Abstract
Background
Guillain–Barré syndrome (GBS) is a rare, immune-mediated disorder of the peripheral nerve and roots often triggered by infections.
Purpose
We report clinical profile, electrophysiological variants and response to treatment in five cases of GBS patients following dengue fever.
Methods
Patients fulfilling the National Institute of Neurological and Communicative Disorders and Stroke criteria for GBS following dengue infections were consecutively enrolled. Their demographic, biochemical and nerve conduction study (NCS) was done. According to NCS, they were categorised into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, acute motor sensory axonal neuropathy (AMSAN), inexcitable motor nerve and equivocal. Disability was assessed using the 0–6 Guillain–Barré Syndrome Disability Scale or Hughes Functional Grading Scale.
Results
Five patients of GBS following dengue fever were recruited (3 male and 2 female) with ages between 24 and 55 years. Diagnosis of dengue was based on serological evidence showing IgM and nonstructural protein 1 positivity. All the patients presented with an acute onset of progressive symmetrical flaccid paralysis. NCS showed a demyelinating pattern in four patients and an AMSAN pattern in one patient. All the patients were treated with intravenous immunoglobulin (IVIG) @2 g/kg/body weight given over 5 days. Modified Hughes grade at presentation was 4 in four patients, and one patient had a modified Hughes grade 5. At 1 month of follow-up, the patient with the AIDP variant showed good recovery and was able to ambulate unaided.
Conclusion
GBS following dengue infection usually presents within 2 weeks of infection. In these patients, AIDP variant GBS are more common, and they show good response to IVIG treatment.
Keywords
Background
The Guillain–Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The annual, worldwide incidence has been reported as 1.1–1.8 cases per 100,000 people per year. 1 Several infectious agents have been perpetuated to cause GBS, which include Campylobacter jejuni, Zika virus, dengue virus, Mycoplasma pneumoniae, Haemophilus influenzae, Cytomegalovirus, Epstein–Barr virus and Influenza virus and post-vaccination.2, 3 Dengue fever is an arthropod-borne viral infection, with the highest global burden of the disease occurring in Asia (~70%). 4 Most commonly reported neurological complications of dengue infection are encephalopathy and encephalitis, acute disseminated encephalomyelitis, optic neuritis, myelitis and GBS. 5 There is a paucity of cases of GBS following dengue infection (few case reports only) from India. We hereby present a case series of five patients who developed GBS following dengue infection. The aim of presenting this case series was to know their clinical profile, electrophysiological variants and response to treatment.
Methods
Five patients with GBS following dengue fever were consecutively enrolled. Patients were diagnosed to have dengue fever based on either serology for IgM dengue or nonstructural protein 1 (NS1) antigen. The diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke diagnostic criteria. 6 All the patients underwent clinical evaluation. Muscle power was graded on a 0–5 Medical Research Council (MRC). Complete blood counts, urinalysis, erythrocyte sedimentation rate in the first hour, fasting blood sugar, renal function test, liver function test and creatine kinase, HIV serology, urine for porphobilinogen, electrocardiogram and radiograph of the chest were done in all cases. Nerve conduction study (NCS) was performed, and based on the NCS, patients were classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, acute motor sensory axonal neuropathy (AMSAN), inexcitable and equivocal.7, 8 The patient’s functional motor disability was assessed by the GBS Disability Score (Hughes Functional Grading Scale: Grade 0, Normal; Grade 1, Minimal signs and symptoms, able to run; Grade 2, able to walk 10 m unaided, but unable to run; Grade 3, able to walk with aid; Grade 4, bed-bound and not able to lift legs; Grade 5, requiring mechanical ventilation; and Grade 6, death. 9
Results
Case-1
A 48-year-old male without any prior comorbidities developed an acute onset of progressive weakness of both lower limbs followed by upper limb involvement within 2–3 days. He became bedridden within 5 days of the onset of symptoms. He had paraesthesia and numbness in both feet, associated with pain in the hands and back pain. Moreover, he had a prior history of fever 12 days back and was diagnosed as a case of dengue fever based on dengue IgM serology positivity (Table 1). On clinical examination, he had areflexic symmetric flaccid quadriparesis with motor power of 1/5 both proximally and distally in both upper and lower limbs. Single breath count was 16, and MRC sum score was 12/60. Cranial nerve examination was normal.
Demographic, Clinical Profile and Outcome of Guillain–Barré Syndrome Patients Following Dengue Infection in Our Study.
NCS was suggestive of sensory-motor demyelinating polyneuropathy (distal latency was prolonged with decreased velocity) in all four limbs. Cerebrospinal fluid (CSF) examination showed albuminocytological dissociation (cells <5, protein 130 mg/dL, sugar 76 mg/dL). He was treated with intravenous immunoglobulin (IVIG) @2 g/kg body weight over 5 days. No ventilatory support was required.
Case-2
A 55-year-old male without any prior comorbidities presented with complaints of back pain, calf pain and paraesthesia in both hands and feet for the last 7 days. He had weakness of the lower limbs for 5 days and the upper limbs for 3 days. He was bedridden for 3–4 days. He had difficulty in swallowing both liquids and solids. He had a history of fever 15 days back, and a diagnosis of dengue fever was made based on NS1 antigen positivity (Table 1). On examination, the single breath count was 13. He had bilateral lower motor neuron type facial weakness, weak gag reflex, neck flexor weakness, areflexia, vibration and proprioception impaired in both feet. Motor power was 2/5 in all four limbs (MRC sum score 24/60). NCS was suggestive of sensory-motor demyelinating polyneuropathy (distal latency was prolonged with decreased velocity). CSF examination showed albuminocytological dissociation (cells <5, protein 110 mg/dL, sugar 80 mg/dL). He was given IVIG was @2 g/kg body weight IV over 5 days. At 2 months of follow-up, the patient was ambulatory without any support.
Case-3
A 40-year-old female complained of paraesthesia of both upper and lower limbs for 5 days, followed by progressive weakness of lower and upper limbs for 2 days, with a prior history of dengue fever 10 days back based on IgM dengue serology positivity (Table 1). The patient came to our emergency department with dyspnoea. She was intubated and put on mechanical ventilation support. GCS were E4VTM6. Motor power was 2/5 on MRC grading, with neck flexor power 3/5 (MRC sum score 24/60). Hypotonia and areflexia were present. Her CSF showed albuminocytological dissociations. Her NCS showed findings suggestive of demyelinating polyneuropathy. She was given IVIG was @2 g/kg body weight IV over 5 days. The patient was off the ventilator after 5 days of admission.
Case-4
A 53-year-old male presented with progressive weakness of all four limbs associated with numbness and paraesthesia for 7 days, with a prior history of dengue fever 14 days (IgM dengue serology positivity) (Table 1). The patient was conscious and oriented. Vitals were stable, and the single breath count was 17. He had areflexic flaccid quadriparesis with motor power of 1/5 in all limbs on MRC grading and MRC sum score 12/60. NCS showed features suggestive of sensory-motor axonal neuropathy involving all four limbs, suggesting the possibility of AMSAN variant GBS. CSF showed albuminocytological dissociations (cells 3/dL, protein 98 mg/dL, sugar 70 mg/dL). The patient was managed with IVIG. The patient was discharged after 15 days of hospitalisation. The patient improved after one month of follow-up, with a modified Huges grade of 1.
Case-5
A 29-year-old female presented to the emergency department with complaints of weakness in all four limbs for 15 days. She had breathing difficulty along with swallowing difficulty for the last 7 days, for which she was on mechanical ventilation, and furthermore, she had a history of fever 11 days prior to developing the above complaints and dengue fever was diagnosed as IgM for dengue was positive (Table 1). The MRC sum score was 12/60 at the time of admission to our hospital. NCS was suggestive of sensory-motor demyelinating polyneuropathy, and CSF showed albuminocytological dissociation. She was treated with IVIG. She was off ventilatory support after 20 days and was discharged on a wheelchair.
Discussion
Guillain–Barré syndrome develops due to involvement of nerves by the body’s own immune system. Activated T lymphocytes in GBS penetrate the blood–nerve barrier and recognise potentially dangerous nerve tissue components. These immune cells release chemicals called cytokines and chemokines, which make the blood–nerve barrier more permeable. As a result, antibodies are able to enter the nerve tissue and attack Schwann cells, the cells responsible for protecting and insulating nerves. This immune attack damages the nerves and leads to the clinical symptoms seen in GBS. The term ‘blood–nerve barrier dysfunction’ refers to this increased permeability of the blood vessels supplying the nerves. 10
Several studies on dengue infection have shown that the body’s immune response can sometimes become abnormal or excessive. This includes the release of cytokines and chemokines, activation of the complement system and overstimulation of immune cells. In severe cases such as dengue haemorrhagic fever, the immune response may even begin to target the body’s own tissues. Patients with dengue can produce antibodies that mistakenly react with human platelets and endothelial cells. An antibody directed against dengue NS1 has been reported to contribute to this cross-reactivity with endothelial cells. These immune-mediated processes are thought to play an important role in the development of neurological complications associated with dengue infection. 11
In our study, the mean age of patients developing GBS following dengue fever was 44 years, with a male-to-female ratio of 3:2. This demographic pattern aligns with the findings of Garg et al., who in their review study reported that dengue patients who developed GBS had a mean age of 37.7 years, with a median age of 40 years. Garg et al. also observed that the gender distribution was almost equally balanced, with both males and females being equally affected by GBS after dengue infection. Our study had a slightly higher mean age, which may be due to reflecting regional or sample-specific variations, but the general trend of GBS occurrence in adult patients following dengue remains consistent with previous literature. 12 Puccioni-Sohler et al. reported a male-to-female ratio in GBS patients that closely mirrors the findings of our study. In both studies, the male-to-female ratio was 3:2, with a higher prevalence of GBS in males compared to females (Table 2). 13
Demographic, Clinical Profile and Outcome of Guillain–Barré Syndrome Patients Following Dengue Infection in Previously Published Literature in Adults.
In our study, all patients had a history of fever lasting for 10–15 days prior to the onset of GBS symptoms. This finding is consistent with the study of Hughes et al., who reported that GBS patients had a history of fever 10–14 days before the onset of neurological symptoms. 10 Similarly, Sulekha et al. observed that GBS following dengue infection typically occurs within 2 weeks of fever onset, with a mean duration of 11.4 days and a range from 2 to 30 days. 14 These findings highlight the temporal relationship between fever and the development of GBS, emphasising the importance of monitoring patients for neurological symptoms 2–3 weeks following dengue fever.
In a report from Brazil during a dengue endemic, among 15 patients with GBS, 7 cases (46.6%) tested positive for a dengue infection. Two of them had IgM dengue antibodies in CSF, but in our study, we included all the GBS patients who had serological evidence of dengue infection during the dengue outbreak season. 15
In a case series study by Soares et al., which included four patients with dengue fever-associated GBS, all patients were found to have the demyelinating variant of GBS (Table 2). 16 This finding is consistent with our own case series, where 4 out of 5 patients were diagnosed with the AIDP variant of GBS. Similarly, Puccioni-Sohler et al., in their case series, reported that four out of five patients also had the demyelinating variant of GBS. 13 The predominance of AIDP in both our case series and those of Soares et al. and Puccioni-Sohler et al. suggests that dengue-induced GBS commonly manifests as a demyelinating neuropathy, further supporting the hypothesis that immune-mediated damage to peripheral nerves is a key mechanism in this post-infectious condition. In contrast to our findings, a case series conducted by Imtiaz et al. involving four patients with GBS following dengue infection revealed that 3 of the 4 patients had the axonal variant of GBS (Table 2). 17 Additionally, Sharma et al. from India reported a case of AMSAN variant GBS following dengue infection, which mirrors one of the cases in our study. 18 These reports highlight the variability in GBS subtypes that can occur post-dengue, underscoring the need for further investigation into the underlying mechanisms and regional differences in clinical manifestations.
In a case series by Sulekha et al. and Fragoso et al., which focused on GBS following dengue infection, the majority of patients presented with the demyelinating variant of GBS.14, 19 All patients were managed with IVIG therapy, in addition to supportive care and showed good recovery outcomes (Table 2). Similarly, in our study, all five GBS patients were treated with IVIG and supportive management, with 4 out of the 5 cases demonstrating good recovery, as evidenced by a modified Hughes grade of 1–2 at 1 month of follow-up. These findings highlight the effectiveness of IVIG in managing post-dengue GBS. One patient in our study, a 24-year-old female, showed poor recovery, which may be due to a delay in receiving treatment. A case report described a 49-year-old male who developed the AIDP variant of GBS following a dengue infection. The patient showed a rapid and good recovery, becoming ambulatory within 2 weeks of onset. 20 In a similar case, Kumar and Prabhakar from India reported a case of AIDP variant post-dengue GBS, who showed significant improvement following treatment with IVIG, further highlighting the potential for positive outcomes with appropriate therapeutic interventions in such cases (Table 2). 21 Similarly, in case reports by Santos et al., Dalugama et al. and Esack et al., patients who developed the demyelinating variant of GBS following dengue infection showed good recovery after treatment with IVIG, reinforcing the positive outcomes for GBS patients who develop the disease after dengue.22–24 This trend emphasises the potential for recovery in patients with the AIDP variant of GBS triggered by dengue infection. A case series by Simon et al. 25 three patients developed GBS following dengue fever, two of whom had the demyelinating variant and one with the axonal variant. All were treated with IVIG, and none had residual weakness or sequelae after 2 months of hospital discharge (Table 2).
Conclusion
GBS following dengue infection usually presents within 2 weeks of infection. AIDP is the most common electrophysiological variant in patients with GBS following post-dengue infection. These patients have a good recovery and better outcome following IVIG treatment. Therefore, early diagnosis and management result in good outcomes and reduce morbidity and mortality in patients with GBS following dengue infection.
Footnotes
Authors’ Contribution
Abhay Ranjan: Conceptualisation, Writing: Original Draft. Satish Kumar: Data collection and curation, Writing: Review & Editing. Neetu Sinha: Data collection and curation, Writing: Review & Editing. Ashok Kumar: Writing: Review & Editing. All authors have read and approved the final version of the manuscript.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Funding
The authors received no financial support for the research, authorship and/or publication of this article.
ICMJE Statement
The manuscript complies with ICMJE guidelines.
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Consent taken by patient and/or their relatives.
