| BackgroundAutoimmune encephalitis(AE),mediated by autoantibodies targeting the central nervous system,recently begins to get recognized as a treatable type of encephalitis.Based on the location of autoantigens,it can be categorized into cell surface antigens,synaptic protein antigens,and intracellular antigen-related AE.Anti-leucine-rich glioma-inactivated protein 1(LGI1)encephalitis is a common type of anti-synaptic protein associated autoimmune encephalitis.The main clinical features of anti-LGI1 encephalitis include cognitive impairment,seizures,faciobrachial dystonic seizure(FBDS),abnormal behavior,sleep disturbances,hyponatremia,and autonomic dysfunction.Seizure attack is a common clinical manifestation of patients with anti-LGI1 encephalitis.It has been reported that 78%～100%of anti-LGI1 encephalitis patients experienc serizure,and 53%of them present epilepsy as the initial symptom.Seizures often occur concurrently with or after cognitive impairment.Most patients may experience more than one form of seizures throughout the disease course.The semiologies include generalized tonic-clonic seizures,complex partial seizures,simple partial seizures,status epilepticus,or subclinical seizures.With the advanced understanding of anti-LGI1 encephalitis and application of video EEG technology,more and more epileptic characteristics are identified.The seizure attacks are typically sudden onset and occur frequently,which often do not respond well to initial antiepileptic drugs.Additionally,autonomic seizure is another common symptomatic manifestation.FBDS,characteristic clinical manifestation of anti-LGI1 encephalitis,may appear before cognitive impairment and thus considered as a marker for early diagnosis of anti-LGI1 encephalitis.FBDS mainly involves unilateral face,ipsilateral upper or lower limbs,and cause abnormal posture.FBDS can occur more than a hundred times a day,but responds well to immunotherapy.Active immunotherapy can reduce the occurrence of later cognitive impairment.Most studies consider FBDS as a seizure attack,while there is ongoing discussion whether FBDS is a seizure or dystonia.In addition to FBDS and epilepsy,there are few studies on other motor symptoms in anti-LGI1 encephalitis patients.Sleep disturbances in patients with anti-LGI1 encephalitis include snoring,dream enanctment behavior,insomnia,hypersominia.Recent analysis on sleep disorders of VGKC encephalitis identified that acute phase may have significantly lower level of N3 sleep and REM sleep,as well as elevated sleep fragmentation.However,studies uncovering in detailed sleep structure of anti-LGI1 encephalitis are still missing.Objective1.The purpose of the present study is to retrospectively analyze the motor symptoms and look for new clinical diagnostic markers of acute phase anti-LGI1 encephalitis through video EEG monitoring.2.To further explore the characteristics of sleep disturbances by analyzing the sleep structure in the acute phase patients and controls.MethodsClinical,electrophysiological,and radiological data of 32 patients who were diagnosed with anti-LGI1 encephalitis in the department of neurology of provincial hospital affiliated to Shandong University from January 2015 to December 2019 were collected respectively.All 32 patients met the established diagnostic criteria for autoimmune limbic encephalitis proposed by Graus et al.The clinical data of patients during the acute phase were obtained by reviewing patient’s hospital medical records,and the clinical data during the recovery phase were obtained through outpatient or telephone follow-up.During the acute phase,32 patients underwent magnetic resonance scanning,28 patients completed video EEG monitoring during hospitalization,19 patients completed overnight VEEG monitoring,and 6 patients completed polysomnography(PSG)monitoring.The control group was composed of 14 patients of neurological outpatients or volunteer without complaints of sleep disorders or paroxysmal symptoms from December 2017 to December 2019.All the controls had finished the overnight VEEG monitoring and the EEG results were normalThe imaging data were independently analyzed by two neuroimaging physicians,and all lesions were agreed by both of them.Video EEG data was analyzed by three neurologists.One neurologist marked the motor events by viewing video data,and the other two neurophysiologists read the EEG data and evaluated the marked motor events.The uncertain events were discussed to ultimately achieve agreement.The structures of sleep were analyzed according to the international scoring standards of the american academy of sleep medicine.The mini-mental state examination(MMSE)and montreal cognitive assessment(MoCA)scales were applied to evaluate patients’ cognitive function.The independent sample t test or Mann-Whitney U test was used to statistically analyze the sleep structure parameters between the acute phase patients and the control group by SPSS.If p<0.05,it is considered that there is a statistical difference between the two groupsResults1.Clinical characteristics of acute phase patients32 patients were enrolled in this study,including 28 males.The median age at disease onset was 53.3 years old(range 28～70),and the median duration from onset to admission was 103.1 days(range 7～540).The common clinical symptoms included subjective cognitive decline(96.9%),seizures(87.5%),sleep disorders(71.9%),FBDS(53.1%),autonomic symptoms(50.0%),and abnormal behavior(34.3%).Hyponatremia was present in 40%of the patients.The results from the CSF were generally normal except for 10 patients.Among those 10 patients,8 patients had increased white blood cell counts and 4 patients presented elevated protein concentrations.In this stydy,the positive rate of antibodies was higher in serum(100%)than that of cerebrospinal fluid(88.9%).MRI showed hyperintensity on T2 flair in 28 of 32 patients(87.5%),with the involvement of the mesial temporal lobe(mTL)in 28 patients,insular cortex in 9.Basal ganglia(BG)hyperintensities on T1 were detected in 3 patients.2.Frequent seizure attacks were common in anti-LGI1encephalitsVEEG was recorded in 28 patients and lasted a median of 11.7 hours(range 4-41).23 patients showed an abnormal EEG background.Persistent and paroxysmal slow activities were found in 7 and 16 patients respectively,and posterior dominant rhythm(PDR)changes in 3 patients.Focal interictal discharges were detected in 6 patients.Eighteen types of seizure attacks were recorded in 13 patients with a frequency of 0.2-11.6/hour,and more than one type of attacks were recorded in 4 patients.Eleven types of attacks were accompanied by typical EEG evolution,four types accompanied by electrodecremental events(EDEs),and three types could only be identified by semiology.3.Study on the origin of FBDSFBDS was recorded in 9 patients with a frequency of 0.2～14/hour,and was immediately followed by seizure attacks in all patients.The incidence was much higher than the previous studies(40%～71.4%).EEG evolution and EDEs were recorded in 3 patients respectively.All FBDS were followed by other seizure semiology immediately and abnormal EEG changes were common,therefor we concluded that FBDS was more likely to be a part of epileptic motor events4.HMs expanded the motor manifestation of anti-LGI1 encephalitisHyperkinetic movements(HMs)were observed in 13 patients.HMs,was a type of myoclonic or twisted movement or manifested as mimicking daily life activities,could be facilitated in sleep periods.HMs appearred nearly continuously during the surface EMG recording,while there were no epileptic dischanges on synchronous EEG recordings5.Sleep structure was obviously disrupted in anti-LGI1encephalitis19 patients had overnight or long-rang VEEG recordings,and lasted a median of 18.4 hours(range 8-41).The normal sleep structure was disrupted-and there was decreased sleep efficiency(SE)and significant sleep fragmentation based on recordings in acute phase of anti-LGI1 encephalitis patients.The sleep disturbances were manifested by significant increase in light sleep,minimal N3 and REM sleep and decreased spindle density.The stages of N3 and REM sleep were absent in 9 and 11 patients,respectively.Three of the eight patients available for analysis were diagnosed as RBD.Nearly persistent HMs were observed in 10 patients.Six patients completed PSG monitoring,and two developed moderate obstructive sleep apnea(OSA)ConclusionPatients with anti-LGI1 encephalitis can develop a variety of motor events,including epileptic events such as FBDS and seizure attacks,and non-epileptic events such as HMs.FBDS is closely associated with seizure attacks,suggesting that FBDS is part of the seizure semiology.HMs expand the phenotype of motor events in LGI1 encephalitis and are closely related to sleep disturbances.Sleep disturbance is also one of the cardinal manifestations of anti-LGI1 encephalitis,which consists of sleep fragmentation,decreased sleep efficiency and spindle density,minimal N3 and REM sleep and RBD. |
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