Researchers at the Johns Hopkins Encephalitis Center are dedicated to advancing the science behind encephalitis causes, diagnosis and treatment to help improve patient care.

Browse by research topic:

• Pathogen discovery
• Immunology
• Biorepository
• Ketogenic diet
• Diagnostic tools, treatments and outcomes
• Prodromal and sequelae post encephalitis
• Biomarkers of autoimmune encephalitis

Pathogen Discovery

Over 60% of the time, the specific cause of encephalitis cannot be determined. We are working with several groups to identify novel pathogens that cause encephalitis. Identifying these organisms is the first step in developing effective treatments.

To identify novel pathogens that cause encephalitis, our team is using cutting-edge genetic techniques in collaboration with several groups of investigators. We anticipate that these approaches, which include newly developed modifications of the polymerase chain reaction (PCR) technique, as well as whole genome sequencing approaches, will enable us to discover new viruses and bacteria that cause encephalitis.

• Venkatesan, A., & Murphy, O. C. (2018). Viral Encephalitis. Neurologic Clinics
• Tan, I. L., McArthur, J. C., Venkatesan, A., & Nath, A. (2012). Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology
• Venkatesan, A. (2013). Advances in Infectious Encephalitis: Etiologies, Outcomes, and Potential Links with Anti-NMDAR Encephalitis. Current Infectious Disease Reports

Immunology of Encephalitis

Encephalitis can be caused by a wide variety of conditions that fall into various categories, including infectious, autoimmune and neoplastic conditions. By characterizing the immune response in the cerebrospinal fluid (CSF), we hope to be able to categorize the type of encephalitis that a patient is experiencing, leading to a more effective treatment.

• Cohen, J., Sotoca, J., Gandhi, S., Yeshokumar, A. K., Gordon-Lipkin, E., Geocadin, R. G., … Venkatesan, A. (2019). Autoimmune encephalitis: A costly condition. Neurology
• Fermo, O. P., Izbudak, I., Sutter, R., Venkatesan, A., Kaplan, P. W., & Probasco, J. C. (2014, December). Autoimmune encephalitis mimicking Creutzfeldt-Jakob disease. Neurology. Clinical Practice
• Freund, B., Probasco, J. C., Cervenka, M. C., Sutter, R., & Kaplan, P. W. (2018). EEG Differences in Two Clinically Similar Rapid Dementias: Voltage-Gated Potassium Channel Complex-Associated Autoimmune Encephalitis and Creutzfeldt-Jakob Disease. Clinical EEG and Neuroscience
• Gordon-Lipkin, E., Yeshokumar, A. K., Saylor, D., Arenivas, A., & Probasco, J. C. (2017). Comparative Outcomes in Children and Adults With Anti- N-Methyl-D-Aspartate (anti-NMDA) Receptor Encephalitis. Journal of Child Neurology
• Kaas, B., Zeiler, S. R., Bahouth, M. N., Llinas, R. H., & Probasco, J. C. (2018, August). Autoimmune limbic encephalitis in association with acute stroke. Neurology. Clinical Practice
• Kaplan, P. W., & Probasco, J. (2017). Limbic and new onset refractory tonic status epilepticus (NORSE) in anti-NMDAR encephalitis. Clinical Neurophysiology Practice
• Venkatesan, A., Michael, B. D., Probasco, J. C., Geocadin, R. G., & Solomon, T. (2019). Acute encephalitis in immunocompetent adults. Lancet (London, England)
• Williams, T. J., Benavides, D. R., Patrice, K.-A., Dalmau, J. O., de Avila, A. L. R., Le, D. T., … Mowry, E. M. (2016). Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer. JAMA Neurology
• Yeshokumar, A. K., Gordon-Lipkin, E., Arenivas, A., Cohen, J., Venkatesan, A., Saylor, D., & Probasco, J. C. (2017). Neurobehavioral outcomes in autoimmune encephalitis. Journal of Neuroimmunology

Biorepository

We are continuing to grow and use our biorepository of CSF and serum from patients with neurological infections and neuroinflammatory disorders, including encephalitis. As new data on encephalitis is reported, we can confirm and extend these findings through our repository.

Ketogenic Diet Therapies for Patients With Encephalitis and RSE/SRSE

Our research team works closely with the Epilepsy Diet Center at The Johns Hopkins Hospital. We are studying the effect of ketogenic diet on patients with encephalitis who have uncontrollable seizures or status epilepticus as inpatients, or those who continue having seizures after the acute phase.

• Cervenka, M. C., Hocker, S., Koenig, M., Bar, B., Henry-Barron, B., Kossoff, E. H., … Geocadin, R. G. (2017). Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology
• McDonald, T. J. W., & Cervenka, M. C. (2018). The Expanding Role of Ketogenic Diets in Adult Neurological Disorders. Brain Sciences
• Thakur, K. T., Probasco, J. C., Hocker, S. E., Roehl, K., Henry, B., Kossoff, E. H., … Cervenka, M. C. (2014). Ketogenic diet for adults in super-refractory status epilepticus. Neurology

Diagnostic Tools, Treatments and Outcomes

The diagnostic tests and treatment options for encephalitis are very limited. Our team is working to find the best treatments for this condition while studying brain imaging and blood tests that might help with identification of encephalitis. And we use advanced neuro-critical care diagnostic and therapeutic modalities to limit brain damage in the acute setting. Seizures, for example, are a major cause of morbidity among encephalitis patients in the acute setting. We are using continuous electrical monitoring of patients’ brains and aggressive anti-epileptic strategies to limit seizure activity. Additional approaches include cutting-edge medical and surgical techniques to monitor and treat the brain swelling that accompanies encephalitis, as well as comprehensive ventilator and nutritional support for such patients.

• Beattie, G. C., Glaser, C. A., Sheriff, H., Messenger, S., Preas, C. P., Shahkarami, M., & Venkatesan, A. (2013). Encephalitis with thalamic and basal ganglia abnormalities: etiologies, neuroimaging, and potential role of respiratory viruses. Clinical Infectious Diseases
• Bradshaw, M. J., & Venkatesan, A. (2019). Emergency Evaluation and Management of Encephalitis and Myelitis in Adults. Seminars in Neurology
• Bradshaw, M. J., & Venkatesan, A. (2016). Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management. Neurotherapeutics
• Chow, F. C., Glaser, C. A., Sheriff, H., Xia, D., Messenger, S., Whitley, R., & Venkatesan, A. (2015). Use of clinical and neuroimaging characteristics to distinguish temporal lobe herpes simplex encephalitis from its mimics. Clinical Infectious Diseases
• Gaspard, N., Foreman, B. P., Alvarez, V., Cabrera Kang, C., Probasco, J. C., Jongeling, A. C., … Hirsch, L. J. (2015). New-onset refractory status epilepticus: Etiology, clinical features, and outcome. Neurology
• George, B. P., Schneider, E. B., & Venkatesan, A. (2014). Encephalitis hospitalization rates and inpatient mortality in the United States. PLoS One
• Saylor, D., Thakur, K., & Venkatesan, A. (2015). Acute encephalitis in the immunocompromised individual. Current Opinion in Infectious Diseases
• Sutter, R., Kaplan, P. W., Cervenka, M. C., Thakur, K. T., Asemota, A. O., Venkatesan, A., & Geocadin, R. G. (2015). Electroencephalography for diagnosis and prognosis of acute encephalitis. Clinical Neurophysiology
• Tan, I. L., Mowry, E. M., Steele, S. U., Pardo, C. A., McArthur, J. C., Nath, A., & Venkatesan, A. (2013). Brainstem encephalitis: etiologies, treatment, and predictors of outcome. Journal of Neurology
• Thakur, K. T., Motta, M., Asemota, A. O., Kirsch, H. L., Benavides, D. R., Schneider, E. B., … Venkatesan, A. (2013). Predictors of outcome in acute encephalitis. Neurology
• Venkatesan, A. (2015). Epidemiology and outcomes of acute encephalitis. Current Opinion in Neurology
• Venkatesan, A., & Adatia, K. (2017). Anti-NMDA-Receptor Encephalitis: From Bench to Clinic. ACS Chemical Neuroscience
• Venkatesan, A., & Geocadin, R. G. (2014). Diagnosis and management of acute encephalitis: A practical approach. Neurology. Clinical Practice

Prodromal and Sequelae Post-Encephalitis

Sequelae post-encephalitis, such as seizures, behavioral changes, headaches, fatigue and cognitive problems, have been described but have not been characterized in a systematic manner. We are trying to measure the severity and impact of these sequelae. Likewise, we are creating strategies to help patients deal with these symptoms in their daily lives.

Biomarkers of Autoimmune Encephalitis: FDG-PET Scan

Our team recently discovered that 85% of patients with autoimmune encephalitis had abnormal fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans, suggesting that this could be a sensitive test for detecting autoimmune encephalitis even when brain MRI and other tests appear normal. We are collaborating with the Johns Hopkins Department of Radiology to explore brain FDG-PET as a biomarker for diagnosis and staging of autoimmune encephalitis.

• Doherty, L., Gold, D., Solnes, L., Probasco, J., & Venkatesan, A. (2017). Anti-DPPX encephalitis: prominent nystagmus reflected by extraocular muscle FDG-PET avidity. Neurology(R) Neuroimmunology & Neuroinflammation
• Probasco, J. C., Benavides, D. R., Ciarallo, A., Sanin, B. W., Wabulya, A., Bergey, G. K., & Kaplan, P. W. (2014). Electroencephalographic and fluorodeoxyglucose-positron emission tomography correlates in anti-N-methyl-d-aspartate receptor autoimmune encephalitis. Epilepsy & Behavior Case Reports
• Probasco, J. C., Solnes, L., Nalluri, A., Cohen, J., Jones, K. M., Zan, E., … Venkatesan, A. (2018). Decreased occipital lobe metabolism by FDG-PET/CT: An anti-NMDA receptor encephalitis biomarker. Neurology(R) Neuroimmunology & Neuroinflammation
• Probasco, J. C., Solnes, L., Nalluri, A., Cohen, J., Jones, K. M., Zan, E., … Venkatesan, A. (2017). Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurology(R) Neuroimmunology & Neuroinflammation
• Solnes, L. B., Jones, K. M., Rowe, S. P., Pattanayak, P., Nalluri, A., Venkatesan, A., … Javadi, M. S. (2017). Diagnostic Value of (18)F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis. Journal of Nuclear Medicine