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Treatment of γ-Aminobutyric AcidBReceptor–Antibody Autoimmune Encephalitis With Oral Corticosteroids FREE

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
[+] Author Affiliations

Author Affiliations: Department of Neurology, University of California, Davis Medical Center, Sacramento (Drs Goldenholz, Bateman, Apperson, Oskarsson, Akhtar, and Wheelock); and Department of Neurology, University of Michigan, Ann Arbor (Dr Wong).


Arch Neurol. 2012;69(8):1061-1063. doi:10.1001/archneurol.2012.197.
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Published online

ABSTRACT

Background Autoimmune encephalitis is increasingly identified as a cause of nonviral, idiopathic encephalitis. Present treatment algorithms recommend costly immune-modulating treatments and do not identify a role for oral corticosteroids.

Objective To present a patient with γ-aminobutyric acidB receptor–antibody encephalitis before and after treatment with oral corticosteroids.

Design Case report.

Setting The inpatient course as well as outpatient follow-up is discussed.

Patient A 43-year-old man with initial presentation of seizures and altered mental status.

Intervention Our patient was treated with an extended course of oral corticosteroids as an outpatient.

Results After treatment with oral corticosteroids, our patient had steady clinical improvement, achieved seizure freedom, and experienced improved mental status to within normal limits.

Conclusions This case supports the use of low-cost oral corticosteroids in treating patients with γ-aminobutyric acidB receptor–antibody encephalitis.

Autoimmune encephalitides involve an inflammatory response attacking the brain itself, occasionally in the context of malignancy. Few cases of autoimmune encephalitis secondary to antibodies to the γ-aminobutyric acidB (GABAB) receptor have been reported. There is little in the clinical neurology literature on management of this specific entity. We present a case of anti–GABAB receptor encephalitis that responded to treatment with oral corticosteroids.

REPORT OF A CASE

A 43-year-old man with no significant medical history presented after having a generalized tonic-clonic seizure preceded by a 3-week history of confusion and memory problems. He had experienced 5 complex partial seizures described as unresponsiveness with left arm flexion and left face chewing movements followed by full-body stiffness for 1 to 2 minutes. Additional conditions included insomnia and disorientation.

Initial examination revealed disorientation, short- and long-term memory loss, and difficulty following commands. He could not recall the names of 2 of his 3 children. Elemental neurologic examination results were nonfocal. After hospital admission, his encephalopathy progressed, with agitation and visual hallucinations. He continued to have 1 to 3 generalized convulsions per week.

Cerebrospinal fluid (CSF) analysis results revealed mild proteinorachia at 51 mg/dL (normal <45 mg/dL), lymphocytic pleocytosis of 52 cells/mm3, and 13 oligoclonal bands. Brain magnetic resonance imaging showed minimal diffuse pial gadolinium enhancement and no parenchymal abnormalities. Results from 3 routine electroencephalograms and a 3-day continuous video-electroencephalogram recording during week 3 of his hospital stay were unremarkable. In week 8, a 4-day continuous video-electroencephalogram recording captured 8 seizures with bitemporal independent onsets. Cerebrospinal fluid and magnetic resonance image abnormalities normalized during the following month, except for the persistent presence of CSF oligoclonal bands.

Two months into the hospital stay, the diagnosis remained unknown after extensive CSF and serum study results to evaluate infectious, inflammatory, and paraneoplastic etiologies were negative. Screenings for malignancy with computed tomographic imaging of the abdomen, chest, and pelvis, as well as a whole-body positron-emission tomography scan were also negative.

Despite treatment with therapeutic doses of phenytoin and levetiracetam, our patient continued to have frequent seizures. A 5-day course of intravenous methylprednisolone, 1 g daily, was initiated 5 weeks into the hospitalization. Seizure frequency improved from 5 seizures in the week prior to initiating steroids to no seizures for 12 days after the initial dose and, subsequently, 2 seizures per month. Despite gradual mental status improvement, his disabling amnesia and dysexecutive dysfunction persisted, requiring 24-hour supervision. He was discharged home 3 months after admission, being prescribed phenytoin, lamotrigine, and levetiracetam. He had 3 generalized seizures in the following month, prompting an increase in the dose of lamotrigine.

One month after hospital discharge, antibodies to the GABAB receptor were identified in the CSF.

Our patient lacked medical insurance and could not afford treatment with intravenous immunoglobulin or plasma exchange. Therefore, we initiated a course of treatment with oral prednisone, 60 mg daily, for 2 months, then 50 mg daily for 2 months, followed by gradual taper, decreasing by 10 mg daily every 4 weeks. Clinical recovery began 2 weeks after initiating prednisone. The patient was seizure free and levetiracetam treatment was stopped 1 month after starting prednisone treatment.

At follow-up 5 months after discharge from the hospital, results from a repeat electroencephalogram were normal. His Folstein Mini-Mental Status Examination1 score was 28 out of 30, much improved compared with his profoundly impaired mental status during the hospitalization. He remains seizure free, with continued improvement in memory deficits and resolution of dysexecutive symptoms. He is now able to perform basic household tasks including dishwashing, laundry, and cooking with little supervision. He continues to gradually taper treatment with oral prednisone.

COMMENT

Our patient initially presented with clinical and laboratory findings suggestive of limbic encephalitis, later confirmed to be associated with antibodies to the GABAB receptor. Overall, the clinical presentation was consistent with a recently published series of 15 cases.2 Our patient presented with early and predominant seizures in the context of memory loss and disorientation, all clinical signs and symptoms typical for GABAB receptor–antibody encephalitis. Cerebrospinal fluid abnormalities and intrathecal IgG synthesis are also commonly seen in this condition.3 However, there are also some atypical features of this case. First, the magnetic resonance image finding of mild pial enhancement in our patient is atypical for this condition, with mesial temporal lobe T2 hyperintensities present in 66% of cases.3 In addition, our patient had no evidence of small cell lung cancer, which is found in 60% of patients with anti–GABAB receptor encephalitis.3

Corticosteroids have long been used to empirically treat cases of suspected autoimmune encephalopathy,36 hence our decision to initiate treatment with intravenous methylprednisolone during the hospitalization. An oral steroid taper was not given, as per our routine protocol for pulsed intravenous steroid treatment. The patient's condition was somewhat improved at discharge, with a plan for close outpatient follow-up. The laboratory diagnosis of anti–GABAB receptor encephalitis was made 1 month after discharge from the hospital. Given the limited treatment options for this uninsured patient, we proceeded with a trial of oral steroids as an inexpensive alternative.

Our patient's chronic severe dysexecutive and amnestic syndrome started to improve after week 2 of oral prednisone therapy, followed by rapid improvement. He became seizure free after initiating prednisone treatment. Given the previously refractory symptoms, the timing of improvement is most consistent with a response to oral steroid treatment. However, spontaneous remissions have also been described in autoimmune encephalitis.3 We decided to proceed with a gradual steroid taper given the dramatic improvement in this patient, the rare incidence of relapses in anti–GABAB receptor encephalitis, and the potential risks of long-term oral steroid treatment. The patient has been monitored closely and has remained clinically stable during the steroid taper.

Autoimmune encephalitis is increasingly identified as a cause of nonviral, idiopathic encephalitis. Immune treatments for these conditions improve overall outcomes but can be costly. We believe that oral corticosteroids are a low-cost alternative therapy that should be considered in patients with anti–GABAB receptor encephalitis given the remarkable improvement seen in this case. There may also be a role for oral corticosteroids in treatment algorithms for suspected cases of autoimmune encephalitis.

ARTICLE INFORMATION

Correspondence: Daniel Goldenholz, MD, PhD, Department of Neurology, University of California, Davis Medical Center, 4860 Y St, Ste 3700, Sacramento, CA 95817 (daniel.goldenholz@ucdmc.ucdavis.edu).

Accepted for Publication: February 3, 2012.

Published Online: April 16, 2012. doi:10.1001/archneurol.2012.197

Author Contributions:Study concept and design: Goldenholz, Apperson, and Wheelock. Acquisition of data: Goldenholz, Bateman, Apperson, Oskarsson, and Akhtar. Analysis and interpretation of data: Wong, Bateman, and Apperson. Drafting of the manuscript: Goldenholz, Wong, and Apperson. Critical revision of the manuscript for important intellectual content: Goldenholz, Wong, Bateman, Apperson, Oskarsson, Akhtar, and Wheelock. Study supervision: Goldenholz, Bateman, Apperson, and Wheelock.

Financial Disclosure: Drs Goldenholz and Wong serve on the Neurology Resident and Fellow Section editorial team. Dr Bateman has received research support from Citizens United for Research in Epilepsy and Forest Laboratories. Dr Apperson has received salary support as a Sylvia Lawry Physician Fellow of the National Multiple Sclerosis Society. Dr Oskarsson serves as a speaker for Avanir Pharmaceuticals and receives research support from the National Institute of Neurological Disorders and Stroke, the Netherlands Institute for Health Sciences, and Biogen Idec. Dr Wheelock has received honorarium from the Huntington's Disease Society of America (HDSA) for co-authorship of A Physician's Guide to Huntington's Disease, an unrestricted educational grant for medical education symposium from Lundbeck Pharmaceuticals, grants TR1-01257-1 (co-investigator) and DR2-05415 (principal investigator) from the California Institute of Regenerative Medicine, grant support from HDSA for the HDSA Center of Excellence at the University of California–Davis, grant support from the Joseph P. Roberson Foundation for Huntington's Disease Program, and a gift from the Charles and Margaret Pue Charitable Foundation for Huntington's Disease Program.

REFERENCES

Folstein MF, Folstein SE, McHugh PR. “Mini-mental state:” a practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res. 1975;12(3):189-198
PubMed   |  Link to Article
Lancaster E, Lai M, Peng X,  et al.  Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen.  Lancet Neurol. 2010;9(1):67-76
PubMed   |  Link to Article
Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins.  Neurology. 2011;77(2):179-189
PubMed   |  Link to Article
Dalmau J, Gleichman AJ, Hughes EG,  et al.  Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies.  Lancet Neurol. 2008;7(12):1091-1098
PubMed   |  Link to Article
Boronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders.  Neurology. 2011;76(9):795-800
PubMed   |  Link to Article
Caselli RJ, Boeve BF, Scheithauer BW, O’Duffy JD, Hunder GG. Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy.  Neurology. 1999;53(7):1579-1581
PubMed   |  Link to Article

Figures

Tables

References

Folstein MF, Folstein SE, McHugh PR. “Mini-mental state:” a practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res. 1975;12(3):189-198
PubMed   |  Link to Article
Lancaster E, Lai M, Peng X,  et al.  Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen.  Lancet Neurol. 2010;9(1):67-76
PubMed   |  Link to Article
Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins.  Neurology. 2011;77(2):179-189
PubMed   |  Link to Article
Dalmau J, Gleichman AJ, Hughes EG,  et al.  Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies.  Lancet Neurol. 2008;7(12):1091-1098
PubMed   |  Link to Article
Boronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders.  Neurology. 2011;76(9):795-800
PubMed   |  Link to Article
Caselli RJ, Boeve BF, Scheithauer BW, O’Duffy JD, Hunder GG. Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy.  Neurology. 1999;53(7):1579-1581
PubMed   |  Link to Article

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