Drug therapy of nystagmus and saccadic intrusions.
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Biomedical subjects
Publications and source records attributed to L Fuhry.
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The mesencephalic interstitial nucleus of Cajal (iC) is considered the neural integrator for vertical and torsional eye movements and has also been proposed to be involved in saccade generation. The aim of this study was to elucidate the function of iC in neural integration of different types of eye movements and to distinguish eye movement deficits due to iC impairment from that of the immediately adjacent rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). We addressed the following questions: (1) According to the neural integrator hypothesis, all eye movements including the saccadic system and the vestibulo-ocular reflex (VOR) share a common neural integrator. Do iC lesions impair gaze-holding function for vertical and torsional eye positions and the torsional and vertical VOR gain to a similar degree? (2) What are the dynamic properties of vertical and torsional eye movements deficits after iC lesions, e.g., the specificity of torsional and vertical nystagmus? (3) Is iC involved in saccade generation? We performed 13 uni- and three bilateral iC inactivations by muscimol microinjections in four alert monkeys. Three-dimensional eye movements were studied under head-stationary conditions during vertical and torsional VOR. Under static conditions, unilateral iC injections evoked a shift of Listing's plane to the contralesional side (up to 20 degrees), which increased (ipsilesional ear down) or decreased (ipsilesional ear up) by additional static vestibular stimulation in the roll plane, i.e., ocular counterroll was preserved. The monkeys showed a spontaneous torsional nystagmus with a profound downbeat component. The fast phases of torsional nystagmus always beat toward the lesion side (ipsilesional). Pronounced gaze-holding deficit for torsional and vertical eye positions (neural integrator failure) was reflected by the reduction of time constants of the exponential decay of the slow phase to 330-370 ms. Whereas the vertical oculomotor range was profoundly decreased (up to 50%) and vertical saccades were reduced in amplitude, saccade velocity remained normal and horizontal eye movements were not affected. Bilateral iC injections reduced the shift of Listing's plane caused by unilateral injections, i.e., back toward the plane of zero torsion. Torsional nystagmus reversed its direction and ceased, whereas vertical nystagmus persisted. In contrast to unilateral injection, there was additional upbeating nystagmus. Time constants of the position integrator of the gaze-holding system did not differ between unilateral and bilateral injections. The range of stable vertical eye positions and saccade amplitude was smaller when compared with unilateral injections, but the main sequence remained normal. Dynamic vestibular stimulation after unilateral iC injections had virtually no effect on torsional and vertical VOR gain and phase at the same time when time constants already indicated severe integrator failure. Torsional VOR elicited a constant slow-phase velocity offset up to 30 degrees toward the contralesional side, i.e., in the opposite direction to spontaneous torsional nystagmus. Likewise, vertical VOR showed a velocity offset in an upward direction, i.e., opposite to the spontaneous downbeat nystagmus. Contralesional torsional and upward vertical quick phases were missing or severely reduced in amplitude but showed normal velocity. In contrast, bilateral iC injections reduced the gain of the torsional and vertical VOR by 50% and caused a phase lead of 10-20 degrees (eye compared with head velocity). We propose that the slow-phase velocity offset during torsional and vertical VOR reflects a vestibular imbalance. It therefore appears likely that the vertical and torsional nystagmus after iC lesions is not only caused by a neural integrator failure but also by a vestibular imbalance. Unilateral iC injections have clearly differential effects on the VOR and the gaze-holding function. (ABSTRACT TRUNCATED)
This prospective study examined the effects of the new antiepileptic drug (AED) gabapentin (GBP) compared to the standard AED carbamazepine (CBZ) and placebo (PLA) on eye movements, posture and finger force control in 12 healthy volunteers who received single doses of 600 mg GBP and 400 mg CBZ in a placebo-controlled, double-blind, cross-over, randomized trial. CBZ and GBP reduced almost equally (8% vs. 10%) the mean peak saccade velocity as compared to PLA (P < 0.05). CBZ, but not GBP, significantly prolonged the duration of saccades as compared to placebo (14-24%) (P < 0.05). GBP produced a greater maximal increase of body sway than CBZ with eyes open (P < 0.01) and eyes closed (P < 0.001). CBZ and GBP did not significantly influence control of grip force. CBZ effects were better correlated with plasma levels. Subjective side effects were more pronounced with CBZ than GBP. Although CBZ and GBP cause similar CNS side effects, the effects on eye movements and body sway were different. CBZ predominantly affects saccadic eye movements, whereas GBP had more impact on posture control. Thus, electro-oculography seems to be more appropriate in the detection of CBZ-induced side effects and posturography appears to be more sensitive in the detection of side effects associated with GBP.
We conducted a double-blind crossover trial comparing gabapentin (up to 900 mg/day) to baclofen (up to 30 mg/day) as therapy for acquired nystagmus in 21 patients. We measured visual acuity and the nystagmus before, and at the end of, 2 weeks on each medication. For a group of 15 patients with acquired pendular nystagmus (APN), visual acuity improved significantly with gabapentin, but not with baclofen. Gabapentin significantly reduced APN median eye speed in all three planes, but baclofen did so only in the vertical plane. In 10 patients with APN, the reduction of nystagmus with gabapentin was substantial and 8 of these elected to continue taking the drug. In 6 patients with downbeat or torsional downbeat nystagmus, changes in median slow-phase eye speed were less consistent with both drugs, either increasing or decreasing, and being dependent on viewing conditions. Only 1 patient showed consistent reduction of median eye speed, and this was achieved by either drug. Our findings suggest that gabapentin may be an effective treatment for many patients with APN and that occasional patients with downbeat nystagmus will respond to gabapentin or baclofen.
OBJECTIVES: To describe a previously healthy patient now suffering from monophasic encephalitis caused by a primary infection with BK virus and to discuss possible risk factors for developing BK virus encephalitis. DESIGN: Case report. SETTING: Referral hospital. PATIENT: The patient was examined on referral. MAIN OUTCOME MEASURES: The main diagnostic tests performed were serology, polymerase chain reaction on cerebrospinal fluid samples, and cranial magnetic resonance imaging. RESULTS: During the course of the patient's encephalitis, an IgM titer developed against polyomavirus, followed by anti-polyomavirus IgG. Wild-type BK virus was demonstrated in cerebrospinal fluid samples. Cranial magnetic resonance imaging showed diffuse reversible white matter changes most prominent on T2-weighted images. CONCLUSION: We conclude that diagnostic tests for BK, a human polyomavirus, should be included in the screening program for encephalitogenic pathogens.
Several areas with different saccade-related functions in the frontal cortex are outlined in this review: the frontal eye field, the supplementary eye field, the supplementary motor area, and the dorsolateral prefrontal cortex. Other recent findings that are discussed are that cerebellar midline lesions, including the oculomotor vermis (lobulus VI and VII), and the caudal fastigial nucleus lead to saccadic dysmetria and smooth pursuit deficits.