Movement disorders in dengue encephalitis: a case report and literature review
Article information
Abstract
Dengue is a mosquito-borne viral disease caused by the dengue virus (DENV). The clinical manifestations of DENV infection range from mild febrile illness to severe dengue shock syndrome and dengue hemorrhagic fever. Recently, its neurological manifestations have been reported. The mechanisms of neurological complications in DENV infection are often attributed to neurotropism or may be immune-mediated. A double-doughnut sign is a radiological pattern of signal changes in the bilateral thalami, resembling a doughnut. Although this sign has been reported with dengue encephalitis, Japanese encephalitis, and other neurotropic infections, its co-occurrence with mixed movement disorders is rare. We report a case of dengue encephalitis involving a spectrum of movement disorders in the form of jaw opening dystonia, stereotypies, parkinsonism, and tremors during recovery. Magnetic resonance imaging showed bilateral thalami involvement with a double-doughnut sign. The patient was managed with pulse steroid therapy and benzodiazepines and showed gradual improvement in symptoms. Movement disorders with DENV infection are rare and self-limiting.
Introduction
Dengue encephalitis is a rare neurological complication of dengue fever, caused by dengue virus (DENV). Diagnosis is confirmed through clinical presentation, cerebrospinal fluid analysis, and detection of DENV RNA or antibodies in the serum or cerebrospinal fluid [1]. Movement disorders in dengue encephalitis are rare but can manifest as part of the neurological complications caused by the virus affecting the brain. These disorders may include tremors, myoclonus, chorea, ataxia, and parkinsonism [2]. The exact mechanisms are unclear, but they likely result from direct viral invasion, immune-mediated injury, or metabolic disturbances affecting the basal ganglia and other motor control regions of the brain. Here, in this case report, we are presenting a case of dengue encephalitis who developed a spectrum of movement disorders in the form of jaw opening dystonia, stereotypies, Parkinsonism, and tremors during the course of his recovery
Case Report
A 60-year-old male presenting with a high-grade fever for 5 days was experiencing arthralgia and myalgia. Two days after the onset of fever, the patient developed gradual deterioration in sensorium and could not communicate, although he could comprehend, and he was lethargic on presentation. He had no history of seizures, headaches, or vomiting. On examination, he had hepatomegaly and was delirious, with neck rigidity and a bilateral extensor plantar response.
Biochemical parameters revealed raised levels of aspartate aminotransferase (150 IU/L) and alanine aminotransferase (100 IU/L) with thrombocytopenia (80,000/mm3). The patient’s blood sample was sent for a fever panel for malarial parasites, Leptospira immunoglobulin M (IgM), dengue non-structural protein 1 (NS1) and IgM, and Typhidot IgM. The serum tested positive for the DENV NS1 antigen. Cerebrospinal fluid (CSF) analysis revealed a cell count of 5 cells/µL, a protein level of 92 mg/dL, a glucose level of 60 mg/dL, and an opening pressure of 8 cm H2O. The gram stain was negative for the cartridge-based nucleic acid amplification test of Mycobacterium tuberculosis, cryptococcal antigens, and other neurotropic viruses. Magnetic resonance imaging (MRI) showed bilateral thalamic involvement with a double-doughnut sign, as in Figure 1 (T1- and T2-weighted MRI). The patient was started on symptomatic treatment with pulse intravenous methylprednisolone, 1 g per day for 5 days. On day 4 of admission, the patient showed spontaneous opening of the eyes and was obeying commands, although he was mildly confused. He had developed jaw-opening dystonia (Supplementary Video 1). He was managed with a benzodiazepine (clonazepam 0.25 mg at bedtime) and tetrabenazine (50 mg in two divided doses). Gradually, his dystonia subsided. After 5 to 6 days, he developed stereotypical kinetic tremor movement of his bilateral upper limbs (left > right) and facial hypomimia. The tetrabenazine was stopped, while treatment with benzodiazepines and low-dose beta blockers was continued. The patient’s symptoms resolved, and he was discharged in stable condition after 2 weeks. Written informed consent for publication of information related to medical condition was obtained from the patient’s attendant.
T1- and T2-weighted magnetic resonance images showing a double doughnut sign with bilateral thalamic involvement
Hypointense signal in the bilateral thalami in the T1-weighted (A) and T2-weighted (B) images.
Discussion
Dengue is an arboviral infection caused by DENV. The neurological manifestations of DENV infection are varied and include encephalitis, myelitis, myositis, Guillain-Barré syndrome, hypokalemic paralysis, acute disseminated encephalomyelitis, and opsoclonus myoclonus syndrome [1]. Movement disorders have been commonly reported in Japanese encephalitis and less commonly with dengue encephalitis [2]. The double-doughnut sign has been described with dengue encephalitis [3,4], Japanese encephalitis [5], and other neurotropic infections; however, its co-occurrence with dystonia is rare [ 6].
We report a case of dengue encephalitis in which the patient developed a spectrum of movement disorders in the form of jaw-opening dystonia, stereotypies, parkinsonism, and tremors during recovery. Dengue is considered an endemic tropical and subtropical arboviral infection caused by the DENV and spread by the mosquito Aedes aegypti. Asia accounts for 70% of the worldwide disease burden. DENV can cause neurological complications and DENV encephalitis, dengue encephalopathy, immune-mediated syndromes, muscle dysfunction, dengue-associated stroke, and neuro-ophthalmic complications [7]. The proposed mechanisms of neurological complications of DENV infection are metabolic alterations or direct viral invasion that includes encephalitis, myositis, meningitis, myelitis, and autoimmune reactions, including acute disseminated encephalomyelitis, neuromyelitis optica, optic neuritis, myelitis, encephalopathy, and Guillain-Barré syndrome [8]. The occurrence rate of movement disorders in dengue encephalitis is reported to be 11%, which includes parkinsonian features [2]. DENV causes direct damage to neurons, leading to cerebral edema and hemorrhage caused by a vascular leakage, which typically affects both sides of the thalamus and basal ganglia and manifests radiologically as the so-called double-doughnut sign [8]. In the present case, dengue encephalitis was diagnosed based on criteria established by Cristiane et al. [9], including the presence of fever, acute signs of cerebral involvement such as altered consciousness or personality and/or seizures and/or focal neurological signs, reactive IgM dengue antibody, NS1 antigen, or positive dengue polymerase chain reaction in serum and/or CSF and the exclusion of other causes of viral encephalitis and encephalopathy. The management of dengue encephalitis is mainly supportive. The patient in this case was administered high-dose steroid therapy (1 g methylprednisolone for 5 days) when he developed dystonia along with other movement disorders. These symptoms responded to symptomatic treatment. MRI showed bilateral thalamic lesions that were hypointense on T1 and hyperintense on T2 (Figure 1), with central blooming suggestive of the double-doughnut sign. The MRI apparent diffusion coefficient scan and diffusion-weighted image are shown in Figure 2. The findings contrast with the indications of Japanese encephalitis, in which the movement disorders appear late and are prolonged with disabling sequelae [2]. That previous case of encephalitis may be attributed to an immune-mediated mechanism, whereas the improvement in the present case could largely be attributed to steroids. The double-doughnut sign with dystonia/parkinsonism was previously reported only in a single case of DENV encephalitis [6].
ADC and DWI magnetic resonance images of the patient
It shows restricted diffusion in DWI (A) and low ADC values with double-doughnut appearance (B).
DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient.
Post-dengue parkinsonism is rare. Extrapyramidal manifestation of dengue has been postulated to be due to its neurotropic effect on basal ganglia. A similar case report from Sri Lanka showed dengue IgM positivity in the CSF of a patient with parkinsonism on day 5 of admission; however, the MRI was normal and portrayed no double-doughnut sign [10]. Moreover, a longitudinal study from Taiwan showed that patients with dengue fever had an increased risk of developing Parkinson disease later in life [11]. Numerous neurotropic viruses have been shown to penetrate the nervous system and cause various forms of encephalopathy/encephalitis, with parkinsonism a probable manifestation. However, it remains unclear how these viruses cause parkinsonism. Repeated attempts to isolate viral particles in the brain or antibodies in the serum or CSF of Parkinson disease patients have failed [12].
Early identification and prompt symptomatic treatment of dengue encephalitis are crucial for a satisfactory clinical outcome. Further studies are needed to elucidate the mechanism of neurological manifestation in dengue infection.
Notes
Conflicts of Interest
No potential conflict of interest relevant to this article was reported.
Author Contributions
Conceptualization, Visualization, Validation, Methodology, Resources, Supervision: Dhiman NR, Joshi D; Data curation, Project administration: Batra P, Hussain I, Kumar A; Writing–review & editing: Joshi D, Dhiman NR; Writing–original draft: Batra P, Hussain I, Kumar A
Supplementary Materials
Supplementary Video 1 can be found via https://doi.org/10.47936.2024.00066.
Showing the movement disorders occurring in the patient