Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact.

The clinical efficacy of deep brain stimulation (DBS) for the treatment of movement disorders depends on the identification of appropriate stimulation parameters. Since the mechanisms of action of DBS remain unclear, programming sessions can be time consuming, costly and result in sub-optimal outcomes. Measurement of electrically evoked compound action potentials (ECAPs) during DBS, generated by activated neurons in the vicinity of the stimulating electrode, could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulation parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1000 to 5000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 µs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters.

Dilation of Schlemm's canal in viscocanalostomy: comparison of 2 viscoelastic substances.

PURPOSE: To study the injection of viscoelastic material into Schlemm's canal adjacent to and 6.0 mm from the scleral flap during viscocanalostomy in an autopsy eye model. SETTING: Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Viscocanalostomy was performed in 8 postmortem human globes. Sodium hyaluronate (Healon GV or Healon5) was injected into 1 side of Schlemm's canal, with the other side serving as a control in some eyes. The eyes were prepared for light microscopic analysis, and serial pathologic sections were taken adjacent to the flap and 6.0 mm circumferentially from the flap. The area of Schlemm's canal was calculated and compared using t tests. RESULTS: Injecting viscoelastic material enlarged the area of Schlemm's canal adjacent to and 6.0 mm from the flap significantly more than not injecting viscoelastic material. While there was no difference between the viscoelastic materials in dilating Schlemm's canal at the flap, with Healon5 there was a small but statistically significantly greater dilation 6.0 mm from the flap. No full-thickness breaks in the trabecular meshwork were noted adjacent to or 6.0 mm from the flap. CONCLUSION: Injecting viscoelastic material significantly increased the cross-sectional area of Schlemm's canal and may play a role in the success of viscocanalostomy. Further study is needed to elucidate the mechanism of this procedure.

Vitreous concentration of topically applied brimonidine tartrate 0.2%.

OBJECTIVE: To determine the vitreous concentration of brimonidine after topical administration of Alphagan. DESIGN: Prospective observational case series. PARTICIPANTS: Eighteen patients scheduled for elective pars plana vitrectomy. METHODS: Brimonidine tartrate, 0.2%, was topically administered twice or three times daily for 4 to 14 days preoperatively in 13 patients. Four patients served as controls, without application of brimonidine. A dry, undiluted vitrectomy specimen obtained intraoperatively was collected, frozen, and sent to an independent bioanalytical facility for quantitative determination of vitreous concentration of brimonidine using gas chromatography/mass spectrometry. MAIN OUTCOME MEASURES: The concentration of brimonidine in human vitreous. RESULTS: All patients treated with brimonidine measured above the lower limit of quantitation with a mean vitreous concentration of 185 +/- 500 nM. All patients not treated with brimonidine measured at or below the lower limit of quantitation of 0.05 nM. There was a trend toward higher concentration in patients who were either aphakic or pseudophakic compared with those that were phakic. CONCLUSIONS: Topically applied brimonidine results in vitreous levels at or above 2 nM, the concentration shown to activate alpha(2)-receptors.

Conjunctival vasculature in the assessment of anemia.

OBJECTIVE: To assess the correlation of the bulbar conjunctival blood column (BCBC) with anemia. DESIGN: A prospective, randomized, masked, two observer case series. PARTICIPANTS: Inpatients on hospital wards; outpatients in both the Hematology-Oncology and Ophthalmology Clinics. METHODS: Observations of the palpebral conjunctival hue (PCH) and BCBC by two observers masked to the patient's diagnosis, laboratory test results, and other's observations. The PCH and BCBC were correlated by slit-lamp examination with serum hemoglobin values. Different threshold levels for anemia were defined as hemoglobin <10, <11, and <12 mg/dl. MAIN OUTCOME MEASURES: The parameters included determination of (1) the conjunctival hue, assessed as pink or pale and (2) the bulbar conjunctival blood column, assessed as full (normal), granular, or discontinuous. These data were compared against the patient's hemoglobin level. RESULTS: Mean hemoglobin was 11.0+/-2.2 mg/dl. Sensitivity of the BCBC and PCH for anemia was 83%-94% and 38%, respectively, regardless of the definition of anemia. Specificity of BCBC improved with increasing hemoglobin threshold levels for anemia: 56% (hemoglobin <10 mg/dl) to 73% (hemoglobin <12 mg/dl); specificity for PCH ranged from 82% to 94%. The BCBC was significantly (P<0.03) associated with anemia for hemoglobin <11 mg/dl for both observers (logistic regression, Spearman correlation). There was a significant (P<0.05) association of PCH with anemia only for hemoglobin <10 mg/dl with logistic regression (one observer only) and with Spearman correlation (both observers). CONCLUSIONS: The BCBC is significantly associated with anemia, with higher sensitivity and only slightly less specificity than PCH.

Interaction of pilocarpine with latanoprost in patients with glaucoma and ocular hypertension.

PURPOSE: To study any interaction between pilocarpine and latanoprost when administered together, and to determine the optimal timing of dosage to maximize reduction of intraocular pressure (IOP). METHODS: Nineteen adult patients with either primary open-angle glaucoma or ocular hypertension participated in a single-center, prospective case study with masked observer. After a baseline measurement of IOP during treatment with latanoprost was obtained, initial treatment with pilocarpine three times daily was added without bedtime administration. This was followed by three different dose regimens in which pilocarpine was administered four times daily, altering the bedtime pilocarpine dose to precede the latanoprost dose by 1 hour, or to follow it by 10 minutes or 1 hour. Intraocular pressure was measured at 8:00 AM and 75 minutes after administration of the morning dose of pilocarpine. RESULTS: Comparison of IOP at 8:00 AM with baseline showed no significant change when pilocarpine was taken three times daily, or when pilocarpine was taken four times daily when the bedtime dose preceded administration of latanoprost by 1 hour. There were significant decreases in IOP versus baseline when the bedtime dose of pilocarpine was taken simultaneously with or 1 hour after administration of latanoprost. Application of pilocarpine immediately after the 8:00 AM IOP measurement revealed a significant additional decrease in pressure. There were no significant differences between dosage schedules in the magnitude of the additional reduction in IOP. CONCLUSION: The order and timing of administration of pilocarpine and latanoprost can significantly alter their ocular hypotensive activity. Pilocarpine is most effective when administered four times daily, and when the bedtime dose is administered 1 hour after administration of latanoprost.

The effects of a transient increase in temperature on cell generation and cell death in the hippocampus and amygdala of the wallaby, Setonix brachyurus (quokka).

We examined the effects of a single exposure to a temperature elevation of 2 degrees C for a 2 h period on the developmental processes of cell division and cell death in the hippocampus and the amygdala of the quokka. Animals aged postnatal day (P) 4045 were injected with tritiated (3H-) thymidine and then exposed to either 37 degrees C (normal) or 39 degrees C (+/-0.2 degrees C) in an incubator for a duration of 2 h. The young were then returned to the nipple and, after a period of 24 h, were sacrificed. Brains were sectioned and selected sections processed for autoradiography, and some were counterstained. Cell division taking place at the time of heating was estimated by counting 3H-thymidine-labelled cells and at the time of sacrifice by counting mitotic figures. Dying cells were visualised as pyknotic profiles in cresyl-violet-stained sections. In both the amygdala and the hippocampus, the number of 3H-thymidine-labelled cells (cells dividing in situ during the heating period) was significantly lower in the experimental than the control group. Such cells were glia in the amygdala and granule cells and glia in the hippocampus. However, the number of dying cells or mitotic figures (cells dividing at the time of sacrifice) did not differ significantly between the two groups. By comparison, the number of 3H-thymidine-labelled cells, dying cells or mitotic figures did not significantly differ in the diencephalon. Therefore, a brief exposure to a slight elevation in temperature results in an immediate alteration in cell division in the hippocampus and amygdala. These findings have implications for the role played by raised temperature, such as during virus infection, in producing developmental anomalies of the brain.

The efficacy and safety of diclofenac 0.1% versus prednisolone acetate 1% following trabeculectomy with adjunctive mitomycin-C.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of diclofenac 0.1% versus prednisolone acetate 1% following trabeculectomy with adjunctive mitomycin-C. PATIENTS AND METHODS: The authors prospectively randomized chronic open-angle glaucoma patients who underwent trabeculectomy with adjunctive mitomycin-C to receive postoperatively either diclofenac 0.1% or prednisolone acetate 1% 4 times daily, to be tapered as inflammation resolved. RESULTS: In the diclofenac group (n = 14), the preoperative intraocular pressure of 30.4 +/- 13.1 decreased to 12.4 +/- 6.5 mm Hg at 6 months postoperatively. In the prednisolone acetate group (n = 12), the preoperative intraocular pressure decreased from 29.1 +/- 10.4 to 12.8 +/- 4.2 mm Hg at 6 months postoperatively (P = .85). The average number of medicines used 6 months postoperatively was 0.50 +/- 0.8 in the diclofenac group and 0.24 +/- 0.6 in the prednisolone acetate group (P = .36). Adverse events were similar between groups (P = .51). One patient in the diclofenac group underwent reoperation at 1 month due to uncontrolled intraocular pressure. CONCLUSIONS: This study shows that following trabeculectomy with adjunctive mitomycin-C, a similar intraocular pressure result may be expected when either diclofenac or prednisolone acetate is prescribed postoperatively for intraocular inflammation.