Electroencephalographic Biomarkers, Cerebral Oximetry, and Postoperative Cognitive Function in Adult Noncardiac Surgical Patients: A Prospective Cohort Study.

BACKGROUND: Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function. METHODS: This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests-Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge. RESULTS: Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = -0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = -0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge. CONCLUSIONS: Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery.

Anesthetic Practice Trends and Perceptions Toward Postoperative Delirium: A Mixed-Methods Analysis.

BACKGROUND: Delirium is the most common postoperative complication in older adults, though anesthesiologist awareness of delirium prevention guidelines-and associated practice trends-remains unknown. METHODS: This was a convergent mixed-methods study, which simultaneously analyzed quantitative and qualitative data to determine delirium guideline awareness among anesthesiologists and practice patterns based on guideline recommendations. Quantitative data were abstracted from the Multicenter Perioperative Outcomes Group database for noncardiac surgery patients (2009-2020) aged 65 years and older. Linear trends were reported for select guideline-based delirium prevention recommendations via regression modeling. Anesthesiologists (n = 40) from a major academic center without a structured delirium reduction program on hospital wards were then surveyed regarding knowledge and practices with respect to postoperative delirium. For qualitative data, 3 focus groups were held to further discuss guideline awareness and identify challenges with delirium prevention. RESULTS: Quantitative results demonstrated a significant decline in the proportion of cases with midazolam between 2009 and 2020, with the largest decrease observed with urologic surgeries (-3.9%/y; 95% confidence interval [CI], -4.2 to -3.6; P < .001). Use of regional anesthesia increased over this period, particularly with gynecologic surgeries (+2.3%/y; 95% CI, 1.2-3.4; P = .001). Anesthesiologist survey results revealed variable guideline awareness, as 21 of 39 (54%) respondents reported being aware of guidelines for anesthetic management of older adults. Importantly, unawareness of delirium management guidelines was the most frequently cited challenge (17 of 37, 46%) when caring for older adults. Finally, focus group participants were largely unaware of postoperative delirium guidelines. However, participants conveyed key barriers to delirium identification and prevention, including the unclear pathophysiology, nonmodifiable risk factors, and system-based hospital challenges. Participants also expressed a desire for decision-support systems, integrated within the perioperative workflow, that provide evidence-based recommendations for reducing delirium risk. CONCLUSIONS: Perioperative practice trends are indicative of an improving environment for postoperative delirium. However, delirium guideline awareness remains variable among anesthesiologists, and key barriers continue to exist for identifying and preventing postoperative delirium.

Correlation between brain tissue oxygen tension and regional cerebral oximetry in uninjured human brain under conditions of changing ventilation strategy.

Controversy surrounds regional cerebral oximetry (rSO2) because extracranial contamination and unmeasured changes in cerebral arterial:venous ratio confound readings. Correlation of rSO2 with brain tissue oxygen (PbrO2), a "gold standard" for cerebral oxygenation, could help resolve this controversy but PbrO2 measurement is highly invasive. This was a prospective cohort study. The primary aim was to evaluate correlation between PbrO2 and rSO2 and the secondary aim was to investigate the relationship between changing ventilation regimens and measurement of PbrO2 and rSO2. Patients scheduled for elective removal of cerebral metastases were anesthetized with propofol and remifentanil, targeted to a BIS range 40-60. rSO2 was measured using the INVOS 5100B monitor and PbrO2 using the Licox brain monitoring system. The Licox probe was placed into an area of normal brain within the tumor excision corridor. FiO2 and minute ventilation were sequentially adjusted to achieve two set points: (1) FiO2 0.3 and paCO2 30 mmHg, (2) FiO2 1.0 and paCO2 40 mmHg. PbrO2 and rSO2 were recorded at each. Nine participants were included in the final analysis, which showed a positive Spearman's correlation (r = 0.50, p = 0.036) between PbrO2 and rSO2. From set point 1 to set point 2, PbrO2 increased from median 6.0, IQR 4.0-11.3 to median 22.5, IQR 9.8-43.6, p = 0.015; rSO2 increased from median 68.0, IQR 62.5-80.5 to median 83.0, IQR 74.0-90.0, p = 0.047. Correlation between PbrO2 and rSO2 is evident. Increasing FiO2 and PaCO2 results in significant increases in cerebral oxygenation measured by both monitors.

COVID-19-Induced Guillain-Barré Syndrome.

This case report involves a 47-year-old male who presented to the emergency department (ED) with a positive coronavirus disease 2019 (COVID-19) test and symptoms of Guillain-Barré syndrome (GBS). Electrodiagnostic (EDX) studies reported an acute inflammatory demyelinating polyradiculoneuropathy (AIDP). The patient underwent intravenous immune globulin (IVIG) treatment and four weeks of acute inpatient rehabilitation with some functional improvement but remained unable to ambulate independently at discharge.

Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study.

OBJECTIVE: To characterise the clinical course of delirium for patients with COVID-19 in the intensive care unit, including postdischarge neuropsychological outcomes. DESIGN: Retrospective chart review and prospective survey study. SETTING: Intensive care units, large academic tertiary-care centre (USA). PARTICIPANTS: Patients (n=148) with COVID-19 admitted to an intensive care unit at Michigan Medicine between 1 March 2020 and 31 May 2020 were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: Delirium was the primary outcome, assessed via validated chart review method. Secondary outcomes included measures related to delirium, such as delirium duration, antipsychotic use, length of hospital and intensive care unit stay, inflammatory markers and final disposition. Neuroimaging data were also collected. Finally, a telephone survey was conducted between 1 and 2 months after discharge to determine neuropsychological function via the following tests: Family Confusion Assessment Method, Short Blessed Test, Patient-Reported Outcomes Measurement Information System Cognitive Abilities 4a and Patient-Health Questionnaire-9. RESULTS: Delirium was identified in 108/148 (73%) patients, with median (IQR) duration lasting 10 (4-17) days. In the delirium cohort, 50% (54/108) of patients were African American and delirious patients were more likely to be female (76/108, 70%) (absolute standardised differences >0.30). Sedation regimens, inflammation, delirium prevention protocol deviations and hypoxic-ischaemic injury were likely contributing factors, and the most common disposition for delirious patients was a skilled care facility (41/108, 38%). Among patients who were delirious during hospitalisation, 4/17 (24%) later screened positive for delirium at home based on caretaker assessment, 5/22 (23%) demonstrated signs of questionable cognitive impairment or cognitive impairment consistent with dementia and 3/25 (12%) screened positive for depression within 2 months after discharge. CONCLUSION: Patients with COVID-19 commonly experience a prolonged course of delirium in the intensive care unit, likely with multiple contributing factors. Furthermore, neuropsychological impairment may persist after discharge.

Stingray-Induced Tarsal Tunnel Syndrome.

This case report involves a 17-year-old male referred for electrodiagnostic (EDX) evaluation with symptoms of tarsal tunnel syndrome after being stung by a stingray. EDX testing revealed moderate axonal injury localized to the tarsal tunnel. Subsequent exploratory surgery removed a stingray barb from the tarsal tunnel. The patient's symptoms nearly completely resolved at five weeks postoperative follow-up. EDX evaluation of this patient with delayed recovery proved to be a valuable component of management.

Video case review for quality improvement during cardiac arrest resuscitation in the emergency department.

BACKGROUND: Out-of-hospital cardiac arrests are a leading global cause of mortality. The American Heart Association (AHA) promotes several important strategies associated with improved cardiac arrest (CA) outcomes, including decreasing pulse check time and maintaining a chest compression fraction (CCF) > 0.80. Video review is a potential tool to improve skills and analyse deficiencies in various situations; however, its use in improving medical resuscitation remains poorly studied in the emergency department (ED). We implemented a quality improvement initiative, which utilised video review of CA resuscitations in an effort to improve compliance with such AHA quality metrics. METHODS: A cardiopulmonary resuscitation video review team of emergency medicine residents were assembled to analyse CA resuscitations in our urban academic ED. Videos were reviewed by two residents, one of whom was a senior resident (Postgraduate Year 3 or 4), and analysed using Spearman's rank correlation coefficient for numerous quality improvement metrics, including pulse check time, CCF, time to intravenous access and time to patient attached to monitor. RESULTS: We collected data on 94 CA resuscitations between July 2017 and June 2020. Average pulse check time was 13.09 (SD ± 5.97) seconds, and 38% of pulse checks were <10 seconds. After the implementation of the video review process, there was a significant decrease in average pulse check time (P = .01) and a significant increase in CCF (P = .01) throughout the study period. CONCLUSIONS: Our study suggests that the video review and feedback process was significantly associated with improvements in AHA quality metrics for resuscitation in CA amongst patients presented to the ED.

The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial.

BACKGROUND: Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively. METHODS: This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups. RESULTS: Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration. CONCLUSIONS: Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence.

Analysis of Linguistically and Culturally Tailored Initiatives in Websites of Kidney Transplant Programs in the United States Between 2013-2018.

INTRODUCTION: Minority patients constitute the majority of the kidney transplant waiting list, yet they suffer greater difficulties in listing and longer wait times to transplantation. There is a lack of information regarding targeted efforts by transplant centers to improve transplant care for minority populations. RESEARCH QUESTION: Our aim was to analyze all kidney transplant websites in the United States to identify changes over a 5-year period in the number of multilingual websites, reported culturally targeted initiatives, and center and provider diversity. DESIGN: Surveys were developed to analyze center websites of all transplant programs in the United States. Those with incomplete information about their nephrology or surgical teams were excluded, resulting in 174 (73%) sites in 2013 and 185 (76%) in 2018. Results: Few websites were available in a language other than English, 6.3% in 2013 and 9.7% in 2018 (P = 0.24). Only 3 websites (1.3%) in 2013 and 7 (3.7%) in 2018 reported any evidence of a culturally targeted initiative (P = 0.23). In 2018, 35% of centers employed a Hispanic transplant physician, 77% had a transplant physician who spoke a language other than English, and 39% had a transplant physician who spoke Spanish. DISCUSSION: Although minority patients are expected to grow in the United States, decreased access to transplantation continues to vex the transplant community. Very little progress has been made in the development of multilingual websites and culturally targeted initiatives.

Delirium, Caffeine, and Perioperative Cortical Dynamics.

Delirium is a major public health issue associated with considerable morbidity and mortality, particularly after surgery. While the neurobiology of delirium remains incompletely understood, emerging evidence suggests that cognition requires close proximity to a system state called criticality, which reflects a point of dynamic instability that allows for flexible access to a wide range of brain states. Deviations from criticality are associated with neurocognitive disorders, though the relationship between criticality and delirium has not been formally tested. This study tested the primary hypothesis that delirium in the postanesthesia care unit would be associated with deviations from criticality, based on surrogate electroencephalographic measures. As a secondary objective, the impact of caffeine was also tested on delirium incidence and criticality. To address these aims, we conducted a secondary analysis of a randomized clinical trial that tested the effects of intraoperative caffeine on postoperative recovery in adults undergoing major surgery. In this substudy, whole-scalp (16-channel) electroencephalographic data were analyzed from a subset of trial participants (n = 55) to determine whether surrogate measures of neural criticality - (1) autocorrelation function of global alpha oscillations and (2) topography of phase relationships via phase lag entropy - were associated with delirium. These measures were analyzed in participants experiencing delirium in the postanesthesia care unit (compared to those without delirium) and in participants randomized to caffeine compared to placebo. Results demonstrated that autocorrelation function in the alpha band was significantly reduced in delirious participants, which is important given that alpha rhythms are postulated to play a vital role in consciousness. Moreover, participants randomized to caffeine demonstrated increased alpha autocorrelation function concurrent with reduced delirium incidence. Lastly, the anterior-posterior topography of phase relationships appeared most preserved in non-delirious participants and in those receiving caffeine. These data suggest that early postoperative delirium may reflect deviations from neural criticality, and caffeine may reduce delirium risk by shifting cortical dynamics toward criticality.

Breaking the circularity in circular analyses: Simulations and formal treatment of the flattened average approach.

There has been considerable debate and concern as to whether there is a replication crisis in the scientific literature. A likely cause of poor replication is the multiple comparisons problem. An important way in which this problem can manifest in the M/EEG context is through post hoc tailoring of analysis windows (a.k.a. regions-of-interest, ROIs) to landmarks in the collected data. Post hoc tailoring of ROIs is used because it allows researchers to adapt to inter-experiment variability and discover novel differences that fall outside of windows defined by prior precedent, thereby reducing Type II errors. However, this approach can dramatically inflate Type I error rates. One way to avoid this problem is to tailor windows according to a contrast that is orthogonal (strictly parametrically orthogonal) to the contrast being tested. A key approach of this kind is to identify windows on a fully flattened average. On the basis of simulations, this approach has been argued to be safe for post hoc tailoring of analysis windows under many conditions. Here, we present further simulations and mathematical proofs to show exactly why the Fully Flattened Average approach is unbiased, providing a formal grounding to the approach, clarifying the limits of its applicability and resolving published misconceptions about the method. We also provide a statistical power analysis, which shows that, in specific contexts, the fully flattened average approach provides higher statistical power than Fieldtrip cluster inference. This suggests that the Fully Flattened Average approach will enable researchers to identify more effects from their data without incurring an inflation of the false positive rate.

Response dependence of reversal-related ERP components in perception of ambiguous figures.

Perceptual multi-stability is characterized by alternating interpretations of an unchanging stimulus input. The reversal negativity (RN) and reversal positivity (RP) ERP components show differences in electrophysiological responses between trials on which participants experience a perceptual reversal of a multi-stable stimulus versus trials without a reversal (i.e., stable). However, it is unclear to what extent these two ERP components reflect reversal-related perceptual processing rather than task and response processes. To address this, we varied task and response requirements while measuring the RN and RP. In the standard reversal task, participants indicated whether they saw a perceptual reversal on each trial. In contrast, in the identity task participants reported perceived identity of the stimulus (e.g., face or vase) without any reference to reversals. In some blocks, reversal trials required a response whereas in other blocks stable trials required a response. We found that the RN appeared independently of task and response style. However, the early latency RP component was only present when participants responded manually. For non-response trials, a component was found during the same latency as the RP but with inverted polarity. Our results suggest that the early RP component is dependent on response-related processes rather than being a pure neural signature of perceptual processes related to endogenous perceptual reversals.

Theta Phase-dependent Modulation of Perception by Concurrent Transcranial Alternating Current Stimulation and Periodic Visual Stimulation.

Sensory perception can be modulated by the phase of neural oscillations, especially in the theta and alpha ranges. Oscillatory activity in the visual cortex can be entrained by transcranial alternating current stimulation (tACS) as well as periodic visual stimulation (i.e., flicker). Combined tACS and visual flicker stimulation modulates BOLD response, and concurrent 4-Hz auditory click train, and tACS modulate auditory perception in a phase-dependent way. In this study, we investigated whether phase synchrony between concurrent tACS and periodic visual stimulation (i.e., flicker) can modulate performance on a visual matching task. Participants completed a visual matching task on a flickering visual stimulus while receiving either in-phase (0°) or asynchronous (180°, 90°, or 270°) tACS at alpha or theta frequency. Stimulation was applied over either occipital cortex or dorsolateral pFC. Visual performance was significantly better during theta frequency tACS over the visual cortex when it was in-phase (0°) with visual stimulus flicker, compared with antiphase (180°). This effect did not appear with alpha frequency flicker or with dorsolateral pFC stimulation. Furthermore, a control sham group showed no effect. There were no significant performance differences among the asynchronous (180°, 90°, and 270°) phase conditions. Extending previous studies on visual and auditory perception, our results support a crucial role of oscillatory phase in sensory perception and demonstrate a behaviorally relevant combination of visual flicker and tACS. The spatial and frequency specificity of our results have implications for research on the functional organization of perception.

Alemtuzumab Induction Is Associated With Equalization of Graft Outcomes Between Elderly and Nonelderly Kidney Transplant Recipients: A Single-Center Report.

OBJECTIVES: Alemtuzumab (monoclonal anti-CD52 antibody) provides profound lymphocyte depletion and offers numerous advantages as an induction agent. Elderly recipients (> 65 years old) traditionally have inferior posttransplant outcomes versus younger recipients. We investigated short-term and long-term patient and graft survival rates following alemtuzumab induction in elderly recipients. MATERIALS AND METHODS: This retrospective analysis, which included 676 renal allograft transplant recipients with alemtuzumab induction, was conducted at the University of Toledo Medical Center between March 2006 and November 2015. We used 2-sided t test, Pearson chi-square test, Fisher exact test, and Cox proportional hazard regressions with 95% confidence interval for analyses. P < .05 was significant. RESULTS: Elderly recipients were more likely to receive a kidney from an inferior donor (deceased donor: 82% vs 72.4%; P = .030) and have higher mean kidney donor profile index (46.2 vs 38.4; P = .024) than nonelderly recipients. Elderly recipients were more likely to experience delayed graft function (15.1% vs 8.5%; P = .038). Elderly recipients demonstrated death-censored graft survival (1 year: 95.4% vs 93.1%; 3 years: 88.5% vs 93.3%; 5 years: 83.1% vs 86.4%) and rejection rates (1 year: 19.8% vs 21.2%; 3 years: 22.1% vs 25.3%; 5 years: 23.8% vs 26.9%) similar to nonelderly recipients. Elderly recipients had significantly higher overall mortality rates than recipients under 65 years old (29.8% vs. 13.2%; P = .001). Although 1-year patient survival was similar to younger recipients (94.8% vs 96.3%; P = .431), 3-year (80.0% vs 91.5%; P = .006) and 5-year (72.9% vs 86.2%; P = .19) rates were significantly decreased in elderly recipients. CONCLUSIONS: Elderly age is not a predictor of rejection or death-censored graft loss in individuals who receive alemtuzumab induction. Despite elevated overall mortality, elderly recipients induced with alemtuzumab demonstrated rejection, graft, and short-term patient survival rates similar to younger recipients.

Alemtuzumab Induction and Steroid Minimization in IgA Nephropathy: A Matched-Cohort Analysis.

OBJECTIVES: Immunoglobulin A nephropathy is the most common primary glomerulonephritis in adults. Transplant can be complicated by immunoglobulin A nephropathy recurrence in up to 60% of allografts, sometimes causing graftloss.The use of alemtuzumab for induction therapy in the setting of steroid minimization for recipients with immunoglobulin A nephropathy is unclear. Here, we investigated patient and graft outcomes in patients with this condition who were induced with alemtuzumab and a steroid minimization protocol. MATERIALS AND METHODS: We performed a retrospective analysis of a database containing 29 patients with immunoglobulin A nephropathy and 646 other recipients who underwent transplant and were induced with alemtuzumab and steroid minimization treatment between March 2006 and May 2015. A matched cohort generated using propensity scoring was also analyzed. RESULTS: Recipients with immunoglobulin A nephropathy were significantly younger at transplant (37.3 ± 11.9 vs 55.6 ± 13.4 years; P < .001), less likely to be African American (6.9% vs 23.2%; P = .04), less likely to have diabetes mellitus (10.3% vs 39.8%; P < .001), and more likely to have private insurance (72.4% vs 45.9%; P = .007). There were no significant differences in graft and patient survival. Recipients with immunoglobulin A nephropathy experienced a higher rate of 1-year rejection (24.1% vs 21.4%; P = .043). Of the 29 patients with immunoglobulin A nephropathy, 8 experienced recurrence (27.6%; average time of 1120.5 ± 982.9 days), with all 8 patients having allograftloss. Matched pair analyses did not yield significant differences in outcomes. CONCLUSIONS: Recurrence rate of immunoglobulin A nephropathy in those induced with alemtuzumab in the setting of steroid minimization is similar to previously reported rates. Although recipients with immunoglobulin A nephropathy had significantly higher 1-year rejection rate, no other differences in graft or patient survival were shown versus recipients without this condition.

Comparison of the effect of nocturnal use of commercial versus custom-made wrist orthoses, in addition to gliding exercises, in the function and symptoms of carpal tunnel syndrome: A pilot randomized trial.

BACKGROUND: Conservative treatment for carpal tunnel syndrome (CTS) often includes wrist orthosis. However, there is no consensus on whether commercial or custom-made wrist orthosis is better for the treatment. PURPOSE: To assess feasibility of a study comparing nocturnal use of commercial versus custom-made wrist orthosis in the treatment of mild/moderate CTS and estimate their potential effects on function and symptoms. STUDY DESIGN: Randomized clinical trial. METHODS: Twenty-four individuals with mild/moderate CTS were randomized to wear either a commercial orthosis (n = 12) or a custom-made orthosis (n = 12). Participants used the assigned orthosis at night for 45 days and performed gliding exercises at home/work. We collected data on access to eligible population and feasibility of protocol. Data on use of orthosis, performance of exercises, and symptoms were collected through a dairy filled by the participant. Outcomes were pain (using Numeric Pain Rating Scale), symptom severity and functional status (using Boston Questionnaire), pinch strength (by dynamometry), and electromyographic activity of forearm muscles (sampled during a reach-to-grasp task). Outcomes were measured before and after the intervention. RESULTS: There were no loses to follow-up in either intervention group. After treatment, we found increased tripod pinch strength and better symptoms and function in both orthosis groups, with better outcomes for the custom-made orthosis, although the differences were not statistically significant. CONCLUSIONS: The preliminary results showed a potential for better outcomes from the custom-made orthosis. We established that a larger study would be feasible and could be designed and conducted based on the estimates provided by this study. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC) - registration number: RBR-74rqnz.

Alice in Wonderland syndrome: "Who in the world am I?"

Alice in Wonderland syndrome (AIWS) is a paroxysmal, perceptual, visual and somesthetic disorder that can be found in patients with migraine, epilepsy, cerebrovascular disease or infections. The condition is relatively rare and unique in its hallucinatory characteristics. OBJECTIVE To discuss the potential pathways involved in AIWS. Interest in this subject arose from a patient seen at our service, in which dysmetropsia of body image was reported by the patient, when she saw it in her son. METHODS We reviewed and discussed the medical literature on reported patients with AIWS, possible anatomical pathways involved and functional imaging studies. RESULTS A complex neural network including the right temporoparietal junction, secondary somatosensory cortex, premotor cortex, right posterior insula, and primary and extrastriate visual cortical regions seem to be involved in AIWS to varying degrees. CONCLUSIONS AIWS is a very complex condition that typically has been described as isolated cases or series of cases.

Alice in Wonderland syndrome: "Who in the world am I?" / Síndrome de Alice no País das Maravilhas: "Quem sou eu no mundo?"

ABSTRACT Alice in Wonderland syndrome (AIWS) is a paroxysmal, perceptual, visual and somesthetic disorder that can be found in patients with migraine, epilepsy, cerebrovascular disease or infections. The condition is relatively rare and unique in its hallucinatory characteristics. Objective: To discuss the potential pathways involved in AIWS. Interest in this subject arose from a patient seen at our service, in which dysmetropsia of body image was reported by the patient, when she saw it in her son. Methods: We reviewed and discussed the medical literature on reported patients with AIWS, possible anatomical pathways involved and functional imaging studies. Results: A complex neural network including the right temporoparietal junction, secondary somatosensory cortex, premotor cortex, right posterior insula, and primary and extrastriate visual cortical regions seem to be involved in AIWS to varying degrees. Conclusions: AIWS is a very complex condition that typically has been described as isolated cases or series of cases.

RESUMO Síndrome de Alice no País das Maravilhas (SAPM) é uma condição paroxística visual perceptiva e somestésica que pode ser encontrada em pacientes com enxaqueca, epilepsia, doença cerebrovascular ou infecções. A condição é relativamente rara e tem características alucinatórias peculiares. Objetivo: Discutir as potenciais vias envolvidas na SAPM. O interesse pelo assunto surgiu com um caso de nosso serviço, onde a distropsia da imagem corporal foi relatada pela paciente, que via isto em seu filho. Métodos: Os autores revisaram e discutiram a literatura médica de casos relatados de SAPM, possíveis vias anatômicas envolvidas e estudos de imagem funcional. Resultados: Uma complexa rede neural incluindo junção temporoparietal direita, córtex somatossensitivo secundário, córtex pré-motor, região posterior da ínsula direita, e regiões do córtex visual primário e extra-estriatal têm diferentes graus de envolvimento na SAPM. Conclusão: SAPM é uma condição complexa que tipicamente foi descrita apenas com casos isolados ou séries de casos.