Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

DeepWMH:无需人工标注训练的脑白质高信号病灶分割工具

White matter hyperintensities(WMHs)on fluid-attenuated inversion recovery(FLAIR)images are imaging features in various neurological diseases and essential markers for clinical impairment and disease progression.WMHs are associated with brain aging and pathological changes in the human brain,such as in Alzheimer’s disease(AD)[1],Parkinson’s disease(PD)[2],cerebral small vessel disease(SVD)[3],multiple sclerosis(MS)[4].

Behavioral Effects of Deep Brain Stimulation of the Anterior Nucleus of Thalamus, Entorhinal Cortex and Fornix in a Rat Model of Alzheimer＇s Disease

Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit,including the anterior nucleus of thalamus （ANT）,the entorhinal cortex （EC）,and the fornix （FX）,on cognitive behaviors in an Alzheimer＇s disease （AD） rat model.Methods：Forty-eight rats were subjected to an intrahippocampal injection ofamyloid peptides 1-42 to induce an AD model.Rats were divided into six groups：DBS and sham DBS groups of ANT,EC,and FX.Spatial learning and memory were assessed by the Morris water maze （MWM）.Recognition memory was investigated by the novel object recognition memory test （NORM）.Locomotor and anxiety-related behaviors were detected by the open field test （OF）.By using two-way analysis of variance （ANOVA）,behavior differences between the six groups were analyzed.Results：In the MWM,the ANT,EC,and FX DBS groups performed differently in terms of the time spent in the platform zone （F（2.23） =6.04,P ＜ 0.01）,the frequency of platform crossing （F（2,23） =11.53,P ＜ 0.001）,and the percent time spent within the platform quadrant （F（2,23） =6.29,P ＜ 0.01）.In the NORM,the EC and FX DBS groups spent more time with the novel object,although the ANT DBS group did not （F（2,23） =10.03,P ＜ 0.001）.In the OF,all of the groups showed a similar total distance moved （F（1.42） =1.14,P =0.29）and relative time spent in the center （F（2,42） =0.56,P =0.58）.Conclusions：Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently thanANT DBS.In addition,hippocampus-independent recognition memory was enhanced by EC and FX DBS.None of the targets showed side-effects of anxiety or locomotor behaviors.

Deep brain stimulation of the nucleus basalis of Meynert modulates hippocampal-frontoparietal networks in patients with advanced Alzheimer’s disease

Background:Deep brain stimulation(DBS)of the nucleus basalis of Meynert(NBM)has shown potential for the treatment of mild-to-moderate Alzheimer’s disease(AD).However,there is little evidence of whether NBM-DBS can improve cognitive functioning in patients with advanced AD.In addition,the mechanisms underlying the modulation of brain networks remain unclear.This study was aimed to assess the cognitive function and the resting-state connectivity following NBM-DBS in patients with advanced AD.Methods:Eight patients with advanced AD underwent bilateral NBM-DBS and were followed up for 12 months.Clinical outcomes were assessed by neuropsychological examinations using the Mini-Mental State Examination(MMSE)and Alzheimer’s Disease Assessment Scale.Resting-state functional magnetic resonance imaging and positron emis-sion tomography data were also collected.Results:The cognitive functioning of AD patients did not change from baseline to the 12-month follow-up.Interestingly,the MMSE score indicated clinical efficacy at 1 month of follow-up.At this time point,the connectivity between the hippocampal network and frontoparietal network tended to increase in the DBS-on state compared to the DBS-off state.Additionally,the increased functional connectivity between the parahippocampal gyrus(PHG)and the parietal cortex was associated with cognitive improvement.Further dynamic functional network analysis showed that NBM-DBS increased the proportion of the PHG-related connections,which was related to improved cognitive performance.Conclusion:The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD,which may be related to the modulation of multi-network connectivity patterns,and the hippocampus plays an important role within these networks.

Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3′,5′-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model

Background:Anterior thalamic nuclei(ATN)deep brain stimulation(DBS)is an effective method of controlling epilepsy,especially temporal lobe epilepsy.Mossy fiber sprouting(MFS)plays an indispensable role in the pathogenesis and progression of epilepsy,but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown.This study aimed to investigate the effect of ATN-DBS on MFS,as well as potential signaling pathways by a kainic acid(KA)-induced epileptic model.Methods:Twenty-four rhesus monkeys were randomly assigned to control,epilepsy(EP),EP-sham-DBS,and EP-DBS groups.KA was injected to establish the chronic epileptic model.The left ATN was implanted with a DBS lead and stimulated for 8 weeks.Enzyme-linked immunosorbent assay,Western blotting,and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus.One-way analysis of variance,followed by the Tukeypost hoc correction,was used to analyze the statistical significance of differences among multiple groups.Results:ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy.The number of ectopic granule cells was reduced in monkeys that received ATN stimulation(P<0.0001).Levels of 3′,5′-cyclic adenosine monophosphate(cAMP)and protein kinase A(PKA)in the hippocampus,together with Akt phosphorylation,were noticeably reduced in monkeys that received ATN stimulation(P=0.0030 andP=0.0001,respectively).ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions(allP<0.0001).Conclusion:ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells,which may be associated with the reduced MFS in chronic epilepsy.The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

Error Analysis and Some Suggestions on Animal Stereotactic Experiment from Inaccuracy of Rhesus Macaques Atlas

The application ofstereotactic technique is rapidly growing. For instance, deep brain stimulation （DBS）, an important neurostimulation technique in the treatment of Parkinson＇s disease, dystonia, essential tremor, and other diseases, uses the stereotactic method to implant electrodes.

The cultivation of epilepsy neurosurgeons:requirements and challenges

Epilepsy surgery has been accepted as an effective treatment in drug-resistant focal epilepsy.However,the number of epilepsy neurosurgeons is not enough in China compared with the huge demand.The content of epilepsy neurosurgeon cultivation includes surgery itself as well as presurgical evaluation.In this article,we review not only different categories of epilepsy surgeries but also the presurgical evaluation approaches including non-invasive methods,such as semiology analysis,high-resolution structural and functional imaging techniques,scalp electroencephalography monitoring as well as invasive methods,such as electrocorticography (ECoG) and stereotactic electroencephalography (SEEG).We also discuss the importance of learning each method briefly.In addition,we suggest that epilepsy neurosurgeons should have a solid structural and functional anatomy basis as it plays pivotal role in localizing epileptogenic zone.Epilepsy neurosurgeons should also be familiar with the staged presurgical evaluation starting from the most preliminary examinations and progressing to more complex and invasive methods.During the diagnosis and therapeutic procedures,collaboration between epilepsy neurosurgeons and other specialists is essential.At last,the necessity of epilepsy neurosurgeon cultivation has been emphasized.

Acute Fornix Deep Brain Stimulation Improves Hippocampal Glucose Metabolism in Aged Mice

Background： A beneficial memory effect of acute formix deep brain stimulation （DBS） has been reported in clinical studies. The aim of this study was to investigate the acute changes in glucose metabolism induced by fornix DBS. Methods： First, the Morris water maze test and novel object recognition memory test were used to confirm declined memory in aged mice （C57BL/6, 20-22 months old）. Then, four groups of mice were used as follows： aged mice with stimulation （n = 12）, aged mice with sham-stimulation （n = 8）, adult mice （3-4 months old） with stimulation （n = 12）, and adult mice with sham-stimulation （n = 8）. lpsilateral hippocampal glucose metabolism and glutamate levels were measured in vivo by microdialysis before, during, and after fornix DBS treatment. Histological staining was used to verify the localization of electrodes and mice with inaccurate placement were excluded from subsequent analyses. The effects of fornix DBS on extracellular glucose, lactate, pyruvate, and glutamate levels over time were analyzed by repeated-measures analysis of variance followed by Fisher＇s least significant difference post hoc test. Results： The aged mice had a higher basal lactate/pyruvate ratio （LPR） and lactate/glucose ratio （LGR） than the adult mice （LPR： 0.34 ± 0.04 vs. 0.13 ± 0.02, t = 4.626, P 〈 0.0001 ; LGR： 6.06± 0.59 vs. 4.14 ± 0.36, t = 2.823, P 〈 0.01 ）. Fomix DBS decreased the ipsilateral hippocampal pyruvate and lactate levels （P 〈 0.05）, but the glucose levels were not obviously changed in aged mice. Similarly, the LGR and LPR also decreased in aged mice after fornix DBS treatment （P 〈 0.05）. Glucose metabolism in adult mice was not significantly influenced by tbrnix DBS. In addition, fornix DBS significantly decreased the ipsilateral hippocampal extracellular levels of glutamate in aged mice （P 〈 0.05）, while significant alterations were not found in the adult mice. Conclusions： The present study provides experimental evidence that fornix DBS could significantly improve bippocampal glucose metabolism in aged mice by promoting cellular aerobic respiration activity.

An Unusual Complication Related to Invasive Electroencephalography Monitoring： Nonhemorrhagic Subdural Fluid Collection

To the Editor： Invasive electroencephalography （EEG） monitoring using subdural electrodes is widely applied in clinical practice. Here, we report a rare complication related to this technique, nonhemorrhagic subdural fluid collection （SFC）.A 14-year-old female was admitted to Beijing Tiantan Hospital with ictal twitch and loss of consciousness. She had no other medical history. Magnetic resonance imaging （MRI） revealed a lesion in the right parietooccipital lobe. Scalp EEG failed to detect abnormal discharges in this area. To further locate the epileptic loci, subdural electrodes were placed on the surface of the parietooccipital area, the temporal lobe, and the frontal lobe. Postoperative computed tomography （CT） scan （8 h after the operation） revealed no signs of hemorrhage [Figure l a]. However, 14 h later, the patient was found drowsy with unequal pupils and a blunt light reflex. Repetitive CT scans showed SFC in the right frontal region near the strip and signs of brain herniation [Figure lb and c]. An emergency operation was performed. No sign of intracranial hemorrhage was found. The electrodes were removed, and the presumed lesion was resected [Figure l d]. After the operation, her condition stabilized and was discharged 2 weeks later. She reported no seizure recurrence in the 10-month＇s follow-up.

An Electrode-preserved Patient after Bilateral Intracranial Hematoma Induced by Deep Brain Stimulation

To the Editor： Deep brain stimulation （DBS） is widely used in Parkinson＇s disease. Here, we report a bilateral hemorrhage case Figure 1： Postoperative computed tomography data indicating the disease evolution in this case. （a） A computed tomography scan 8 h after the first operation; （b） A computed tomography scan 8 h after the second operation; （c） A computed tomography scan 13 day after the second operation.