Disease-a-month : DM 2011 Mar

Authors: Novak KE, Dalvi A, Nenonene EK, Bernstein LP

PMID: 21447423 [PubMed - as supplied by publisher]

Bosnian journal of basic medical sciences 2009 Oct

Authors: Limthongkul W, Savage J, Nenonene EK, Karaikovic EE

Abstract
The pedicle screw diameter, composite and design are variables that can affect the threshold of intraoperative electromyographic monitoring. Even though we know that larger diameter objects tend to have less resistance, no study documented the effect that this variable could have on pedicle screw resistance. Using high quality equipment, resistance and resistivity of ten pedicle screws (from four manufacturers) were calculated based on known constant current and measured voltage. Voltage was measured three times for each screw to determine intraobserver measurement variability. Resistance of all screws ranged from 1.4 to 3.9 m ohm (mean = 2.69+/-0.71 m ohm). The screw with largest diameter (7.75 mm) had lower resistance than screws with other diameters. Resistivity of screws ranged from 7.12 to 12.63 micro ohm*m (mean = 9.9+/-1.82 micro ohm*m). Based on the screw design, one manufacturer's pedicle screws (A) had significantly lower resistivity compared to three other manufacturers (p<0.01). Larger diameter screws (7.75 mm in diameter) had lower resistance. Screw design (polyaxial or monoaxial) had no effect on its resistance. Screws of one manufacturer (A) showed lower resistivity compared to those manufactured by other three companies.

PMID: 19912122 [PubMed - as supplied by publisher]

Stereotactic and functional neurosurgery 2008

Authors: Novak KE, Nenonene EK, Bernstein LP, Vergenz S, Cozzens JW, Rezak M

Abstract
Several subcortical structures have been targeted for surgical treatment of dystonia, including motor thalamus, internal segment of globus pallidus (GPi), and more recently, the subthalamic nucleus (STN). Deep brain stimulation of GPi is currently the preferred surgical treatment, but it is unclear if targeting other structures would yield better results. Patients who have already had a pallidotomy yet continue to experience dystonic symptoms may be limited in further treatment options.
A patient with medically intractable, segmental, early-onset, primary torsion dystonia presented for surgical consultation after exhausting nearly all treatment options. Medications, botulinum toxin injections, cervical denervation surgery, and left-sided pallidotomy failed to give adequate relief. The patient was implanted with STN stimulating leads bilaterally according to standard procedures.
The patient received a 36% improvement in dystonic symptoms as measured by several dystonia rating scales. These benefits persisted for 2 years after surgery despite several hardware-related complications, and the patient reported being very satisfied with the outcome.
This result supports the efficacy of STN deep brain stimulation in dystonia patients, even those with prior pallidotomy.

PMID: 18073520 [PubMed - as supplied by publisher]

Brain research 2007 Jun 25

Authors: Gdowski MJ, Miller LE, Bastianen CA, Nenonene EK, Houk JC

Abstract
We recorded extracellular single unit discharges of globus pallidus internal segment (GPi) neurons in monkeys performing a visually driven forearm rotation movement task in order to quantify how discharge patterns changed in relation to kinematic parameters. Subjects grasped a handle that rotated about its axis while facing a video screen displaying visual targets. Continuous visual feedback of handle rotation position was provided. Monkeys generated forearm rotation movements of +/-35 degrees and +/-70 degrees amplitude in order to align the cursor and targets. Trial records were aligned to forearm rotation onset in order to compare the discharge patterns that were associated with movements of different amplitudes, velocities, and directions. In addition, we quantified the depth of modulation of neuronal discharge associated with movements generated in two different task phases. Comparisons of discharge patterns were made between the visually guided, rewarded phase ("cued movements") and the self-paced, unrewarded phase that returned the monkey to the task start position ("return movements") by quantifying the goodness of fit between neuronal discharge during cued and return movements. Our analyses revealed no systematic relationship between the depth of modulation of GPi neurons and forearm rotation amplitude, direction, or velocity. Furthermore, comparisons between the two behavioral contexts revealed a systematic attenuation of modulation that could not be attributed to differences in movement velocity. Collectively, these findings suggest that the GPi neurons that we studied were not significantly involved in mediating movement kinematics, but may have instead been instrumental in the processing of information about the behavioral context during which movements were generated.

PMID: 17499221 [PubMed - as supplied by publisher]

The Laryngoscope 2006 Sep

Authors: Meier JD, Wenig BL, Manders EC, Nenonene EK

Abstract
To assess whether the use of continuous intraoperative facial nerve monitoring correlates to postoperative facial nerve injury during parotidectomy.
A retrospective analysis.
Forty-five consecutive parotidectomies were performed using an electromyograph (EMG)-based intraoperative facial nerve monitor. Of those, 37 had complete data for analysis. Intraoperative findings and final interpretation of the EMGs were analyzed by a senior neurologist and neurophysiologist. All patients were analyzed, including those with preoperative weakness and facial nerve sacrifice.
The overall incidence of facial paralysis (House-Brackmann scale > 1) was 43% for temporary and 22% for permanent deficits. This includes an 11% incidence of preoperative weakness and 14% with intraoperative sacrifice. An abnormal EMG occurred in only 16% of cases and was not significantly associated with permanent or temporary facial nerve paralysis (chi, P < 1.0; Fisher's exact P < .68). Of the eight patients with permanent paralysis, only two had abnormalities on the facial nerve monitor. Also, only one of five patients with intraoperative sacrifice of the facial nerve had an abnormal EMG. Factors significantly associated with the incidence of facial paralysis include malignancy, advanced age, extent of parotidectomy, and dissection beyond the parotid gland (chi and Fisher's, P < .05).
The results suggest that abnormalities on the intraoperative continuous facial nerve monitor during parotidectomy do not predict facial nerve injury. The incidence of permanent and temporary facial nerve paralysis compare favorably with the literature given that this study includes patients with revision surgery, intraoperative sacrifice, and preoperative paralysis. Standard of care implications will be discussed.

PMID: 16954980 [PubMed - as supplied by publisher]

Movement disorders : official journal of the Movement Disorder Society 2006 Sep

Authors: Novak KE, Nenonene EK, Bernstein LP, Vergenz S, Medalle G, Prager JM, Eller TW, Cozzens JW, Rezak M

Abstract
Deep brain stimulation is generally a safe and effective method of alleviating motor impairment in advanced-stage Parkinson's disease patients. However, adverse events of surgery have been noted, such as hemorrhage, infection, seizures, and device failure. In this report, we describe 2 cases of the unusual adverse event of ischemia associated with subthalamic nucleus stimulator implantation. We present the intraoperative neurological symptoms, microelectrode recording data, imaging findings, and other correlated events. In the first case, the clinical effects of ischemia were evident intraoperatively and coincided with silence during microelectrode recording from the ischemic region. In the second case, the timing of the ischemic event could not be determined precisely but also was associated with a difficult mapping. Subcortical ischemia may be an underrecognized event that confounds neurophysiological mapping of deep brain structures and affects clinical outcomes.

PMID: 16721751 [PubMed - as supplied by publisher]

Journal of neurophysiology 2001 Feb

Authors: Gdowski MJ, Miller LE, Parrish T, Nenonene EK, Houk JC

Abstract
Extracellular discharges from single neurons in the internal segment of the globus pallidus (GPi) were recorded and analyzed for rate changes associated with visually guided forearm rotations to four different targets. We sought to examine how GPi neurons contribute to movement preparation and execution. Unit discharge from 108 GPi neurons recorded in 35 electrode penetrations was aligned to the time of various behavioral events, including the onset of cued and return movements. In total, 39 of 108 GPi neurons (36%) were task-modulated, demonstrating statistically significant changes in discharge rate at various times between the presentation of visual cues and movement generation. Most often, strong modulation in discharge rate occurred selectively during either the cued (n = 32) or return (n = 2) phases of the task, although a few neurons (n = 5) were well-modulated during both movement phases. Of the 34 neurons that were modulated exclusively during cued or return movements, 50% (n = 17) were modulated similarly in association with movements to any target. The remaining 17 neurons exhibited considerable diversity in their discharge properties associated with movements to each target. Cued phases of behavior were always rewarded if executed correctly, whereas return phases were never rewarded. Overall, these data reveal that many GPi neurons discharged in a context-dependent manner, being modulated during cued, rewarded movements, but not during similar self-paced, unrewarded movements. When considered in the light of other observations, the context-dependence we have observed seems likely to be influenced by the animal's expectation of reward.

PMID: 11160530 [PubMed - as supplied by publisher]

General pharmacology 1997 Nov

Authors: Pou C, Nénonéné EK, Reader TA, Fargin A

Abstract
1. The binding characteristics of tritium labeled 8-hydroxy-dipropyl-aminotetralin, or [3H]8-OH-DPAT, to the serotonin1A (5-HT1A) receptor in the stably transfected HeLa cell clone HA6 and in human cortical tissue were examined and compared. 2. A series of kinetic studies of [3H]8-OH-DPAT binding to the transfected HA6 cell line demonstrated two components in both the association and the dissociation reactions. 3. In saturation experiments, at least two affinity states were unequivocally detected in the HA6 cell line and the human cortical tissue. Using isotopic dilutions, the binding isotherms were best fitted to a two-site model, and similar affinity values were obtained in both systems (KH approximately 1.1 nM and KL approximately 12-223 nM). 4. Most of the drugs used in competitions inhibited [3H]8-OH-DPAT binding, following a two-site model, and maintained their rank order of binding potency in both systems; that is, 5-HT > or = 8-OH-DPAT > buspirone > pindolol. Inconsistencies, however, were found for the antagonists NAN-190 and pindolol; only one inhibition constant was determined for HA6 cells, but two affinities were detected with cortical tissue. 5. The results indicate that, although data from binding studies using the cell expression system reflect, to a certain extent, those obtained with the cortical tissue, some discrepancies remained. 6. Finally, and in contrast with what is observed with the 5-HT1A receptor expressed in the HA6 cell line, it is possible that different receptors, or subtypes of one receptor, or even uptake sites normally expressed in cortical tissue, could interact with [3H]8-OH-DPAT or the competing drugs or both, thus leading to the observation of additional binding sites.

PMID: 9347319 [PubMed - as supplied by publisher]

Neurochemical research 1996 Feb

Authors: Nénonéné EK, Radja F, Carli M, van Gelder NM, Afkhami-Dastjerdian S, Reader TA

Abstract
The binding of tritiated 8-hydroxy-2-(di-n-propyl-amino)tetralin, or [3H]8-OH-DPAT, to membranes from rat cerebral cortex and hippocampus could be inhibited by serotonin (5-HT) and buspirone, and by the 5-HT antagonists propranolol, NAN-190, pindolol, pindobind-5-HT(1A), WAY1OO135, spiperone and ritanserin. All competition curves, except for ritanserin, best fitted a two-site model. In vitro treatment of the membranes with N-ethylmaleimide (NEM), to alkylate sulfhydryl groups, caused dose-dependent decreases of binding; the inhibition curves were biphasic, and the effects irreversible. Reduction of disulfide bonds with L-dithiothreitol (L-DTT) also decreased binding, but in a monophasic way; these effects were fully reversible in cortex, but only partially reversible in hippocampus. In the latter region, but not in cerebral cortex, previous occupancy by [(3)H]8-OH-DPAT partially protected binding from the effects of both L-DTT and NEM, suggesting that the thiol groups in the receptor recognition site(s) of this brain region are readily accessible. The binding characteristics were examined with the aid of saturation curves, carried out with increasing concentrations, up to 140 nM, of [(3)H]8-OH-DPAT. The saturation data were suggestive of a two-site receptor model incorporating a high-affinity site (K(H) of 0.3-0.5 nM) corresponding to the 5-HT(1A) receptor, and a low-affinity site (KL of ca 25 nM). After in vivo alkylations, carried out by treating rats with N-ethoxycarbonyl-2-ethoxy-1,2-dihydro-quinoline (EEDQ), the saturation curves from both control and EEDQ-treated rats were again best fitted to a two-site model. For EEDQ-treated animals, a drastic decrease of 5-HT(1A) receptor binding activity was noted; this loss was greater in hippocampus than in cerebral cortex. Since the decrease in 5-HT(1A) receptors was not associated with changes in low-affinity binding, the results suggest independent regulations of the two [(3)H]8-OH-DPAT binding proteins. Altogether, the present data further supports the notion that [(3)H]8-OH-DPAT, besides labelling 5-HT(1A) receptors, also binds to other structures in rat cerebral cortex and hippocampus.

PMID: 9182242 [PubMed - as supplied by publisher]

Journal of neurochemistry 1994 May

Authors: Nénonéné EK, Radja F, Carli M, Grondin L, Reader TA

Abstract
The selective serotonin (5-HT) agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT) has been extensively used to characterize the physiological, biochemical, and behavioral features of the 5-HT1A receptor. A further characterization of this receptor subtype was conducted with membrane preparations from rat cerebral cortex and hippocampus. The saturation binding isotherms of [3H]8-OH-DPAT (free ligand from 200 pM to 160 nM) revealed high-affinity 5-HT1A receptors (KH = 0.7-0.8 nM) and low-affinity (KL = 22-36 nM) binding sites. The kinetics of [3H]8-OH-DPAT binding were examined at two ligand concentrations, i.e., 1 and 10 nM, and in each case revealed two dissociation rate constants supporting the existence of high- and low-affinity binding sites. When the high-affinity sites were labeled with a 1 nM concentration of [3H]8-OH-DPAT, the competition curves of agonist and antagonist drugs were best fit to a two-site model, indicating the presence of two different 5-HT1A binding sites or, alternatively, two affinity states, tentatively designated as 5-HT1AHIGH and 5-HT1ALOW. However, the low correlation between the affinities of various drugs for these sites indicates the existence of different and independent binding sites. To determine whether 5-HT1A sites are modulated by 5'-guanylylimidodiphosphate, inhibition experiments with 5-HT were performed in the presence or in the absence of 100 microM 5'-guanylylimidodiphosphate. The binding of 1 nM [3H]8-OH-DPAT to the 5-HT1AHIGH site was dramatically (80%) reduced by 5'-guanylylimidodiphosphate; in contrast, the low-affinity site, or 5-HT1ALOW, was seemingly insensitive to the guanine nucleotide. The findings suggest that the high-affinity 5-HT1AHIGH site corresponds to the classic 5-HT1A receptor, whereas the novel 5-HT1ALOW binding site, labeled by 1 nM [3H]8-OH-DPAT and having a micromolar affinity for 5-HT, may not belong to the G protein family of receptors. To further investigate the relationship of 5-HT1A sites and the 5-HT innervation, rats were treated with p-chlorophenylalanine or with the neurotoxin p-chloroamphetamine. The inhibition of 5-HT synthesis by p-chlorophenylalanine did not alter either of the two 5-HT1A sites, but deafferentation by p-chloroamphetamine caused a loss of the low-affinity [3H]8-OH-DPAT binding sites, indicating that these novel binding sites may be located presynaptically on 5-HT fibers and/or nerve terminals.

PMID: 8158133 [PubMed - as supplied by publisher]