Non-inflammation cerebrospinal fluid and normal brain magnetic resonance images of Autoimmune encephalits


 Background

We set out to investigate the characteristics and factors related to non-inflammation cerebrospinal fluid (CSF) and normal brain magnetic resonance images (MRI) of autoimmune encephalitis (AE) in patients.

Methods

The distribution and characteristics of brain MRI and CSF in 124 patients who were living with anti-NMDAR(71), LGI1(26),CASPR2(4),GABAR(23) encephalitis and who had been admitted between October 2016 and May 2018 were analyzed prospectively.

Results

12 of the 124 patients(1%) had a normal MRI and non-inflammation CSF.Ten of them were LGI1(83%),while the remaining 1 patient was NMDAR(8.3%),1 patient was CASPR2(8.3%).The clinical symptoms including epilepsy, psychosis, cognitive disorders, conscious disorders, headache, faciobrachial dystonic seizure (FBDS), speech disorders and hypoventilation. AE with non-inflammation CSF and normal MRI with good clinical prognosis. The median modified Rankin Scale (mRS) was low, and recurrence rate was also low.

Conclusion

The clinical manifestations of on-inflammation CSF and brain MRI-negative patients with AE are not specific, but suggest a better prognosis and a lower recurrence rates.

Non-inflammation cerebrospinal fluid and normal brain magnetic resonance images of Autoimmune encephalits CURRENT  We set out to investigate the characteristics and factors related to non-inflammation cerebrospinal fluid (CSF) and normal brain magnetic resonance images (MRI) of autoimmune encephalitis (AE) in patients.

Methods
The distribution and characteristics of brain MRI and CSF in 124 patients who were living with anti-NMDAR(71), LGI1 (26),CASPR2(4),GABAR(23) encephalitis and who had been admitted between October 2016 and May 2018 were analyzed prospectively.

Results
12 of the 124 patients(1%) had a normal MRI and non-inflammation CSF.Ten of them were LGI1(83%),while the remaining 1 patient was NMDAR(8.3%),1 patient was CASPR2(8.3%).The clinical symptoms including epilepsy, psychosis, cognitive disorders, conscious disorders, headache, faciobrachial dystonic seizure (FBDS), speech disorders and hypoventilation. AE with non-inflammation CSF and normal MRI with good clinical prognosis. The median modified Rankin Scale (mRS) was low, and recurrence rate was also low.

Conclusion
The clinical manifestations of on-inflammation CSF and brain MRI-negative patients with AE are not specific, but suggest a better prognosis and a lower recurrence rates.
Background AE is considered one of the most common causes of noninfectious acute encephalitis.It is estimated that 20% of all encephalitis cases in northern Europe are immune-mediated [1].AE is typically an acute or subacute onset and that may become chronic later [2].AE 3 has a wide variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders and seizures [2] [3].Suggested mechanisms that may trigger AE include tumors (paraneoplastic), infections (parainfectious),or it may be cryptogenic [3].Immunotherapy and tumor removal lead to substantial improvement in about 80% of the patients, especially when treated at an early disease stage [4].

Methods
Clinical data from 124 patients who were diagnosed with AE in the Department of Neurol diagnostic criteria [2]. Inclusion criteria were normal brain MRI manifestations, CSF leukocytes were less than 5*10 6 , lymphocyte was less than 70%, electrophoresis ALB quotient was less than 9, oligoclonal band negative. 12 patients met the criteria.We antibodies. In addition, to detect any potential tumors, all the participants underwent 4 chest, abdominal and pelvic Computed Tomography (CT).

Evaluation of prognosis
Clinical outcome were evaluated in each patients, and the modified Rankin Scale (mRS) was obtained at a 6-month follow-up. We also collected the recurrence rate of patients  All patients had no abnormal brain lesions on MRI. The white blood cell count and lymphocyte count in CSF were normal, the ALB quotient was less than 9, and the oligoclonal bands were negative. 12 patients were examined for autoimmune antibodies in 5 CSF. The results showed that one of the antibodies was positive for LGI1, NMDA and One clinical study on anti-NMDAR encephalitis found that inflammatory changes were detected in the CSF of only 44.8% of patients. Levels of elevated leukocytes, lymphocytes or proteins in the CSF was associated with the time between symptom onset and diagnosis/treatment [12]. Oligoclonal bands were rarely observed at the early stages of the disease, becoming more evident at later stages [11]. This suggests that CSF can be negative for inflammatory changes and markers of blood brain barrier damage in the early stages of the disease.
In our study, only 1 out of the 71 anti-NMDAR encephalitis patients (1.4%) was negative for both inflammatory changes in the CSF and brain MRI. A confirmed diagnosis was obtained early and immunotherapy was initiated. On follow-up after 9 months, no recurrence was found, and no sequela was observed. This suggests that the early diagnosis of anti-NMDAR encephalitis and the initiation of immunotherapy as soon as possible are key factors for a good prognosis [4].
In addition to commonly observed symptoms of limbic encephalitis (such as cognitive 7 impairment, epilepsy, and mental disorder), anti-LGI1 encephalitis is associated with faciobrachial dystonic seizures (FBDS) and refractory hyponatremia [13]. In contrast to other limbic encephalitis, anti-LGI1 encephalitis is rarely accompanied by tumors [14] and responds well to immunotherapy [15]. In this study, the 8 patients with anti-LGI1  [22]. This suggests that FDG-PET examinations can be used to identify intracranial metabolic lesions in anti-LGI1 encephalitis patients with normal MRI results. This would also aid in differentiating whether FBDS is epilepsy or dystonia [23], and should be considered in future studies. Our patients did not undergo FDG-PET examination; therefore, we cannot ascertain whether this would prove useful in our study.
Ten patients had intracranial pressure lower than 180 mm H 2 O, with no apparent symptoms of meningeal damage and no significant inflammatory changes in the CSF.
Recently proposed diagnostic criteria for AE are less restrictive, and do not require evidence of inflammatory response in the central nervous system (CNS) [24]. Our study support that these criteria were suitable. After treatment with first-line immunotherapy for 2 weeks, clinical symptoms were alleviated in all patients. After 3-17 months of follow-up, 70% of patients had a good prognosis, 2 patients were unable to be followed up with, and 1 patient died (due to epileptic seizures). One patient was given oral AEDs and 9 patients were not given oral glucocorticoids. The major legacy symptoms were memory impairment and dizziness. Overall prognosis was good and mRS score was 0-1.
Some patients with anti-CASPR2 encephalitis may progress to Morvan's syndrome or limbic encephalitis [15]. The characteristics of Morvan's syndrome are encephalopathy with prominent mental symptoms, insomnia, dysautonomia, and neuromuscular rigidity, almost always in male patients [25] [26]. In this study, 1 young female patient developed anti-CASPR2 encephalitis, accounting for 25% (1/4). The patient sought medical attention on the first day of disease onset, when she experienced fever and apparent mental symptoms accompanied by headaches, but no apparent autonomic nervous system symptoms, muscle tremors, myotonia, or pathological pain. Immunotherapy was given the next day, and symptoms rapidly improved following treatment. During the 14-month follow-up period, the patient only experienced headaches and did not have thymomas or other 9 tumors.
anti-NMDAR and anti-CASPR2 encephalitis acute onset and obtained early diagnosis and immunotherapy. Brain MRI and cerebrospinal fluid tests carried out at the early stages of the disease were negative, suggesting that patients with early AE may not experience inflammation. However, more case studies are required for verification.
In this study, we analyzed the clinical characteristics of AE patients with no inflammatory changes in CSF and normal brain MRI results, and found that most patients had anti-LGI1

Consent for publication
Written informed consent was obtained from the patients for publication of this research and any accompanying images or from the patient's next-of-kin.

Availability of data and materials
All data generated or analyzed during this study are included in this published article.

Competing interests
The authors declare that they have no competing interest.