C and HIV serologies were negative. ANA was low at 1:100. CSF study was done on 5^th day of illness and revealed protein 0.2g/L, cells 2/mm3 and 100% lymphocyte, glucose was 2.8mmol/L which was 70% of blood sugar. Due to limitation in investigation, CSF dengue PCR was not done. Nerve conduction study showed acute motor sensory axonal polyneuropathy. He underwent 10 days of plasma exchange and motor weakness improved on day three of plasma exchange. He fully recovered motor strength and sensation 3 months post dengue fever.

Case 2 was a 16-year-old man who presented with 7 days’ fever with cough, muscle and joint pain. On day three of fever, he developed bilateral lower limbs weakness which was ascending in nature with muscle power of grade 4/5, aflexia without sensory, sphincter and cranial nerve involvement. His vital signs were stable with no respiratory distress. Investigations revealed dengue NS1 Ag positive, Ig M and Ig G negative. But ELISA for dengue IgM was positive and serum dengue PCR was also done to confirm the diagnosis and it revealed DEN-3. Full blood count was done on admission i,e 7th day of illness – Hgb 11, Hct 40, Wbc 3.0 and Plt 100. On serial monitoring WBC nadir was 2 and Plt count nadir was 90. Both WBC and Plt count returned back to their normal value on 10th day of fever. His liver function revealed ALT 23 U/L,AST 118 U/L with normal serum bilirubin and ALP. Renal function was normal. Hepatitis B, C and HIV serologies were negative. ANA was low at 1:100. CSF study revealed protein 0.5g/L, cell count 0 with normal sugar which was more than 60% of blood sugar on 8th day of illness. Nerve conduction study showed acute motor axonal neuropathy. As his motor weakness was mild, he did not need immunotherapy and was referred for physiotherapy. He fully recovered motor strength one month post dengue fever.

Discussion

Guillain-Barré syndrome is a rare presentation of dengue fever. Common infections preceding Guillain-Barré’ syndrome include Campylobacter jejuni, Influenza, Cytomegalovirus, Epstein-Barr virus, Zika virus, Hepatitis A, B, C, D and E, HIV and Mycoplasma.⁹ There are four closely related dengue serotypes (DEN-1, DEN-2, DEN3 and DEN-4). DEN-2 and DEN-3 are the most reported serotypes associated with neurological complications such as meningitis, myelitis and encephalitis.¹³ In our second case dengue serotype 3 was found. There are numerous case reports of GBS complicating dengue fever. Some cases had only mild weakness while others ended with severe weakness requiring ventilation support.^2,14 Other causes of motor weakness more common in Asia such as hypokalemic periodic paralysis and acute myopathy need to be excluded. Serum potassium were 4 and 3.8 and serum creatinine kinase were 130 U/L and 148 U/L respectively in case 1 and 2, thus excluding hypokalemic periodic paralysis and acute myopathy. In both case 1 and 2, muscle weakness developed within the first week of fever, unlike other case reports in which GBS usually developed after one week of fever.^1,14 Neurological manifestations in dengue can occur between two and 30 days after the onset of fever like our cases.¹⁷ GBS can occur due to autoimmune causes is well established. But GBS can also occur be due infections which directly affect peripheral nerves. That point was highlighted in Simon et al’s report regarding three cases about early GBS associated with acute dengue fever. In those cases, GBS developed during 1 week of fever, similar to our cases. In those cases, dengue fever was confirmed by serum and CSF DENV. Unfortunately, CSF DENV cannot be done in our hospital. Those 3 cases also revealed normal CSF results like ours. They all ended with complete recovery with IV Ig treatment.⁷ Typical CSF result of GBS (i,ecytoalbuminous dissociation) is seen in only 50% of patients with GBS.^11,7 Normal CSF results in both our cases may have been due to lumbar puncture occurring within one week of onset of GBS. ¹¹ Nerve conduction study of first case revealed acute motor axonal neuropathy and second case showed acute motor-sensory axonal neuropathy. Nerve conduction studies in both cases were consistent with variants of GBS which are more common in Asian countries.⁵ Variant GBS is more likely due to infectious origin, as opposed to a post-infectious, immune mediated mechanism for GBS. This similar finding was reported by Simon et al in 2016. ¹⁵ Both of our cases were primary dengue infection. The dengue serotype of second case was dengue type 3 which is regarded as a neurotrophic type of dengue virus.^13,4,5 Our first case underwent plasma exchange for 10 days because of severe motor weakness but the second case had mild motor weakness and only needed conservative treatment with physiotherapy. Finally both cases ended with complete recovery. Despite immunotherapy, 20% of patients remain severely disabled and approximately 5% die.⁷ Clinicians need to keep a high index of suspicion for dengue with GBS when patients present with any motor or sensory disturbance, immediately after dengue symptoms begin, and up to one month after presentation.

Figure 1- (A) Case 1 motor weakness and sensory impairment started to improve on Day 3 of plasma exchange (B) case 1 regained normal daily activity 3 months post-dengue infection.

Figure 2 – Case 2 regained normal motor power one-month post-dengue infection

Consent

Written informed consent was obtained from both patients for publication of these case reports and any accompanying images, respectively.

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Author Information

Aye Mya Theingi Win¹, Moe Moe San²

Tropical and Infectious Diseases Department, Yangon General Hospital