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.