Intracranial hemorrhage after a single dose of Yohimbine in a chronic user of clonidine.

INTRODUCTION: Yohimbine, an alpha-2 adrenoreceptor antagonist found in a variety of supplements, has been historically used to treat libido, erectile dysfunction, xerostomia, and as a weight loss enhancement. Yohimbine toxicity causes a sympathomimetic syndrome as demonstrated by the case below of a female who developed an intracranial hemorrhage (ICH) following an ingestion of yohimbine. CASE: This case follows a 39-year-old female who presented to the emergency department (ED) with complaints of nausea, emesis, and flushing following the ingestion of a female sexual enhancement supplement labeled to contain yohimbine (BioXgenic Nature's Desire) one hour prior. The patient took her prescribed 0.1 mg clonidine when the symptoms commenced. Upon arrival, the patient's blood pressure was 198/93. She developed neurological sequelae including a left-sided facial droop and weakness of her right extremities. A computed tomography scan demonstrated an acute basal ganglia hemorrhage with mild mass effect and mild subarachnoid hemorrhage. She was transferred to a regional referral hospital and discharged 16 days later to a rehabilitation center with persistent neurological sequelae. DISCUSSION: This patient exhibited sympathetic toxicity temporally associated with yohimbine ingestion. Our patient also had a variety of risk factors that increased the likelihood of a poor outcome with yohimbine. Chronic use of clonidine is known to down-regulate alpha-2 receptors. This leads to dependence of clonidine to maintain adrenergic homeostasis and could potentiate the effects of yohimbine. To compound effects, our patient was also taking bupropion and desvenlafaxine, which inhibit norepinephrine reuptake, likely worsening our patient's sympathomimetic response. Despite the temporal relationship of our patient's ICH and ingestion of yohimbine, a definitive relationship cannot be inferred due to our lack of confirmatory testing of yohimbine content and possibility of adulterants. The U.S. Food and Drug Administration (FDA) does not regulate the supplement market strictly, with multiple studies illustrating variation among ingredients of supplements despite stated quantities on the labels. CONCLUSION: Dietary supplements are not required by the FDA to undergo efficacy or safety testing, necessitating clear post-marketing communication regarding potential adverse events from various supplements. Users should be aware of yohimbine-containing products and the possible side effects of toxicity. It is crucial that physicians and patients be aware of possible drug-supplement interactions of yohimbine and the presentation of sympathomimetic syndromes.

Effect of Load, Angle, and Contraction Type on Clinically Assessed Knee Joint Position Sense.

CONTEXT: Proprioception is an individual's awareness of body position in 3-dimensional space. How proprioceptive acuity changes under varying conditions such as joint position, load, and concentric or eccentric contraction type is not well understood. In addition, a limitation of the variety of techniques to assess proprioception is the lack of clinically feasible methods to capture proprioceptive acuity. The purpose of this study was to implement a readily available instrument, a smartphone, in the clinical evaluation of knee active joint position sense and to determine how joint angle, joint loading, and quadriceps contraction type affect an individual's active joint position sense. DESIGN: Cross-over study. METHODS: Twenty healthy, physically active university participants (10 women and 10 men: 21.4 [2.0] y; 1.73 [0.1] m; 70.9 [14.3] kg) were recruited. Individuals were included if they had no neurological disorder, no prior knee surgery, and no recent knee injury. The participants were given a verbal instruction to locate a target angle and then were tasked with reproducing the target angle without visual or verbal cues. An accelerometer application on a smartphone was used to assess the angle to the nearest tenth of a degree. Three variables, each with 2 levels, were analyzed in this study: load (weighted and unweighted), contraction type (eccentric and concentric), and joint position (20° and 70°). A repeated-measures analysis of variance was conducted to assess the within-subjects factors of load, contraction, and position. RESULTS: A significant difference of 0.50° (0.19°) of greater error with eccentric versus concentric contraction (P = .02) type was identified. In addition, a significant interaction was found for contraction × position, with a mean increase in error of 0.98° (0.33°) at the 20° position when contracting eccentrically (P = .03). CONCLUSIONS: Contraction type, specifically eccentric contraction at 20°, showed significantly greater error than concentric contraction. This suggests that, during eccentric contractions of the quadriceps, there may be decreased proprioceptive sensitivity compared with concentric contractions.

Neural Correlates of Knee Extension and Flexion Force Control: A Kinetically-Instrumented Neuroimaging Study.

Background: The regulation of muscle force is a vital aspect of sensorimotor control, requiring intricate neural processes. While neural activity associated with upper extremity force control has been documented, extrapolation to lower extremity force control is limited. Knowledge of how the brain regulates force control for knee extension and flexion may provide insights as to how pathology or intervention impacts central control of movement. Objectives: To develop and implement a neuroimaging-compatible force control paradigm for knee extension and flexion. Methods: A magnetic resonance imaging (MRI) safe load cell was used in a customized apparatus to quantify force (N) during neuroimaging (Philips Achieva 3T). Visual biofeedback and a target sinusoidal wave that fluctuated between 0 and 5 N was provided via an MRI-safe virtual reality display. Fifteen right leg dominant female participants (age = 20.3 ± 1.2 years, height = 1.6 ± 0.10 m, weight = 64.8 ± 6.4 kg) completed a knee extension and flexion force matching paradigm during neuroimaging. The force-matching error was calculated based on the difference between the visual target and actual performance. Brain activation patterns were calculated and associated with force-matching error and the difference between quadriceps and hamstring force-matching tasks were evaluated with a mixed-effects model (z > 3.1, p < 0.05, cluster corrected). Results: Knee extension and flexion force-matching tasks increased BOLD signal among cerebellar, sensorimotor, and visual-processing regions. Increased knee extension force-matching error was associated with greater right frontal cortex and left parietal cortex activity and reduced left lingual gyrus activity. Increased knee flexion force-matching error was associated with reduced left frontal and right parietal region activity. Knee flexion force control increased bilateral premotor, secondary somatosensory, and right anterior temporal activity relative to knee extension. The force-matching error was not statistically different between tasks. Conclusion: Lower extremity force control results in unique activation strategies depending on if engaging knee extension or flexion, with knee flexion requiring increased neural activity (BOLD signal) for the same level of force and no difference in relative error. These fMRI compatible force control paradigms allow precise behavioral quantification of motor performance concurrent with brain activity for lower extremity sensorimotor function and may serve as a method for future research to investigate how pathologies affect lower extremity neuromuscular function.