Faculty Bibliography

It is often unclear to the clinical investigator whether observational studies should be submitted to a research ethics committee (REC), mostly because, in general, no active or additional interventions are performed. Moreover, obtaining an informed consent under these circumstances may be challenging, either because these are very large epidemiological registries, or the subject may no longer be alive, is too ill to consent, or is impossible to contact after being discharged. Although observational studies do not involve interventions, they entail ethical concerns, including threats such as breaches in confidentiality and autonomy, and respect for basic rights of the research subjects according to the good clinical practices. In this context, in addition to their main function as evaluators from an ethical, methodological, and regulatory point of view, the RECs serve as mediators between the research subjects, looking after their basic rights, and the investigator or institution, safeguarding them from both legal and unethical perils that the investigation could engage, by ensuring that all procedures are performed following the international standards of care for research. The aim of this manuscript is to provide information on each type of study and its risks, along with actions to prevent such risks, and the function of RECs in each type of study.

The prevalence of nocturia in patients with multiple sclerosis (MS) is high, ranging from 20.9% to 48.8% in this population. Its underlying pathophysiology is complex and different from the non-neurogenic population. In the MS population, the pathophysiology may involve neurogenic lower urinary tract dysfunction (NLUTD) such as detrusor overactivity (NDO), detrusor-sphincter dyssynergia, or detrusor underactivity resulting in reduced bladder capacity. Nocturnal polyuria is also a significant contributor to the pathogenesis of nocturia in MS patients and may be the result of specific mechanisms such as nocturnal hypertension through autonomic cardiovascular dysfunction or lack of diurnal variation of antidiuretic hormone production (ADH) due to demyelinating lesions of the spinal cord. Nocturia might be particularly burdensome in MS patients by contributing to fatigue, a common and highly debilitating symptom in this population. There is likely a complex and multidirectional relationship between nocturia, other sleep disorders, and fatigue in the MS population that has yet to be explored. The assessment of nocturia in MS should rely upon a thorough history and physical examination. Urinalysis should be done to rule out urinary tract infection, a frequency-volume chart might help elucidating the underlying mechanisms, and post-void residual volume may be of interest to screen for urinary retention that could be asymptomatic in MS patients. Other tests such as urodynamics or polysomnography are indicated in selected patients. The treatment should be tailored to the underlying cause. The first steps involve behavioral interventions and treatment of cofactors. When possible, the predominant mechanism should be addressed first. In case of predominant NDO, antimuscarinics and beta-3 agonists should be offered as a first-line treatment and intradetrusor injections of botulinum toxin as a second-line treatment. In cases of incomplete bladder emptying, clean-intermittent self-catheterization is often used as part of multiple other interventions. In cases of nocturnal polyuria, desmopressin may be offered, inclusive of use of newer formulations (desmopressin acetate nasal spray, desmopressin orally disintegrated tablet) in countries where they are approved.

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