Guillain-Barré Syndrome Secondary to Snake Bite: A Report of a Rare and Fatal Case

Introduction

Guillain-Barré syndrome (GBS) is a rare neurological condition typically characterized typically by bilaterally symmetrical, progressive ascending paralysis, often accompanied by autonomic and/or sensory involvement. Globally, GBS affects about 1–2 people per 100 000 population each year [1], with higher incidence rates reported in certain regions, such as Asia and Western Europe [2]. It typically manifests 2–4 weeks after a triggering event, which may include infections, vaccination, surgeries, or, rarely, snake-bite envenomation.

Snake bite remains a significant public health issue globally, especially in tropical regions such as India. Most snake bites in India are from non-venomous species, and even bites from venomous snakes often result in dry bites without envenomation. The ‘Big Four’ species – Russell’s viper, common krait, Indian cobra, and saw-scaled viper – account for approximately 98% of snake envenomations [3]. Among these, Russell’s viper is the leading cause, followed by common krait and Indian cobra. Elapid venoms (cobras and kraits) are primarily neurotoxic, leading to neuromuscular paralysis; whereas viperid venoms are predominantly hemotoxic, causing disseminated intravascular coagulation and severe hemorrhage. The venoms of sea-snakes tend to be mainly cytotoxic, but these are rarely found in inland regions.

Here, we present a rare case of an Indian farmer who initially developed transient descending post-snakebite motor weakness, followed by a second episode of ascending paralysis 2 weeks later, ultimately diagnosed as GBS. Progression of illness, compounded by a delay in seeking care, and complications such as aspiration pneumonia and sepsis, resulted in the patient’s death. This case underscores the need for early recognition of GBS in post-snakebite presentations and highlights the importance of both physician awareness and patient education to improve outcomes.

Case Report

INITIAL PRESENTATION:

A 52-year-old male farmer with no known chronic illnesses was brought to the emergency department of a government tertiary facility in New Delhi with an alleged history of a snake bite to the back of his neck while sleeping on the grass. He had initially sought care at a rural primary care clinic in northern India, but was referred to our center due to the unavailability of anti-snake venom (ASV). By the time of arrival at our facility, several hours later, he had developed progressive weakness in both upper limbs, which subsequently spread to the lower limbs, and was associated with difficulty in breathing. Upon arrival, his vital signs were stable, except for a mild tachypnea. Physical examination revealed 2 small puncture wounds on the right posterior aspect of the neck, without any redness or swelling. His muscle strength was graded at 1/5 in the upper limbs and 2/5 in the lower limbs, with areflexia in all extremities. No sensory deficits were noted, and the remainder of the physical examination was unremarkable. Initial laboratory test results, including complete blood count (CBC), comprehensive metabolic panel, coagulation studies, and serum creatine phosphokinase (CPK), showed no abnormalities. A 20-minute bedside whole-blood clot test, performed upon arrival, was also negative. He received 10 vials of polyvalent ASV, a tetanus toxoid (TT) injection, IV neostigmine, and supportive care, including 2-day mechanical ventilation for hypercapnic respiratory failure. With ongoing physiotherapy, he gradually regained muscle strength and was discharged in stable condition after a 10-day hospital stay.

SUBSEQUENT PRESENTATION:

The patient was readmitted to the hospital 2 weeks after the previous discharge, due to a 3-day history of ascending progressive weakness involving bilateral lower and upper limbs, initially dismissed as ‘a few bad days in the recovery process’. He also reported difficulty swallowing and breathing, along with a few episodes of coughing within the past 24 hours. There was no preceding history of any recent flu-like symptoms or diarrheal illness.

On admission, he was conscious and oriented, and mildly febrile at 37.8°C, with a pulse rate of 117 bpm, a respiratory rate of 19/min, and an oxygen saturation of 92% on room air increasing to 95% on 4 L oxygen via venturi. Neurological examination revealed reduced muscle tone in all limbs, with power of 1/5 in the upper limbs and 0/5 in the lower limbs. Deep-tendon reflexes were absent throughout, and plantar reflexes were mute. Sensory examination was unremarkable. Chest auscultation revealed equal air entry with bilateral coarse crepitations in the infra-axillary regions. The rest of the physical examination was unremarkable. Initial laboratory investigations, including CBC and BMP (Table 1), revealed a leukocytosis of 16.6/ml with 95% neutrophils and an elevated procalcitonin of 1.4 ng/mL. A chest X-ray showed bilateral lower-zone infiltrates, suggestive of aspiration pneumonia. Thus, the patient was started on empirical IV piperacillin-tazobactam (Zosyn), along with other supportive management. A non-contrast CT scan of the head reported by the late evening of the first day was unrevealing.

On hospital day 2, while continuing current management, further neurological investigations were undertaken to identify the cause of the new-onset symptoms. A contrast-enhanced MRI of the brain and spinal cord showed no acute abnormalities. Lumbar puncture with CSF analysis (Table 2) demonstrated albuminocytologic dissociation pattern: 5 WBCs/mm3 (all lymphocytes), elevated protein at 120 mg/dL, and normal glucose levels. Motor nerve conduction studies (NCS) (Table 3) showed markedly reduced conduction velocities and compound motor action potential (CMAP) amplitudes in the bilateral peroneal nerves, consistent with severe demyelination and axonal loss. Similar but milder findings were observed in bilateral tibial nerves. Ulnar and median nerve studies revealed mildly reduced conduction velocities, indicative of mild demyelination. Sensory NCS (Table 4) showed borderline low conduction velocities in the bilateral median nerves, while ulnar and sural nerves were normal bilaterally, demonstrating a sural-sparing pattern. F-waves (Table 5) were absent in the lower limbs, suggestive of axonopathy, and were prolonged in the upper limbs, indicating demyelination. Overall, these findings were consistent with acute demyelinating polyneuropathy with secondary axonal loss.

Intravenous immunoglobulin (IVIG) therapy was initiated thereafter, at a dose of 0.4 g/kg/day with an intended total duration of 5 days. Plasmapheresis could not be done due to unavailability at the institution. The patient’s condition rapidly worsened thereafter, with increasing oxygen requirements – now at 6L on venture – to maintain a saturation of 92%. Blood gas at this point showed 68 mmHg paO2, and 44 mmHg paCO2. Overnight, he continued to feel short of breath, with use of accessory muscles. A repeat blood gas analysis on the early morning of the hospital day 3 had shown a pO2 of 59 mmHg and pCO2 of 49 mmHg, indicating concurrent hypoxic and hypercapnic respiratory failure, likely due to progression of GBS and/or underlying infection. He was urgently intubated and placed on mechanical ventilation. Despite that, over the ensuing hours, he became hemodynamically unstable, with mean arterial pressure dropping to 56 mmHg. Echocardiography did not reveal any abnormalities, but the cardiac monitor and ECG showed unusually mild tachycardia (86–94 bpm) with no evidence of any arrhythmias. Blood cultures did not reveal any growth. IV vasopressors and empiric meropenem and vancomycin were initiated, but failed to noticeably improve his condition. He remained on mechanical ventilation for a few hours before experiencing cardiac arrest with failure to return to spontaneous circulation despite adequate resuscitation efforts. An overview of all the key events leading up to the final outcome is shown in the timeline in Figure 1.

Discussion

This case highlights a rare, diagnostically challenging, and ultimately fatal presentation of GBS in a rural Indian farmer. The condition developed approximately 3 weeks after the snake bite, and had progressed quite rapidly. By the time he presented to the hospital, the illness had likely already advanced significantly, as evidenced by bulbar dysfunction and difficulty breathing. Furthermore, a delay in establishing the diagnosis until hospital day 2 resulted in postponement of treatment initiation. The clinical course was further complicated by the development of aspiration pneumonia and septic shock, likely exacerbated by vasomotor dysfunction from GBS-associated autonomic neuropathy.

The initial presentation – characterized by rapid-onset descending paralysis, absent local inflammation, and puncture marks on the posterior neck – was suggestive of neurotoxic envenomation, likely from a krait. Unlike cobras (Naja sp.), kraits (Bungarus sp.) lack cytotoxic venom components, producing few or no local signs [4]. The patient’s respiratory failure requiring mechanical ventilation may be attributed to delayed ASV administration, due to unavailability at the primary center. As previously shown, ASV has limited benefit after the alpha-bungarotoxin, produced by kraits, binds irreversibly to the postsynaptic acetyl-choline receptors, and recovery depends on regeneration of these receptors [5]. This may also explain the limited efficacy of empiric neostigmine therapy in this case.

During the second hospital stay, the initial differential diagnosis included cerebrovascular accident. However, the patient’s symmetrical limb weakness was atypical for a stroke, and both cranial and spinal imaging ruled out any acute intracranial pathology. Given the recent history of hospitalization following a snake bite, delayed neurotoxicity from envenomation was also considered. However, venom-induced neuromuscular dysfunction typically presents as a descending paralysis with rapid progression over a matter of hours, followed by recovery in an ascending pattern. In contrast, our patient demonstrated a more gradual progression of weakness in an ascending pattern over several days, which aligned more closely with GBS. Also, it seemed highly unlikely that neurotoxic effects would persist for such an extended period following a near-complete recovery, especially given that 10 vials of ASV had been administered during the prior admission, which should have neutralized any circulating venom proteins.

Critical illness neuropathy and/or myopathy (CINM) was also considered, particularly given the recent ICU stay. CINM is known to occur in the context of severe illnesses such as sepsis, and often presents with difficulty in weaning from mechanical ventilation with muscle atrophy [6]. Although the prior mechanical ventilation may have contributed to some degree of neuromuscular deconditioning, several factors argued against this diagnosis. Symptoms usually begin during or shortly after critical illness, not with a delayed onset 2 weeks after hospital discharge. Additionally, CINM is typically a reversible self-limiting condition, whereas our patient developed progressively worsening weakness. Finally, the albuminocytologic dissociation pattern on CSF, and the NCS findings of sural-sparing pattern, along with absent F-waves in the lower limbs, were more characteristic of GBS [7].

The etiology of GBS involves an immune trigger leading to generation of auto-antibodies against certain nerve proteins such as GM1, GD1a, and GQ1B that trigger an inflammatory cascade resulting in demyelination and/or axonal degeneration [8]. While certain gastrointestinal (eg, Campylobacter jejuni) and respiratory infections are the most common immune trigger points, an increasing number of cases have been recently reported after snake bite, especially in tropical countries. In such scenarios, several factors could possibly serve as the immune stimulus, such as the TT vaccine, ASV, or the snake-bite venom itself. The literature suggests a temporal association of GBS with certain vaccines, such as the swine influenza vaccine in use during 1967–77, older variants of rabies vaccines [9], and certain COVID-19 vaccines [10]; however, the association with the TT vaccine has remained non-significant [9]. ASV could be a potential culprit in our case; however, cases could be identified where GBS was seen after snake bites, even when ASV was not given (Table 6) [13,19]. Moreover, a study by Niel et al did establish similarity in the molecular structures of krait venom glycoproteins and GM2 gangliosides in neurons – classic molecular mimicry [13]. Immune priming with generation of faulty antibodies against the venom glycoproteins that can also cross-react with neurons seems to be the likely cause. This explains the similar subtype of GBS – primarily demyelinating polyneuropathy in their case and in our case.

GBS has been characterized into several subtypes. Acute inflammatory demyelinating polyneuropathy (AIDP) involves demyelination with or without secondary axonal injury, while acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) are primarily axonal. AIDP remains the most common variant globally. In our review of all the post-snakebite GBS cases reported to date, AIDP with secondary axonopathy was the predominant subtype, closely followed by AMAN (Table 6) [11–20]. Axonal variants – AIDP with secondary axonopathy, AMAN, or AMSAN – tend to have a more severe course, with mechanical ventilation required in up to 40% of cases, which is double the overall GBS cases [21], and are linked to higher rates of infection and mortality [22]. Our patient similarly exhibited a severe AIDP variant with axonal involvement, and had developed sepsis secondary to aspiration pneumonia. Although IVIG was initiated by hospital day 2 (day 5 after GBS symptom onset), the disease may have already progressed significantly. While septic shock seems to be the main cause of death, we suspect a substantial role of GBS-associated autonomic neuropathy, particularly the involvement of sympathetic neurons that regulate vascular tone and heart rate. This could be supported by the patient’s inappropriately low heart rates at <100 bpm, despite the presence of shock and vasopressor infusion, indicating impaired sympathetic compensation. A similar clinical course was described by Cakirgoz et al in a patient with AMAN variant, who developed refractory septic shock and died due to the illness [19]. A comparison of all the cases of post-snake-bite GBS cases reported so far is shown in Table 6 [11–20].

This report also highlights several key challenges often encountered in resource-limited settings where snake bites are common. First, the unavailability of ASV at the referring rural center delayed the timely administration; had this not been the case, the patient might have never required ventilatory support during the first hospitalization. In addition, lack of patient and caregiver education about potential sequelae of snake bite, combined with inadequate follow-up by healthcare providers, led to delayed diagnosis and treatment. Furthermore, availability of bedside sequential spirometry could have facilitated earlier recognition of impending respiratory failure from GBS and timely initiation of ventilatory support.

Conclusions

GBS, though an underrecognized complication following snake bites, has epidemiological and clinical relevance in tropical regions. Mortality rates in GBS can reach as high as 3–10%, with even worse outcomes when the treatment is delayed [23]. Subtypes involving axonal damage – such as AMAN, and AIDP with secondary axonopathy – suggest severe inflammation. These are seen at higher rates in post-snakebite presentations, and are associated with poor prognosis.

This case highlights the critical need for patient and/or caregiver education for early recognition of symptoms. Clinicians managing snake-bite victims should remain alert for delayed-onset neuromuscular symptoms suggestive of GBS, and ensure scheduled neurological evaluations after snake bite. Timely recognition and empiric initiation of treatment (IVIG) while awaiting diagnosis could be lifesaving.