Clinical presentation of anti-LGI1 encephalitis with teratoma
The patient was a 48-year-old woman with past medical history of nodular goiter and suspected teratoma. She began to suffer from anxiety six months prior to diagnosis, and have been treated with anxiolytics with no effect and with gradual deterioration. In the two months prior to admission, she had been hyperglycemic, and for the prior month had suffered from short term memory dysfunction and drowsiness.
She was admitted to the endocrinology department firstly with increased glucose level of 15.79 mmol/L (normal range 3.9-6.1 mmol/L), hemoglobin A1c (HbA1c) 10.90% (normal range 4.27%-6.07%), urine sugar 4+ (normal range none). And once glucose control was established, she was transferred to the neurology department because of ongoing cognitive impairment. The patient frequently forgot whether she had taken her medication, where her bed was located in the hospital, and who had visited her. MMSE was 13 (details in Table1) and she could not complete the MoCA because of irritability. Laboratory data confirmed slightly decreased sodium level of 135.4 mmol/L (normal range 136-145 mmol/L), potassium 2.87mmol/L (normal range 3.5-5.1 mmol/L), thyroid stimulating hormone 0.324 uIU/ml (normal range 0.35-4.94 uIU/ml), free triiodothyronine (FT(3)) 1.03 pg/ml (normal range 1.71-3.71 pg/ml) and free thyronine (FT(4)) 0.65 ng/dl (normal range 0.70-1.48ng/ml), increased glucose level of 12.48 mmol/L ( normal range 3.9-6.1 mmol/L), but normal complete blood counts, urinalysis, liver and renal function, myocardial infarction markers, coagulation functions and rheumatic antibody detection results (antinuclear antibodies, anti-dsDNA antibodies, antinuclear chromatin antibodies, anti-RNP A antibodies, anti-RNP B antibodies, anti-Sm/nRNP antibodies, anti-Sm antibodies, anti-SS-A antibodies, anti-Ro-52 antibodies, anti-SS-B antibodies, anti-Scl-70 antibodies, anti-Jo-1 antibodies, Anti-centromeric B antibody, and anti-ribosomal P protein antibodies) and immunity results (IgG, IgA, IgM, C3 and C4). On day 6 after admission, lumbar puncture was performed with normal routine and biochemical testing results, except for elevated glucose level of 4.74 mmol/L (normal range 2.22-3.89 mmol/L). Autoimmune encephalitis antibody panel (including NMDA, LGI1, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 (AMPA1), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 2 (AMPA2), gamma-aminobutyric acid-B receptor (GABAB) and Casper-2) of serum and CSF was also performed. On day 7, she developed visual hallucinations, and routine EEG was performed showing diffuse slow waves. Brain MRI showed bilateral hippocampal hyperintensity on T2 and T2-FLAIR sequences. Methylprednisolone (200mg/d, I.V.) and 2.5mg olanzapine were given immediately with the diagnosis of possible AE.
On day 8, she was transferred to intensive care unit (ICU) because of convulsive status epilepticus (SE) for 20 minutes unresponsive to diazepam (10mg I.V.) twice and phenobarbital (200mg I.M.) begun given 5 minutes after seizure onset. In the ICU, endotracheal intubation was followed by antibiotic therapy because blood oxygen saturation dropped to 70% and symptoms and signs of pneumonia were evident. Meanwhile, she was treated with midazolam, fentanyl and levetiracetam (LEV) initially followed by LEV monotherapy once she had been seizure-free for 24 hours. The diagnosis of anti-LGI1 encephalitis was confirmed by the detection of LGI1 antibody both in blood (1:32) and CSF (1:3.2), whereas other autoimmune antibodies were all negative. Considering her hyperglycemia and that seizures were controlled, methylprednisolone pulse therapy (MPT) was deferred; instead the dose was maintained at 200mg/d with combined intravenous immunoglobulin (IVIG) ((0.4mg/kg/d), I.V. 5 days) therapy. She was extubated on day thirteen at which point her vital signs were continuously stable.
After her seizures and pulmonary infection were well controlled, she returned from the ICU to the neurology ward with impaired cognitive function, visual hallucinations and irritability. We reduced the daily dose of methylprednisolone gradually with a transition to oral prednisone acetate, and continued drugs for control of seizures and psychosis. At day 25 after admission, the patient could answer simple questions and complained of stomachache (right lower quadrant). Considering her past history of suspected teratoma, ultrasound examination of uterus and appendages was performed and indicated a right adnexal mixed cystic-solid lesion. Further abdominal CT indicated a possible teratoma in this region. Gynecologic oncologists recommended elective surgery after the anti-LGI1 encephalitis was stable. One week later, neuropsychological assessment was performed with MMSE of 19 and MOCA of 20 (details in Table1). She was discharged with continued oral prednisone acetate (10mg/d), LEV (1500mg/d) and olanzapine (1.66mg/d).
At month 1 followup, the patient presented to the clinic with impaired short term memory and spatial disorientation, but no hallucinations. She was intermittently unaware of where she was and why she had come. Short term memory was impaired to the extent that she had to write down her daily plan and what she did every day in her notebook. She was partially reliant on a home caregiver. Repeated MRI (3 months after onset of memory dysfunction) showed reduced swelling of the bilateral hippocampus on T2 and T2-FLAIR sequence, slightly improved. Considering her improved anti-LGI1 encephalitis, she was admitted to the gynecological oncology department for laparoscopic oophorocystectomy. Postoperative pathological examination confirmed the diagnosis of teratoma: part of the left ovarian tissue was filled with colloidal substance, most of which was goiter, meanwhile also with a few components from multiple embryonal layers and was consistent with mature teratoma. And immunohistochemistry showed partial or focal positive nuclear staining of LGI1 was appreciated in some tumor cells.
At month 2 followup, her spatial disorientation was gone; she knew where she was and how to get back home when she went out, but she complained that she felt anxious when facing daily activities such as answering phone calls, and her short term memory was still bad. Neuropsychological assessment showed improved cognitive function with MMSE of 26, MOCA of 24 (details in Table1) and a mild mood problem with HAMA (Hamilton Anxiety Scale) of 8 and HAMD of 12. LGI1 antibody titer in blood was 1:32 at this time (one month after surgery).
At month 3 followup, her anxiety was greatly improved, but she still had short term memory impairment. EEG background had improved and showed focal, bilateral frontal slowing. Neuropsychological assessment showed very mild cognitive impairment and normal HAMA and HAMD scores (details in Table1).
At month 4 followup, the patient’s anxiety was totally relieved and she could live independently and return to work as her memory had gradually improved and she could recall what she had done without checking her notebook.
At month 5 followup, she complained once again of short term memory impairment during work, she frequently forgot where to find her working tools and documents. She was afraid of being alone and she preferred to stay at home with her family rather than having social contact. Neuropsychological assessment scores were 27 for MMSE, 29 for MOCA, 4 for HAMA, 3 for HAMD (details in Table1), 8 for ADAS-Cog (scored 5 for memory, 2 for word recognition and 1 for orientation) and 100 for BI. Repeated MRI including structural and functional sequences indicated improvement: hyperintensity on T2 and FLAIR were now gone on the left hippocampus though still present on the right side without volume swelling; no progressive brain atrophy was observed; DWI and DTI were symmetric bilaterally and normal; ASL showed slightly decreased blood flow in her left temporal lobe.