Chikungunya with Neurological Manifestations

Chikungunya virus, an alphavirus, causes a syndrome characterized by debilitating arthralgia, along with fever, myalgia, headache, and rash during its acute phase. The name “chikungunya” originates from the Makonde language, meaning “that which bends up,” describing the stooped posture due to pain. While the first outbreaks were documented in the 1960s, chikungunya became a significant public health issue in 2004 with explosive outbreaks in tropical regions.[1] Despite being a usually self-limiting viral illness, chikungunya is often misdiagnosed, underreported, and underestimated, especially in resource-limited settings.[2] In India, the largest outbreak occurred in 2006, with over 10,000 confirmed cases annually. Maharashtra had the second-highest prevalence of this disease.[3] Previously considered a nonfatal disease, the chikungunya epidemic from 2004 to 2008 saw an increase in mortality rates, with India reporting between 4.5% and 4.9% mortality.[4] Neurological involvement in chikungunya is rare, generally including peripheral neuropathy, encephalitis, and acute inflammatory demyelinating polyradiculoneuropathy.[1] Here, we report two rare cases of neurological complications of chikungunya infection with varying outcomes. Case 1, a 67-year-old man, resident of Pune, with well-controlled diabetes mellitus for 7 years, presented with intermittent high-grade fever, polyarthralgia, facial puffiness, and pedal edema for 3 days. On the 4th day, he developed fresh blood per rectum. On examination, the patient was tachycardic (120 beats/min), hypotensive (BP: 78/44 mmHg), pale, and had multiple ecchymotic patches. Laboratory findings revealed anemia (Hb: 6.6 g/dl), neutrophilic leukocytosis (TLC: 20,900/cumm with 86% neutrophils), thrombocytopenia (65,000/cumm), and acute kidney injury (urea: 175 mg/dl, creatinine: 3.8 mg/dl). His coagulation profile was deranged with an INR of 2.4 and prolonged APTT (46s). Serum chikungunya polymerase chain reaction (PCR) was positive. During hospitalization, he experienced a generalized tonic-clonic seizure, requiring intubation due to poor sensorium. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis (24 WBCs/cumm, 96% lymphocytes), elevated proteins (136 mg/dl), and normal glucose levels. Noncontrast computed tomography head was normal. CSF PCR for chikungunya was positive, confirming the diagnosis of complicated chikungunya with encephalitis, acute kidney injury, and disseminated intravascular coagulation. The patient was managed with broad-spectrum antibiotics (meropenem and teicoplanin), anti-epileptics, and component therapy (four packed red blood cells, six fresh-frozen plasma, and six cryoprecipitates). He also underwent two sessions of hemodialysis due to worsening renal function. Despite aggressive treatment, the patient succumbed to his illness on the 4th day of admission. In Case 2, a 62-year-old man with a 10-year history of hypertension was admitted with fever, chills, and polyarthralgia of 6 days duration. 3 days into his illness, he developed slurred speech, difficulty walking, and tremors in both hands. On examination, he was hemodynamically stable, with cerebellar signs such as ataxia, bilateral dysmetria, and dysdiadochokinesia. No nystagmus or hypotonia was noted. As per laboratory findings, he had euvolemic hyponatremia (serum sodium 124 mEq/L) and was diagnosed with a syndrome of inappropriate antidiuretic hormone secretion, managed with fluid restriction and oral salt supplementation. Despite the correction of sodium levels, his neurological symptoms persisted. Magnetic resonance imaging brain revealed no abnormality. Lumbar puncture revealed an acellular CSF with elevated proteins (115 mg/dL), and both serum chikungunya immunoglobulin M and CSF PCR for chikungunya were positive, leading to a diagnosis of complicated chikungunya with cerebellitis. The patient was treated with intravenous immunoglobulin (IVIG) at 0.4 g/kg/day for 5 days. He showed significant clinical improvement, with complete recovery of ataxia and speech over the 2 weeks. Chikungunya virus can involve various organ systems, including the liver, heart, and nervous system. Neurological complications occur in up to 25% of atypical and 60% of severe cases, leading to significant morbidity and mortality.[5] Both central and peripheral nervous systems can be affected, with conditions such as encephalitis, Guillain–Barré syndrome (GBS), and retrobulbar neuritis.[6] Cerebellitis, as seen in Case 2, has been reported only once in the literature.[7] To the best of our knowledge, this is the second documented case of cerebellitis associated with chikungunya. Two mechanisms for neurological complications of chikungunya have been proposed. First, direct viral invasion affects the choroid plexus, meninges, and ependymal cells, especially in vulnerable populations such as infants, the elderly, and the immunocompromised. Second, an autoimmune mechanism may lead to demyelination and neurotoxicity through molecular mimicry. The autoimmune pathway is believed to be more common in the Indian subcontinent.[8] The treatment for chikungunya remains largely supportive, with Nonsteroidal anti-inflammatory drugs and antipyretics used for symptom relief. Targeted therapies, such as steroids for myelitis or IVIG/plasma exchange for GBS, are recommended for neurological manifestations.[1] In Case 2, the favorable response to IVIG highlights the potential role of immunomodulation in managing severe neurological manifestations of chikungunya.[9] IVIG has shown success in treating other neurological complications of chikungunya, such as GBS, encephalomyelitis, and dermatological conditions.[10] Early and aggressive immunomodulation may be crucial for managing severe cases of chikungunya with neurological involvement. Our cases highlight the importance of recognizing cerebellitis as a neurological complication of chikungunya. The positive response to IVIG in our second patient underscores the potential role of immunomodulation in treating severe chikungunya infections. While chikungunya is typically self-limiting, these cases demonstrate the need for prompt recognition and specialized intervention for patients with atypical manifestations. Further research into the mechanisms driving these complications and the role of immunomodulatory therapies is essential. Clinicians should maintain a high index of suspicion for neurological complications in chikungunya, especially when symptoms deviate from the typical presentation. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.