General information of CASPR2-IgG positive patients
Indications for antibody testing for the patients included clinically suspected autoimmune encephalitis, demyelinating encephalopathy, and epilepsy of unknown cause with an Epilepsy and Encephalopathy (APE2:as a model to predict the detection of these Abs based on patients’ clinical presentation and initial neurologic evaluation) score ≥ 4 [9]. Over a 7-year period, more than 3000 samples from pediatric patients with clinically suspected neurological autoimmunity were tested. The most common positive antibodies were against NMDAR (128/1358 in CSF), MOG (96/550 in serum) and GFAP (45/278 in serum). Three LGI1 antibody-positive patients (3/2658 in serum) were found among our samples. There was no GAD-65 antibody positive in our study. A total of 26 anti-CASPR2-positive patients (26/2658 in serum, and 3/2016 in CSF) were identified among those examine. The results of the antibody titers for anti-CASPR2 were as follows: +++ for 2 patients, ++ for 2 patients, and + for 22 patients; 25 patients showed serum positivity and 3 showed CSF positivity (including 2 patients with both serum and CSF positivity). Three patients were double-antibody positive for anti-NMDAR antibody (2 in CSF, 1 in both serum and CSF) and 1 patient was double-antibody positive for anti-GABABR antibody in CSF.
The oligoclonal bands were detected in 4 patients, and no positive results were obtained. All the patients had done tumor screen examinations, including chest X-ray or lung CT, color Doppler ultrasound or CT for thyroid, reproductive system, organs or lymph nodes in abdominal and pelvic cavity; and peripheral blood tumor antibody screening in partial patients. No cases with tumors beyond the central nervous system were found.
Among the 26 anti-CASPR2-positive patients, 17 were male and 9 were female. The age of onset ranged from 5 months to 14 years: 4 patients had an age of onset of 0–3 years; 6 patients, 4–6 years; 11 patients, 7–9 years; 4 patients, 10–12 years; and 1 patient had an age of onset of over 12 years. The most common onset age was 4–9 years. The median follow-up period was 22 months (range, 3–62).
Clinical Spectrum Analysis Of Caspr2 Autoantibody-related Disease
The clinical features, radiological and electrophysiological findings, treatment strategies and prognoses are summarized in Table 1. The key clinical phenotypes included encephalitis phenotype (including autoimmune encephalitis/encephalopathy/cerebellitis), intractable epilepsy, psychobehavioral abnormalities and combined tumors. Considering the possibility of false positive anti-CASPR2 antibodies, we classified the patients according to their main clinical phenotype, auxiliary examination, treatment and prognosis.
Table 1
Clinical features, auxiliary examinations, diagnosis and treatment strategies, prognosis in pediatric patients seropositive for CASPR2-IgG.
Patient no. Sex/ age of onset | Summary clinical | EEG | CSF | MRI | Anti-CASPR2 and other antibodies | Clinical syndrome | Treatment | mRS at onset/last f/u | Follow-up time (months) | outcome |
| Mainly manifestated as autoimmune encephalitis/encephalopathy/cerebellitis: |
1.M/3y | Fever, seizures, coma, weakness | Slow wave background | N | Cortical lesions in O/T/P lobes | +/serum | Autoimmune encephalopathy | IVIG | 5/0 | 56 | Improved to normal |
2.M/7y | Fever, neuropathic pain, ataxia, dysfunction with sleep, and consciousness, psychiatric symptoms | Slow wave background | N | N | ++/serum | Autoimmune encephalitis | Symptomatic | 4/0 | 40 | Improved, back to school, emotional agitation |
3.M/9y | Fever, dysfunction with consciousness and sleep, myotonia and autonomic symptoms | Slow wave background | WBC 214, Pro 0.593 | Lesions in O/P cortex, thalamus, globus pallidus, hippocampus and cerebral peduncle | +++/serum, +/CSF, GABABR: +/CSF | Morvan syndrome | IVIG + IVMP + Prednisone + Rituximab | 5/0 | 14 | Improved to normal |
4.M/9y | Seizures, slow response, sleep disturbance, psychiatric symptoms | Slow wave background, delta rhythm bursts | N | N | +/serum | Autoimmune encephalitis | IVIG + Prednisone | 5/0 | 24 | Improved, back to school, memory loss |
5.M/5m | Fever, seizures, coma, weakness, sleep disturbance | Slow wave background, sharp waves in right F | N | Lesions in globus pallidus, corpus callosum and cerebral peduncle | +/serum | Autoimmune encephalopathy | Symptomatic | 5/1 | 34 | Developmental retardation. He could walk and speak independently at 2 years and 6 months old. |
6.F/2y | Fever, seizures, unconsciousness, sleep and movement disorders, psychiatric symptoms | Slow wave background, sharp waves in left T | WBC 70 | Cortical lesions in F/T/P/O lobes, hippocampus and thalamus | +/serum, NMDAR: ++/CSF | Autoimmune encephalitis | IVIG + IVMP + Prednisone | 5/0 | 23 | Improved to normal |
7.F/12y | Fever, psychiatric symptoms sleep and movement disorders, myotonia | Slow wave background | N | N | +/serum | Morvan syndrome | IVIG + Prednisone | 4/0 | 18 | Improved to normal |
8.F/5y | Fever, seizures, slow response | Slow wave background, delta rhythm bursts | N | Lesions in F/T/P/O lobes, and caudate nucleus | +/serum | Autoimmune encephalopathy | IVIG | 2/0 | 11 | Improved to normal |
9.M/6y | Fever, seizures, weakness | spikes in left F | N | Cortical and subcortical lesions in F/T lobes | +/serum | Autoimmune encephalopathy | IVMP + IVIG + Prednisone | 3/0 | 9 | Improved to normal |
10.M/6y | Fever, ataxia, slow response, progress to hemiplegia, irritability | Slow wave background | WBC 138 | Lesion in thalamus, caudate nucleus and cerebral peduncle | +/CSF, NMDAR: +/CSF | Autoimmune encephalitis | IVIG + IVMP + Prednisone + Rituximab | 4/1 | 4 | Hemiplegia slightly |
11.F/12y | Fever, headache, seizures, unconsciousness, psychological symptoms | Slow wave background | Pro 0.67 | Lesion in bilateral thalamus | +/serum | Autoimmune encephalitis secondary to Japanese encephalitis | IVIG + IVMP + Prednisone | 5/0 | 14 | Improved to normal |
12.F/14y | Ataxia gait | N | WBC 59 Pro 0.72 | N | +/serum | Autoimmune cerebellitis | IVIG + IVMP + Prednisone | 3/0 | 11 | Improved to normal |
13.M/9y | Abnormal mental and behavior, seizures, unconsciousness | Slow wave background, Spikes or sharp slow wave in left F/T area, EPC | N | Multiple lesions in white matter | +/serum, NMDAR: +++/CSF and serum | Autoimmune encephalitis | IVIG + IVMP + Prednisone + PE | 5/0 | 4 | Improved to normal |
14.F/7y | Fever, headache, slow response | Slow wave background | WBC 390 Pro 0.6 | Cortex edema, Lesion in bilateral thalamus and right T lobe | ++/serum, +/CSF | Autoimmune encephalitis | IVIG + IVMP + Prednisone | 2/0 | 11 | Improved to normal |
15.F/2y | Seizures, ataxia, irritability | Slow wave background | N | N | +++/serum | Autoimmune encephalitis | IVIG | 3/0 | 23 | Improved to normal |
| Mainly manifestated as refractory epilepsy: |
16.M/9y | Recurrent focal seizures | Right temporal spikes and sharp waves | N | Multiple cortical lesions | +/serum | Refractory epilepsy; TSC | IVIG + AEDs | 1/1 | 49 | Epilepsy, seizure frequency decreased |
17.M/6y | Recurrent focal seizures, neuropathic pain, irascibility | Slow wave background, delta rhythm bursts | N | N | +/serum | Refractory epilepsy | IVIG + Prednisone + AEDs | 2/1 | 28 | Epilepsy, seizure frequency decreased |
18.F/5y | Recurrent focal seizures | Left frontal sharp waves | NA | N | +/serum | Refractory epilepsy | IVMP + Prednisone + AEDs | 2/1 | 40 | Epilepsy, seizure frequency decreased |
19. M/7y | Recurrent focal seizures, EPC | Slow wave background, spikes in right frontal area, EPC | N | N | +/serum | Refractory epilepsy | AEDs, IV Midazolam | 2/0 | 21 | Seizure free |
20. M/8y | Recurrent focal seizures | Spikes or sharp slow wave in left P/T/O area | N | N | +/serum | Refractory epilepsy | AEDS | 1/1 | 62 | Epilepsy, seizure frequency decreased |
21.M/9y | Recurrent focal seizures | Spikes or sharp slow wave in left P/T area | N | Cortical lesions in left P area | +/serum | Refractory epilepsy, FCD | IVMP + Prednisone + AEDS + lesion excision | 2/0 | 24 | Seizure free after lesion excision |
| Mainly manifestated as psychobehavioral abnormalities:20 |
22.M/10y | Behavioral and psychological symptoms | N | N | N9 | +/serum | Psychobehavioral abnormalities | IVIG + Prednisone | 3/0 | 20 | Improved to normal |
23.M/5y | Behavioral and psychological symptoms | N | NA | N16 | +/serum | Psychobehavioral abnormalities | Symptomatic | 3/3 | 9 | Abnormal mental and behavior |
24.F/9y | Personality change and sleep disorder | N | NA | N9 | +/serum | Psychobehavioral abnormalities | Symptomatic | 1/0 | 16 | Improved to normal |
25.M/8y | Behavioral and psychological symptoms | N | N | N3 | ++/serum | Psychobehavioral abnormalities | IVIG + IVMP + Prednisone + Mycophenolate mofeil | 3/3 | 9 | Abnormal mental and behavior |
| Accompanied with tumor: |
26.F/12y | Hemiplegia, headache | Low voltage in right C/P/T | N | Lesions in right globus pallidus and midbrain | +/serum | Germinoma | IVMP + Prednisone | 3/3 | 3 | Hemiplegia |
Legends: M: male; F: female; N: normal; F: frontal; P: parietal, O: occipital; T: temporal; AED: antiepileptic drug; CSF: cerebrospinal fluid; WBC: white blood cell in CSF; Pro: protein in CSF; EEG: electroencephalography; MRI: magnetic resonance imaging; mRS: modified Rankin Scale. IVIG: intravenous immunoglobulin; IVMP: intravenous methylprednisolone; TSC: tuberous sclerosis; NA: not available; PE: plasma exchange; EPC: epilepsia partialis continua; FCD: focal cortical dysplasia |
CASPR2 autoantibody-related disease mainly manifested as encephalitis phenotype in 15 patients.
Fifteen patients presented with encephalitis phenotype: 10 with autoimmune encephalitis (2 of whom presented with Morvan syndrome), 4 with typical clinical features of autoimmune encephalopathy, and 1 with autoimmune cerebellitis. Three patients presented with autoimmune encephalitis coexisting with anti-NMDAR antibody positivity. One patient presented with Morvan syndrome coexisting with anti-GABABR antibody positivity. One patient presented with autoimmune encephalitis secondary to Japanese encephalitis. The results of the antibody titers for anti-CASPR2 were as follows: +++ for 2 patients, ++ for 2 patients, and + for 11 patients; 3 patients showed CSF positivity (including 2 with both serum and CSF positivity).
The age of onset ranged from 5 months to 14 years, the median onset age was 6 years and 5months. The most common symptoms of those 15 patients included disorders of consciousness (10/15), fevers (8/15), psychological symptoms/abnormal behaviors (8/15), sleep disorders (8/15), seizures (7/15), movement disorder (5/15), autonomic symptoms (5/15), peripheral nerve hyperexcitability/neuromyotonia (5/14) and weakness/hemiplegia (4/15). The autonomic symptoms (5/15) included 5 cases of hyperhidrosis, 4 cases of hypertension, 4 cases of gastrointestinal dysfunction and 2 cases of paroxysmal arrhythmia. The symptoms such as hyperhidrosis, irritability and tachycardia caused by high-dose of steroid administration were not included. There was no patient with simple visual impairment or paraplegia.
Brain MRI (Fig. 2) revealed abnormalities in 10 patients (66.7%). The most common sites of lesions were the cerebral cortex (6/15, widely distributed across the frontal, parietal, occipital and temporal lobes), thalamus (5/15), caudate nucleus (3/15), cerebral peduncle (3/15), white matter (2/15), hippocampus (2/15), globus pallidus (2/15) and corpus callosum (1/15). Electroencephalography (EEG) recordings revealed a slow wave background in 13 patients (86.7%), 2 (21.43%) of whom had bursts of delta rhythm (Fig. 3). Epileptiform discharges, originating from the frontal and temporal lobes, were found in 4 patients (26.7%), and one patient manifested with epilepsia partialis continua (EPC). All 15 patients underwent lumbar puncture examinations, 5/15 showed elevated WBC (range 59–390) in CSF, and 4/15 showed elevated protein (range 0.593–0.72) in CSF. Changes in the CSF were not very common in CASPR2-related patients. The CSF pathogen tests were negative in all patients.For the treatment strategies, 13 patients received immunotherapy, including intravenous immunoglobulin (IVIG) in 3, IVIG plus prednisone in 2, IVIG plus intravenous methylprednisolone (IVMP) plus prednisolone in 5, IVMP plus prednisone in 1, IVIG plus IVMP plus prednisone plus rituximab in 1, and IVIG plus IVMP plus prednisone plus plasma exchange (PE) in 1. The modified Rankin Scale (mRS) scores before treatment were 5 in six patients, 4 in two patients, 3 in three patients, and 2 in two patients. After treatment, twelve patients had an mRS score of 0, and one of them had memory loss. One patient had an mRS score of 1, with fine motor disorder of left hand; the follow-up time of the patient was only 3 months after immunotherapy, and the patient is in recovery. Two patients received symptomatic therapy (for economic reasons and given the side effects of hormones, the family refused immunotherapy). The mRS scores before treatment were 4 and 5. After 3 years of follow-up, the symptoms of these 2 patients improved gradually, and the mRS scores were 1 and 0, respectively; one patient had emotional agitation, and the other had developmental delay.
Brief Case Descriptions
Patient N.3, a boy aged 6 years, developed neuromyotonia and neuropathic pain, movement disorders, sleep disorders, irritability, eating difficulties and cognitive changes. Both CASPR2 and GABABR antibodies were detected in his serum and CSF. He was treated with intravenous immune globulin (IVIG) (2 g/kg/day for 5 days) and IV methylprednisolone (IVMP) (3 cycles of 20 mg/kg/day for 3 days alternating with 4 days of rest). One month later, his symptoms had not been relieved, his CASPR2 titers had not decreased, and brain MRI (Fig. 2-A1/A2) revealed new lesions. He was treated with rituximab (375 mg/m2, once a week, 4 times) and improved remarkably. One month after rituximab treatment, all his symptoms were relieved, his MRI results had become normal, and the CASPR2 antibody test was negative. Moreover, during the treatment, we found that carbamazepine had a significant effect on relieving the symptoms of myotonia.
Patient N.5 was the youngest patient, only 5 months old at symptom onset. His main symptoms included fever, recurrent seizures, disturbance of consciousness, and irritability. Brain MRI (Fig. 2-B1/B2) showed lesions in the globus pallidus, corpus callosum and cerebral peduncle. The WBC, protein, bacterial culture and macrogene examination for virus nucleic acid in CSF were normal. CASPR2 antibody positive was found in the serum. He received symptomatic treatment, including ventilator-assisted ventilation. His symptoms gradually improved, and his development gradually progressed after rehabilitation training. At the age of 2 years and 6 months, he could speak and walk independently.
Patient N.6, a girl aged 2 years, developed fever, recurrent seizures, unconsciousness, sleep and movement disorders, and psychological symptoms. Both CASPR2 and NMDAR antibodies were detected. Brain MRI (Fig. 2-C1/C2) showed extensive lesions in the cortex and thalamus, with meningeal enhancement of the cortical lesions. The symptoms in the acute stage were very severe but improved greatly after IVIG and half a year of steroid treatment. The patient was able to attend school normally and had normal intelligence.
Patient N.8, a girl aged 5 years, presented with two episodes of fever and seizures within a week. The symptoms were resolved without treatment. Brain MRI showed extensive cortical lesions (Fig. 2D). However, we still used IVIG to prevent aggravation of the clinical symptoms. During the 15-month follow-up, no symptom recurrence was observed.
Patient N.10, a boy aged 6 years, was admitted to the hospital because of fever, ataxia, and slow responses. EEG showed a low wave background, and brain MRI showed lesions in the thalamus and caudate nucleus (Fig. 2-E1/E5), with elevated WBCs in the CSF. Anti-CASPR2 antibody was positive in the CSF and negative in the serum, while NMDAR was initially negative in both the CSF and serum. He was treated with IVIG + IVMP, and the clinical symptoms were improved. One month after he was discharged from the hospital, he presented with hemiplegia and irritability. Brain MRI revealed new lesions in the cerebral peduncle (Fig. 2-E2/E5), and anti-NMDAR antibody was positive in the CSF, but anti-CASPR2 antibody was negative. He was treated with IVMP again and then rituximab. The lesions on brain MRI (Fig. 2; E3/E4/E7/E8, E1/E5, E2/E6, E3/E7, and E4/E8 represent D4, D16, D30, and D50 after onset, respectively) were decreased after immunotherapy. The hemiplegia was improved (at 1 month after discharge) but incompletely, and the patient remains in follow-up.
Patient N.11, a 12-year-old girl, was initially diagnosed with Japanese encephalitis. On 24, July,2021, she presented high fever, convulsions, disturbance of consciousness and central respiratory failure. Brain MRI showed symmetrical lesions of bilateral thalamus, elevated WBC and positive antibody to Japanese encephalitis in CSF in acute stage. After symptomatic treatment, her clinical symptoms gradually relieved and she was discharged home on August 19. On August 24, she developed convulsions, psychological symptoms and disturbance of consciousness again. Brain MRI shown lesions in the bilateral thalamus. CASPR2 antibody was positive, while NMDAR and other immune antibodies were negative. She was considered to have CASPR2 antibody-related autoimmune encephalitis secondary to encephalitis B, and the symptoms were cured after immunotherapy.
Patient N.12, a 14-year-old girl, mainly presented with an ataxic gait, elevated WBC and protein in the CSF, without symptoms of encephalitis or encephalopathy. Her EEG and brain MRI were normal. She was diagnosed with autoimmune cerebellitis and recovered to normal after administration of IVIG + IVMP, and oral prednisone for 1month. She was the only patient with a normal EEG among 15 patients diagnosed with CASPR2-related autoimmune diseases.
CASPR2 autoantibody-related disease mainly manifested as refractory epilepsy in 6 patients.
Six patients presented with refractory epilepsy, which manifested as recurrent focal seizures. The antibody titers for anti-CASPR2 were + in serum for all patients. Brain MRI revealed abnormalities in one patient with tuberous sclerosis (TSC) and another with focal cortical dysplasia (FCD), while the remaining 4 patients had normal MRIs. EEG results were abnormal in all patients: epileptic charges were observed in 5 (83.3%) patients, a slow wave background in 2 (33.3%) patients, bursts of delta rhythm in one patient, and epilepsia partialis continua (EPC) in one patient. WBC, protein concentration and autoimmune antibodies in CSF were examined in four patients and were normal.
Patient N.16 presented with focal seizures. Brain MRI revealed multiple cortical lesions. He was treated with IVIG and antiepileptic drugs (AEDs), but recurrent seizures persisted. Genetic tests showed TSC1 gene pathogenic mutations, which supported a diagnosis of TSC.
Patient N.17 had neuropathic pain and irascibility, with no specific changes on MRI and CSF examination. He was treated with IVIG plus prednisolone and AEDs, but recurrent seizure attacks persisted during the 3-year follow-up.
N.21 also presented with recurrent focal seizures, and EEG and MRI indicated left parietal abnormalities. He was treated with IVMP plus prednisone and AEDs but responded poorly. Finally, he achieved a seizure-free status after surgery, and pathological examination confirmed a diagnosis of FCD.
For the treatment strategies, all patients were treated with antiepileptic drugs (AEDs); 1 patient was treated with IVIG, one with IVIG plus prednisolone, and one with IVMP plus prednisolone. The mRS scores before treatment were 2 in four patients and 1 in two patients. After treatment, the mRS scores were 1 in four patients. One patient achieved a seizure-free status after AED treatment. The FCD patient was seizure free after surgery. The seizure frequency of the other 4 patients decreased. Among these 6 patients, the use of immunotherapy had little correlation with prognosis.
CASPR2 autoantibody-related disease mainly manifested as psychobehavioral abnormalities in 4 patients.
Four patients presented with psychobehavioral abnormalities. Three patients mainly manifested with self-talking, giggling, hallucinations, irritability, social disorders, fear, etc. One patient manifested with personality changes and sleep disorders. The results of the eCASPR2 antibody titers were all positive in serum: ++ for 1 patient and + for 3 patients. Brain MRI and EEG were normal in all patients. WBC, protein concentration and autoimmune antibodies in CSF were examined in two patients, and both were normal.
Patient N.22 was treated with IVIG plus prednisolone. His symptoms improved, with pre-/posttreatment mRS scores of 3/0. Patients N.23 and N.24 were only given symptomatic treatment; N.24 improved to normal, with mRS scores before/after treatment of 1/0, while the clinical symptoms of N.23 did not improve, with mRS scores before/after treatment of 3/3. Patient N.25 (with antibody titer ++) was treated with IVIG + IVMP + prednisone + mycophenolate mofeil, but the clinical symptoms did not improve; the mRS scores before/after treatment were 3/3.
CASPR2 autoantibody-related disease accompanied with tumor in 1 patient.
Patient N.26 manifested with hemiplegia of the left limb and headache. Brain MRI showed lesions in the right globus pallidus and midbrain. EEG showed low voltages in the right central, parietal and temporal areas, with normal WBC and protein concentrations in the CSF. The CASPR2 antibody titer was + in serum. He was treated with IVMP + prednisone but showed no improvement. Finally, he was pathologically diagnosed with germinoma by brain biopsy.
Comprehensive Analysis Of Patients False Positive For Anti-caspr2 Neurological Autoimmunity
Based on the clinical symptoms, MRI, EEG, CSF changes, antibody titers, copositivity with other antibodies, response to immunotherapy and other significant findings (such as past history and pathological examinations), we conducted a comprehensive analysis of the 26 patients (Table 2) to distinguish between true- and false-positive cases of CASPR2-related autoimmunity and to explore the correlation between the clinical phenotype and positive anti-CASPR2 antibody.
Table 2
The Summary of clinical symptoms, auxiliary examination and treatment response between different phenotypes of the patients seropositive for CASPR2-IgG.
| Autoimmune encephalitis/ encephalopathy/cerebellitis | Refractory epilepsy | Psychobehavioral abnormalities | Accompanied with tumor |
Number | 15 | 6 | 4 | 1 |
M:F | 8:7 | 5:1 | 3:1 | 1:0 |
Symptoms |
disorders of consciousness | 10 | 0 | 0 | 0 |
fever | 8 | 0 | 0 | 0 |
psychological symptoms/ abnormal behavior | 8 | 1 | 4 | 0 |
sleep disorders | 8 | 0 | 2 | 0 |
seizures | 7 | 6 | 0 | 0 |
movement disorder | 5 | 0 | 0 | 0 |
autonomic symptoms | 5 | 0 | 0 | 0 |
peripheral nerve hyperexcitability/neuromyotonia | 5 | 1 | 0 | 0 |
weakness/ hemiplegia | 4 | 0 | 0 | 1 |
Elevated WBC/protein in CSF | 6 | 0 | 0 | 0 |
MRI changes |
cortical lesions | 6 | 2 | 0 | 0 |
thalamus | 5 | 0 | 0 | 0 |
caudate nucleus | 3 | 0 | 0 | 0 |
cerebral peduncle | 3 | 0 | 0 | 1 |
white matter | 2 | 0 | 0 | 0 |
hippocampus | 2 | 0 | 0 | 0 |
globus pallidus | 2 | 0 | 0 | 1 |
corpus callosum | 1 | 0 | 0 | 0 |
EEG |
slow wave background | 13 | 2 | 0 | 0 |
epileptiform discharges | 4 | 5 | 0 | 0 |
Higher antibody titers | 4 | 0 | 0 | 0 |
Co-positive with other antibodies | 4 | 0 | 0 | 0 |
Good response to immunotherapy | 13/13 | 1/4 | 1/2 | 0/1 |
Other situations | 1 case was secondary to Japanese encephalitis | FCD: 1 case; TSC: 1 case | - | Germinoma |
Among the 26 anti-CASPR2-positive patients, the 15 patients who presented with autoimmune encephalitis/encephalopathy could probably be diagnosed with anti-CASPR2 neurological autoimmunity, as their clinical symptoms and signs and EEG, CSF and MRI changes were consistent with the characteristics of autoimmune diseases. The anti-CASPR2 antibody titers were higher and more frequently accompanied by other autoimmune antibodies than those of the other patients. The responses to immunotherapy were very good: the prognoses of the 13 patients who received immunotherapy were very good, and the 2 patients who did not receive immunotherapy had certain degrees of sequelae.
For the 6 patients who manifested with refractory epilepsy, we could not confirm that their etiology was related to the CASPR2 antibody. The core symptoms of these patients were mainly recurrent epilepsy. Patient N.17 was accompanied by emotional changes such as irritability, but the effect of immunotherapy was poor; the CSF and MRI results showed no specific changes, and the antibody titers were low. The use of immunotherapy had little effect on prognosis.
For the 4 patients who manifested with psychobehavioral abnormalities, we cannot confirm that their etiology was related to the CASPR2 antibody. They showed no solid evidence of encephalopathy and encephalitis except for psychobehavioral abnormalities and no specific changes in the CSF and on MRI. The use of immunotherapy had little effect on prognosis.
Obviously, in the patient diagnosed with germinoma, the positive CASPR2 antibody was likely to be related to the tumor, and immunotherapy was not effective. This suggests that the CASPR2 antibody positivity in this patient may be a paraneoplastic syndrome.