From initial suspicion to accurate diagnosis: unmasking rabies in a case of suspected Guillain-Barre syndrome

Abstract

Background

Rabies is a fatal viral infection with clinical presentation that can mimic other neurological disorders, such as Guillain-Barre Syndrome (GBS). Both conditions can present in early stages with same signs, including muscle weakness and paralysis, leading to diagnostic confusion. In this case report, we present a patient residing in Palestine who was initially diagnosed with GBS but was later found to have rabies. Early diagnosis of rabies is important because once clinical symptoms appear, the disease almost fatal. This case highlights the importance of increased awareness and consideration of rabies in differential diagnoses, especially in areas where the disease is endemic.

Case presentation

We describe an 8-year-old male patient presenting with bilateral lower limb weakness, areflexia, urinary incontinence, and progressive respiratory decline, leading to intubation and mechanical ventilation. A lumbar puncture indicated elevated protein and zero cells, Brain and spinal MRI revealed enhancement of the cauda equina roots consistent with GBS. Despite treatment with intravenous immunoglobulin (IVIG), his condition worsened. Rabies was suspected after a history of a stray dog scratch two months prior and a nuchal biopsy confirmed the diagnosis. The patient’s condition worsened, and he developed seizures, heart block, and cardiorespiratory arrest, leading to death on hospital day 17.

Conclusion

This case emphasizes the need to include rabies in the differential diagnosis for patients with rapidly worsening neurological symptoms, especially in endemic areas. Early detection of rabies is crucial as its progression is rapid and fatal, highlighting the importance of early intervention and post-exposure prophylaxis for individuals at risk.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12887-025-05994-x.

Background

Rabies virus is a highly neurotropic pathogen that affects the central nervous system (CNS), causing acute encephalitis. It’s a single-stranded negative RNA virus belonging to the Rhabdoviridae family and the Lyssavirus genus. The virus is mainly transmitted by the saliva of wild animals that infect wounds, bites, or scratches. Common reservoirs include dogs, bats, raccoons, skunks, and foxes [1, 2]. Following viral inoculation, it travels through the peripheral nerves to replicate in the spinal ganglia, where the signs and symptoms begin. These include pain and paresthesias at the wound site, flu-like symptoms, fever, delirium, convulsions, hydrophobia, and paralysis [3, 4]. Rabies can present in two distinct forms: the furious (encephalitic) form which is the most common (80% of cases), characterized by fluctuating consciousness, inspiratory spasms, hydrophobia, and signs of autonomic dysfunction; and the paralytic form, which begins with ascending muscle weakness and preserves consciousness until the later stages of the disease. Without treatment, both forms inevitably lead to coma and death [3].

Guillain-Barre syndrome (GBS) is an acute autoimmune disorder in which the body’s immune system attacks the peripheral nerves. Demyelinating polyradiculoneuritis is the classic form of GBS, characterized by ascending paralysis, areflexia, and elevated CSF protein without pleocytosis [4]. Paralytic rabies can mimic GBS due to its similar presentation, starting with weakness in the bitten extremity and progressing to quadriparesis and bifacial weakness [5, 6].

The encephalitic stage of rabies frequently indicated by hydrophobia and anxiety. Fever, tachycardia, excessive salivation, delirium and other signs of autonomic instability become more apparent as the disease progress. As the encephalitis worsen, cranial nerve deficit may occur such as ophthalmoplegia, facial palsy and bulbar dysfunction. The presence of these signs raises the possibility of an infectious etiology rather than autoimmune processes [7].

Despite being a well-known clinical entity, paralytic rabies remains challenging to diagnose and requires a high index of suspicion, especially when it presents with atypical features, as seen in our case that closely resembled GBS.

Case presentation

An 8-year-old male patient from Palestine, with no significant past medical history was in good health until 10 days ago when he developed undocumented fever and hypoactivity. He visited an outpatient clinic, was treated for tonsillitis, and discharged on unknown oral antibiotics for three days. The following day, his mother observed abnormal gait and bilateral symmetrical lower limb weakness, eventually leading to his inability to stand. He presented to the emergency department of another hospital, where he was found to have bilateral lower limb weakness with areflexia. Muscle power was assessed using the Medical Research Council (MRC) scale, showing a grade of 1/5 in the lower limbs and 3/5 in the upper limbs, alongside urinary incontinence and a positive gag reflex, with no signs of encephalopathy. A lumbar puncture revealed elevated protein (69 mg/dL) with normal glucose and zero cells. In addition, brain and spinal Magnetic resonance imaging (MRI) showed enhancement of the anterior roots of the cauda equina, findings consistent with a diagnosis of GBS (Figs. 1 and 2). The patient was treated with two doses of intravenous immunoglobulin (IVIG). He was febrile upon admission, and a full septic workup was conducted. He was started on IV ceftriaxone but continued to experience high-grade fever daily, leading to his admission to our pediatric intensive care unit (PICU).

Fig. 1.

A Normal Sagittal T2 weighted image of the cervical and thoracic spine. B Post contrast T1 weighted image of the lumbar spine shows cauda equina nerve roots enhancement

Fig. 2.

A Brain MRI: Normal axial T2/FLAIR weighted image. B Brain MRI: Normal axial T2 weighted image

During the hospital stay, the patient exhibited a gradual deterioration in his respiratory function. He developed dysarthria, had a weak gag reflex, experienced drooling, and showed bradypnea. His level of consciousness decreased (Glasgow coma scale (GCS) 10/15), and he had absent deep tendon reflexes and anisocoria, characterized by right-sided mydriasis that was non reactive to light, along with oxygen desaturation. Consequently, the patient was intubated and placed on mechanical ventilation. Cerebrospinal fluid (CSF) and blood samples were sent to the laboratory to investigate the cause of his encephalitis (Table 1) and Azithromycin (300 mg) was administered once daily via nasogastric tube for five days. An urgent brain CT scan with IV contrast was performed but revealed no abnormalities. The anisocoria was considered part of GBS with ophthalmoplegia, and a GQ1b test was ordered and back to be negative.

Table 1.

Cerebrospinal fluid and blood samples analysis results

Test	Value	Normal range
CMV IgM	Negative	-
CMV IgG	Positive	-
EBV IgM	Negative	-
EBV IgG	Positive	-
Mycoplasma IgM	Positive	-
Lumper puncture
WBCs, cells/microliter	37 (94% lymph, 6% PMN)	0–5
RBCs, cells/microliter	200	0–10
Protein, mg/dL	2273	15–45
Glucose, mg/dL	75	40–70
PCR tests for viral panel	Negative	-

By day 8, there were concerns about a new brain insult, prompting an urgent brain MRI with IV contrast. This MRI showed a prominent ventricular system (most noticeable in the lateral ventricles) with minimal subependymal edema. On the same day, the family reported that the patient had a history of being scratched by a stray dog two months ago on the face and scalp. He had sought medical attention at outpatient clinics and was treated with Amoxicillin and clavulanic acid, but he did not receive a vaccine or immunoglobulin. During this period, the patient experienced a febrile illness that was treated as tonsillitis and exhibited increased agitation and anxiety, although he had no insomnia or excessive salivation, and no additional symptoms were reported. There was no further information available about the dog.

On examination, the patient was found to have a linear hyperpigmented scar near the right eye and a hypertrophied skin lesion on the right parietal area (at the site of the previous dog scratch). Additionally, a small laceration was noted on the left parietal area. Given these cutaneous findings, rabies infection was suspected. Blood, urine, and CSF specimens were sent for analysis, including cultures, viral PCR panels all of which returned negative results. A nuchal biopsy was then performed for rabies testing, which subsequently confirmed a positive result, leading to a new diagnosis of rabies infection.

From hospital day 9 to day 16, the patient experienced focal convulsions characterized by eye blinking occurring three times. the patient also developed bradycardia; An ECG revealed a complete heart block. In response to the bradycardia, Laboratory tests were conducted (Table 2) and it was concluded that the patient had SA node dysfunction likely secondary to toxins, so He was started on an isoproterenol infusion at 0.1 mcg/kg/min. Despite these interventions, the patient continued to have a complete heart block.

Table 2.

Laboratory tests results

Test	Result	Normal range
CK-MB	44.6 U/L	0–25 U/L
Troponin	11.8 ng/ml	< 0.04 ng/ml
TSH	0.06 mIU/L	0.4-4.0 mIU/L
Free T4	14.8 pmol/L	10–23 pmol/L
Free T3	1.96 pmol/L	4.1–8.0 pmol/L

By day 17, the patient suffered a sudden cardiorespiratory arrest. Cardiopulmonary resuscitation (CPR) was performed according to Paediatric advanced life support (PALS) guidelines; however, the rhythm progressed to pulseless electrical activity and asystole. Unfortunately, despite resuscitation efforts, the patient died.

Discussion

Rabies can be in the form of either furious or paralytic [3]. One third of patients develop the paralytic form [8]. Although the paralytic form resembles GBS, there are several points that help differentiating these two disorders [3] (Table 3). Our patient initially presented with fever which treated as tonsillitis. Later, acute lower limb paralysis occurred. CSF and MRI findings increased the index of suspicion for GBS and treated as such. However, the rapid progression of symptoms and the subsequent emergence of encephalitic features, along with a later history of a dog scratch, were key factors that guided us to the correct diagnosis of the paralytic form of rabies.

Table 3.

Comparison between furious and paralytic forms of rabies

	GBS [8, 9]	Paralytic rabies [3, 8, 10]
Preceding events	viral infections, surgeries, inculcations, mycoplasma infection	bites by rabid animals
Pathophysiology	autoimmune mediated	viral infection
Progression	days to 1–4 weeks	from bite onset to 7 days- 4 years
Motor features	motor weakness more than one limb	flaccid weakness and fasciculation in bitten extremity
Sensory features	mild signs and symptoms	at bitten segment: severe paresthesia, loss of pinprick sensation followed by loss of joint position sense
Reflexes	areflexia	preserved in full conscious patient
Symmetry	relative symmetry of neurological deficits	bitten extremity more affected
Others	cranial nerves defect, autonomic dysfunction	phobic spasms (half of patients only), myoedema autonomic dysfunction and cranial nerve defects as common as GBS
Fever	absent	common during prodromal phase
CSF findings on LP	elevated Protein, and up to 10 mononuclear leukocytes/mm3	elevated proteins with varying pleocytosis
Electrophysiological features	nerve conduction block or slowing at some point during illness	peripheral demyelination or axonopathy
Immunophenotypic study	predominance of CD8 + T cells	macrophage-rich infiltrates in paralytic rabies (high CSF IFN-γ and IL-6, and low tumor necrosis factor (TNF)-α and IL-4)
Recovery	start in 2–4 weeks after progression ceases	rapid progression with eventual CNS involvement and death

It’s challenging to distinguish between GBS and paralytic rabies based on neuroimaging without a typical history of a dog bite as both can present with cauda equina nerve root enhancement [11] (Table 4). Furthermore, in contrast to the typical Brain MRI findings of comatose phase of rabies as well as furious form of rabies, our patient’s brain MRI remained unremarkable during the course of the disease even when repeated at later stages.

Table 4.

Neuroimaging differences between Guillain-Barre syndrome and paralytic rabies

	GBS[12]	paralytic rabies [3, 12, 13]
MRI findings	Thickening and contrast enhancement of the spinal nerve roots (mostly in the anterior part), especially in the region of the cauda and conus medullaris with no abnormalities on pre-contrast images, sparing brain parenchyma	prodromal phase: Increasing hyperintensity on T2-weighted images is observed along the brachial plexus and spinal nerve roots at the levels corresponding to the affected extremity. Faint hyperintensity without enhancement is noted in the spinal cord, temporal lobe cortices, hippocampal gyri, and cerebral white matter.
		Non-comatose phase: Increased hyperintensity of T2-weighted changes
		comatose phase has same findings of furious form: The brainstem, deep grey matter, thalamus, substantia nigra, tectal plates, limbic structures, cranial nerve nuclei, spinal cord, and cranial and spinal nerve roots all exhibit mild to moderate enhancement

A study by Gadre et al. [10] involving 47 patients diagnosed with rabies postmortem found that 34 had paralytic rabies, with 17 initially misdiagnosed as GBS due to the lack of definitive diagnostic criteria for GBS and antemortem rabies testing. Of those 17 patients, 13 had a clear history of a rabid animal bite; 5 exhibited signs of paresthesia, hydrophobia, or fasciculations; 9 had prodromal symptoms; 7 had elevated CSF protein levels; 6 had pleocytosis; and 5 had weakness in all four limbs or only the upper limbs. In contrast, our case didn’t have a clear history of a bite, showed no signs of hydrophobia or fasciculations, and symptoms began with lower limb weakness only, which, unfortunately, is initially consistent with GBS. In the same study, 11 patients were treated with plasmapheresis, which seemed have no effect on increasing life expectancy or altering the duration of the disease, since the median duration of illness from onset of symptoms until death was 11 days (range 2 days to 6 months) [10]. In addition, a study by Kumar et al. 2019, the challenges of diagnosing rabies that mimics GBS are discussed, in which the classical symptoms of rabies were absent (i.e., hydrophobia). However, unlike our case, the presence of a clear bite history, more MRI findings that correlates with rabies, distal limb paresthesia at the wound site and bladder involvement in Kumar’s patient increased suspicion for rabies over GBS [14].

According to WHO, there is currently no test to detect human rabies prior to the disease’s clinical onset. Diagnosis of the disease is difficult due to the absence of antemortem diagnostic criteria [15]. Laboratory tests and encephalitic features can be used to confirm the diagnosis once clinical signs have appeared. One of these is direct microscopy of infected neuronal cells, which shows “Negri bodies,” intracytoplasmic viral particles. Viral antigens in corneal smears and nuchal skin biopsies can also be found using the fluorescent antibody technique (FAT). Similarly, enzyme immunoassays and immunohistochemical methods are used in rapid rabies enzyme immunodiagnosis (RREID) to identify antigens. However, due to their requirement for brain tissue, FAT and RREID are both limited and cannot be used for antemortem diagnosis [16].

To confirm the diagnosis, virus isolation methods like the rapid tissue culture infection test (RTCT) and mouse inoculation test (MIT) are frequently required. In the absence of a history of vaccination, the diagnosis may also be supported by the finding of rabies antibodies in CSF. PCR can detect viral RNA in saliva, CSF, urine, and hair follicles [3, 16].

Since the prognosis is very poor in both types of rabies, recovery is extremely rare. There is no proven standard treatment for rabies; the mainstay is to use rabies immunoglobulins, vaccination, antiviral medications (ribavirin), and interferon alpha. Benzodiazepines, barbiturates, ketamine, or intravenous morphine can be used for symptom relief. Nimodipine can also be used to relieve vasospasm [3].

Large doses of intravenous immunoglobulins have shown success in alleviating autonomic symptoms, as occurred in our patient. However, once the virus enters the CNS, the prognosis is very poor, and death is inevitable [8].

When an animal bite occurs, the wound should be cleaned right away. To lower the risk of infection, the World Health Organisation (WHO) advises delaying wound suturing. Prompt administration of post-exposure prophylaxis (PEP), which includes the rabies vaccination and immunoglobulin, is necessary. If a dog or other biting animal is available, it should be monitored for ten days. PEP should be started right away if the animal is unavailable. Additionally, conventional precautions should be taken to isolate patients suspected of having rabies [17].

Early diagnosis of paralytic rabies is vital to provide the patient’s family with the true prognosis, to implement proper infection control measures, and to consider newer treatment modalities.

Conclusion

In conclusion, paralytic rabies should be considered in the differential diagnosis for any case of acute flaccid paralysis, particularly in endemic areas. Despite the atypical presentation and imaging findings that may mislead the diagnosis, early suspicion of paralytic rabies is critical for improving patient outcomes and ensuring appropriate management.

Abbreviations

CNS

Central nervous system

GBS

Guillain barre syndrome

MRI

Magnetic resonance imaging

IVIG

Intravenous immunoglobulins

PICU

Pediatric intensive care unit

GCS

Glasgow coma scale

CSF

Cerebrospinal fluid

PALS

Pediatric advanced life support

Authors’ contributions

Writing the manuscript: Mahmoud N. Khadra, Wasef Abdat.Review and editing the manuscript: Maysa Alawneh, Abdulkareem Saymeh, Ahmed Abushama, Issa AlawnehAll authors read and approved the final manuscript.

Funding

Non-declared.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Our study approved by An-Najah National University Institutional Review Board (IRB) committee.

Consent for publication

Written informed consent was obtained from the patient’s father for this report publication and any images needed. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Competing interests

The authors declare no competing interests.