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Weil Syndrome A Rare Cause of Cerebral Venous Thrombosis Thiago Cardoso Vale, MD; Gustavo Camargos de Toledo Santos, MD; Saulo Fernandes Saturnino, PhD, MD; Adao Soares Antunes Neto; Frederico Figueiredo Amâncio, MD; Marluce Aparecida Assuncao Oliveira, PhD; Breno Franco Silveira Fernandes, MD; Rodrigo Santiago Gomez, MD; Marcus Vinícius Andrade, MD, PhD; Antonio Lucio Teixeira, MD, PhD

A 50-year-old previously healthy woman presented with a 4-day history of low back pain, nausea, vomiting, diarrhea, jaundice, and fever. She developed hypoxemic respiratory insufficiency and a chest radiograph showed diffuse alveolar and interstitial infiltrates. She was promptly intubated and became hemodynamically unstable and developed dialytic-renal insufficiency. At this time, laboratory workup revealed a hemoglobin level of 6.1 mg/dL (to convert to grams per liter, multiply by 10), leukocyte count of 0.2603/μL (to convert to ×109/L, multiply by 0.001), C-reactive protein level of 59 000 mg/L (to convert to nanomoles per liter, multiply by 9.524), platelet count of 28×103/μL (to convert to ×109/L, multiply by 1), serum urea level of 80 mg/dL (to convert to millimoles per liter, multiply by 0.357), serum creatinine level of 2.24 mg/dL (to convert to micromoles per liter, multiply by 88.4), serum potassium level of 0.72 mEq/L (to convert to millimoles per liter, multiply by 1), and abnormal coagulation profile (international normalized ratio of 1.8; D-dimer level of

125 200 mg/mL [to convert to nanomoles per liter, multiply by 5.476). A presumptive diagnosis of hemolytic-uremic syndrome led to a day of plasmapheresis, but then no schizocytes were found in the peripheral blood and results of the Coombs test were negative. Empirical antibiotic and antiviral treatment were started with ceftriaxone sodium, clarithromycin, and oseltamivir phosphate. Her blood and urine culture findings were negative. After 4 days of intensive care unit treatment, the patient progressively recovered and became hemodynamically stable. She no longer needed daily hemodialysis and she was being ventilated in spontaneous mode without sedative drugs. However, no awakening occurred. Neurological examination revealed a comatose patient with decorticated posturing after noxious stimuli, with normal brainstem functions and pupillary responses, without focal signs. Cranial computed tomographyshowed widespread cortical and deep brain hemorrhages (Figure, A and B). Brain magnetic resonance imaging and

Figure. Cranial Computed Tomography (CT) and Brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) A





A, Nonenhanced cranial CT showing bilateral temporal-parietal hemorrhages. B, Nonenhanced cranial CT showing multiple foci of hemorrhage, predominantly on the occipital lobes, left frontoparietal cortex, and corpus callosum. C, T1-weighted brain MRI showing diffuse hyperintensive signals with a bilateral occipital and frontal predominance. The corpus callosum and left internal capsule were also affected. D, Gradient-echo brain MRI showing




multiple foci of hemorrhage in either the cortex and subcortical regions. E, Sagittal brain MRI showing a hyperintense signal in the frontal lobe, genu of the corpus callosum, and parietal cortex. F, Sagittal brain MRA showing absence of flow in the inferior sagittal sinus. G, Coronal brain MRA showing absence of flow in the right internal jugular vein and in the thrombosed right transverse and sigmoid sinuses.

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Images in Neurology Clinical Review & Education

magnetic resonance angiography (Figure, C-G) revealed several foci of hemorrhages, internal jugular vein thrombosis, and thrombosis of multiple sinuses. Given the presence of cerebral venous thrombosis, a thorough search for autoimmune, prothrombotic, and infectious conditions was done. Serum human immunodeficiency virus; human T-lymphotropic virus; hepatitis A, B, and C; Venereal Disease Research Laboratory test; dengue and yellow fever; Rickettsial spotted fever; and leishmaniasis serologies were negative. An IgM immunoassay (enzyme-linked immunosorbent assay) for leptospirosis (Leptospira interrogans serovar icterohemorrhagiae) came out positive and was followed by microscopic agglutination test (MAT) titers of 1/400 at the first sample collected 5 days after the onset of symptoms. Another IgM enzyme-linked immunosorbent assay for leptospirosis performed 30 days after the onset of symptoms was still positive, with MAT titers of 1/100 for the serovar icterohemorrhagiae, lower than the initial values probably because a day of plasmapheresis was inadvertently performed before a hemolytic-uremic syndrome was ruled out. The final diagnosis was Weil syndrome complicated with cerebral venous thrombosis. The patient received low-molecular-weight heparin to treat the underlying prothrombotic state as well as ceftriaxone for 14 days. She was discharged from the intensive care unit without active interaction and without following commands, but her eyes had spontaneous opening. A cranial computed tomography scan was repeated 12 days after anticoagulation and showed a reduction of parenchymal edema and all hemorrhagic lesions. She was discharged from the hospital after 45 days with gastrostomy, tracheostomy, and an anticoagulation scheme. She started to follow simple commands but remained with anarthria and spastic tetraparesis.

Discussion Leptospirosis has recently been classified as a reemerging infectious disease, particularly in tropical and subtropical regions. Low but persisting rates of autochthonous illness and death still occur ARTICLE INFORMATION Author Affiliations: Neurology Division, University Hospital, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (Vale, Santos, Fernandes, Gomez); Department of Internal Medicine, University Hospital, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (Saturnino, Amâncio, Andrade, Teixeira); medical student, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (Neto); Tropical Medicine Division, Department of Internal Medicine, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (Oliveira).

in developed countries.1,2 It is primarily transmitted to humans by direct or indirect exposure to water, mud, or soil that is contaminated with the urine of mammals chronically infected with Leptospira interrogans.1 The diagnosis of leptospirosis is based on clinical suspicion and laboratory confirmation. Laboratory diagnosis is mainly based on serological methods, because culture is difficult and time consuming. Antibodies are detected in the blood 5 to 7 days after the onset of symptoms. Enzyme-linked immunosorbent assay is usually the serological test of choice for screening samples for the presence of IgM class antibody, which has a sensitivity of 90% and specificity of 94%. All positive screening test results should be confirmed by a serogroup-specific MAT in which patient serum is reacted with suspensions of live or formolized leptospires. Polymerase chain reaction assays for leptospiral DNA have the potential to facilitate the rapid diagnosis of acute leptospirosis during the acute phase of illness, complementing the IgM antibody detection assays. Therapy usually involves the use of penicillin for severe disease and tetracyclines, often doxycycline, for milder disease. Cephalosporins are equally effective and often comprise ceftriaxone or cefotaxime.2 Weil syndrome is the worst clinical spectrum of the disease and comprises jaundice, renal dysfunction, and hemorrhagic manifestations.1,3 The central nervous system is most commonly affected by aseptic meningitis, but intracranial hemorrhages, cerebellitis, and myelitis can occur.1,3,4 The intracranial bleeding due to leptospirosis may arise from the combination of several mechanisms, including thrombocytopenia, hypoprothrombinemia, and immune-mediated vasculitis, and commonly manifests as subarachnoid bleed and extradural hematoma. To our knowledge, cerebral venous thrombosis as a complication of leptospirosis was reported only once.4 Although dehydration, hypovolemia, and critical illnesses might determine cerebral venous thrombosis, the most likely cause in our patient was the extensive vessel wall damage associated with leptospirosis. The therapeutic option was to anticoagulate the patient.

Corresponding Author: Thiago Cardoso Vale, MD, Servico de Neurologia do Hospital das Clinicas, Avenida Professor Alfredo Balena 110, Bairro Santa Efigênia, CEP 30130-100, Belo Horizonte (Minas Gerais), Brazil ([email protected]). Published Online: December 23, 2013. doi:10.1001/jamaneurol.2013.2175. Conflict of Interest Disclosures: None reported. REFERENCES 1. Panicker JN, Mammachan R, Jayakumar RV. Primary neuroleptospirosis. Postgrad Med J. 2001;77(911):589-590.

2. Forbes AE, Zochowski WJ, Dubrey SW, Sivaprakasam V. Leptospirosis and Weil’s disease in the UK. QJM. 2012;105(12):1151-1162. 3. Mathew T, Satishchandra P, Mahadevan A, et al. Neuroleptospirosis revisited: experience from a tertiary care neurological centre from south India. Indian J Med Res. 2006;124(2):155-162. 4. Turhan V, Senol MG, Sonmez G, Oncul O, Cavuslu S, Tanridag O. Cerebral venous thrombosis as a complication of leptospirosis. J Infect. 2006;53(6):e247-e249.

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Weil syndrome: a rare cause of cerebral venous thrombosis.

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