Multiple Sleep Latency Test/Maintenance of Wakefulness Test and Central Hypersomnias: Evolving Diagnostic and Therapeutic Approaches.

SUMMARY: Central disorders of hypersomnolence include a spectrum of conditions, such as narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome, in which excessive daytime sleepiness is the primary feature. Subjective testing with tools, such as sleep logs and sleepiness scales, are often helpful in the evaluation of these disorders but do not necessarily correlate well with objective testing, such as polysomnography and multiple sleep latency test and maintenance of wakefulness test. The most recent International Classification of Sleep Disorders-Third Edition has incorporated biomarkers, such as cerebrospinal fluid hypocretin level, into the diagnostic criteria and have restructured the classification of conditions based on our evolved understanding of their underlying pathophysiologic mechanisms. Therapeutic approaches largely consist of behavioral therapy, with a focus on optimizing sleep hygiene, optimizing opportunity for sleep, and strategic napping, along with judicious use of analeptic and anticataleptic agents when necessary. Emerging therapy has revolved around hypocretin-replacement therapy, immunotherapy, and nonhypocretin agents, with the goal of better targeting the underlying pathophysiology of these disorders rather than addressing symptoms. The most novel treatments have targeted the histaminergic system (pitolisant), dopamine reuptake transmission (solriamfetol), and gamma-aminobutyric acid modulation (flumazenil and clarithromycin) to promote wakefulness. Continued research is required for a more solid understanding of the biology of these conditions to develop a more robust armamentarium of therapeutic options.

Clinician-Focused Overview and Developments in Polysomnography.

PURPOSE OF REVIEW: Polysomnography (PSG) represents a fundamental diagnostic tool used in the evaluation of sleep disorders. It represents a simultaneous recording of sleep staging, eye movements, electromyographic tone, respiratory parameters, and electrocardiogram. It is particularly helpful in the assessment of sleep-disordered breathing and its management, propensity for excessive sleepiness, complex behaviors during sleep, including motor disturbances of sleep, sleep-related epilepsy, and parasomnias. This review is intended to summarize the indications for PSG, the limitations and challenges of this diagnostic tool, indications for home sleep apnea testing options, and new developments and trends in polysomnography. RECENT FINDINGS: The polysomnogram is fundamentally important in the evaluation of sleep-disordered breathing in the setting of cardiovascular comorbidities and neurologic conditions such as neuromuscular disease, stroke, and epilepsy and in the evaluation of dream enactment behavior in the setting of REM sleep behavior disorder (RBD). Because RBD is predictive of neurodegenerative disorders, recent data highlights the importance of PSG in corroborating the diagnosis of RBD and identifying people who may be at risk. However, due to cost as well as limitations in access to care, further testing has been developed and implemented including the home sleep apnea test (HSAT). The evolution of consumer wearable devices has also been a growing trend in sleep medicine; however, few have received appropriate validation. SUMMARY: PSG has been used in both the clinical and research settings and remains the gold standard clinical diagnostic test for suspected obstructive sleep apnea (OSA) or central sleep apnea (CSA). Clinicians must be familiar with the basic indications for a PSG but also recognize when it is absolutely required. At this time, the PSG is essential in the evaluation of nocturnal hypoventilation disorders of sleep, periodic limb movements of sleep, and central nervous system hypersomnia (in the absence of CSF hypocretin) when combined with the multiple sleep latency test (MSLT) and is probably the only way to help differentiate among complex behaviors during sleep, especially in the setting of RBD. The capacity to establish an early diagnostic risk of potential dementia would be of critical importance once neuroprotective agents become available.

Formalizing a Residency Mentorship Program with a "Business of Medicine" Curriculum.

BACKGROUND: Mentorship is critical for achieving success in academic medicine and is also considered one of the core professional competencies for residency training. Despite its importance, there has been a decline in the mentor-mentee relationship, largely due to time constraints and lack of clear guidelines for productive discussions. We provide a mentorship curriculum with an easily adoptable workbook which may serve as a guide for programs seeking more formalized mentorship opportunities. METHODS: We created a mentorship curriculum that was divided into 4 quarterly sessions, each with topics to facilitate career guidance and development, and to provide insight into the practical aspects of business of medicine. The mentorship pilot curriculum was implemented during the 2017 to 2018 academic year. Specific questions were provided to stimulate reflection and appropriate discussion between resident mentee and faculty mentor. A post-curriculum survey was distributed to evaluate the effectiveness and satisfaction of the curriculum. RESULTS: A total of 23 residents participated in this pilot project. A majority had not had any formal teaching related to the business aspects of medicine (82%). Upon completion of the curriculum, most residents felt several topics were sufficiently covered, and a majority were satisfied with the course and relationship developed with their mentor (87%). CONCLUSIONS: Our pilot curriculum provides a model to address a knowledge gap in the practical aspects of medicine while simultaneously enhancing residency mentorship. The one-year course was generally well-received by residents and can serve as a model to other academic residency programs with similar challenges and goals.

Neurology Clerkship: Predictors of Objective Structured Clinical Examination and Shelf Performance.

BACKGROUND: We sought to determine whether the following factors are associated with stronger performance on the medical school neurology clerkship: (1) structure of the outpatient rotation (working with a single general neurologist or multiple subspecialists), (2) dedicated shelf exam preparation, and (3) clerkships completed prior to neurology rotation. METHODS: A total of 439 Feinberg medical students between 2014 and 2016 were analyzed based on the 3 variables of interest listed above. Student performance was evaluated using the National Board of Medical Examiner shelf exam and Objective Structured Clinical Examination/standardized evaluation scores. Univariate and multivariate analyses were conducted. RESULTS: The format of the 2-week outpatient rotation did not significantly affect shelf examination (P = .59), or standardized evaluation (P = .34) scores. Taking a shelf pre-test correlated with overall higher standardized evaluation scores (P < .01), and higher shelf examination scores (P < .01). No individual clerkship correlated with better performance; however, the total number of core clerkships was associated with higher shelf examination scores (P = .007). Each additional core clerkship taken prior to neurology was associated with 0.72 points greater shelf examination score. CONCLUSIONS: Greater attending continuity did not appear to be associated with stronger performance perhaps due to a difference in types of cases observed. Students who took a practice shelf exam did better on both their shelf exam and standardized evaluation, suggesting that acquisition of knowledge translates to a better clinical performance. No individual clerkship offers an advantage, but rather it is the total number of clerkships that is correlated with stronger performance.

Corneal abrasion in hysterectomy and prostatectomy: role of laparoscopic and robotic assistance.

BACKGROUND: Radical prostatectomy (RP) is most commonly performed laparoscopically with a robot (robotic-assisted laparoscopic radical prostatectomy, R/PROST). Hysterectomy, which may be open hysterectomy (O/HYST) or laparoscopic hysterectomy (L/HYST), has been increasingly frequently done via robot (R/HYST). Small case series suggest increased corneal abrasions (CAs) with less invasive techniques. METHODS: The authors identified RP (166,942), O/HYST (583,298), or L/HYST (216,890) discharges with CA in the Nationwide Inpatient Sample (2000-2011). For 2009-2011, they determined odds ratios (ORs) and 95% confidence intervals (CIs) for CA, in R/PROST, non-R/PROST, L/HYST, O/HYST, and R/HYST. Uni- and multivariate models studied CA risk depending on surgical procedure, age, race, year, chronic illness, and malignancy. RESULTS: In 2000-2011, 0.18% RP, 0.13% L/HYST, and 0.03% O/HYST sustained CA. Compared with 17,554 non-R/PROSTs (34 abrasions, 0.19%) in 2009-2011, OR was not significantly higher in 28,521 R/PROSTs (99, 0.35%; OR 1.508; CI 0.987 to 2.302; P < 0.057). CA significantly increased in L/HYST (70/51,323; 0.136%) versus O/HYST (70/191,199; 0.037%; OR 3.821; CI 2.594 to 5.630; P < 0.0001), further increasing in R/HYST (63/21, 213; 0.297%; OR 6.505; CI 4.323 to 9.788; P < 0.0001). For hysterectomy, risk of CA increased with age (OR 1.020; CI 1.007 to 1.034; P < 0.003) and number of chronic conditions (OR 1.139; CI 1.065 to 1.219; P < 0.0001). CA risk was likewise elevated in R/HYST with number of chronic conditions. Being African American significantly decreased CA risk in R/PROST and in R/HYST or L/HYST. CONCLUSIONS: L/HYST increased CA nearly four-fold, and R/HYST approximately 6.5-fold versus O/HYST. Identifiable preoperative factors are associated with either increased risk (age, chronic conditions) or decreased risk (race).

Positive and negative predictors for good outcome after decompressive surgery for Chiari malformation type 1 as scored on the Chicago Chiari Outcome Scale.

OBJECTIVE: Posterior fossa decompression (PFD) is commonly applied as treatment for Chiari malformation type 1 (CM1), an entity which is associated with a variety of presenting symptoms but little data correlating symptoms to surgical outcome. We applied the Chicago Chiari Outcome Scale (CCOS), a novel 16-point tool for evaluating outcome, to a consecutive series of CM1 patients to identify specific factors or symptoms that predispose to a better or worse surgical outcome. METHODS: A series of 167 CM1 patients who underwent initial PFD at our institution (consisting of suboccipital craniectomy, C1 laminectomy, subarachnoid exploration, and expansile autologous pericranial duraplasty) were reviewed. Pre-operative signs, symptoms, and characteristics were recorded, and odds ratios were calculated to identify significant pre-operative factors corresponding to a better or worse outcome on the CCOS. RESULTS: Sensory deficits and peripheral neuropathy correlated with a lower score on the CCOS. Younger age at the time of surgery and, strikingly, presence of syringomyelia both correlated with a higher CCOS score. DISCUSSION: Our results identify specific presenting factors that correlated with a better or worse outcome after CM1 decompression. These data also demonstrate that CCOS scoring allows for a rigorous comparison of outcome in different patient populations and between variable operative techniques. Application of CCOS scoring to a larger patient population undergoing a variety of operative CM1 treatments should allow for better-informed decisions regarding patient selection and treatment options for CM1.

A novel scoring system for assessing Chiari malformation type I treatment outcomes.

BACKGROUND: Outcome assessment for the management of Chiari malformation type 1 is difficult because of the lack of a reliable and specific surgical outcome assessment scale. Such a scale could reliably correlate postoperative outcomes with preoperative symptoms. OBJECTIVE: We developed a novel scoring system and applied it retrospectively to 146 patients treated at our institution in order to create and verify a simple and quantifiable assessment of Chiari outcomes. METHODS: The Chicago Chiari Outcome Scale (CCOS) uses 4 postoperative outcome categories (pain, nonpain symptoms, functionality, and complications) graded 1 to 4 for a total possible score of 16. As a comparison with current Chiari outcome methodology, each patient was also placed into a gestalt outcome group of "improved," "unchanged," or "worse" (I/U/W). Patients were stratified by CCOS scores and by I/U/W group. RESULTS: Stratifying patients by total CCOS scores showed that patients who achieved CCOS scores between 13 and 16 were predominantly in the I/U/W improved group (n = 101, 69%); scores between 9 and 12 were predominantly I/U/W unchanged (n = 39, 27%), and scores between 4 and 8 were I/U/W worse (n = 6, 4%). Symptom subscore results provided insight into the specifics of the overall outcome in addition to the more quantitative nature of the 16-point scale. CONCLUSION: We describe a CCOS that assigns higher scores to patients judged improved by gestalt I/U/W ratings and lower scores to those who were unchanged or worse while defining outcome in 4 specific subcategories. As such, this CCOS should allow for a more unified and quantifiable outcome assessment after Chiari surgery.

Protein kinase B (Akt) and mitogen-activated protein kinase p38α in retinal ischemic post-conditioning.

In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. However, the mechanisms of post-conditioning in the retina have not been elucidated. We hypothesized that two kinases, mitogen-activated protein kinase p38α and protein kinase B (Akt), were involved in the mechanism of post-conditioning. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 8 min of post-conditioning early in the reperfusion period after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia. We examined the role of p38α and Akt subtypes 1-3 in post-conditioning by intravitreal injection of interfering RNA 6 h prior to ischemia and post-conditioning and compared the results to injection of non-silencing interfering RNA sequence. The blockade of p38α significantly decreased the recovery after ischemia and post-conditioning, and enhanced cell loss and disorganization of the retina. Blockade of Akt1, and to a lesser degree, Akt2, significantly decreased the recovery after ischemia and enhanced cell loss and disorganization. These differences in the effects of blockade of Akt subtypes were not explainable by distribution of Akt subtypes in the retina, which were similar. In conclusion, both p38 and Akt are essential components of the neuroprotection induced by post-ischemic conditioning in the retina.

Increased prevalence of val(66)met BDNF genotype among subjects with cervical dystonia.

Abnormalities of cortical representational maps and their plasticity have been described in dystonia. A common polymorphism for BDNF has been associated with abnormal cortical plasticity, and thus might contribute to pathogenesis of dystonia in some subjects. As a first step towards this suggestion, the current study examined the prevalence of this polymorphism. BDNF genotype was examined in 34 subjects with cervical dystonia, 54 age-matched healthy controls, and 53 subjects with a different movement disorder, Parkinson's disease. ApoE genotype, known to influence neurological outcome in some conditions, was also examined as a control. In subjects with cervical dystonia, the val(66)met polymorphism was approximately twice as prevalent when compared to either control group. This was not true of ApoE genotype, which was similarly distributed across subject groups. The current findings suggest that the BDNF val(66)met polymorphism might play a role in the pathogenesis of cervical dystonia in some subjects.