OBSERVATION ␥ Treatment of -Aminobutyric AcidB Receptor–Antibody Autoimmune Encephalitis With Oral Corticosteroids

Daniel M. Goldenholz, MD, PhD; Victoria S. S. Wong, MD; Lisa M. Bateman, MD, FRCPC; Michelle Apperson, MD, PhD; Bjorn Oskarsson, MD; Shahrzad Akhtar, MD; Vicki Wheelock, MD

Background: Autoimmune encephalitis is increas- Patient: A 43-year-old man with initial presentation of ingly identified as a cause of nonviral, idiopathic en- seizures and altered mental status. cephalitis. Present treatment algorithms recommend costly immune-modulating treatments and do not identify a role Intervention: Our patient was treated with an ex- for oral corticosteroids. tended course of oral corticosteroids as an outpatient.

Results: After treatment with oral corticosteroids, our Objective: To present a patient with ␥-aminobutyric patient had steady clinical improvement, achieved sei- acidB receptor–antibody encephalitis before and after treat- zure freedom, and experienced improved mental status ment with oral corticosteroids. to within normal limits.

Conclusions: This case supports the use of low-cost oral Design: Case report. corticosteroids in treating patients with ␥-aminobutyric acidB receptor–antibody encephalitis.

Setting: The inpatient course as well as outpatient fol- Arch Neurol. 2012;69(8):1061-1063. Published online low-up is discussed. April 16, 2012. doi:10.1001/archneurol.2012.197

UTOIMMUNE ENCEPHALITI- full-body stiffness for 1 to 2 minutes. Ad- des involve an inflamma- ditional conditions included insomnia and tory response attacking the disorientation. brain itself, occasionally in Initial examination revealed disorien- the context of malig- tation, short- and long-term memory loss, nancy.A Few cases of autoimmune encepha- and difficulty following commands. He litis secondary to antibodies to the ␥-ami- could not recall the names of 2 of his 3 chil- nobutyric acidB (GABAB) receptor have dren. Elemental neurologic examination been reported. There is little in the clini- results were nonfocal. After hospital ad- cal neurology literature on management mission, his encephalopathy progressed, of this specific entity. We present a case with agitation and visual hallucinations. of anti–GABAB receptor encephalitis that He continued to have 1 to 3 generalized responded to treatment with oral cortico- convulsions per week. steroids. Cerebrospinal fluid (CSF) analysis re- sults revealed mild proteinorachia at 51 Ͻ REPORT OF A CASE mg/dL (normal 45 mg/dL), lympho- cytic pleocytosis of 52 cells/mm3, and 13 Author Affiliations: oligoclonal bands. Brain magnetic reso- Author Affil Department of Neurology, A 43-year-old man with no significant nance imaging showed minimal diffuse pial Department University of California, Davis medical history presented after having a gadolinium enhancement and no paren- University o Medical Center, Sacramento generalized tonic-clonic seizure pre- chymal abnormalities. Results from 3 rou- Medical Cen (Drs Goldenholz, Bateman, ceded by a 3-week history of confusion and tine electroencephalograms and a 3-day (Drs Golden Apperson, Oskarsson, Akhtar, continuous video-electroencephalogram Apperson, O and Wheelock); and memory problems. He had experienced 5 and Wheeloc Department of Neurology, complex partial seizures described as un- recording during week 3 of his hospital Department University of Michigan, responsiveness with left arm flexion and stay were unremarkable. In week 8, a 4-day University o Ann Arbor (Dr Wong). left face chewing movements followed by continuous video-electroencephalogram Ann Arbor (

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 recording captured 8 seizures with bitemporal indepen- ties and intrathecal IgG synthesis are also commonly seen dent onsets. Cerebrospinal fluid and magnetic reso- in this condition.3 However, there are also some atypi- nance image abnormalities normalized during the fol- cal features of this case. First, the magnetic resonance im- lowing month, except for the persistent presence of CSF age finding of mild pial enhancement in our patient is oligoclonal bands. atypical for this condition, with mesial temporal lobe T2 Two months into the hospital stay, the diagnosis re- hyperintensities present in 66% of cases.3 In addition, our mained unknown after extensive CSF and serum study patient had no evidence of small cell lung cancer, which results to evaluate infectious, inflammatory, and para- is found in 60% of patients with anti–GABAB receptor en- neoplastic etiologies were negative. Screenings for ma- cephalitis.3 lignancy with computed tomographic imaging of the Corticosteroids have long been used to empirically treat abdomen, chest, and pelvis, as well as a whole-body posi- cases of suspected autoimmune encephalopathy,3-6 hence tron-emission tomography scan were also negative. our decision to initiate treatment with intravenous meth- Despite treatment with therapeutic doses of phe- ylprednisolone during the hospitalization. An oral ste- nytoin and levetiracetam, our patient continued to have roid taper was not given, as per our routine protocol for frequent seizures. A 5-day course of intravenous meth- pulsed intravenous steroid treatment. The patient’s con- ylprednisolone, 1 g daily, was initiated 5 weeks into the dition was somewhat improved at discharge, with a plan hospitalization. Seizure frequency improved from 5 sei- for close outpatient follow-up. The laboratory diagnosis zures in the week prior to initiating steroids to no sei- of anti–GABAB receptor encephalitis was made 1 month zures for 12 days after the initial dose and, subse- after discharge from the hospital. Given the limited treat- quently, 2 seizures per month. Despite gradual mental ment options for this uninsured patient, we proceeded status improvement, his disabling amnesia and dysex- with a trial of oral steroids as an inexpensive alternative. ecutive dysfunction persisted, requiring 24-hour super- Our patient’s chronic severe dysexecutive and amnes- vision. He was discharged home 3 months after admis- tic syndrome started to improve after week 2 of oral pred- sion, being prescribed phenytoin, lamotrigine, and nisone therapy, followed by rapid improvement. He be- levetiracetam. He had 3 generalized seizures in the fol- came seizure free after initiating prednisone treatment. lowing month, prompting an increase in the dose of la- Given the previously refractory symptoms, the timing of motrigine. improvement is most consistent with a response to oral One month after hospital discharge, antibodies to the steroid treatment. However, spontaneous remissions have 3 GABAB receptor were identified in the CSF. also been described in autoimmune encephalitis. We de- Our patient lacked medical insurance and could not cided to proceed with a gradual steroid taper given the afford treatment with intravenous immunoglobulin or dramatic improvement in this patient, the rare inci- plasma exchange. Therefore, we initiated a course of treat- dence of relapses in anti–GABAB receptor encephalitis, ment with oral prednisone, 60 mg daily, for 2 months, and the potential risks of long-term oral steroid treat- then 50 mg daily for 2 months, followed by gradual ta- ment. The patient has been monitored closely and has per, decreasing by 10 mg daily every 4 weeks. Clinical remained clinically stable during the steroid taper. recovery began 2 weeks after initiating prednisone. The Autoimmune encephalitis is increasingly identified as patient was seizure free and levetiracetam treatment was a cause of nonviral, idiopathic encephalitis. Immune treat- stopped 1 month after starting prednisone treatment. ments for these conditions improve overall outcomes but At follow-up 5 months after discharge from the hos- can be costly. We believe that oral corticosteroids are a pital, results from a repeat electroencephalogram were low-cost alternative therapy that should be considered 1 normal. His Folstein Mini-Mental Status Examination in patients with anti–GABAB receptor encephalitis given score was 28 out of 30, much improved compared with the remarkable improvement seen in this case. There may his profoundly impaired mental status during the hos- also be a role for oral corticosteroids in treatment algo- pitalization. He remains seizure free, with continued im- rithms for suspected cases of autoimmune encephalitis. provement in memory deficits and resolution of dysex- ecutive symptoms. He is now able to perform basic Accepted for Publication: February 3, 2012. household tasks including dishwashing, laundry, and Published Online: April 16, 2012. doi:10.1001/ cooking with little supervision. He continues to gradu- archneurol.2012.197 ally taper treatment with oral prednisone. Correspondence: Daniel Goldenholz, MD, PhD, Depart- ment of Neurology, University of California, Davis Medi- COMMENT cal Center, 4860 Y St, Ste 3700, Sacramento, CA 95817 ([email protected]). Author Contributions: Study concept and design: Gold- Our patient initially presented with clinical and labora- enholz, Apperson, and Wheelock. Acquisition of data: tory findings suggestive of limbic encephalitis, later con- Goldenholz, Bateman, Apperson, Oskarsson, and Akhtar. firmed to be associated with antibodies to the GABAB re- Analysis and interpretation of data: Wong, Bateman, and ceptor. Overall, the clinical presentation was consistent Apperson. Drafting of the manuscript: Goldenholz, Wong, with a recently published series of 15 cases.2 Our pa- and Apperson. Critical revision of the manuscript for im- tient presented with early and predominant seizures in portant intellectual content: Goldenholz, Wong, Bate- the context of memory loss and disorientation, all clini- man, Apperson, Oskarsson, Akhtar, and Wheelock. Study cal signs and symptoms typical for GABAB receptor– supervision: Goldenholz, Bateman, Apperson, and Whee- antibody encephalitis. Cerebrospinal fluid abnormali- lock.

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Financial Disclosure: Drs Goldenholz and Wong serve dation for Huntington’s Disease Program, and a gift from on the Neurology Resident and Fellow Section editorial the Charles and Margaret Pue Charitable Foundation for team. Dr Bateman has received research support from Citi- Huntington’s Disease Program. zens United for Research in Epilepsy and Forest Labo- ratories. Dr Apperson has received salary support as a Syl- REFERENCES via Lawry Physician Fellow of the National Multiple Sclerosis Society. Dr Oskarsson serves as a speaker for 1. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state:” a practical method for Avanir Pharmaceuticals and receives research support grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; from the National Institute of Neurological Disorders and 12(3):189-198. 2. Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(B) receptor in limbic Stroke, the Netherlands Institute for Health Sciences, and encephalitis with seizures: case series and characterisation of the antigen. Lancet Biogen Idec. Dr Wheelock has received honorarium from Neurol. 2010;9(1):67-76. the Huntington’s Disease Society of America (HDSA) for 3. Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to syn- co-authorship of A Physician’s Guide to Huntington’s Dis- aptic and neuronal cell surface proteins. Neurology. 2011;77(2):179-189. 4. Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case ease, an unrestricted educational grant for medical edu- series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091- cation symposium from Lundbeck Pharmaceuticals, grants 1098. TR1-01257-1 (co-investigator) and DR2-05415 (princi- 5. Boronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in pal investigator) from the California Institute of Regen- limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology. 2011; 76(9):795-800. erative Medicine, grant support from HDSA for the HDSA 6. Caselli RJ, Boeve BF, Scheithauer BW, O’Duffy JD, Hunder GG. Nonvasculitic au- Center of Excellence at the University of California– toimmune inflammatory meningoencephalitis (NAIM): a reversible form of Davis, grant support from the Joseph P. Roberson Foun- encephalopathy. Neurology. 1999;53(7):1579-1581.

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