Advances in treatment of narcolepsy / 浙江大学学报·医学版

Narcolepsy is the most common cause of excessive daytime sleepiness (EDS) following obstructive sleep apnea. Its treatment aims to reduce EDS and cataplexy, improve nighttime sleep disturbance, sleep paralysis and sleep-related hallucinations. Pitolisant (a histamine H3 receptor antagonist) and solriamfetol (a norepinephrine reuptake inhibitor) have recently been approved effective for narcolepsy in the United States and the European Union. Pitolisant has proved to be effective for both EDS and cataplexy. Besides being effective on EDS, solriamfetol seems to have advantages in abuse potential and withdrawal syndrome. As potential treatments for EDS and cataplexy associated with narcolepsy, several new drugs are being developed and tested. These new drugs include new hydroxybutyrate preparations (controlled release sodium hydroxybutyrate FT218, low sodium hydroxybutyrate JZP-258), selective norepinephrine reuptake inhibitor (AXS-12), and modafinil combined with astroglial junction protein inhibitor (THN102). This paper reviews the recently approved drugs and potential treatments for narcolepsy.

Advances in sleep-related hypermotor epilepsy / 浙江大学学报·医学版

Sleep-related hypermotor epilepsy (SHE), formerly known as nocturnal frontal epilepsy, is characterized by asymmetrical tonic or complex hypermotor seizures during sleep, with transient, frequent and clustering attack. The accurate incidence is not known but somehow low, which is estimated about 1.8/100 000. The differential diagnosis between SHE and parasomnias may be challenging due to possible similarities between the two sleep-related manifestations. In a majority of patients, the etiology is unknown. Identified etiologies are heterogeneous and structural abnormalities,which are involved in the severity and prognosis of SHE. In terms of treatment, it mainly includes pharmacological therapy and surgery. Carbamazepine seems to be the drug of choice in SHE patients, and epilepsy surgery provides excellent results in selected drug-resistant SHE cases. This review will focus on diagnosis, pathogenesis, treatment and prognosis of SHE, aiming to promote its early diagnosis and appropriate treatment.

Abnormal eye movements in patients with idiopathic rapid eye movement sleep behavior disorder / 浙江大学学报·医学版

OBJECTIVE@#To analyze the characteristics of eye movements in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD).@*METHODS@#Twenty two patients with iRBD and 20 controls were enrolled between January 2017 and May 2019 from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Clinical data including polysomnogram (PSG) results were collected. Videonystagmography (VNG) including spontaneous nystagmus, gaze, saccade, tracking and optokinetic test were performed. The difference of VNG results between iRBD patients and controls were analyzed. The factors related to the abnormal VNG results were analyzed by using logistic regression analysis.@*RESULTS@#No significant differences were found between the iRBD and control groups in the spontaneous nystagmus, gaze nystagmus, square wave jerk, involuntary eye movement, saccade and optokinetic nystagmus (all >0.05). In smooth pursuit of 0.4-0.5 Hz and 0.6-0.7 Hz, iRBD patients had more type Ⅲ-Ⅳ curve than controls (=5.177 and 5.301, both <0.05). Logistic regression analysis indicated that less sleep time of N3 stage was related to the abnormal results in smooth pursuit of 0.4-0.5 Hz (=0.963, <0.05). iRBD patients with Ⅲ-Ⅳ type curve in smooth pursuit of 0.4-0.5 Hz had less N3 sleep time than iRBD patients with Ⅰ-Ⅱ type curve (52±28 min vs. 76±23 min, =2.197, <0.05).@*CONCLUSIONS@#Abnormal smooth pursuit was found in iRBD patients, which might be related to the pathological mechanism of iRBD.

Relationship between sleep architecture and severity of obstructive sleep apnea / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effect of obstructive sleep apnea (OSA) on different sleep stages, and the relationship between N3 stage of non-rapid eye movement sleep and respiratory abnormal events.@*METHODS@#A total of 188 adult patients who underwent overnight polysomnography(PSG)monitoring in Sir Run Run shaw Hospital of Zhejiang University from June 24th to December 26th 2019 were enrolled in the study. OSA patients were classified into 3 groups (mild, moderate and severe) according to the apnea-hypopnea index (AHI). PSG data, AHI and the lowest SPO in each stage of sleep were compared among three groups.@*RESULTS@#There was no significant difference in total sleep time and sleep efficiency among patients with different severity of OSA (all >0.05). The proportion of N3 stage in moderate and severe OSA groups were significantly smaller than that in mild OSA group (all <0.05). The proportion of N3 stage in severe OSA group was also smaller than that in moderate OSA group (<0.05). In addition, severe OSA group had a longer latency of N3 stage than mild and moderate OSA groups (all <0.05). The latency of N3 stage in moderate OSA group was longer than that in mild OSA group (<0.05). The AHI in N3 stage was markedly lower than that in other sleep stages (all <0.01), regardless of the severity of OSA. Supine AHI in N3 stage in mild and moderate groups was significantly lower than that in N1, N2 and rapid eye movement (REM) stages (all <0.01). Supine AHI in N3 stage in severe group was also lower than that in N2 and REM stages (<0.05 or <0.01). The lowest SPO in N3 stage was significantly higher than that in N1, N2 and REM stages (<0.05 or <0.01), regardless of the severity of OSA.@*CONCLUSIONS@#s The proportion of N3 stage is lower in OSA patients, and N3 stage has less sleep respiratory events than non-N3 stages. The results suggest that the increased N3 stage proportion may indicate less severity of OSA.

Correlation between suicidal ideation and polysomnography parameters in late-life depression patients / 浙江大学学报·医学版

OBJECTIVE@#To investigate the relationship between sleep parameters and suicidal ideation in patients with late-life depression (LLD).@*METHODS@#Seventy-seven LLD patients over 60 years old from Sir Run Run Shaw Hospital of Zhejiang University during July 2017 and July 2018 were included in the study. All patients were assessed with Hamilton Depression Rating Scale (HAMD) and polysomnography (PSG) overnight. The suicidal score of item 3 in HAMD (HAM-D3)was used to define whether there was a suicidal ideation. Participants were subsequently grouped according to endorsement of presence (HAM-D3 score ≥1, =46) versus absence (HAM-D3 score=0, =31) of suicidal ideation symptoms. The sleep efficiency, total sleep time, wakefulness after sleep onset, rapid eye movement percent/latency, and non-rapid eye movement sleep stages 1-3 (N1-N3) were assessed. ANOVA analyses were conducted to explore the correlation of sleep parameters with suicidal ideation between the groups with and without suicidal ideation. In model 1, the HAM-D3 constituted the independent variable in separate ANOVA tests; in model 2 the impact of depressive symptoms were assessed as a covariate with sleep parameters.@*RESULTS@#There was less stage N3 [(55±41)min, =-4.731, <0.05] and the reduced percentage of N3 [(15±11)%, =-4.194, <0.05] in LLD patients with suicidal ideation, compared with the LLD patients without suicidal ideation [(104±49) min, (26±11)%]. Correlation analyses revealed that there was a significant correlation between the suicidal ideation and the percentage of stage N3 and sleep time of stage N3 (both <0.05).@*CONCLUSIONS@#Suicidal ideation is associated with less N3 sleep in LLD patients.

Restless legs syndrome in ischemic stroke patients: clinical features and significance / 浙江大学学报·医学版

OBJECTIVE@#To investigate the clinical features and implication of restless legs syndrome (RLS) in ischemic stroke patients.@*METHODS@#A total of 199 ischemic stroke patients were enrolled and assessed by polysomnography (PSG). RLS was identified according to criteria of International Restless Legs Syndrome Study Group. Epworth Sleepiness Scale (ESS), Mini-mental State Examination (MMSE) and Patient Health Questionnaire (PHQ-9) were used to evaluate the sleep quality, cognitive function and post-stroke depression, respectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the neurological function 3 months after stroke onset. Gender-and age-matched non-ischemic stroke patients with RLS (primary PLS) were selected as controls.@*RESULTS@#Twenty-two cases of RLS were identified among 199 ischemic stroke patients (11.1%). Generalized linear model and logistic regression showed that low serum ferritin level (=-133.3 mg/L, 95%:-200.4--0.1, <0.01), subcortical infarction (=4.05, 95%:1.15-14.18, <0.05) and female (=2.54, 95%:1.04-6.23, <0.05) were identified as the risk factors of RLS in ischemic stroke patients. Compared with ischemic stroke patients without RLS, ESS increased by 4.37 (95%:2.33-6.41, <0.01), PHQ-9 increased by 2.17 (95%:0.39--3.94, <0.05), and reduced NIHSS from the baseline deceased by 0.97 (95%:-1.79--0.15, <0.05) in ischemic stroke patients with RLS. In addition, the incidence of moderate-severe depression increased (=4.27, 95%:1.40-13.10, <0.05) in ischemic stroke patients with RLS. The index of periodic leg movements of sleep (PLMS) with arousal in ischemic stroke patients with RLS was significantly higher than that in patients with primary RLS (=12.85, 95%:2.04-23.67, <0.05).@*CONCLUSIONS@#RLS is common in ischemic stroke patients and has adverse influences on patients.

Screening efficiencies of obstructive sleep apnea screening scales in patients with acute ischemic stroke / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the application of various obstructive sleep apnea (OSA) screening scales in patients with acute ischemic stroke.</p><p><b>METHODS</b>One hundred and two patients with acute ischemic stroke were enrolled continuously during July 2016 and March 2017 from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. All patients were assessed by the same physician with various OSA screening scales, including Epworth scale, Berlin questionnaire, STOP-Bang questionnaire, SOS scale, four-variable scale and its modified version. Polysomnography was performed in Sleeping Disorder Center on each patient. According to the apnea-hypopnea index (AHI) acquired from polysomnography, patients were divided into moderate-severe OSA group (AHI ≥ 15, =58) and normal-mild OSA group (AHI<15, =44). The efficiencies of the scales in identification of patients with moderate or severe OSA were analyzed and compared.</p><p><b>RESULTS</b>The ROC curves showed that the four-variable scale and its modified version had higher area under curve (0.806 and 0.807, both <0.01) for diagnosis of moderate-severe OSA, and the cut-off values for Epworth scale, Berlin questionnaire, STOP-Bang questionnaire, SOS scale, four-variable scale and its modified version were 9, 2, 4, 15, 11, 10, respectively. The sensitivities, specificities, positive and negative predictive values of four-variable scale and its modified version in diagnosis of moderate-severe OSA were higher than those of other scales.</p><p><b>CONCLUSIONS</b>Compared with Epworth scale, Berlin questionnaire, STOP-Bang questionnaire and SOS scale, the four-variable scale and its modified version are more effective in screening of OSA for patients with acute ischemic stroke.</p>

Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats / 浙江大学学报·医学版

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.

Video head impulse test for evaluation of vestibular function in patients with vestibular neuritis and benign paroxysmal positional vertigo / 浙江大学学报·医学版

To assess the clinical application of video head impulse test (vHIT) for vestibular function in vestibular neuritis (VN) and benign paroxysmal positional vertigo (BPPV) patients.Thirty-three patients with VN and 43 patients with BPPV were enrolled from Sir Run Run Shaw Hospital and Ningbo Second Hospital from March 15 to September 10, 2015; and 50 healthy controls were also enrolled in the study. vHIT was used to quantitatively test the vestibulo-ocular reflex (VOR) gains of a pair of horizontal semicircular canals. VOR gains two pairs of vertical semicircular canals, and the corresponding asymmetrical value of three VOR gains. The saccades information was also recorded.Compared with the healthy control group and BPPV patients, the affected horizontal and vertical VOR gains were declined and the corresponding asymmetries were increased in VN patients (all<0.01). BPPV group also showed higher vertical VOR gain asymmetries compared with the healthy control group (all<0.01), but no significant difference was observed in VOR gains and horizontal VOR gain asymmetry (all>0.05). The sensibility of vHIT in diagnosis of VN was 87.9%. Among 33 VN patients, 22 were diagnosed with superior vestibular nerve dysfunction, 7 were found with inferior vestibular nerve dysfunction and 3 were with both dysfunction; and 1 case was not distinguished.Video head impulse test can quantitatively evaluate the vestibular dysfunction of VN and can help early diagnosis of VN, which may be widely used in clinic.

Sequential enteral nutrition support for patients with severe cerebral stroke / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the efficacy of sequential enteral nutrition support in patients with severe cerebral stroke.</p><p><b>METHODS</b>Forty-nine patients with severe cerebral stroke met the inclusion criteria were randomly divided into sequential enteral nutrition group (Group A, n=24) and conventional enteral nutrition group (Group B, n=25). Patients in Group A received short-peptide-based enteral nutrition support first, then gradually transferred to intact protein enteral nutrition. Meanwhile, patients in Group B constantly received intact protein enteral nutrition support. The nutritional indexes and the rate of complications were compared between two groups.</p><p><b>RESULTS</b>The nutritional indexes were decreased in both groups within 4 weeks after admission, but the decreasing levels of hemoglobin and albumin in Group A were significantly lower than those in Group B (P<0.05), and the incidence of infections and gastrointestinal hemorrhage in Group A was also lower than that in Group B (P<0.05). However, there were no significant differences in body weight, BMI, triceps skinfold thickness, biceps circumference, arm muscle circumference between two groups (P>0.05).</p><p><b>CONCLUSION</b>Sequential enteral nutritional support can improve the nutritional status and decrease the incidence of complications in critical patients with cerebral stroke.</p>

Mechanisms of Wuling mycelia powder on memory retrieval impairment in rats with chronic epilepsy / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms of Wuling mycelia powder on memory retrieval impairment in rats with chronic epilepsy.</p><p><b>METHOD</b>SD rats were randomly divided into four groups: the pentylenetetrazole-kindling group (the model control group), the low dose of Wuling mycelia powder (0.3 g x kg(-1), ig) group, the high dose of Wuling mycelia powder (0.6 g x kg(-1), ig) group and the blank control group. After being successfully trained in the 8-arm (4-arm baited) radial maze, the rats were intraperitoneally injected with a subconvulsive dose (35 mg x kg(-1)) of pentylenetetrazole (saline in control group) every 48 h for 12 times. Wuling mycelia powder were orally administered 30 min before every pentylenetetrazole injection. Memory retrieval was tested at the same maze. Phosphorylated CREB were analyzed by Western blot. Brain pathological sections were stained using HE, hippocampal nerve cells were observed under optical microscopes.</p><p><b>RESULT</b>Both of reference and working memory abilities of these chronic epilepsy rats were impaired as expressed in the 8-arm radial maze but reversed by Wuling mycelia powder to some extent. Chronic epilepsy caused a decreasing p-CREB in hippocampal nerve cells and injury in hippocampal CA1 region and CA3 region among rats. Wuling mycelia powder inhibited hippocampal p-CREB from decreasing and protected hippocampal nerve cells.</p><p><b>CONCLUSION</b>Wuling mycelia powder could ameliorate memory impairment induced by epilepsia. Its mechanism may be related to the increase in p-CREB expression in brain and the protective effect on hippocampal nerve cells.</p>