Recently, AE has been recognized more and more. Compared with paraneoplastic encephalitis,
AE has or does not have tumors and has a better response to immunotherapy. The
clinical manifestations and imaging manifestations of AE were various. Epilepsy seizures
and disturbance of consciousness were the most common clinical symptoms. Hippocampal
damage was also a common imaging manifestation.
In this study, 1 anti-NMDAR encephalitis patient presented with onset of headache
accompanied by vomiting, irritability, and reduced visual acuity, with no apparent
history of infection. Subsequent lumbar puncture showed that CSF pressure was high
(240 mm H2O). The patient was diagnosed early, and admitted on the second day of symptom onset.
Studies have found that 80% of anti-NMDAR encephalitis patients have non-specific
symptoms accompanied by a preceding infection, such as fever, headaches, or viral-like
presentations (gastrointestinal or respiratory symptoms) . However, AE can present
with core symptoms that are similar to infectious encephalitis, except for fever and
elevated polymorphous cells in the cerebrospinal fluid .
In this patient, no abnormality was observed in brain MRI. There was no parenchymal
injury and no evidence of damage to the limbic system. According to the literature,
only 35% of anti-NMDAR encephalitis patients have abnormal brain MRI results on disease
onset. In fact, only 50% of patients have abnormal MRI results during the entire course
of the disease, which mainly present as grey and white matter hyperintensities .
When present, MRI abnormalities can involve the limbic system (e.g.; medial temporal
lobe, cingulate gyrus, etc.), which could facilitate the early diagnosis of
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.
Oligoclonal bands were rarely observed at the early stages of the disease, becoming
more evident at later stages . 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.
In addition to commonly observed symptoms of limbic encephalitis (such as cognitive
impairment, epilepsy, and mental disorder), anti-LGI1 encephalitis is associated with
faciobrachial dystonic seizures (FBDS) and refractory hyponatremia . In contrast
to other limbic encephalitis, anti-LGI1 encephalitis is rarely accompanied by tumors
 and responds well to immunotherapy. In this study, the 8 patients with anti-LGI1
encephalitis had initial clinical presentation of tonic-clonic seizures, with 1 having
headaches at disease onset and 1 having memory impairment at disease onset. During
the entire course of the disease, only 1 patient showed typical FBDS episodes.
Around 70% of anti-LGI1 encephalitis patients show T2/FLAIR MRI hyperintensities in
the hippocampus or temporal lobe (unilateral or bilateral), with some that extended
to the amygdala, insula, or striatum. MRI is atypical in the early stage of
the disease, especially in the FBDS stage,although there are cases of high T2 signal
in individual cases.During the limbic encephalitis phase, unilateral or bilateral
T2/FLAIR hyperintensities can be detected in the medial temporal lobe in most patients,
which may be accompanied with basal signal changes [15,18,20-21].
These results suggest that the occurrence or disappearance of abnormal MRI is related
to the time of onset. Different MRI examination time may lead to the illusion that
the imaging results are inconsistent with the clinical symptoms. Therefore, the occurrence
time and existence time of T1 and T2 anomalies need to be further studied. In this study, the duration from disease onset to confirmed diagnosis was 20 to 120
days. Only 1 patient with tonic-clonic seizures was absent of clinical presentations
of limbic system damage. The remaining 9 patients all had memory, cognitive, mental,
and behavioral abnormalities, all of which were symptoms of damage to the limbic system.
No evidence of damage to the basal ganglia and limbic system were observed in our
patients. Bilateral striatal hypermetabolism had been observed in FDG-PET in a patient with frequent bilateral FBDS episodes with no cognitive impairment and
no MRI basal ganglia abnormalities. 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 , 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. </p>
Ten patients had intracranial pressure lower than 180 mm H2O, 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)
. 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. The characteristics of Morvan's syndrome are encephalopathy with
prominent mental symptoms, insomnia, dysautonomia, and neuromuscular rigidity, almost
always in male patients. 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 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
encephalitis and very few patients had anti-NMDAR encephalitis. There were no significant
differences in the clinical presentations of these patients and those with elevated
cell counts in the cerebrospinal fluid and/or MRI abnormalities. Early disease detection
and initiation of immunotherapy as soon as possible was significantly associated with
improved clinical prognosis.
This study has some limitations. It only included 124 patients with AE, a relatively
small sample size. Nonetheless, we found that even if patients have negative MRI results
and no inflammatory changes in the cerebrospinal fluid, diagnosis of AE cannot be
excluded when clinical presentations such as epileptic seizures, memory impairment,
and abnormal mental behavior are present. Further comprehensive testing of the AE
antibody in blood and cerebrospinal fluid is needed to prevent misdiagnosis.
The main clinical manifestations of AE are epilepsy, cognitive impairment, memory
impairment, mental and behavioral abnormalities, and cerebrospinal fluid and brain
MRI can be completely normal.
Early diagnosis of AE and early immunotherapy therapy have better prognosis. The diagnosis
of autoimmune encephalitis should not be omitted because of normal cerebrospinal fluid
and brain MRI.