Guillain-Barré Syndrome and Encephalitis Following a Cytomegalovirus Infection in an Immunocompetent Adult: A Case Report

Introduction

Cytomegalovirus (CMV) is a widely prevalent herpesvirus, primarily known for causing asymptomatic or mild infections in immunocompetent adults [1,2]. However, in immunocompromised patients, such as those living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), undergoing organ transplantation, or receiving immunosuppressive therapy, CMV infection can lead to severe complications, including Guillain-Barré syndrome (GBS) and encephalitis [3,4].

GBS, an acute immune-mediated polyneuropathy, is characterized by rapidly progressive bilateral ascending paralysis, often following an infectious trigger [5]. CMV has been recognized as a potential triggering factor for GBS, particularly in immunocompromised individuals [6]. Encephalitis, the inflammation of the brain parenchyma, can also occur in the context of CMV infection, especially when there is suppression of the immune system, presenting symptoms ranging from mild headaches and fever to severe neurological deficits and altered mental status [7,8]. To the best of our knowledge, while cases of GBS and encephalitis have been documented in immunocompetent individuals [9,10], an overlapping clinical presentation of these conditions in this population has not been previously described.

In this case report, we present a unique occurrence of simultaneous CMV-associated GBS and encephalitis in a 58-year-old immunocompetent woman. The patient’s medical history, including poorly controlled diabetes, added a layer of complexity to the clinical scenario, as diabetes can modulate immune responses and potentially influence the course and severity of infections. This case emphasizes the diagnostic challenges and the importance of considering CMV as a potential etiological factor in patients presenting with neurological symptoms, regardless of their immune status.

Case Report

A 58-year-old woman presented to the emergency department with bilateral ascending paraparesis. The symptoms began 1 week after experiencing low-grade fever, self-limiting diarrhea, nausea, and vomiting.

The patient had a medical history remarkable only for poorly controlled diabetes. Her treatment regimen included metformin, administered at a dosage of 1500 mg daily. She had no prior history of neurological disorders or history suggestive of any immune diseases. Additionally, her lifestyle history indicated no tobacco smoking, alcohol consumption, or drug use.

Upon admission, her vital signs were stable, with a temperature of 36.7°C, blood pressure of 136/80 mmHg, heart rate of 98 beats per minute, SpO2 of 98%, and respiratory rate of 18 breaths per minute. Cardiac, respiratory, and abdominal examinations were unremarkable.

In the neurological assessment, she exhibited significant bilateral decreased muscle strength in both lower (1+/5+) and upper limbs (2+/5+), according to the Medical Research Council (MRC) scale for muscle strength. This was coupled with diminished deep tendon reflexes (1+/4+), and decreased tactile and pain sensations. Cranial nerves I–XII were intact, and there were no signs of other focal neurological deficits or nuchal rigidity.

Laboratory tests showed 7200/mm3 leukocytes (reference values 4500–11 000/mm3) with a predominance of lymphocytes (62%), as indicated in Table 1. A cranial computed tomography (CT) scan was performed, which was unremarkable. A lumbar puncture demonstrated abnormal cerebrospinal fluid (CSF) findings, including elevated protein levels (135.6 mg/dL), an albuminocytologic dissociation, and a mononuclear cell predominance, as depicted in Table 2.

The patient was categorized into level 2 of the Brighton Criteria for GBS. This classification was based on her presentation of bilateral weakness of limbs, diminished deep tendon reflexes, and the onset of symptoms within 1 week. In addition, CSF analysis showed a white blood cell count less than 50 cells/μl and a protein count greater than 60 mg/dL. We could not conduct nerve conduction studies due to unavailability at our hospital.

Based on these clinical symptoms and CSF findings of GBS, plasma exchange therapy was promptly initiated with a 12-h hospitalization. Despite initial treatment, the patient’s neurological status deteriorated within 24 h, with progressing paraparesis extending to facial muscles, along with altered mental status and generalized tonic-clonic seizures, necessitating sedation and orotracheal intubation.

A subsequent cranial CT scan indicated no significant abnormalities, and further evaluation with magnetic resonance imaging (MRI) was not feasible due to the patient being on mechanical ventilation. Blood serology tests, including HIV, syphilis, and hepatitis viruses, were negative, but CMV, Epstein-Barr virus (EBV), and herpes simplex virus (HSV) showed reactive immunoglobulin G (IgG) levels, as indicated in Table 3. Additional CSF analysis was negative for bacteriology, Ziehl-Neelsen staining, and Mycobacterium tuberculosis GeneXpert® tests. Nevertheless, polymerase chain reaction (PCR) testing was positive for the presence of CMV.

Following orotracheal intubation and clinical stabilization, the patient underwent a total of 7 plasma exchange therapy sessions, with a dosage of 40–50 mL/kg per session. Furthermore, she received ganciclovir for 14 days at a dosage of 5 mg/kg twice daily. This treatment regimen led to improvement in her muscle strength, particularly in the limbs, where MRC scale scores increased to +3/5+. Of note, no adverse effects were encountered during the treatment.

However, on the 15th day of mechanical ventilation, she developed acute lung edema and failed extubation, leading to cardiorespiratory arrest. Despite efforts and without sedation, she remained unconscious. Further assessments confirmed no biochemical alterations that could explain her condition. A cranial CT scan showed no signs of ischemic lesions, infarctions, or midline shifts. A subsequent electroencephalogram revealed a diffuse depression of cerebral bioelectric activity, a pattern indicative of encephalopathy and consistent with findings typically seen in anoxic brain injury. Considering the unfavorable neurological prognosis, the patient’s family was consulted, and a decision was made to transition to palliative care. The patient died 2 weeks later due to ventilator-acquired pneumonia.

Discussion

In this case report, we describe a 58-year-old woman with a rare clinical presentation of simultaneous GBS and encephalitis associated with CMV infection.

GBS is a neurologic syndrome characterized by bilateral ascending paralysis [5]. The exact pathophysiological mechanism is still not fully understood, but it is believed to occur when an infectious organism triggers the production of antigens that cross-react with epitopes on the peripheral nerves [11]. Multiple pathogens have been implicated in GBS, including CMV and the bacteria Campylobacter jejuni [6]. Notably, both CMV and Campylobacter can present with gastrointestinal symptoms [12–14]. The estimated incidence of CMV in GBS is 0.6–2.2 per 1000 cases, and Campylobacter is estimated at 0.25–0.65 per 1000 cases [15]. Although Campylobacter testing was not performed in this case, the detection of CMV in the CSF supports CMV as the likely causative agent of GBS.

The initial presentation of GBS in our patient aligns with previously reported cases [5]. The patient had a history of CMV infection 1 week before the onset of ascending progressive paraparesis. Neurological deficits, a normal cranial CT scan, and CSF analysis showing elevated protein levels, albuminocytologic dissociation, and mononuclear cell predominance, are typical findings in GBS [5].

In our assessment of GBS, the Brighton criteria served as an important structured diagnostic tool, enabling us to evaluate the likelihood of GBS based on clinical manifestations, laboratory findings, and the limited availability of supplementary tests [16]. The criteria include: 1) Bilateral and flaccid weakness of limbs; 2) Diminished or absent deep tendon reflexes in weak limbs; 3) A monophasic course with the time between onset and nadir of symptoms ranging from 12 hours to 28 days; 4) CSF cell count below 50 cells/µL; 5) Elevated CSF protein concentration exceeding the normal threshold (commonly >60 mg/dL); 6) Absence of an alternative diagnosis that could account for the weakness; and 7) Nerve conduction study findings consistent with GBS subtypes [17].

In our case, the patient fulfilled the first 6 criteria of the Brighton classification, placing her at level 2 for GBS. Of note, she did not exhibit other neurological features like ataxia or ophthalmoplegia, which are seen in variants of post-infectious demyelinating diseases such as Bickerstaff brainstem encephalitis or Miller-Fisher syndrome [18,19]. The final criterion, involving nerve conduction studies, was not assessed due to the unavailability of this diagnostic modality in our hospital.

The sensitivity of the Brighton criteria for GBS diagnosis is strongly associated with the level of criteria applied [17]. In a study by Roodbol et al (2017) [20], it was determined that levels 1, 2, and 3 of the Brighton criteria had sensitivities of 72%, 96%, and 98%, respectively. Another study, conducted in India, revealed that level 3 of the Brighton criteria was able to detect 86% of GBS cases, while level 2 detected 84% and level 1 detected 62% of the cases [21]. The Brighton criteria, while not replacing the accuracy provided by the electrophysiological studies, are particularly valuable in low-resourced settings where nerve conduction studies may not be available, as in our case [17].

After establishing the diagnosis of GBS, plasma exchange therapy was initiated, aiming to remove circulating autoantibodies and immune complexes that contributed to nerve damage [22,23]. Nevertheless, despite the initiation of the treatment regimen, our patient experienced a worsening neurological status within 24 h, including altered mental status and generalized tonic-clonic seizures, which raised concerns about encephalitis.

Encephalitis is characterized by inflammation of the brain parenchyma and can be caused by various etiological factors, such as infectious agents and autoimmune disorders [7,8]. The diagnostic criteria for encephalitis typically involve both major and minor clinical features [24]. The major criterion requires the presence of altered mental status lasting 24 h or more without an alternative explanation [24]. The minor criteria, where at least 3 should be present for a confirmed diagnosis, are the following: 1) generalized or partial seizures, which cannot be attributable to a preexisting seizure disorder; 2) new onset of focal neurologic deficits; 3) CSF leukocyte count greater than 5/mm3; 4) fever documented within 72 h after admission; 5) neuroimaging findings suggestive of encephalitis, appearing as acute changes; 6) electroencephalogram abnormalities consistent with encephalitis and not attributable to another cause [24].

In our case, the patient fulfilled the major criteria and the first 3 minor criteria. While her cranial CT scan was unremarkable, this imaging modality has limited sensitivity for detecting CMV encephalitis [25]. An MRI might have provided more definitive findings, such as ventriculitis, ependymitis, or periventricular enhancement [26], but was not feasible due to the patient’s mechanical ventilation status. However, the detection of CMV in the CSF, with a mononuclear cell predominance and the absence of contamination by blood cells, coupled with negative PCR results for other infectious agents and no medical history of autoimmune disorders, suggests a diagnosis of CMV-associated encephalitis [26]. To the best of our knowledge, while there is existing literature on CMV-associated GBS and encephalitis in immunocompetent individuals [9,10], there are no reported cases of both occurring concurrently in this population.

Our patient was HIV-negative and had no history of transplantation or immunosuppressive therapy. Her only identified risk factor was poorly controlled diabetes. We postulate that this underlying condition may have contributed to an increased susceptibility to CMV infection, leading to the rare and concurrent development of GBS and encephalitis. Hyperglycemia in diabetes is known to cause immune dysfunction, which can impair the individual’s response to control the spread of invading pathogens [27]. This increased susceptibility to infections is caused by various mechanisms, including leukocyte recruitment inhibition; defects in pathogen recognition, neutrophil, natural killer, and macrophage dysfunctions; inhibition of antibodies and complement effectors; and impairment of cytokine production [27].

With regard to treatment, our patient received 7 further plasma exchange therapy sessions (each with 40–50 mL/kg per session) and ganciclovir for 14 days (5 mg/kg twice daily) [19,25], with no adverse effects observed. This treatment regimen led to improvement in muscle strength in her extremities, as measured on the MRC scale [28]. Specifically, strength in the lower limbs improved from 1+/5, indicating only trace muscle activation without a full range of motion, to 3+/5+, where muscles could move against gravity through a full range of motion. In the upper limbs, strength improved from 2+/5+, where muscles could move only when gravity was eliminated, to 3+/5+, indicating movement against gravity across a full range of motion. Unfortunately, the patient experienced acute lung edema and failed extubation, leading to cardiorespiratory arrest with neurological sequelae. After consulting the patient’s family, it was decided to provide palliative care, and the patient died 2 weeks later due to pneumonia.

Conclusions

This case report highlights an unusual clinical presentation of concurrent GBS and encephalitis following a CMV infection in an immunocompetent patient with diabetes as the only risk factor. It emphasizes the importance of recognizing and promptly treating such complications to prevent adverse outcomes in this population and underscores the need for considering a broad differential diagnosis, including viral etiologies, in atypical neurological presentations. Further research is warranted to elucidate the underlying mechanisms and improve our understanding of this rare overlapping clinical manifestation.