Brain MRI findings in a patient with scrub typhus infection
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.185397
Source of Support: None, Conflict of Interest: None
A 55-year-old man was referred to our hospital and got admitted to the intensive care unit (ICU) with a provisional diagnosis of acute febrile illness (etiology unknown) with multiorgan failure and was placed on ventilator and vasopressor support. He had got admitted to the previous hospital with a history of fever for 3 days and breathlessness for 2 days. The laboratory findings of the previous hospital were as follows: Hemoglobin (Hb), 11.6 g/dl; total leukocyte count (TLC), 12,000/mm 3; differential leukocyte count (DLC), N87 L12; platelet count (PLT), 78,000/mm 3; serum creatinine, 1.3 mg/dl; blood urea nitrogen (BUN), 57 mg/dl; bilirubin (total), 2.7 mg/dl, bilirubin (direct), 1.5 mg/dl; albumin, 2.5 g/dl; serum glutamic oxaloacetic transaminase, 853 U/L; serum glutamic pyruvic transaminase, 360 U/L; and alkaline phosphatase, 380 U/L. Blood and urine cultures were negative. Both lungs were normal on chest X-ray. Electrocardiogram was normal. Test for hepatitis B surface antigen, hepatitis C virus, human immunodeficiency virus, malaria, and dengue were also negative. He received empirical antimicrobial therapy with symptomatic management. During the previous hospitalization of 2 weeks, his clinical course worsened and he developed an altered sensorium and septic shock requiring mechanical ventilation and vasopressor along with acute kidney injury. Noncontrast computed tomography of the brain was normal.
At admission to our ICU, he was afebrile and sedated, pupils were bilaterally 3 mm in size and reacting to light, heart rate was 94/min, blood pressure was 136/62 mmHg (on noradrenaline intravenous infusion at 0.1 μg/kg/min), and peripheries were cold and edematous. Arterial blood gas parameters were as follows: pH, 7.35; PaO2, 96 mmHg; PaCO2, 56 mmHg with pressure controlled ventilation (FiO2, 0.5; positive end-expiratory pressure (PEEP), 10 cmH2O; Pressure control above positive end expiratory pressure (PEEP), 22 cmH2O; respiratory rate, 15/min). The urine output was as low as 20–30 ml/h. Laboratory workup at admission to our ICU revealed the following: Hemoglobin, 10 g/dl; TLC, 8000/mm 3; DLC, N50 L48 E2; platelets, 15,000/mm 3; serum creatinine, 5 mg/dl; blood urea nitrogen, 138 mg/dl; Na/K, 139/3.8; international normalized ratio, 1.2; activated partial thromboplastin time, 45 s; fibrinogen, 550 mg/dl; creatinine phosphokinase, 4185 U/L; and procalcitonin, 26 ng/ml. Chest X-ray showed bilateral lower-zone fluffy opacities suggestive of consolidation. Ultrasonography of the abdomen was normal. Repeat tropical workup results, including malaria, dengue, enteric fever, and leptospirosis, were negative; however, the result was positive for scrub typhus, with a raised antibody titer against Orientia tsutsugamushi on the Weil–Felix test. Empirical antibiotics, vasopressors, and mechanical ventilation were continued with invasive hemodynamic monitoring and other supportive care as per the ICU protocol. Doxycycline was added after the report of scrub typhus was obtained. He also received platelet transfusions and hemodialysis. In the third week of his illness, magnetic resonance imaging (MRI) of the brain was done in view of his poor sensorium, which revealed bilateral symmetrical hyperintensities in the subcortical white matter with diffusion restriction [Figure 1]. A focal area of cortical T2-weighted/fluid-attenuated inversion recovery hyperintensity was noted in the right frontal opercular region with foci of blooming on susceptibility-weighted images suggestive of microhemorrhage. In further clinical course, he had a refractory septic shock, acute respiratory distress syndrome, and overt disseminated intravascular coagulation with multiple-site bleeding, which did not respond to medical management. Subsequently, the patient succumbed to his illness on the fifth day of his ICU stay (day 19 of illness).
Scrub typhus is an acute febrile illness that may affect multiple organs, including the central nervous system (CNS).O. tsutsugamushi, an obligate intracellular gram-negative bacterium, is maintained by transovarian transmission in trombiculid mites. The larvae of trombiculid mite usually feed on rats, which are the reservoir hosts. Humans are accidentally infected when they come in contact with mite-infested scrub vegetation during the wet season. It is a common health problem in Asia, including India. Outbreaks of scrub typhus have been reported in northern sub-Himalayan belt from Himachal Pradesh to Darjeeling. Scrub typhus is also commonly reported from various parts of southern India. Scrub typhus commonly involves the central nervous system; however, MRI findings are sparingly reported in the literature.
The common symptoms are fever, headache, myalgia, nausea, and vomiting, followed by breathlessness, gastrointestinal complaints, rash, and jaundice. An eschar at the site of larval feeding is the single most important diagnostic clue; however, it is less frequently seen in dark skinned people. Many patients may present with features suggestive of capillary leak syndrome in the form of generalized anasarca, pedal edema, hypotension, and low serum albumin. Although the pathogenesis of scrub typhus is complex, the principal target site is the endothelial cell. Involvement of endothelial cells of various organs produces changes of vasculitis and perivasculitis. Complications in scrub typhus usually develop after first week of illness; they include acute renal failure, hepatitis, hemorrhagic manifestations, disseminated intravascular coagulation, adult respiratory distress syndrome, circulatory collapse, pancreatitis, meningitis, myocarditis, and multiorgan dysfunction.
Meningoencephalitis/encephalopathy may be seen in two-thirds of patients with scrub typhus. Common neurological features are headache, altered sensorium, seizure, focal weakness, and neck stiffness. Systemic manifestations are more frequent in patients with CNS involvement. Rarely, immune-mediated CNS involvement may result in optic neuritis, myelitis, acute disseminated encephalomyelitis, and neuropathy. Very few cases of Guillain–Barre syndrome (GBS) have also been reported. Pathologic findings of CNS involvement in scrub typhus include diffuse or focal mononuclear cellular infiltration of the leptomeninges, clusters of microglial cells, and brain hemorrhage. Cerebrospinal fluid (CSF) examination may reveal lymphocytic pleocytosis and raised protein levels., The presence of the organism has been detected (O. tsutsugamushi) in the CSF of patients with CNS manifestations.
Diagnosis of scrub typhus can be suggested if there is a significant increase in the serum antibody titer measured with Weil–Felix agglutination test, indirect immunofluorescence assay, or immunochromatographic assay., Our case was diagnosed using the Weil–Felix test, which is cheap and highly specific, although it has a lower sensitivity. Results of routine laboratory investigations are nonspecific; however, elevated liver enzymes are frequently observed. Other common abnormalities noted are anemia, hypoproteinemia, leukocytosis, thrombocytopenia, and deranged renal function.
Differential diagnosis of patients presenting with encephalopathy along with systemic manifestations such as thrombocytopenia, coagulopathy, and liver and kidney dysfunction includes malaria, dengue, leptospirosis, and chikungunya. Scrub typhus is mild and self-limiting in most cases; however, few cases have a long and/or severe course, which may be fatal if appropriate antibiotic therapy is not given in time. Doxycycline is the antibiotic of choice. Chloramphenicol, azithromycin, and rifampicin are other antibiotics used for the treatment of scrub typhus. In our case, the patient presented very late to our institute with respiratory distress, altered sensorium, and multiorgan dysfunction. Antibiotic therapy for scrub typhus was instituted very late, and the patient succumbed to the illness. Although we have not noticed eschar or lymphadenopathy in our patient, he was a farmer by occupation who had a high chance of being exposed to mites.
Although features of meningoencephalitis or encephalopathy may be seen in two-thirds of patients with scrub typhus, MRI findings are less frequently discussed ,,,,,,,,, [Table 1]. In addition to direct and immune-mediated CNS involvement, scrub typhus can also produce encephalopathy due to hepatorenal dysfunction, thrombocytopenia, coagulopathy, electrolyte abnormalities, and hypotension. As there are few case reports of MRI findings in scrub typhus, most radiologists are not familiar with them. White matter lesions have been described in many case reports in patients with scrub typhus,,,, mainly in the subcortical, periventricular, and deep white matter areas. Our case had subcortical white matter lesions, with small-area cortical involvement, and microhemorrhage. Susceptibility weighted imaging has helped in the demonstration of microhemorrhage in scrub typhus; microhemorrhage detected on susceptibility weighted imaging has been reported by Sood et al. Diffusion restriction has been reported in white matter lesions in scrub typhus. Contrast enhancement is usually not seen, but a ring-enhancing lesion in the corpus callosum and multiple nodular parenchymal enhancements have been reported in two different cases., Meningeal enhancement has been reported is some cases.,, Involvement of the cerebellum, brain stem, putamen, thalamus, and spinal cord has been reported; however, in our case, these areas were spared.,, MR angiography results are mostly normal; however, in one case, occlusion of the right internal carotid artery and the middle cerebral artery has been reported. Thrombosis of the superior sagittal sinus has also been reported in one case.
On the basis of MRI, a close differential diagnosis in our case will be posterior reversible encephalopathy syndrome (PRES). PRES is known to be associated with hypertensive encephalopathy, electrolyte imbalance, infection, drugs, and various forms of vasculitis. Subcortical white matter lesions are common in PRES; however, the lesions usually lack diffusion restriction. Areas of diffusion restriction have been reported in 11–26%, and hemorrhagic changes have been reported in 15% of cases with PRES. As scrub typhus also causes vasculitis-like changes and electrolyte imbalance, an associated PRES cannot be ruled out.
In patients presenting with meningoencephalitis/encephalopathy-like features with cerebral microhemorrhages and white matter abnormalities, scrub typhus should be kept in the differential diagnosis, especially in endemic regions. Early diagnosis and administration of antibiotics effective against scrub typhus are necessary. Susceptibility-weighted and diffusion-weighted MR sequences may be helpful for delineation of brain lesions in scrub typhus.
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