Đặc điểm lâm sàng của bệnh nhân nguy kịch có biểu hiện thần kinh do virus Chikungunya

Abstract

This study presents 6 cases of severe meningoencephalitis associated with chikungunya virus infection in older adults with comorbid conditions who were admitted to an intensive care unit in Paraguay. The patients exhibited classic symptoms, such as fever and arthralgia, as well as sensory impairment. They required mechanical ventilation and vasoactive support. Reverse-transcription-polymerase chain reaction confirmed the infection in the cerebrospinal fluid, and the inflammatory and metabolic characteristics were suggestive of severe neurologic involvement. The 50% mortality rate highlights the severity of this complication in older patients. This emphasizes the need for a high index of suspicion for timely diagnosis and management.

Background

The chikungunya virus infection is usually characterized by fever, arthralgia, myalgia, and rash. It is a mosquito-borne disease transmitted by the Aedes aegypti and Aedes albopictus mosquitoes, and it generally resolves on its own. Occasionally, atypical presentations involving different systems and organs occur (for example, cardiovascular, neurologic, respiratory, and renal) 1–3.

Neurological complications are uncommon but are well documented. Due to the neurotropism of the virus, it can present an extensive spectrum, including meningoencephalitis, myelitis, Guillain–Barré syndrome, uveitis, and cranial nerve palsies (4).

These atypical neurologic manifestations can be severe, especially in infants, older patients, and patients with preexisting comorbid conditions. They are accompanied by multiorgan failure and a high mortality rate. Many of these patients require admission to intensive care units (ICU) for monitoring and treatment due to the severity of their condition 5, 6.

In Paraguay, important chikungunya outbreaks were documented from October 2022 to mid-2023. There were more than 80 000 suspected, probable, or confirmed cases, and many of these patients required intensive care, especially those with severe neurologic manifestations 7–9.

Case Report

This study included all patients older than 18 years of age who were admitted between January and June 2023 with a diagnosis of chikungunya virus infection and neurologic involvement, confirmed by a positive polymerase chain reaction (PCR) test, which detected the virus in the patients’ cerebrospinal fluid (CSF). Patients with a prior history of neurologic disease were excluded to minimize potential confounding factors in the interpretation of neurologic manifestations associated with the infection.

It presents a series of 6 cases of meningoencephalitis associated with chikungunya virus infection. The proportion of male and female patients was equal. Median patient age was 80.5 years (Interquartile range [IQR], 13). All patients had underlying comorbid conditions, the most common was hypertension (66.7%). Fever, arthralgia, and asthenia were present in 83.3% of individuals. The main reasons of admission to the intensive care unit were altered sensorium, hemodynamic instability, and the need for mechanical ventilation (MV). The median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores on admission were 24.5 and 8, respectively. Relevant laboratory data were recorded (Table 1).

The diagnosis of chikungunya virus-associated meningoencephalitis was made based on the concordance of clinical, epidemiologic, laboratory, and reverse transcription (RT)-PCR data, and results for chikungunya virus in the CSF of all cases were studied. The CSF cultures were negative for common microorganisms in all cases. The cytochemical and cytologic characteristics of the CSF are presented in (Table 2).

Regarding the evolution of patients in intensive care unit, all of them received MV, for a median number of 11.5 days (IQR 8). A large percentage (83.7%) required vasopressor administration (noradrenaline), and hemodialysis was performed in 2 cases (33.3%). The treatment was symptomatic for the chikungunya condition. Some patients received corticosteroids (methylprednisolone), but none received immunoglobulins or plasmapheresis (Table 3).

The median length of stay in the ICU was 15 days (IQR 10). Three patients died, and one death was due to gastrointestinal bleeding. In the remaining 2 cases, death was attributed to ventilator-associated pneumonia.

Discussion

Chikungunya meningoencephalitis is a severe and atypical presentation of the viral infection. The presence of this condition may be indicated by neurologic symptoms alongside fever and arthralgia, corroborated by specific laboratory data in the CSF, which reveals the neurologic tropism of the virus. Older patients and those with preexisting conditions tend to experience more severe symptoms requiring intensive care, resulting in high morbidity and mortality rates.

Atypical forms of chikungunya disease are more likely to occur in older adults, especially those with comorbid conditions 5, 10. In our study, as well as in the study by Das and colleagues 11, almost all patients were close to the eighth decade of life (>85 years) and had comorbid conditions, as reported by Vairo and colleagues, Badawi and colleagues, and Sharp and colleagues 1, 12, 13.

Among severe atypical manifestations, 25% to 60% affect the nervous system. The 6 cases reported in this study correspond to cases of meningoencephalitis that presented altered consciousness in addition to the classic symptoms (fever, arthralgia, myalgia, and rash). Cerny and colleagues and Lima and colleagues have mentioned abnormal neurologic behavior, including psychomotor agitation and sensory alteration, as the main reason for hospitalization in critical areas 14, 15. The severity of these patients’ symptoms was reflected by elevated APACHE II and initial SOFA scores 16.

All of our patients had positive RT-PCR test results in their cerebrospinal fluid (CSF), which confirmed neurologic involvement. Regarding cytochemical characteristics, they presented with proteinorrachia in all cases and decreased glucose in most cases. Similar results have been reported in other publications (10, 17). The pleocytosis observed in our patients was predominantly at the expense of polymorphonuclear cells. Different from other studies, we did not observe an increase in lymphocytosis, which is characteristic of viral infections (6, 18).

These severe forms of chikungunya presented with organ failure and metabolic acidosis on admission. All patients required mechanical respiratory assistance at some point during their intensive care hospitalization, probably due to multifactorial reasons, such as airway protection due to severe sensory alterations and/or shock. Other publications refer to the requirement of mechanical respiratory assistance (MV) in 50% to 65% of subjects with severe atypical presentations 16–18. Eighty percent of our patients required vasopressor support due to shock, which is a higher percentage than that recorded in other studies 16, 18. The need for renal replacement therapy was similar to that reported by Nazneen and colleagues, Gupta and colleagues, and Crosby and colleagues 5, 16, 18.

Several infectious diseases should be considered in the differential diagnosis of patients presenting with acute neurologic involvement. These include viral infections such as herpes viruses, Zika virus, and dengue virus, as well as bacterial infections (for example, Neisseria meningitidis and Mycobacterium tuberculosis) and autoimmune encephalitis. However, in the present study, only patients with chikungunya virus detected in cerebrospinal fluid by PCR testing were included. This approach allowed confirmation of the viral cause in the context of the observed clinical presentation and substantially reduced the likelihood of alternative causes of diagnostic confusion (4, 19, 20).

The mortality rate for severe atypical cases is approximately 30% (14) This figure increases considerably with age and in patients with comorbid conditions. Additionally, neurologic involvement of the central nervous system is a sign of potential lethality (10, 21). In this series of neurologic cases admitted to the ICU, the mortality rate was 50%, similar to rates described by Lemant and colleagues and Azevedo and colleagues (17, 22). This high mortality rate is explained by the presence of comorbid conditions in older patients with organ failure on admission.

Chikungunya meningoencephalitis is a severe presentation of the viral infection. The presence of this condition may be indicated by fever and arthralgia followed by neurologic symptoms, requiring a high degree of suspicion in conjunction with specific CSF laboratories that provide evidence of causality between the viral infection and its neurologic tropism or autoimmune phenomena, which confirm the diagnosis and allow for adequate and early treatment. Older age groups and individuals with preexisting conditions are most affected, resulting in high morbidity and mortality rates.