Pharmacokinetics and Safety of Atogepant Co-administered with Quinidine Gluconate in Healthy Participants: A Phase 1, Open-Label, Drug-Drug Interaction Study.

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, is approved for the preventive treatment of migraine. Atogepant is a substrate of P-glycoprotein (P-gp), breast cancer resistance protein, organic anion transporting polypeptide transporters, and cytochrome P450 (CYP)3A4 and 2D6. Quinidine is a strong P-gp and CYP2D6 inhibitor. A phase 1 open-label study evaluated the effect of P-gp and CYP2D6 inhibition by quinidine on the pharmacokinetics of atogepant, and the safety and tolerability of atogepant and quinidine gluconate (QG) when co-administered and when given alone in 33 healthy adults. There was no significant change in the atogepant maximum plasma concentration with QG co-administration. The overall systemic exposure, the area under the plasma concentration-time curve (from time 0 to time t or to infinity), of atogepant increased by 25% when co-administered with QG. However, such an increase was not considered clinically relevant. Atogepant did not alter the mean plasma concentration of quinidine at steady state. The incidence of treatment-emergent adverse events (TEAEs) was highest when QG was administered alone (42.4%), which was primarily due to QT prolongation. Most TEAEs reported were mild in severity and resolved within 1-2 days. Co-administration of atogepant with QG did not result in any unexpected tolerability findings in this phase 1 study in healthy participants. The increase in atogepant exposure during QG co-administration could be due to inhibition of CYP2D6 (a minor contributor to atogepant clearance) as well as inhibition of P-gp.

Effects of Quinidine or Rifampin Co-administration on the Single-Dose Pharmacokinetics and Safety of Rilzabrutinib (PRN1008) in Healthy Participants.

This open-label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug-drug interaction between rilzabrutinib and quinidine (an inhibitor of P-glycoprotein [P-gp] and CYP2D6) or rifampin (an inducer of CYP3A and P-gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash-out period, after co-administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing). Quinidine had no significant effect on rilzabrutinib pharmacokinetics. Rifampin decreased rilzabrutinib exposure (the geometric mean of Cmax and AUC0-∞ decreased by 80.5% and 79.5%, respectively). Single oral doses of rilzabrutinib, with or without quinidine or rifampin, appeared to be well tolerated. These findings indicate that rilzabrutinib is a substrate for CYP3A but not a substrate for P-gp.

Effect of one-year dextromethorphan/quinidine treatment on management of respiratory impairment in amyotrophic lateral sclerosis.

Treatment with Dextromethorphan/Quinidine (DM/Q) has demonstrated benefit on pseudobulbar affect and bulbar function in amyotrophic lateral sclerosis (ALS). The aim of this study was to assess whether DM/Q could provide long-term improvement in bulbar function and thereby prolong noninvasive respiratory management in ALS. MATERIALS AND METHODS: This prospective, case-cohort study, recruited ALS patients with bulbar dysfunction. Subjects included were compared with cross-matched historical controls. Cases received DM/Q (20/10 mg twice daily) during one-year follow-up; bulbar dysfunction was evaluated with the Norris scale bulbar subscore (NBS) and bulbar subscale of AlSFRS-R (ALSFRSb). RESULTS: In total, 21 cases and 20 controls were enrolled, of whom noninvasive respiratory muscle assistance failed in 6 (28.5%) patients in the DM/Q group, compared with 4 patients (20.0%) in the control group (p = 0.645). Time from study onset to failure of respiratory muscle aids was 5.50 + 1.31 months in the DM/Q group and 5.20 + 1.15 months in the control group (p = 0.663). The adjusted OR for the effect of treatment on failure of noninvasive respiratory muscle aids was 2.12 (95%CI 0.23-33.79, p = 0.592). In the DM/Q group an impairment in scores was found in NBS (F = 19.26, p = 0.000) and ALSFRS-Rb (F = 12.71, p = 0.001) across different months of the study. CONCLUSION: Treatment with DM/Q in ALS is unable to prolong noninvasive respiratory management, and moreover, has no effect on long-term deterioration of bulbar function. Notwithstanding the results on bulbar function, DM/Q was found to improve pseudobulbar affect during one-year follow-up.

"Pill in the Pocket" Antiarrhythmic Drugs for Orally Administered Pharmacologic Cardioversion of Atrial Fibrillation.

The therapy of atrial fibrillation often involves the use of a rhythm control strategy, in which 1 or more antiarrhythmic drugs (AAD), ablative procedures, and/or hybrid approaches involving both of these options are utilized in an attempt to restore and maintain sinus rhythm. For chronic therapy, an AAD is taken daily. However, for patients with symptomatic but infrequent, acute, but nondestabilizing episodes, the use of an AAD only at the time of an episode that can quickly restore sinus rhythm, generally as an out-patient, without the burden of a daily drug regimen, may be better. This is called "pill-in-the-pocket" therapy. This manuscript reviews the "pill-in-the-pocket" concept, traces its development from its origins using quinidine, to its expansion using class IC AADs, to the more recent investigation of ranolazine for this purpose. Who should get it, what it involves, its efficacy rates and concerns are all discussed.

Assessment of the rapid and sustained antidepressant-like effects of dextromethorphan in mice.

The glutamatergic system has emerged as a novel pathway for treating major depressive disorder (MDD) with the focus on producing both rapid and sustained antidepressant effects. Dextromethorphan is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that has produced antidepressant-like effects in forced swim and tail suspension tests (TST); however, the rapid and sustained antidepressant-like effects of dextromethorphan have not been evaluated. This study evaluated the rapid and sustained (24 h) antidepressant-like effects of dextromethorphan (0-32 mg/kg) in C56BL/6 mice using the novelty-induced hypophagia (NIH) test and TST, respectively. Additionally, we evaluated anxiety-related behavior and locomotor effects of dextromethorphan (0-56.0 mg/kg) using the light-dark and open field tests. Dextromethorphan (32 mg/kg) produced acute (30 min) antidepressant-like effects in TST, but failed to produce antidepressant-like effects 24 h after drug administration. Treatment of dextromethorphan (32 mg/kg) alone or in combination with CYP2D6 enzyme inhibitor Quinidine (32 mg/kg) failed to produce rapid antidepressant-like effects by increasing the latency to drink in the NIH test rather than decreasing the latency to drink. Dextromethorphan (56 mg/kg) produced an anxiogenic-like effect by decreasing the time spent in the light side, number of entries, and latency to enter the light side in the light-dark test. Administration of dextromethorphan (0-56 mg/kg) did not significantly alter locomotor activity. Although dextromethorphan is considered a noncompetitive NMDA receptor antagonist, dextromethorphan binds to several monoaminergic receptors (SERT and NET) and likely produces the antidepressant-like effects through these receptors similar to traditional antidepressant drugs. Additionally, these results suggest that the therapeutic window for dextromethorphan in the clinical population is small as similar doses produce antidepressant-like and anxiogenic-like behaviors.

Modulation of nose-to-brain delivery of a P-glycoprotein (MDR1) substrate model drug (quinidine) in rats.

During the last decades several new drug formulations were developed to target the central nervous system (CNS) from the nasal cavity. However, in these studies less attention was paid to the possible drug-drug interactions in case of multi-drug therapy. In our pilot study first we compared a nasal solution and a nasal gel to demonstrate their distribution in the nasal cavity (3D printed rat skull model and histology). Due to the aspiration induced high mortality at administration of nasal solution the study was continued only with the gel formulation of quinidine. The aim of our experiments was to identify the possible functional role of P-glycoprotein (P-gp) in the drug absorption in nasal cavity and to test drug-drug interactions at nose-to-brain delivery. Therefore, a P-gp substrate model drug, quinidine was tested by intranasal (IN) administration in presence of PSC-833 (specific P-gp inhibitor) given intravenously (IV) or IN and adrenaline (IN) at low (50 ng) or high (20 µg) dose. In control animals the brain penetration of quinidine was at the level of detection limit, but in combination therapy with IV PSC-833 the brain levels increased dramatically, similarly to high dose IN adrenalin, where due to vasoconstriction peripheral distribution was blocked. These results indicate that P-gp has an important role in drug absorption and efflux at nasal cavity, while adrenaline is also able to modify the penetration profile of the P-gp substrate model drug at nasal application as it decreases nose-to-blood absorption, letting more quinidine to reach the brain along with the nasal nerves.

Physiologically-Based Pharmacokinetic Modeling Approach to Predict Rifampin-Mediated Intestinal P-Glycoprotein Induction.

Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool to quantitatively describe drug disposition profiles in vivo, thereby providing an alternative to predict drug-drug interactions (DDIs) that have not been tested clinically. This study aimed to predict effects of rifampin-mediated intestinal P-glycoprotein (Pgp) induction on pharmacokinetics of Pgp substrates via PBPK modeling. First, we selected four Pgp substrates (digoxin, talinolol, quinidine, and dabigatran etexilate) to derive in vitro to in vivo scaling factors for intestinal Pgp kinetics. Assuming unbound Michaelis-Menten constant (Km ) to be intrinsic, we focused on the scaling factors for maximal efflux rate (Jmax ) to adequately recover clinically observed results. Next, we predicted rifampin-mediated fold increases in intestinal Pgp abundances to reasonably recover clinically observed DDI results. The modeling results suggested that threefold to fourfold increases in intestinal Pgp abundances could sufficiently reproduce the DDI results of these Pgp substrates with rifampin. Hence, the obtained fold increases can potentially be applicable to DDI prediction with other Pgp substrates.

Quinidine therapy and therapeutic drug monitoring in four patients with KCNT1 mutations.

Several recent studies have reported potassium sodium-activated channel subfamily T member 1 (KCNT1) mutations in epilepsy patients on quinidine therapy. The efficacy and safety of quinidine for epilepsy treatment, however, remains controversial. We herein report the cases of four patients with KCNT1 mutations treated with quinidine. A reduction in seizures of more than 50% after quinidine treatment was observed in one patient with epilepsy of infancy with migrating focal seizures (EIMFS), whereas two patients with EIMFS and one with focal epilepsy did not achieve apparent seizure reduction. The relationship between quinidine dose and serum quinidine concentration was inconsistent, particularly at high quinidine doses. One patient with EIMFS developed ventricular tachycardia the day after an increase in quinidine dose from 114 to 126 mg/kg/day. The serum trough quinidine concentration and the corrected QT interval (QTc) before arrhythmia onset were 2.4 µg/ml and 420 ms, respectively, and peak serum quinidine concentration after arrhythmia onset was 9.4 µg/ml. Another patient with EIMFS showed aberrant intraventricular conduction with a quinidine dose of 74.5 mg/kg/day and a serum trough concentration of 3.2 µg/ml. Given that serum quinidine levels may elevate sharply after a dose increase, careful monitoring of electrocardiographs and serum concentrations is required. Based on a review of previous reports and our experience with this case, quinidine should be considered as a promising drug for patients with EIMFS harbouring KCNT1 mutations, however, its efficacy remains controversial due to the limited number of cases, and more information on optimal serum concentrations and appropriate titration methods is required.

Efficacy of Dextromethorphan/Quinidine for Patients With Psychosis-Related Aggression: A Retrospective Case Series.

BACKGROUND: Treatment-resistant aggressive behavior is a complex psychoneurological phenomenon with high health care and societal costs commonly observed in mental illnesses involving psychosis. Here, we report a preliminary evaluation of treatment with dextromethorphan/quinidine in 4 adult patients with significant history of psychosis-related aggression and impulsive behaviors. METHODS: The files of 4 inpatients with DSM-5-defined psychotic disorder and treatment-resistant aggression treated at the Oregon State Hospital (Salem, Oregon) between June and November of 2017 were retrospectively analyzed. The patients (age: mean ± SD = 59.8 ± 7.6) received open-label treatment with dextromethorphan/quinidine (final dose 20 mg/10 mg twice daily) for at least 12 weeks. Outcome was measured on the basis of patient self-report, treatment team evaluation, and physical examination by psychiatrists and primary care physicians. RESULTS: Three of the 4 patients were considered responders to dextromethorphan/quinidine based on clinical impressions of reduction in aggression and impulsive behavior. The nonresponder, who had a history of multiple traumatic brain injuries, showed mild improvement in agitation but continued to display impulsive self-harm behavior despite treatment. Dextromethorphan/quinidine was generally well-tolerated. No metabolic, gastrointestinal, or cardiovascular side effects were observed. CONCLUSIONS: These preliminary findings support dextromethorphan/quinidine as a potential alternative to conventional regimens for treating aggression and impulsive behavior in patients with psychotic disorder. These results should be interpreted cautiously, as extended, double-blinded, placebo-controlled studies with a larger sample size are needed to validate findings from this retrospective case series.

Treatment of recent-onset atrial fibrillation with quinidine and flecainide in Thoroughbred racehorses: 107 cases (1987-2014).

OBJECTIVE To compare the efficacy of quinidine and flecainide in treating naturally occurring, recent-onset atrial fibrillation (AF) in Thoroughbred racehorses. DESIGN Retrospective case series. ANIMALS 107 Thoroughbred racehorses. PROCEDURES Medical records of racehorses with AF that were treated with quinidine or flecainide between 1987 and 2014 were reviewed. Signalment, history, treatments, complications, and outcome data were collected. Horses were allocated to 2 groups according to the initial treatment: initial treatment with quinidine (group 1) or initial treatment with flecainide (group 2). Horses in group 2 that did not convert to sinus rhythm with flecainide were then administered quinidine (group 3). Complications, total quinidine dose, and duration of treatment were compared. Rates of conversion for horses treated with quinidine versus flecainide were also compared. RESULTS Overall rate of cardioversion was 91% (97/107). There was a significant difference in the rate of cardioversion for quinidine alone (91% [71/78]), compared with flecainide alone (41% [12/29]). In group 3, the conversion rate after the addition of quinidine treatment was 82% (14/17). Total quinidine dose and treatment duration did not differ significantly between groups 1 and 3. CONCLUSIONS AND CLINICAL RELEVANCE Overall rate of cardioversion for Thoroughbred racehorses with AF was similar to that in previous reports. Flecainide treatment was less effective than quinidine treatment, but the frequency of complications did not differ between quinidine and flecainide. Further investigation is suggested to evaluate the efficacy of flecainide for cardioversion in athletic horses.

Safety, Tolerability, and Effectiveness of Dextromethorphan/Quinidine for Pseudobulbar Affect Among Study Participants With Traumatic Brain Injury: Results From the PRISM-II Open Label Study.

BACKGROUND: Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI). OBJECTIVE: To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. DESIGN: Open-label trial evaluating twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90. SETTING: 150 U.S. centers. MAIN OUTCOME MEASUREMENTS: Primary endpoint was change in Center for Neurologic Study-Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE). RESULTS: DM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, -5.6 [5.2]; day 90, -8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had "much improved" or "very much improved" on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (-3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (-3.2 [5.3], P<.001) and 90 (-5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%). CONCLUSIONS: DM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials. LEVEL OF EVIDENCE: II.

Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome.

BACKGROUND: Short QT syndrome (SQTS) is a rare and life-threatening arrhythmogenic syndrome characterized by abbreviated repolarization. Hydroquinidine (HQ) prolongs the QT interval in SQTS patients, although whether it reduces cardiac events is currently unknown. OBJECTIVES: This study investigated whether long-term treatment with HQ reduces the occurrence of life-threatening arrhythmic events (LAE) (cardiac arrest or sudden cardiac death) in SQTS patients. METHODS: In this cohort study on consecutive SQTS patients, 2 analyses were performed: 1) a matched-period analysis for the occurrence of LAE in 17 SQTS patients who received long-term HQ; and 2) a comparison of the annual incidence of LAE off- and on-HQ in 16 SQTS patients who survived a cardiac arrest. RESULTS: A total of 17 patients (82% male, age 29 ± 3 years, QTc before treatment 331 ± 3 ms) received HQ therapy (584 ± 53 mg/day). Therapy was stopped in 2 cases (12%) due to gastrointestinal intolerance, and 15 patients continued treatment for 6 ± 1 year. QTc prolongation was observed in all patients (by 60 ± 6 ms; p < 0.001). We compared the occurrence of LAE during 6 ± 1 years before and after HQ, observing that patients on HQ experienced a reduction in both the rate of LAE from 40% to 0% (p = 0.03) and the number of LAE per patient from 0.73 ± 0.3 to 0 (p = 0.026). Furthermore, the annual rate of LAE in the 16 patients with a previous cardiac arrest dropped from 12% before HQ to 0 on therapy (p = 0.028). CONCLUSIONS: We demonstrated for the first time that treatment with HQ was associated with a lower incidence of LAE in SQTS patients. These data point to the importance that quinidine, that in several countries has been removed from the market, remains available worldwide for patients with SQTS. In the present study, therapy with HQ has been proven to be safe, with a relatively low rate of side effects.

Pharmacokinetic interaction of green tea beverage containing cyclodextrins and high concentration catechins with P-glycoprotein substrates in LLC-GA5-COL150 cells in vitro and in the small intestine of rats in vivo.

OBJECTIVES: Possible interaction of green tea beverage (GT) containing cyclodextrins and high concentration catechins, a drinking water, with P-glycoprotein (P-gp) substrates was examined in vitro and in vivo. METHODS: Effects of GT on the uptake of rhodamine 123 by LLC-GA5-COL150 cells and intestinal efflux of rhodamine 123 from blood, intestinal absorption of quinidine from ileum loop and oral absorption of digoxin were examined in rats. Effects of GT and GT components on digoxin solubility were also examined. KEY FINDINGS: Green tea increased the uptake of rhodamine 123 by LLC-GA5-COL150 cells, suppressed the intestinal efflux of rhodamine 123 from blood and increased the absorption of quinidine in the ileum of rats. Also, GT increased the solubility of digoxin, and ingestion of GT significantly increased the oral absorption of digoxin given at a high dose in rats. CONCLUSIONS: Green tea suppressed the P-gp-mediated efflux transport of hydrophilic compounds and increased the solubility of lipophilic compounds. Thus, GT may cause interaction with various P-gp substrates, due to the combined effects of catechins and cyclodextrins. Especially, cyclodextrin alone can cause interaction with various low-solubility compounds in vivo. In taking low-solubility drugs including low-solubility P-gp substrates, cyclodextrin-containing foods and beverages such as GT should be avoided.

Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.

BACKGROUND: At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. METHODS: The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. RESULTS: There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t19=5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t19=4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. LIMITATIONS: Open-label, proof-of-concept design. CONCLUSIONS: Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted.

Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia. METHODS: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events. RESULTS: A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events. CONCLUSION: This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society.

A report of cerebral malaria treated with automated red blood cell exchange.

BACKGROUND: Adjunctive automated whole blood or red blood cell exchange (RBCEx) can rapidly decrease malarial hyperparasitemia. Several case reports and series suggest improvement in clinical symptomatology; however, recent Centers of Disease Control and Prevention (CDC) recommendations concluded that RBCEx has no efficacy as an adjunctive therapy. We present a case of mental status changes secondary to cerebral malaria treated with automated RBCEx resulting in rapid and dramatic neurologic improvement. CASE REPORT: An 84-year-old Somali woman presented with a 3-day history of altered mental status, spiking fevers, chills, bilateral leg pain and weakness, and intermittent diarrhea. Her travel history included a recent trip to Kenya for 1 month without antimalarial chemoprophylaxis. During the hospital stay, her health declined, and she became obtunded. Physical examination revealed fever, tachypnea, hypertension, hypoxia, and no response to verbal or physical stimuli. Her hemoglobin decreased from 12.6 to 6.5 g/dL with 12% intraerythrocytic parasitemia by thin smear. Intraerythrocytic trophozoites and banana-shaped gametocytes were present consistent with Plasmodium falciparum. An emergent 1.5-volume RBC mass automated RBCEx and quinidine infusion decreased her parasitemia to 2%. The patient's mental status improved throughout the procedure, and after the 2½-hour procedure, the patient was alert, oriented, and speaking coherently. The patient continued to receive quinidine and artesunate 1 day later from CDC. CONCLUSION: Automated RBCEx transfusion reduced the parasite burden and restored neurologic functioning in a patient with cerebral malaria while awaiting definitive treatment with artesunate.