Involvement of microRNAs in epileptogenesis Cattani, Adriano A.; Allene, Camille; Seifert, Volker ...
Epilepsia (Copenhagen),
July 2016, Letnik:
57, Številka:
7
Journal Article
Recenzirano
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Summary
Patients who have sustained brain injury or had developmental brain lesions present a non‐negligible risk for developing delayed epilepsy. Finding therapeutic strategies to prevent ...development of epilepsy in at‐risk patients represents a crucial medical challenge. Noncoding microRNA molecules (miRNAs) are promising candidates in this area. Indeed, deregulation of diverse brain‐specific miRNAs has been observed in animal models of epilepsy as well as in patients with epilepsy, mostly in temporal lobe epilepsy (TLE). Herein we review deregulated miRNAs reported in epilepsy with potential roles in key molecular and cellular processes underlying epileptogenesis, namely neuroinflammation, cell proliferation and differentiation, migration, apoptosis, and synaptic remodeling. We provide an up‐to‐date listing of miRNAs altered in epileptogenesis and assess recent functional studies that have interrogated their role in epilepsy. Last, we discuss potential applications of these findings for the future development of disease‐modifying therapeutic strategies for antiepileptogenesis.
Ventriculoperitoneal shunt (VPS) with adjustable differential pressure valves are commonly used to treat infants with hydrocephalus avoiding shunt related under- or overdrainage. The aim of this ...study was to analyse the influence of VPS adjustable differential pressure valve on the head circumference (HC) and ventricular size (VS) stabilization in infants with post intraventricular haemorrhage, acquired and congenital hydrocephali.
Forty-three hydrocephalic infants under 6 months old were prospectively included between 2014 and 2018. All patients were treated using a VPS with adjustable differential pressure valve. HC and transfontanelle ultrasonographic VS measurements were regularly performed and pressure valve modifications were done aiming HC and VS percentiles between the 25th and 75th. The patients were divided into two groups: infants with hydrocephalus due to an intraventricular haemorrhage (IVH-H), and infants with hydrocephalus due to other aetiologies (OAE-H).
The mean of pressure valve modification was 3.7 per patient in the IVH-H group, versus 2.95 in the OAE-H group. The median of last pressure valve value was higher at 8.5 cm H2O in the IVH-H group comparing to 5 cm H2O in the OAE-H group (p = 0.013).
Optimal VPS pressure valve values could be extremely difficult to settle in order to gain normalisation of the HC and VS in infants. However, after long term follow up (mean of 18 months) and several pressure valve modifications, this normalisation is possible and shows that infants with IVH-H need a higher pressure valve value comparing to infants with OAE-H.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Developing cortical networks generate a variety of coherent activity patterns that participate in circuit refinement. Early network oscillations (ENOs) are the dominant network pattern in the rodent ...neocortex for a short period after birth. These large-scale calcium waves were shown to be largely driven by glutamatergic synapses albeit GABA is a major excitatory neurotransmitter in the cortex at such early stages, mediating synapse-driven giant depolarizing potentials (GDPs) in the hippocampus. Using functional multineuron calcium imaging together with single-cell and field potential recordings to clarify distinct network dynamics in rat cortical slices, we now report that the developing somatosensory cortex generates first ENOs then GDPs, both patterns coexisting for a restricted time period. These patterns markedly differ by their developmental profile, dynamics, and mechanisms: ENOs are generated before cortical GDPs (cGDPs) by the activation of glutamatergic synapses mostly through NMDARs; cENOs are low-frequency oscillations (approximately 0.01 Hz) displaying slow kinetics and gradually involving the entire network. At the end of the first postnatal week, GABA-driven cortical GDPs can be reliably monitored; cGDPs are recurrent oscillations (approximately 0.1 Hz) that repetitively synchronize localized neuronal assemblies. Contrary to cGDPs, cENOs were unexpectedly facilitated by short anoxic conditions suggesting a contribution of glutamate accumulation to their generation. In keeping with this, alterations of extracellular glutamate levels significantly affected cENOs, which are blocked by an enzymatic glutamate scavenger. Moreover, we show that a tonic glutamate current contributes to the neuronal membrane excitability when cENOs dominate network patterns. Therefore, cENOs and cGDPs are two separate aspects of neocortical network maturation that may be differentially engaged in physiological and pathological processes.
Precise robotic or stereotactic implantation of stereoelectroencephalography (sEEG) electrodes relies on the exact referencing of the planning images in order to match the patient's anatomy to the ...stereotactic device or robot. We compared the accuracy of sEEG electrode implantation with stereotactic frame versus laser scanning of the face based on computed tomography (CT) or magnetic resonance imaging (MRI) datasets for referencing.
The accuracy was determined by calculating the Euclidian distance between the planned trajectory and the postoperative position of the sEEG electrode, defining the entry point error (EPE) and the target point error (TPE). The sEEG electrodes (n = 171) were implanted with the robotic surgery assistant (ROSA) in 19 patients. Preoperative trajectory planning was performed on three-dimensional (3D) MRI datasets. Referencing was accomplished either by performing (A) 1.25-mm slice CT with the patient's head fixed in a Leksell stereotactic frame (CT-frame, n = 49), fused with a 3D-T1-weighted, contrast enhanced- and T2-weighted 1.5 Tesla (T) MRI; (B) 1.25 mm CT (CT-laser, n = 60), fused with 3D-3.0-T MRI; (C) 3.0-T MRI T1-based laser scan (3.0-T MRI-laser, n = 56) or (D) in one single patient, because of a pacemaker, 3D-1.5-T MRI T1-based laser scan (1.5-T MRI-laser, n = 6).
In (A) CT-frame referencing, the mean EPE amounted to 0.86 mm and the mean TPE amounted to 2.28 mm (n = 49). In (B) CT-laser referencing, the EPE amounted to 1.85 mm and the TPE to 2.41 mm (n = 60). In (C) 3.0-T MRI-laser referencing, the mean EPE amounted to 3.02 mm and the mean TPE to 3.51 mm (n = 56). In (D) 1.5-T MRI, surprisingly the mean EPE amounted only to 0.97 mm and the TPE to 1.71 mm (n = 6). In 3 cases using CT-laser and 1 case using 3.0 T MRI-laser for referencing, small asymptomatic intracerebral hemorrhages were detected. No further complications were observed.
Robot-guided sEEG electrode implantation using CT-frame referencing and CT-laser-based referencing is most accurate and can serve for high precision placement of electrodes. In contrast, 3.0-T MRI-laser-based referencing is less accurate, but saves radiation. Most trajectories can be reached if alternative routes over less vascularized brain areas are used.
This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".
Objective
Recent studies with robot‐guided stereotaxy use computed tomography (CT) scans for referencing. We will provide evidence that using preoperative MRI datasets referenced with a laser scan of ...the patient's face is sufficient for sEEG implantation.
Methods
In total, 40 sEEG electrodes were implanted in five patients by the robotic surgical assistant (ROSA). The postoperative CT scan for identifying electrode positions was fused with the preoperative MRI‐based planning data. The accuracy was determined by the target point error (TPE) and the entry point error (EPE), applying the Euclidean distance.
Results
The mean TPE amounted to 2.96 mm, the mean EPE to 2.53 mm. The accuracy was improved in 1.5 T MRI: the mean TPE amounted to 1.72 mm, the EPE to 0.97 mm. No complications, haemorrhages, infections, etc., were observed.
Conclusions
Robot‐guided sEEG based on 3 T MRI reduces radiation exposure for the patient and can still be performed safely.
OBJECTIVE Isolated acute subdural hematoma (aSDH) is increasing in older populations and so is the use of oral anticoagulant therapy (OAT). The dramatic increase of OAT-with direct oral ...anticoagulants (DOACs) as well as with conventional anticoagulants-is leading to changes in the care of patients who present with aSDH while receiving OAT. The purpose of this study was to determine the management and outcome of patients being treated with OAT at the time of aSDH presentation. METHODS In this single-center, retrospective study, the authors analyzed 116 consecutive cases involving patients with aSDH treated from January 2007 to June 2016. The following parameters were assessed: patient characteristics, admission status, anticoagulation status, perioperative management, comorbidities, clinical course, and outcome as determined at discharge and through 6 months of follow-up. Oral anticoagulants were classified as thrombocyte inhibitors, vitamin K antagonists, and DOACs. Patients were stratified based on which type of medication they were taking, and subgroup analyses were performed. Predictors of unfavorable outcome at discharge and follow-up were identified. RESULTS Of 116 patients, 74 (64%) had been following an OAT regimen at presentation with aSDH. The patients who were taking oral anticoagulants (OAT group) were significantly older (OR 12.5), more often comatose 24 hours postoperatively (OR 2.4), and more often had ≥ 4 comorbidities (OR 3.2) than patients who were not taking oral anticoagulants (no-OAT group). Accordingly, the rate of unfavorable outcome was significantly higher in patients in the OAT group, both at discharge (OR 2.3) and at follow-up (OR 2.2). Of the patients in the OAT group, 37.8% were taking a thrombocyte inhibitor, 54.1% a vitamin K antagonist, and 8.1% DOACs. In all cases, OAT was stopped on discovery of aSDH. For reversal of anticoagulation, patients who were taking a thrombocyte inhibitor received desmopressin 0.4 μg/kg, 1-2 g tranexamic acid, and preoperative transfusion with 2 units of platelets. Patients following other oral anticoagulant regimens received 50 IU/kg of prothrombin complex concentrates and 10 mg of vitamin K. There was no significant difference in the rebleeding rate between the OAT and no-OAT groups. The in-hospital mortality rate was significantly higher for patients who were taking a thrombocyte inhibitor (OR 3.3), whereas patients who were taking a vitamin K antagonist had a significantly higher 6-month mortality rate (OR 2.7). Patients taking DOACs showed a tendency toward unfavorable outcome, with higher mortality rates than patients on conventional OAT or patients in the vitamin K antagonist subgroup. Independent predictors for unfavorable outcome at discharge were comatose status 24 hours after surgery (OR 93.2), rebleeding (OR 9.8), respiratory disease (OR 4.1), and infection (OR 11.1) (Nagelkerke R
= 0.684). Independent predictors for unfavorable outcome at follow-up were comatose status 24 hours after surgery (OR 12.7), rebleeding (OR 3.1), age ≥ 70 years (OR 3.1), and 6 or more comorbidities (OR 3.1, Nagelkerke R
= 0.466). OAT itself was not an independent predictor for worse outcome. CONCLUSIONS An OAT regimen at the time of presentation with aSDH is associated with increased mortality rates and unfavorable outcome at discharge and follow-up. Thrombocyte inhibitor treatment was associated with increased short-term mortality, whereas vitamin K antagonist treatment was associated with increased long-term mortality. In particular, patients on DOACs were seriously affected, showing more unfavorable outcomes at discharge as well as at follow-up. The suggested medical treatment for aSDH in both OAT and no-OAT patients seems to be effective and reasonable, with comparable rebleeding and favorable outcome rates in the 2 groups. In addition, prior OAT is not a predictor for aSDH outcome.
OBJECTIVE Synovial cysts of the spine are rare lesions, predominantly arising in the lumbar region. Despite their generally benign behavior, they can cause severe symptoms due to compression of ...neural structures in the spinal canal. Treatment strategies are still a matter of discussion. The authors performed a single-center survey and literature search focusing on long-term results after minimally invasive surgery. METHODS A total of 141 consecutive patients treated for synovial cysts of the lumbar spine between 1997 and 2014 in the authors' department were analyzed. Medical reports with regard to signs and symptoms, operative findings, complications, and short-term outcome were reviewed. Assessment of long-term outcome was performed with a standardized telephone questionnaire based on the Oswestry Disability Index (ODI). Furthermore, patients were questioned about persisting pain, symptoms, and further operative procedures, if any. Subjective satisfaction was classified as excellent, good, fair, or poor based on the Macnab classification. RESULTS The approach most often used for synovial cyst treatment was partial hemilaminectomy in 70%; hemilaminectomy was necessary in 27%. At short-term follow-up, the presence of severe and moderate leg pain had decreased from 93% to 5%. The presence of low-back pain decreased from 90% to 5%. Rates of motor and sensory deficits were reduced from 40% to 14% and from 45% to 6%, respectively. The follow-up rate was 58%, and the mean follow-up period was 9.3 years. Both leg pain and low-back pain were still absent in 78%. Outcome based on the Macnab classification was excellent in 80%, good in 14%, fair in 1%, and poor in 5%. According to the ODI, 78% of patients had no or only minimal disability, 16% had moderate disability, and 6% had severe disability at the time of follow-up. In this cohort, 7% needed surgery due to cyst recurrence, and 9% required a delayed stabilization procedure after the initial operation. CONCLUSIONS Surgical treatment with resection of the cyst provides favorable results in outcome. Excellent or good outcome persisting for a long-term follow-up period can be achieved in the vast majority of cases. Complication rates are low despite an increased risk of dural injury. With facet-sparing techniques, the stability of the segment can be preserved, and resection of spinal synovial cysts does not necessarily require segmental fusion.
Highlights • Overall incidence of ePTS (lPTS) is 28% (43) in aSDH and 10% (5.3) in cSDH in 2–3 years. • Recurrence rate of seizures is higher in patients with late PTS compared to early PTS. • There ...are different risk factors for seizures in a- and cSDH. • aSDH: 24 h postoperative GCS < 9, craniotomy, preoperative GCS < 8. • cSDH: alcohol abuses, mental change, previous stroke and density of haematoma in CT.
Robotic guidance might be an alternative to classic stereotaxy for biopsies of intracranial lesions. Both methods were compared regarding time efficacy, histopathological results and complications.
A ...retrospective analysis enrolling all patients undergoing robotic- or stereotactic biopsies between 01/2015 and 12/2018 was conducted. Trajectory planning was performed on magnetic resonance imaging (MRI). With the Robotic Surgery Assistant (ROSA), patient registration was accomplished using a facial laser scan in the operating room (OR), immediately followed by biopsy. In stereotaxy, patients were transported to the CT for Leksell Frame registration, followed by biopsy in the OR.
The average overall procedure time amounted in robotics to 169 min and in stereotaxy to 179 min (p = 0.005). The difference was greatest for temporal targets, amounting in robotics to 161 min and in stereotaxy to 188 min (p = 0,0007). However, the average time spent purely in the OR amounted in robotics to 140 min and in stereotaxy to 113 min (p < 0.001). In 150 robotic biopsies, diagnostic yield amounted to 98%, in 266 stereotactic biopsies to 91%. Symptomatic postoperative hemorrhages were observed in 3 patients (2%) in robotic biopsy and 7 patients (2,7%) in stereotactic biopsy.
Robotics showed a shorter overall procedure time as there is no need for a transport to the CT whereas the pure OR time was shorter in stereotaxy due to skipping the laser registration process. Diagnostic yield was higher in robotics, most likely due to case selection, complication rates were equal.
Stereoelectroencephalography (sEEG) is a diagnostic procedure for patients with refractory focal epilepsies that is performed to localize and define the epileptogenic zone. In contrast to grid ...electrodes, sEEG electrodes are implanted using minimal invasive operation techniques without large craniotomies. Previous studies provided good evidence that sEEG implantation is a safe and effective procedure; however, complications in asymptomatic patients after explantation may be underreported. The aim of this analysis was to systematically analyze clinical and imaging data following implantation and explantation.
We analyzed 18 consecutive patients (mean age: 30.5 years, range: 12–46; 61% female) undergoing invasive presurgical video-EEG monitoring via sEEG electrodes (n = 167 implanted electrodes) over a period of 2.5 years with robot-assisted implantation. There were no neurological deficits reported after implantation or explantation in any of the enrolled patients. Postimplantation imaging showed a minimal subclinical subarachnoid hemorrhage in one patient and further workup revealed a previously unknown factor VII deficiency. No injuries or status epilepticus occurred during video-EEG monitoring. In one patient, a seizure-related asymptomatic cross break of two fixation screws was found and led to revision surgery. Unspecific symptoms like headaches or low-grade fever were present in 10 of 18 (56%) patients during the first days of video-EEG monitoring and were transient. Postexplantation imaging showed asymptomatic and small bleedings close to four electrodes (2.8%).
Overall, sEEG is a safe and well-tolerated procedure. Systematic imaging after implantation and explantation helps to identify clinically silent complications of sEEG. In the literature, complication rates of up to 4.4% in sEEG and in 49.9% of subdural EEG are reported; however, systematic imaging after explantation was not performed throughout the studies, which may have led to underreporting of associated complications.
•Consecutive analysis of 167 sEEG electrodes for periprocedural complications.•Standardized CT scans after implantation and explantation were used to identify asymptomatic complications.•Minor complications occurred in 4.2% and major complications were reported in 1.2% per electrode.•All complications were asymptomatic and became visible on post-explantation CT scan or during electrode removal.•SEEG is a safe and well-tolerated procedure but standardized imaging post explanation is advisable.
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