Deep brain stimulation (DBS) is commonly and safely performed for selective Parkinson's disease patients. Many centers perform DBS lead positioning exclusively under local anesthesia, to optimize ...brain microelectrode recordings (MER) and testing of stimulation-related therapeutic and side effects. These measures enable physiological identification of the DBS borders and subdomains based on electrophysiological properties like firing rates and patterns, intra-operative evaluation of therapeutic window, and improvement of lead placement accuracy. Nevertheless, due to the challenges of awake surgery, some centers use sedation or general anesthesia, despite the distortion of discharge properties and interference with clinical testing, resulting in potential impact on surgical outcomes. Thus, there is a need for a novel anesthesia regimen that enables sedation without compromising intra-operative monitoring.
This open-label study investigates the use of low-dose ketamine for conscious sedation during microelectrode recordings and lead positioning in subthalamic nucleus (STN) DBS for Parkinson's disease patients.
Three anesthetic regimens were retrospectively compared in 38 surgeries (74 MER trajectories, 5962 recording sites) across three DBS centers: 1) Interleaved propofol-ketamine (PK), 2) Interleaved propofol-awake (PA), and 3) Fully awake (AA).
All anesthesia regimens achieved satisfactory MER. Detection of STN borders and subdomains by expert electrophysiologist was similar between the groups. Electrophysiological signature of the STN under ketamine was not inferior to either control group. All patients completed stimulation testing.
This study supports a low-dose ketamine anesthesia regimen for DBS which allows microelectrode recordings and stimulation testing that are not inferior to those conducted under awake and propofol-awake regimens and may optimize patient experience. A prospective double-blind study that would also compare patients' satisfaction level and clinical outcome should be performed to confirm these findings.
•Deep brain stimulation is commonly performed for Parkinson's disease patients.•Microelectrode recordings, which may optimize accuracy, are distorted by anesthesia.•Recordings done under low-dose ketamine were not inferior to those done awake.•Stimulation testing could be satisfactorily performed under low-dose ketamine.
The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the ...genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion.
Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation.
Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2%) carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted.Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes.
MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms.Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.
Essential tremor (ET) is a common disease in the elderly population. Severe, medication‐refractory ET may require surgical intervention via ablation or deep brain stimulation (DBS). Thalamic Vim ...(Ventral intermediate nucleus), targeted indirectly using atlas‐based coordinates, is the classical target in these procedures. We present a case of an ET patient with a non‐MR‐compatible cardiac orphaned leads who was a candidate for DBS surgery. Due to the lead constraints of MR use, we used a head computed tomography (CT) with contrast media as the reference exam to define the AC, PC, and midline, and to register and indirectly target the Vim. For target validation, we used intraoperative electrophysiological recordings and intraoperative CT. We implanted bilateral directional leads at the target location. We used the‐essential‐tremor‐rating‐assessment‐scale (TETRAS) pre and postoperatively to clinically evaluate tremor. Intraoperative micro‐electrode recordings (MERs) showed individual tremor cells and a robust increase in normalized root mean square (NRMS) indicating entry to the Vim. Postoperative visualization using lead‐DBS along with dramatic clinical improvements show that we were able to accurately target the Vim. Our results show that CT‐only registration and planning for thalamic Vim DBS is feasible, and that MERs and intraoperative CT are useful adjuncts for Vim target validation.
The neurophysiologic aberrations underlying the auditory hypersensitivity in Williams syndrome (WS) are not well defined. The P1‐N1‐P2 obligatory complex and mismatch negativity (MMN) response were ...investigated in 18 participants with WS, and the results were compared with those of 18 age‐ and gender‐matched typically developing (TD) controls. Results revealed significantly higher amplitudes of both the P1‐N1‐P2 obligatory complex and the MMN response in the WS participants than in the TD controls. The P1‐N1‐P2 complex showed an age‐dependent reduction in the TD but not in the WS participants. Moreover, high P1‐N1‐P2 complex was associated with low verbal comprehension scores in WS. This investigation demonstrates that central auditory processing is hyperactive in WS. The increase in auditory brain responses of both the obligatory complex and MMN response suggests aberrant processes of auditory encoding and discrimination in WS. Results also imply that auditory processing may be subjected to a delayed or diverse maturation and may affect the development of high cognitive functioning in WS.
Objective To comprehensively assess auditory impairments in velocardiofacial syndrome (VCFS) and Williams syndrome (WS). Study design Audiologic measurements were conducted with 62 subjects with VCFS ...and 44 subjects with WS, as well as two control groups consisting of 22 subjects with idiopathic developmental disability and 23 typically developing controls. An association between severity of hearing loss in VCFS and the158 Val/Met polymorphism of the catechol-O-methyltransferase gene ( COMT ) was explored. Results Hearing was significantly more impaired in the VCFS and WS groups compared with the developmental disability and typically developing groups. Audiologic abnormalities identified in both the VCFS and WS groups included high-tone hearing loss (predominantly sensorineural or mixed type), loss of acoustic reflex, and middle ear pathologies. In both the VCFS and WS groups, hearing loss severity was positively correlated with age. In the VCFS group, hearing loss was more severe in the subgroup carrying the COMT Val allele compared with the subgroup carrying the COMT Met allele. Conclusions Hearing impairments, including sensorineural hearing loss and acoustic reflex dysfunction, are very common in both VCFS and WS. Hearing loss is less severe in subjects with the COMT Met allele, possibly due to the protective effect of dopamine on the hearing system.
Background
A reliable, real-time method for the detection of pedicle wall breaching during funnelling in spine deformity surgery could be accessible to any surgeon assisted with neuromonitoring.
...Methods
Fifty-six consecutive patients (1066 pedicles), who were submitted to spinal deformity surgery from December 2013 to July 2015 were included in the study group. A control group of 13 consecutive patients (226 pedicles) with spinal deformity surgery were operated on from January to December 2013 and were excluded from finder stimulation. In the study cohort, continuous stimulation during funnelling was delivered via a finder and subsequently a compound muscle action potential (CMAP) threshold was determined. Following funnelling, manual inspection of the pedicular internal walls was performed. The CMAP thresholds were compared with the results of palpation to determine the sensitivity and specificity of the technique for detecting pedicular breaching. To cover common ranges of damage, the medial and lateral breaches were compared and the concave-apical breaches compared to the non-apical or convex-apical breaches. In addition, a pedicle screw test was estimated for all patients.
Results
ROC analysis showed 9 mA cut-off to have a sensitivity of 88.0% and a specificity of 89.5% for predicting pedicular breaching, with an area under the curve of 0.92 (95% confidence interval 0.90–0.94;
P
< 0.001). Using 9 mA threshold as an alert criterion, funnelling at the concave-apical pedicles showed significantly more true and false positive alerts and fewer true negative alerts when compared with the non-apical and convex-apical pedicles (
P
< 0.001). Medial breaches had significantly lower stimulation thresholds than lateral breaches (
P
< 0.001). Thresholds of screw-testing were significantly higher for study than for control-patients (
P
= 0.002).
Conclusions
Finder stimulation has a considerably higher sensitivity and specificity for prediction of pedicular breaching, most prominent for medial breaches. Screw-testing displayed significantly better results in patients undergoing the finder stimulation technique, as compared with the control group. The main advantages of our method are its high safety level and low cost, which may be critical in less affluent countries.
Level of evidence
III.
Background 22q11.2 deletion syndrome (22q11.2DS) is the most common genetic syndrome associated with schizophrenia. The catechol- O -methyltransferase ( COMT ) gene is located in the obligatory ...deletion region, and possible associations between COMT variants and neuropsychiatric manifestations in 22q11.2DS have been reported. The purpose of the current study was to evaluate the effect of COMT hemizygosity and molecular haplotypes on gene expression and enzyme activity and its association with psychotic symptoms in 22q11.2DS. Methods Lymphoblast samples were drawn from 53 individuals with 22q11.2DS and 16 typically developing control subjects. We measured COMT messenger (m)RNA and protein expression and enzyme activity using standard procedures. The presence of a psychotic disorder and cognitive deficits were also evaluated using structured testing. Results There was an approximately 50% reduction in COMT mRNA, protein, and enzyme activity levels in 22q11.2DS samples. Haplotype analysis revealed clear phenotypic differences between various Val-containing haplotypes on COMT -3′ untranslated region extended mRNA, soluble COMT and membrane-bound proteins, and enzyme activity. The G variant of rs165599, a 3′ untranslated region single nucleotide polymorphism, was associated with low levels of COMT expression and with the presence of psychosis and lower performance IQ scores in our 22q11.2DS sample. Finally, we demonstrate that the COMT rs74745580 “T” mutation is associated with absent soluble COMT expression and very low COMT activity in two 22q11.2DS individuals. Conclusions Our findings confirm a robust effect of COMT hemizygosity on COMT activity and show complex interactions of variants within the COMT gene that influence COMT biology and confound conclusions based on associations with the Val158Met genotype alone.
Abstract The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two ...schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH , affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age.
Objectives/Hypothesis
During robot‐assisted transaxillary thyroidectomy, the patient's arm is maintained in an overhead flexed position for a prolonged time, which poses a risk of postoperative ...brachial plexopathy. The aim of the study was to identify the causes of brachial plexopathy and to assess the benefit of intraoperative neurophysiological monitoring (IONM) in preventing positional brachial plexopathy in this setting.
Study Design
Retrospective case series.
Methods
The computerized database of a tertiary medical center was searched for all consecutive patients who underwent robot‐assisted transaxillary thyroidectomy between 2012 and 2014. Clinical, operative, and outcome parameters were collected from the medical files. Findings were compared between patients operated with and without IONM.
Results
The cohort included 30 patients, 14 operated with IONM and 16 without. Three events of impending brachial plexopathy were detected in the monitored group. The monitored group had significantly better shoulder movement (P = .003), a lower rate of hypoesthesia (P = .011), less pain (P = .001) in the early postoperative period than the nonmonitored group and higher quality of life in the early postoperative period (P = .012). The monitored group was significantly younger than the nonmonitored one (P = .02) and had a significantly larger diameter of thyroid nodule than the nonmonitored group (P = .043).
Conclusions
IONM during robot‐assisted transaxillary thyroidectomy may improve short‐term postoperative pain and shoulder movement and longer‐term quality of life.
Level of Evidence
4 Laryngoscope, 126:2187–2193, 2016
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