Prediction of ovarian response using the automated Elecsys anti-Müllerian hormone assay in gonadotrophin-releasing hormone antagonist cycles.

RESEARCH QUESTION: What is the capability of serum anti-Müllerian hormone (AMH) measured using the automated Elecsys® AMH immunoassay to (Roche Diagnostics International Ltd) determine ovarian response after fertility treatment? DESIGN: Single-centre, retrospective, observational, cohort study including women undergoing ovarian stimulation. Serum AMH concentrations were determined using the Elecsys AMH immunoassay based on one blood sample drawn 6 months or less before treatment. Stimulation was conducted in accordance with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Patients were divided into four ovarian response categories based on their oocyte yield: low (0-3), suboptimal (4-9), optimal (10-15) and high (>15). Areas under the curve were calculated for each ovarian response group. RESULTS: Overall, 1248 patients were enrolled. The AMH concentration had a strong positive correlation with oocyte yield (Spearman's rho = 0.74, P < 0.001). Areas under the curve (95% CI) for AMH predicting ovarian response were 0.85 (0.83 to 0.88) for low and 0.89 (0.87 to 0.91) for high response. Optimal serum AMH cut-offs for predicting a low and high response using the Elecsys AMH immunoassay were 6.4 pmol/l (0.89 ng/ml) and 14.2 pmol/l (1.99 ng/ml), respectively. Multivariable regression analysis showed that 47% (R2 = 0.470) of variation in ovarian response could be attributed to AMH alone, increasing to 50.9% (R2 = 0.509) with the addition of age, body weight, and total dose of gonadotrophin. CONCLUSION: Ovarian response and oocyte yield after stimulation in a GnRH antagonist cycle can be predicted with high accuracy using a single determination of serum AMH before ovarian stimulation.

The Neurophysiology of Sleep in Parkinson's Disease.

Sleep disturbances are among the most common nonmotor complications of Parkinson's disease (PD), can present in prodromal stages, and progress with advancing disease. In addition to being a symptom of neurodegeneration, sleep disturbances may also contribute to disease progression. Currently, limited options exist to modulate sleep disturbances in PD. Studying the neurophysiological changes that affect sleep in PD at the cortical and subcortical level may yield new insights into mechanisms for reversal of sleep disruption. In this article, we review cortical and subcortical recording studies of sleep in PD with a particular focus on dissecting reported electrophysiological changes. These studies show that slow-wave sleep and rapid eye movement sleep are both notably disrupted in PD. We further explore the impact of these electrophysiological changes and discuss the potential for targeting sleep via stimulation therapy to modify PD-related motor and nonmotor symptoms. © 2021 International Parkinson and Movement Disorder Society.

Amantadine Associated Myoclonus: Case Report and Review of the Literature.

PURPOSE: Amantadine is commonly used to treat Parkinson's disease. A case of myoclonus and asterixis was associated with amantadine is reported. CASE SUMMARY: An 80-year-old man with Parkinson's disease diagnosed in 2015 was started on amantadine for treatment of progressive tremor and orofacial dyskinesias induced by levodopa. He took amantadine 100mg orally daily for 7 days, then increased to 100mg twice a day thereafter. The patient complained of "worsening tremor" after 9 days and amantadine was decreased to 100mg daily. After 1 month on this dose, the patient reported that his "tremor" persisted and experienced visual hallucinations. His examination demonstrated diffuse myoclonus throughout his extremities and trunk, as well as asterixis when attempting to stand or holding his arms antigravity. Laboratory testing for renal and hepatic failure was unrevealing. Amantadine was reduced to 50mg daily for 4 days and then discontinued. Myoclonus resolved 3 days after discontinuation of amantadine. CONCLUSION: While amantadine-induced myoclonus is rare, health care providers should be vigilant in monitoring for signs and symptoms of myoclonus following amantadine initiation.

Sleep Issues in Parkinson's Disease and Their Management.

Parkinson's disease (PD) is an alpha-synucleinopathy that leads to prominent motor symptoms including tremor, bradykinesia, and postural instability. Nonmotor symptoms including autonomic, neurocognitive, psychiatric symptoms, and sleep disturbances are also seen frequently in PD. The impact of PD on sleep is related to motor and nonmotor symptoms, in addition to the disruption of the pathways regulating sleep by central nervous system pathology. Rapid eye movement sleep behavior disorder is a parasomnia that can lead to self-injury and/or injury to partners at night. Restless legs syndrome is a subjective sensation of discomfort and urge to move the legs prior to falling asleep and can lead to insomnia and reduced sleep quality. Excessive daytime sleepiness is common in PD and exerts a negative impact on quality of life in addition to increasing the risk of falls. Obstructive sleep apnea is a breathing disorder during sleep that can cause frequent awakenings and excessive daytime sleepiness. Circadian rhythm dysfunction can lead to an advanced or delayed onset of sleep in patients and create disruption of normal sleep and wake times. All of these disorders are common in PD and can significantly reduce sleep quantity, sleep quality, or quality of life for patients and caretakers. Treatment approaches for each of these disorders are distinct and should be individualized to the patient. We review the literature regarding these common sleep issues encountered in PD and their treatment options.

The Impact of Deep Brain Stimulation on Sleep in Parkinson's Disease: An update.

BACKGROUND: Parkinson's disease (PD) can have a significant impact on sleep. Deep brain stimulation (DBS) is an effective treatment for motor features of PD, but less is understood about the impact DBS may have on sleep architecture and various sleep issues commonly seen in PD. OBJECTIVE: To review the impact of DBS on various sleep issues in PD. METHODS: We reviewed the literature regarding the impact of DBS on sleep patterns, nocturnal motor and non-motor symptoms, and sleep disorders in PD. RESULTS: Objective sleep measures on polysomnography (PSG), including sleep latency and wake after sleep onset improve after subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS. Subjective sleep measures, nocturnal motor symptoms, and some non-motor symptoms (nocturia) also may improve. Current evidence suggests STN DBS has no impact on Rapid Eye Movement Behavior Disorder (RBD), while STN DBS may improve symptoms of Restless Legs Syndrome (RLS). There are no studies that have evaluated the impact of GPi DBS on RBD, while it is unclear if GPi has an effect on RLS in PD. CONCLUSION: DBS therapy at either site appears to improve objective and subjective sleep parameters in patients with PD. Most likely, the improvement of motor and some non-motor nocturnal symptoms leads to an increase in total sleep time by up to an hour, as well as reduction of sleep fragmentation. DBS most likely has no impact on RBD, while there is evidence that STN DBS appears to help reduce RLS severity. Further studies are needed.

Promoting Careers in Neurology: Mentorship of Medical Students.

Research in neurological disorders is expanding at a phenomenal pace, and the need for neurologists is increasing as the population ages. This results in a critical requirement for medical students entering the neurology pipeline. Mentoring, whether formal or informal, ensures that students are inspired and supported to enter the field of neurology. Students should also receive structured mentoring throughout their longitudinal curriculum. Informal mentoring programs enable expanded opportunities for collaborations in education, research, and outreach. Faculty, residents, fellow medical students, and other health professionals all participate in medical student mentoring. Each relationship offers unique aspects to individual growth and development. Specific programmatic guidance and mentoring qualities are presented in this paper.

A survey based study on sleep disturbance in postural tachycardia syndrome.

BACKGROUND: Postural tachycardia syndrome (POTS) is an autonomic disturbance characterized by an excessive increase in heart rate when an individual moves from a sitting to an upright position. POTS patients often complain of fatigue, daytime sleepiness and insomnia, but there is limited evidence to elucidate the mechanism or the prevalence of sleep-related symptoms in POTS, as well as the effect on patient quality of life. Here, we investigated the prevalence of sleep disturbances in POTS patients, as well as the use of medication and effects on daily life. METHODS: A survey was administered to 30 patients with POTS. The survey contained 22 questions on various characteristics of sleep disturbances in POTS. Answers were recorded on a five-point Likert rating scale. RESULTS: The majority of the patients reported fatigue (96.7%) and low energy (93.3%) during the day. Most (83.3%) patients reported that they do not feel well rested when waking up in the morning. More than half of the patients reported trouble falling asleep at night (63.3%) and maintaining sleep through the night (62.1%). Despite the frequent complaint of sleep disturbance, a very low percentage of POTS patient actually report seeking treatment. CONCLUSION: In this study, we explored the prevalence of sleep disturbance in patients with POTS. Almost all POTS patients reported trouble with sleep and fatigue; however, there is major discrepancy between the high percentage of symptoms and small percentage of patients seeking medical assistance for better sleep quality.

Comprehensive Opportunities for Research and Teaching Experience (CORTEX): A mentorship program.

OBJECTIVE: We developed a program to promote medical student interest in pursuing a career in neurology. This program focuses on medical student mentorship. It also offers opportunities in teaching and clinical research in order to provide students with marketable skills for an academic career in neurology. METHODS: Through this program, students are provided with guidance in developing a fourth-year clerkship schedule and an application package for residency programs. Students are involved and mentored in clinical research. Opportunities are also provided for students to teach their peers, with sessions focusing on examination preparation. RESULTS: Since the implementation of this program in 2010, the number of students entering into the field of neurology from our institution significantly increased from 14 students between 2006 and 2010, to 30 students between 2011 and 2014 (p < 0.05). Medical student research productivity increased from 7 publications during 2006-2010, to 22 publications, 14 poster presentations, and a book chapter after implementation of this program in 2010 (p < 0.05). CONCLUSIONS: In this mentoring program, students are prepared for residency application and provided with research and teaching opportunities. Students develop a highly desirable academic skill set for residency and have matched at top-ranked institutions. This program has been successful in improving student productivity in clinical research and garnering student interest in neurology.

The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: Is it hypoandrogenic?

STUDY QUESTION: What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles? SUMMARY ANSWER: Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women. WHAT IS KNOWN ALREADY: Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired. STUDY DESIGN, SIZE AND DURATION: A prospective case-control study including 94 women, 36 normal controls and 58 LR patients (19 Young ≤ 35 years LR and 39 Aged >35 years LR) from 2009 to 2011. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Fifty-eight LR women were divided into two groups: Young LR (age ≤ 35; n = 19) and Aged LR (ALR; age >35; n = 39). The control group (group C) comprised 36 egg donors undergoing an unstimulated cycle in our IVF unit. Serum and follicular fluid hormonal concentrations for estradiol (E2), progesterone, testosterone and androstendione were measured. The spindle parameters of metaphase II oocytes generated from these groups were also analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Pre-ovulatory follicles from LR patients had similar androgenic and LH concentrations to those observed in the control group. However, higher intrafollicular concentrations of FSH and progesterone were observed in ALR. Moreover, no differences were found for the spindle evaluation of oocytes between groups by the Oosight technology. LIMITATIONS, REASONS FOR CAUTION: The controls were younger and had a lower BMI than the LR women. The sample size available restricted statistical power. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that the problem with LR women is not the final pre-ovulatory follicular androgen concentration since this is similar to normal responders, but in the ability to respond to controlled ovarian stimulation protocols. Therefore, efforts should be focused on long-interval androgen priming to potentially increase the recruitment of small antral follicles rather than increasing the intraovarian androgen levels within the current cycle. STUDY FUNDING/COMPETING INTEREST: The present project has been supported by the R+D programme from the Generalitat Valenciana (Regional Valencian Government) IMPIVA MIDTF/2010/95. The authors have no conflict of interest to declare.

Writing from the wards: advice for residents.

INTRODUCTION: Published articles share information and ideas across fields and can be a part of educational and career development. Academic and personal interests are the typical motivators, but many residents have trouble with the logistics of writing and the simple act of getting started. OBJECTIVE: The following article gives concrete advice, structural recommendations and addresses logistical concerns in writing manuscripts, focusing on case reports. METHODS: The process of writing a paper results in self-teaching, while striving to teach others. Working on case reports often produces posters and presentations on the way to writing the manuscript. This article reviews different types of case reports: from the classic sentinel case, to case series, and video submissions, to teaching cases. A "how to" strategy is presented in the writing process, from idea, to data, to writing itself. Aspects such as choosing your audience and journal are discussed, as well as employing coauthors and working together to produce a polished manuscript. CONCLUSIONS: Residents and fellows are immersed in clinical medicine but may not possess experience in writing journal articles. Presented is advice on and logistics of writing manuscripts that are based on clinical data and clinical experience. Through utilizing a structured approach and understanding the practicalities involved, more physicians in training can write from the wards.

Differences in motor and cognitive function in patients with Parkinson's disease with and without orthostatic hypotension.

Patients with Parkinson's disease (PD) often present with orthostatic hypotension (OH) as a result of the dysautonomia associated with the disease or as a side effect of the dopaminergic medications used to treat the disease. The purpose of this study was to investigate differences in motor and cognitive function in patients with PD with and without OH. Forty-four patients with a diagnosis of PD were evaluated and stratified by the presence of OH based on orthostatic blood pressure recordings. Both groups underwent assessments of motor and cognitive function. OH was present in 17 of 44 patients (39%) with PD. These patients with OH had significantly lower scores in gross motor, balance, and cognitive function (p < .05). No significant difference between groups was found in the finger tapping scores. These results suggest that patients with PD should be routinely screened for OH as it commonly occurs and may negatively impact gross motor, balance, and cognitive function.

The effect of obesity on kidney length in a healthy pediatric population.

Over the past decade, the percentage of children who are obese has rapidly increased. As weight has been shown to correlate strongly with the size of various organs, we have observed that obese children have larger kidneys than their normal-weight counterparts. This study sought to quantify this observation by establishing the normal limits of renal length for this population. We examined 204 healthy patients seen for benign hematuria between January 2000 and May 2008. Both right and left kidney lengths significantly correlated with age, height, weight, body mass index and body surface area in our obese patients (n = 59). Height was also found to be a significant predictor of kidney length, in the obese group, by multiple linear regression analysis and was used to create renal length nomograms for the obese pediatric population (P < 0.01). According to this analysis, obese patients had significantly larger kidneys than those of normal-weight patients (P < 0.01). By defining the normal limits of renal length for this group, unnecessary evaluation for nephromegaly will be avoided.

Systemic methotrexate to treat ectopic pregnancy does not affect ovarian reserve.

OBJECTIVE: To evaluate whether methotrexate (MTX) compromises ovarian reserve and future reproductive outcome in women undergoing assisted reproductive technology (ART), when it is used as first-line treatment for ectopic pregnancy (EP). DESIGN: Prospective, observational study. SETTING: University-affiliated private IVF unit. PATIENT(S): Twenty-five women undergoing IVF-ICSI who were treated with MTX (1 mg/kg IM) for an EP after ART. INTERVENTION(S): Evaluation of reproductive outcome and serum anti-Müllerian hormone (AMH) levels. Serum AMH was evaluated before administering MTX and >or=1 week after the resolution of the EP. Reproductive outcome was evaluated by comparing subsequent IVF-ICSI cycles after EP resolution. MAIN OUTCOME MEASURE(S): Serum AMH levels, cycle length, gonadotropin dose required, peak serum E(2) level, oocytes collected, and embryos obtained. RESULT(S): Serum AMH levels before MTX were not statistically significantly different from those after treatment (3.7 +/- 0.3 ng/mL vs. 3.9 +/- 0.3 ng/mL). Patients undergoing a subsequent cycle after systemic treatment for EP had similar cycle durations (10.3 vs. 10.8 d), gonadotropin requirements (2,775 vs. 2,630.3 IU), peak E(2) levels (1,884.3 vs. 1,523.6 pg/mL), number of oocytes retrieved (12.1 vs. 10.5), and total number of embryos obtained (7.1 vs. 6.5). CONCLUSION(S): Single-dose MTX is a safe first-treatment choice that does not compromise future reproductive outcomes in women who are diagnosed with EP after ART.