Faculty Bibliography

Introduction Tranexamic Acid (TXA) is an intravenous antifibrinolytic agent that is used routinely for elective surgery. We report a case of inadvertent intrathecal injection of TXA resulting in refractory status epilepticus. Methods Case report. Results A 71-year-old healthy female admitted for bilateral total knee replacement was inadvertently administered 300mg of TXA intrathecally instead of bupivacaine. Soon after administration, she developed myoclonic jerking. When the error was identified, 15cc of CSF was removed. She was intubated, administered levetiracetam, started on a propofol infusion, and transferred to the neurointensive care unit (NICU). She developed persistent spontaneous and stimulus induced generalized myoclonus refractory to propofol. Midazolam infusion was added. NCHCT and CTA demonstrated pneumocephalus, but no acute arterial or venous thrombosis or stroke. vEEG revealed generalized nonconvulsive seizures occurring once per minute, not correlating with spinal myoclonus . Propofol and midazolam infusions were increased to 150 mcg/kg/min and 2.6 mg/kg/hr, respectively, to achieve burst suppression, and valproic acid was added. Over the following week, the drips were adjusted to suppress seizure activity. By hospital day 8, she was weaned off all infusions without recurrence of seizures. By hospital day 19, she was on levetiracetam monotherapy. She was discharged to rehab after a 22-day hospital course, and was discharged home 45 days after initial presentation. Residual deficits at the time of discharge included mild cognitive impairment and gait instability. She remains seizure-free since hospital day 45 on levetiracetam 500mg BID. Conclusions We report a case of refractory status epilepticus and spinal myoclonus after accidental intrathecal TXA administration. With aggressive management, the patient survived with mild residual deficits. The mechanism by which TXA causes status epilepticus and spinal myoclonus is hypothesized to be related to its inhibitory effects on GABA and glycine receptors, respectively

Background/UNASSIGNED:Progressive multifocal leukoencephalopathy (PML), a potentially fatal demyelinating disease caused by the John Cunningham virus (JCV), can occur as a complication of treatment with rituximab, fingolimod, and dimethyl fumarate. The primary objective of this study was to determine changes in anti-JCV antibody index values in multiple sclerosis (MS) patients treated with these three medications. Second, we explored the relationship between absolute lymphocyte count (ALC), anti-JCV antibody index values, and various patient characteristics. Methods/UNASSIGNED:In this retrospective chart review, we evaluated changes in JCV serology and ALC in 172 MS patients treated with fingolimod, rituximab, or dimethyl fumarate (2013-2016). Only those with known anti-JCV antibody and ALC values before starting the study medications were included. Subsequent values were obtained on an ad hoc basis throughout the study. Results/UNASSIGNED:= 0.014, respectively). A non-significant decreasing trend in anti-JCV antibody index values occurred in patients treated with dimethyl fumarate. Notably, there was no relationship between ALC and anti-JCV antibody index values for patients treated with rituximab, fingolimod, or dimethyl fumarate. Conclusions/UNASSIGNED:Anti-JCV antibody index values significantly decreased in MS patients treated with fingolimod and rituximab; however, this did not occur with dimethyl fumarate. Fingolimod and rituximab may impair the humoral response to the JCV. Nevertheless, a declining anti-JCV antibody index in MS patients treated with fingolimod or rituximab should not necessarily be interpreted as correlating with a decreased risk for PML.

Phantom limb pain (PLP) following amputation, which is experienced by the vast majority of amputees, has been reported to be relieved with daily sessions of mirror therapy. During each session, a mirror is used to view the reflected image of the intact limb moving, providing visual feedback consistent with the movement of the missing/phantom limb. To investigate potential neural correlates of the treatment effect, we measured brain responses in volunteers with unilateral leg amputation using functional magnetic resonance imaging (fMRI) during a four-week course of mirror therapy. Mirror therapy commenced immediately following baseline scans, which were repeated after approximately two and four week intervals. We focused on responses in the region of sensorimotor cortex corresponding to primary somatosensory and motor representations of the missing leg. At baseline, prior to starting therapy, we found a strong and unexpected response in sensorimotor cortex of amputees to visually presented images of limbs. This response was stronger for images of feet compared to hands and there was no such response in matched controls. Further, this response to visually presented limbs was no longer present at the end of the four week mirror therapy treatment, when perceived phantom limb pain was also reduced. A similar pattern of results was also observed in extrastriate and parietal regions typically responsive to viewing hand actions, but not in regions corresponding to secondary somatosensory cortex. Finally, there was a significant correlation between initial visual responsiveness in sensorimotor cortex and reduction in PLP suggesting a potential marker for predicting efficacy of mirror therapy. Thus, enhanced visual responsiveness in sensorimotor cortex is associated with PLP and modulated over the course of mirror therapy.

Gradient-based approaches to brain function have recently unmasked fundamental properties of brain organization. Diffusion map embedding analysis of resting-state fMRI data revealed a primary-to-transmodal axis of cerebral cortical macroscale functional organization. The same method was recently used to analyze resting-state data within the cerebellum, revealing for the first time a sensorimotor-fugal macroscale organization principle of cerebellar function. Cerebellar gradient 1 extended from motor to non-motor task-unfocused (default-mode network) areas, and cerebellar gradient 2 isolated task-focused processing regions. Here we present a freely available and easily accessible tool that applies this new knowledge to the topographical interpretation of cerebellar neuroimaging findings. LittleBrain illustrates the relationship between cerebellar data (e.g., volumetric patient study clusters, task activation maps, etc.) and cerebellar gradients 1 and 2. Specifically, LittleBrain plots all voxels of the cerebellum in a two-dimensional scatterplot, with each axis corresponding to one of the two principal functional gradients of the cerebellum, and indicates the position of cerebellar neuroimaging data within these two dimensions. This novel method of data mapping provides alternative, gradual visualizations that complement discrete parcellation maps of cerebellar functional neuroanatomy. We present application examples to show that LittleBrain can also capture subtle, progressive aspects of cerebellar functional neuroanatomy that would be difficult to visualize using conventional mapping techniques. Download and use instructions can be found at https://xaviergp.github.io/littlebrain.