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Secretory carrier membrane proteins (SCAMPs) play an important role in exocytosis in animals, but the precise function of SCAMPs in human disease is unknown. In this study, we identified a homozygous mutation, SCAMP5 R91W, in a Chinese consanguineous family with pediatric epilepsy and juvenile Parkinson's disease. Scamp5 R91W mutant knock-in mice showed typical early-onset epilepsy similar to that in humans. Single-neuron electrophysiological recordings showed that the R91W mutation significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) at a resting state and also increased the amplitude of evoked EPSCs. The R91W mutation affected the interaction between SCAMP5 and synaptotagmin 1 and may affect the function of the SNARE complex, the machinery required for vesicular trafficking and neurotransmitter release. Our work shows that dysfunction of SCAMP5 shifted the excitation/inhibition balance of the neuronal network in the brain, and the deficiency of SCAMP5 leads to pediatric epilepsy. [ABSTRACT FROM AUTHOR]

Background:Symptomatic intracranial hemorrhage (ICH) may lead to permanent neurological disability of patients and has impeded the extensive clinical application of deep brain stimulation (DBS). The present study was conducted to discuss the incidence, prevention, and treatment of symptomatic ICH after DBS surgery. Methods:From January 2009 to December 2014, 396 patients underwent DBS with a total of 691 implanted leads. In all, 10 patients had symptomatic ICH. We analyzed these cases’ clinical characteristics, including comorbid diagnoses and coagulation profile. We described the onset of ICH, imaging features, clinical manifestations, treatment, neurological impairment, and outcome of DBS. Results:Of the 10 patients with symptomatic ICH, 2 had hypertension. Three cases of ICH occurred within 12 h of the procedure; four cases within 24 h. Five experienced grand mal seizures concurrently with hemorrhage. Unilateral frontal lobe hemorrhage occurred in all cases. In seven cases, hematomas occurred around the electrodes. Some hematomas were not well-circumscribed and had perihematomal edema. Conservative therapy was administered to 8 patients, and 2 patients underwent craniotomy and hematoma evacuation. All electrodes were successfully preserved. Neurological dysfunction in all patients gradually improved. Nine patients ultimately experienced effective symptom relief of Parkinson’s disease with DBS. Conclusions:Symptomatic ICH should be identified as soon as possible after implantation surgery and treated effectively to limit neurological deficit and preserve DBS leads. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the long-term effects of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) on depression in patients with Parkinson''s disease (PD) and to discuss the mechanism. Methods: A STN–DBS group (n = 27) and anti-Parkinson''s medication control group with paired designing were set up. The evaluation of the depression and motor function was performed a total of six times. Depression was evaluated by the Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HAMD). Motor function was evaluated by the third part of the Unified Parkinson''s Disease Rating Scale (UPDRS-III). Results: Compared with the preoperative and the medication control group, the UPDRS-III scores of the STN–DBS group decreased remarkably within 18 months postoperatively (P ≤ 0.001), and the SDS scores decreased notably within 6 months postoperatively (P ≤ 0.05), and the HAMD scores decreased notably within 3 months postoperatively (P ≤ 0.05). The UPDRS-III scores were strongly correlated with their SDS scores within 6 months postoperatively (P ≤ 0.05), especially at 5 weeks postoperation (P ≤ 0.001). UPDRS-III scores were also strongly correlated with HAMD scores at 5 weeks postoperation (P ≤ 0.05). The mean value of the bilateral voltages was obviously correlated with SDS and HAMD scores (P ≤ 0.05) within 18 months postoperatively. Conclusion: The improvement in motor symptoms resulting from STN–DBS can improve depression in PD patients, but its long-term effects were unremarkable. Within the treatment range, the higher the mean value of bilateral voltages then the more severe was the depression in PD patients. [Copyright &y& Elsevier]

Objective: The goal of the present study was to evaluate the effects of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on olfaction in patients with Parkinson’s disease (PD). Methods: 15 patients suffering from sporadic PD-related dysosmia were implanted with bilateral electrodes aimed at the STN. One week before the surgery, odor detection threshold (DT) and identification threshold (IT) were evaluated in all patients using the ‘five odor olfactory detection arrays’ in both medication-off and medication-on conditions. 15 healthy age-matched controls also received the same olfactory evaluation. Patient evaluations were repeated at 6 and 12 months postoperatively in a medication-off/stimulator-on or medication-off/stimulator-off condition. Odor DT and IT scores were compared pre- and postoperatively, as well as between the medication-off/stimulator-on or -off conditions. Results: The motor symptoms of all 15 PD patients, including rigidity, tremor, bradykinesia, postural instability, and gait were significantly improved after stimulator implantation. The UPDRS motor (UPDRS III) scores decreased significantly in the medication-off/stimulator-on condition (p < 0.01). The odor DT and IT scores of PD patients were higher than those of healthy controls (p < 0.01). In the medication-off/stimulator-off condition, there was no significant difference in the odor DT and IT scores in PD patients pre- vs. postoperatively (p > 0.05). Notably, there were no significant alterations to DT scores in the stimulator-on and -off conditions at the 6- and 12-month follow-up (p > 0.05), whereas IT scores were significantly improved in the stimulation-on relative to the stimulation-off condition at the 6- and 12-month follow-up. Conclusions: STN DBS can significantly improve olfactory cognitive function in PD patients. The possible mechanisms include an improvement in striatal metabolism and neuronal activity in the orbitofrontal cortex mediated by STN DBS, as well as increased glucose metabolism in the striatum, midbrain, cingulate gyrus, and motor and higher-order somatosensory association cortices. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: With respect to three kinds of familiar tremor, including essential tremor (ET), Parkinsonian disease (PD) tremor, and physiological tremor (PT), which are subjected to frequent clinical misdiagnosis, a new fusion diagnosis method for tremor based on multi-features extraction, back-propagation neural network (BPNN), and Dempster–Shafer (D–S) evidence theory is proposed to overcome the clinical misdiagnosis. First the features of hand acceleration signals of subjects with ET, PD, and PT were extracted using bispectrum, empirical mode decomposition (EMD) and discrete wavelet transform (DWT) analysis methods, respectively. Second the resulting features were subsequently recognized by three independent BPNNs, respectively, the outputs of which were further processed and acted as basic probability assignments for tremor. Finally, the basic probability assignments were fused by the D–S evidence theory and decision-making analysis was performed. The experimental analysis results indicate that the accuracy of fusion results of the D–S evidence theory is markedly higher than the independent diagnosis of BPNN. The method proposed in this paper is able to adequately utilize the complementary multi-features information for accurately recognizing tremor types, thus providing practical guiding significance for diagnosing tremor types in clinic. [Copyright &y& Elsevier]

Highlights: [•] Alpha-synuclein can induce an increase of exosomal secretion by microglia. [•] Activated exosomes expressed a high level of MHC class II molecules and mTNF-α. [•] Activated exosomes can cause increased apoptosis. [•] Exosomes might be important mediator of neurodegeneration in PD. [ABSTRACT FROM AUTHOR]

Abstract: Studies on patients with Parkinson''s disease and in animal models have observed enhanced synchronization of oscillations in several frequency bands within and between the cortical–basal ganglia (BG) structures. Recent research has also shown that synchronization of high-voltage spindles (HVSs) in the cortex, striatum and substantia nigra pars reticulate is increased by dopamine depletion. However, more evidence is needed to determine whether HVS activity in the whole cortex–BG network represents homologous alteration following dopamine depletion. As the globus pallidus (GP) is in a central position to propagate and synchronize oscillations in the cortical–BG circuits, we employed local-field potentials and electrocorticogram to simultaneously record oscillations in the GP and primary (M1) and secondary (M2) motor cortices on freely moving 6-hydroxydopamine (6-OHDA) lesioned and control rats. Results showed that HVS episodes recorded from GP, and M2 and M1 cortex areas were more numerous and longer in 6-OHDA lesioned rats compared to controls. Relative power associated with HVS activity in the GP, and M2 and M1 cortices of 6-OHDA lesioned rats was significantly greater than that for control rats. Coherence values for HVS activity between the GP, and M2 and M1 cortex areas were significantly increased by dopamine depletion. Time lag between the M1 cortex HVS and GP HVS was significantly shorter for dopamine depleted than normal rats. Findings indicate a crucial rule for dopamine in the regulation of HVS activity in the whole cortical–BG circuit, and suggest a close relationship between abnormally synchronized HVS oscillations in the cortex–BG network and Parkinson''s disease. [Copyright &y& Elsevier]

Objective To evaluate the clinical effect of the position of stimulation contacts relative to the hyperdirect pathway (HDP) on the alleviation of motor symptoms in patients with Parkinson disease (PD). Methods A group of 11 patients diagnosed with idiopathic PD were included in this study, and all selected targets were in the subthalamic nucleus (STN). In 1 patient, a single side electrode was implanted because of unilateral symptoms; in all other patients, bilateral electrodes each containing 4 discrete contacts were implanted. Nine contacts were excluded due to adverse reactions caused by stimulation, and thus a total of 75 active contacts were evaluated using the same stimulus parameters. Fiber tractography results were individually processed using StealthViz software before all data were subjected to statistical analysis. Results Under the same stimulus parameters, the shortest distance of each contact to the HDP was smaller in group I ( n = 45; >50% improvement rate) compared with group II ( n = 30; ≤50% improvement rate) (mean, 1.18 ± 0.86 mm vs. 2.14 ± 1.20 mm; t = 3.78; P < 0.05), and the shortest distance had a negative correlation with the improvement of motor symptoms ( r = −0.48; P < 0.05). Conclusions Stimulation of the HDP coincided with the improvement of motor symptoms in patients with PD. We propose an improvement of the direct visualization method based on diffusion tensor imaging fiber tractography of the HDP to select the motor part of the STN. Further rigorous clinical trials are needed to verify the value of this method for achieving precise target location and individualized treatment. [ABSTRACT FROM AUTHOR]