77 patients in this study were from 24 provinces nationwide with 50 cases from the central region of Thailand. 31 cases (40.3%) presented with neuronal surface antibodies while 25 cases (32.5%) had intracellular antibodies. 28% of patients belonged to the systemic autoimmune diseases (NPLE and Hashimoto’s encephalopathy), coexisting neuronal antibodies, antibody-negative autoimmune encephalitis, infection-related neuronal antibody positive group (syphilis and listeria monocytogenes infections) and atypical AQP4-IgG, which presented with encephalitis syndrome (Figure 1). The prevalence and characteristics of autoantibodies from each group of autoimmune encephalitis are described in Figure 1 and Table 1.
Table 1: Description of autoantibodies seen in neuronal surface antibody group, intracellular antibody group and coexisting-antibodies group
Antibodies
|
Number of serum positive patients
|
Number of CSF positive patients
|
Age range (year)
|
% Male
|
Presenting symptoms
|
Evidence of tumor at 1st screening (cases)
|
Anti-NMDAr (25 cases)
|
24
|
16 (8 N/A)
|
5-79
|
44.1
|
Behavior, psychosis, dyskinesia, seizures, memory impairment, catatonia, mood disorders
|
Ovarian tumor (3)
|
Anti-AMPAr (2 cases)
|
2
|
1 (1 N/A)
|
2-72
|
50.0
|
Behavior, stiff-person syndrome
|
NSCLC (1)
|
Anti-GABA-Br (2 cases)
|
2
|
1 (1 N/A)
|
42-70
|
50.0
|
Behavior, seizures, myoclonus
|
Stomach cancer (1)
|
Anti-LGI1 (2 cases)
|
2
|
1 (1 N/A)
|
67-75
|
50.0
|
Behavior, seizures, FBDS
|
None
|
Anti-Ri (ANNA2) (7 cases)
|
7
|
1 (6 N/A)
|
44-82
|
42.9
|
Seizures, psychosis, dyskinesia, weakness
|
None
|
Anti-Yo (PCA1) (3 cases)
|
3
|
1 (2 N/A)
|
11-31
|
66.7
|
Seizures, diplopia, drowsiness, weakness
|
Germ cell tumor (1), high CA-125 (1)
|
Anti-PNMA2 (3 cases)
|
3
|
1 (1 N/A)
|
35-80
|
66.7
|
Behavior, dyskinesia, rapidly progressive dementia, weakness
|
Pancreatic cancer(1) ,high CA-125 (1)
|
Anti-recoverin (3 cases)
|
3
|
0
|
40-71
|
66.7
|
Behavior, ataxia, numbness
|
None
|
Anti-CV2 (CRMP5) (2 cases)
|
2
|
1 (1 N/A)
|
59-65
|
50.0
|
Psychosis, memory impairment
|
Ovarian cancer (1)
|
Anti-Hu antibody (2 cases)
|
2
|
N/A
|
28-29
|
0.0
|
Behavior, seizures, weakness, numbness
|
None
|
Anti-GAD65 (2 cases)
|
2
|
1 (1 N/A)
|
1-16
|
50.0
|
Seizures, opsoclonus-myoclonus, ataxia
|
Neuroblastoma (1)
|
Anti-SOX1 (2 cases)
|
2
|
2
|
33-66
|
50.0
|
Behavior, dyskinesia
|
None
|
Anti-titin (1 case)
|
1
|
0
|
86
|
0:0
|
Drowsiness, psychomotor retardation
|
None
|
Anti-NMDAr +ANA (2 cases)
|
2
|
2
|
15-30
|
0:0
|
Behavior, psychosis, seizures
|
Ovarian tumor (1)
|
Anti-NMDAr +anti-Ri (1 case)
|
1
|
N/A
|
18
|
100.0
|
Seizures
|
None
|
Anti-NMDAr +AQP4 (1 case)
|
1
|
1
|
24
|
0.0
|
Behavior, dyskinesia, weakness
|
None
|
NSCLC = non-small cell lung cancer FBDS = fasciobrachial dystonic seizure N/A = data not available
Neuronal Surface Antibody Group
Anti-NMDAr antibody is the most common antibody in the neuronal surface group (25/31 cases, 81%). Most patients (28 cases, 90.3%) had encephalitis with two and one cases of myelitis and encephalomyelitis respectively. The median age and range are shown in Table 2. Half of this group (16 cases, 51.6%) had no underlying diseases. Four patients were previously diagnosed with anti-NMDAr encephalitis with median recurrent time of 287.5 days (ranged from 61-456 days). One patient had HIV infections with CD4 count less than 200 cells/mm.3 A quarter of the patients (8 cases, 25.8%) also presented with prodromal symptoms such as headache and/or fever. However, they were absent in the remaining patients (23 cases, 74.2%).
Behavioral change was the most common presenting complaint with 14 cases (45.2%), followed by seizures (12 cases, 38.7%) and abnormal movements (9 cases, 29.0%) (Table 2). Among the nine patients with abnormal movements, five had chorea/dyskinesia (all had anti-NMDAr with one patient also presented with catatonia), two had faciobrachial dystonic seizures (both had anti-LGI1), one had stiff-person syndrome (anti-AMPAr-2), and one had myoclonus (anti-GABAr).
CSF examination was obtained from 27 patients in this group. There were ten cases of CSF pleocytosis (37.0%) and all had CSF white cell count below 100 cells/mm3. Most of the remaining cases had normal CSF protein and glucose level. Only one patient (anti-NMDAr) had a high CSF protein level of 242 mg/dl. Neuroimaging data were available in 27 cases. The majority presented with normal and non-specific findings (17 cases, 63.0%). The most common abnormality in brain MRI was increased signal intensity in T2-weighted image at the temporal lobe (3 cases, 11.1%). Other findings were leptomeningeal enhancement, subcortical, basal ganglia and multifocal lesions. In the neuronal surface antibody group, three cases of tumor (9.7%) were found on admission or during the first follow-up (Table 1).
14 patients (45.2%) received immunotherapy (IVIg 2g/kg/course or plasmapheresis 5 cycles) and 18 patients (58.1%) were given intravenous methyl prednisolone 1g/kg/day for 5 days. Tumors were appropriately treated upon discovery. Median length of stay in the hospital was 24 days (ranged from 4-150 days). Seven patients (22.6%) had poor outcome at discharge from hospital (mRS score 4-5) and one died from hospital acquired infection.
Intracellular Antibody Group
Anti-Ri was the most common autoantibody detected in the intracellular antibody group (7/25 cases, 28%). Eleven (44.0%) had no underlying disease, four had SLE, one had chronic HIV infections and one was previously diagnosed with malignant tumor (germ cell tumor).
As seen in Table 2, seizure was the most common presenting symptom (8 cases, 32.0%), followed by motor weakness (5 cases, 20.0%) and. behavioral change (4 cases, 16.0%). There were four cases (16.0%) of abnormal movements: one opsoclonus-myoclonus (anti-GAD65) and three generalized chorea (anti-Ri and anti-Sox1). Memory impairment was the first presenting complaint in two patients (8.0%). Six patients (24.0%) had tumors or evidence of malignancy with two patients presented with high blood level of CA-125 (anti-Yo, PNMA2) and the other four patients each presented with germ cell tumor (anti-Yo), ovarian tumor (anti-CV2), neuroblastoma (anti-GAD) and pancreatic cancer (PNMA2).
Neuroimaging data were available in 22 patients. Nine (40.9%) had normal or non-specific lesions. Predominantly increased signal intensity lesions in a T2-weighted image and FLAIR image at medial temporal lobe was found in three patients (13.6%). Other lesions were found in the cerebral cortex, subcortical white matter, basal ganglia, thalamus, brainstem and cerebellum. CSF examination was performed on 21 patients. Five (23.8%) had a white blood cell count of more than 5 cells/mm3, fifteen (71.4%) had a protein level of less than 100mg/dl and all had a normal glucose level.
Eight patients (32.0%) received IVIg 2g/kg/course and seven (28.0%) were given IV methyl prednisolone 1mg/kg/day for 5 days. Median length of stay in the hospital was 31 days (range 5-126). Six patients (24.0%) had poor outcome at discharge from hospital (mRS score 4-5) and four (16.0%) died. The causes of death were hospital acquired pneumonia (2 cases) and septicemia (2 cases).
Systemic Autoimmune Encephalitis Group
There were nine cases in the systemic autoimmune encephalitis group with six resulted from neuropsychiatric lupus erythematosus (NPLE). The median age of patients in this group was 33 (range 17-67) and most of the cases were female (88.9%). Four patients had been diagnosed with SLE prior to admission and two had underlying thyroid disease. Two cases presented with myelitis, while the remaining seven had encephalitis symptoms such as behavioral changes, seizure, psychosis, memory impairment and altered consciousness. Most patients in this group had normocellular CSF with normal CSF glucose level. Only three cases had a CSF protein level of over 60mg/dl. Six patients underwent brain MRI and half of them presented with normal or non-specific findings. Others showed increased signal intensity lesions in a T2-weighted image and FLAIR image at the cortical area, subcortical white matter and midline structures. No evidence of tumor was detected in this group. A large proportion of patients (44.4%) received high dose corticosteroids for treatment with a median hospital stay of 20 days. In terms of outcome at discharge from hospital, four patients partially recovered while the other four became disabled. One patient with NPLE had died.
Mixed Autoantibodies Group
There were four cases of mixed autoantibodies with all four presented with anti-NMDAr antibody and one additional autoantibody (Table1). Neuropsychiatric lupus was diagnosed in two patients who both had systemic SLE and ANA level of 1:2560. They also presented with behavioral change and psychosis. Neuroimaging was unremarkable except for the patient with coexisting NMO antibody who had lesions at the midline and cortical structures.
Table 2: Comparison between neuronal surface antibody group and intracellular antibody group
mRS = modified Rankin Scale
Characteristics
|
Neuronal surface antibodies
(n = 31)
|
Intracellular antibodies
(n = 25)
|
P value
|
Baseline Gender - male - female median age (years)
|
14 (45.2%) 17 (54.8%) 30.5 (2-79)
|
12 (48%) 13 (52%) 45.5 (1-86)
|
0.83
0.04
|
Presenting symptoms Behavior Psychosis/mood Seizures Abnormal movements (total) Generalized dyskinesia/chorea
|
14 (45.2%) 7 (22.6%) 12 (38.7%) 12 (38.7%) 5 (16.1%)
|
4 (16%) 3 (12%) 8 (32%) 6 (24%) 3 (12%)
|
0.02 0.30 0.60 0.24 0.66
|
CSF profile median CSF white blood cell (cells/mm3) median CSF protein (mg/dl) median CSF glucose (mg%)
|
2 (0-82) 26.5 (11-242) 65.5 (44-149)
|
1 (0-31) 44 (2-440) 67 (42-95)
|
0.12 0.27 0.46
|
Duration of disease onset to treatment(days)
|
15 (1-420)
|
20 (1-700)
|
0.385
|
Median hospital stay (days)
|
23 (4-150)
|
31.5 (5-126)
|
0.57
|
Outcome at discharge from hospital Completely recovered (mRS 0-1)
Partially recovered (mRS 2-3) Disable (mRS 4-5) Dead
|
3 (9.7%)
20 (64.5%) 7 (22.6%) 1 (3.2%)
|
0 (0%)
15 (60%) 6 (24%) 4 (16%)
|
0.25
0.73 0.9 0.16
|