The relationship between mast cell activation syndrome, postural tachycardia syndrome, and Ehlers-Danlos syndrome.

Background: Postural tachycardia syndrome (POTS), hypermobile Ehlers-Danlos syndrome (EDS), and mast cell activation syndrome (MCAS) can occur in the same patient. In this study, we investigated the relationship among these three syndromes. Objective: To establish the relationship of MCAS in patients diagnosed with POTS and hypermobile EDS as well as characterize the demographics of the patients affected by these syndromes. Methods: A total of 195 medical records of patients by using a diagnostic codes data base search for disorders of autonomic dysfunction were identified. The demographics of the patients and diagnoses of POTS, EDS, or MCAS were recorded. Confidence intervals of the proportion of patients MCAS within a population of patients with POTS and EDS were compared with the proportion of patients with MCAS and without POTS and EDS. Odds ratios were also calculated within these groups. Results: The percentage of MCAS within the group of POTS and EDS was 31% in comparison with 2% within the non-POTS and EDS group. The 95% confidence interval calculated for the MCAS in the POTS and EDS group did not overlap with 2%, which showed a statistically significant result. The odds ratio between the two groups was found to be 32.46. Conclusion: There was a marked percentage of MCAS among the patients with diagnoses of POTS and EDS.

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.

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial.

IMPORTANCE: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES: Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795859.

Treatment of idiopathic intracranial hypertension with gastric bypass surgery.

Idiopathic intracranial hypertension (IIH) is defined by elevated intracranial pressure and associated headaches, changes in vision and pulsatile tinnitus, among other symptoms. It occurs most frequently in young, obese women. Gastric bypass surgery has been used to treat morbid obesity and its comorbidities, and IIH has recently been considered among these indications. We present a case report of a 29-year-old female with a maximum BMI of 50.3 and a 5-year history of severe headaches and moderate papilledema due to IIH. She also developed migraine headaches. After a waxing and waning course and various medical treatments, the patient underwent laparoscopic Roux-en-Y gastric bypass surgery with anterior repair of hiatal hernia. Dramatic improvement in IIH headaches occurred by 4 months postprocedure and was maintained at 1 year, when she reached her weight plateau with a BMI of 35. Presurgery migraines persisted. This adds to the small number of case reports and retrospective analyses of the successful treatment of IIH with gastric bypass surgery, and brings this data from the surgical literature into the neurological domain. It offers insight into an early time course for symptom resolution, and explores the impact of weight-loss surgery on migraine headaches. This treatment modality should be further investigated prospectively to analyze the rate of headache improvement with weight loss, the amount of weight loss needed for clinical improvement, and the possible correlation with improvement in papilledema.

Management of orthostatic hypotension in patients with Parkinson's disease.

Orthostatic hypotension is common in Parkinson's disease. The current recommended management of orthostatic hypotension related to Parkinson's disease involves first general measures and then medications with little risk of severe adverse side effects.

An enigmatic brainstem posterior fossa ganglioglioma in an adult.

Ganglioglioma is a rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occurs in the pediatric population with an incidence of 7.6%. These tumors are usually slow-growing and well-circumscribed solid or cystic lesions. Gangliogliomatosis infrequently occurs in the frontal lobe, pineal gland, basal ganglia, hypothalamus, and optic chiasm, with very few reports of brainstem ganglioglioma. We report a case of a 35-year-old female who initially presented with headache, vertigo, ataxia, saccadic dysfunction, dysarthria, and dysmetria for several years due to an unknown etiology. Her brain imaging showed multiple lesions in the pons and the cerebellum with cystic changes and size reduction and enlargement over the next few years while her neurological symptoms continued to worsen. The patient received courses of steroid treatment that improved her neurological symptoms, suggesting an inflammatory component of her disease. Extensive workup for an inflammatory or infectious etiology was unfruitful and two brain biopsies were inconclusive. A third biopsy showed atypical glial nuclei, binucleated cells, and Rosenthal fibers and the presence of BRAF V600E mutation was detected. The diagnosis of gangliogliomatosis was consequently established. This case illustrates that gangliogliomatosis may present with the waxing-and-waning neurological signs and symptoms. It can masquerade inflammatory processes in the central nervous system on brain imaging and deserves careful consideration in the diagnosis of patients with an indolent course of neurological deterioration.

A new SETX mutation producing AOA2 in two siblings.

OBJECTIVE: In this paper, we document two cases of a new SETX mutation (820:A>G) combined with an established recessive SETX mutation (5927:T>G) causing ataxia with oculomotor apraxia type 2 (AOA2). METHODS: The patients had a detailed neurological history and examination performed. Radiological imaging was obtained and genetic analysis was obtained. RESULTS: Both siblings demonstrated healthy and normal growth until adolescence. At that time, slowed speech, hypophonia, dysarthria, extraocular muscle dysfunction and some mild choreiform movements began to appear. Family history included some movement disorder difficulties in second degree relatives. The diagnosis of AOA2 was confirmed by genetic testing. CONCLUSIONS: We describe a new SETX gene mutation, which when combined with a recognized SETX mutation results in AOA2. The clinical, radiographic and ancillary testing are described.

Dynamic networks of cortico-muscular interactions in sleep and neurodegenerative disorders.

The brain plays central role in regulating physiological systems, including the skeleto-muscular and locomotor system. Studies of cortico-muscular coordination have primarily focused on associations between movement tasks and dynamics of specific brain waves. However, the brain-muscle functional networks of synchronous coordination among brain waves and muscle activity rhythms that underlie locomotor control remain unknown. Here we address the following fundamental questions: what are the structure and dynamics of cortico-muscular networks; whether specific brain waves are main network mediators in locomotor control; how the hierarchical network organization relates to distinct physiological states under autonomic regulation such as wake, sleep, sleep stages; and how network dynamics are altered with neurodegenerative disorders. We study the interactions between all physiologically relevant brain waves across cortical locations with distinct rhythms in leg and chin muscle activity in healthy and Parkinson's disease (PD) subjects. Utilizing Network Physiology framework and time delay stability approach, we find that 1) each physiological state is characterized by a unique network of cortico-muscular interactions with specific hierarchical organization and profile of links strength; 2) particular brain waves play role as main mediators in cortico-muscular interactions during each state; 3) PD leads to muscle-specific breakdown of cortico-muscular networks, altering the sleep-stage stratification pattern in network connectivity and links strength. In healthy subjects cortico-muscular networks exhibit a pronounced stratification with stronger links during wake and light sleep, and weaker links during REM and deep sleep. In contrast, network interactions reorganize in PD with decline in connectivity and links strength during wake and non-REM sleep, and increase during REM, leading to markedly different stratification with gradual decline in network links strength from wake to REM, light and deep sleep. Further, we find that wake and sleep stages are characterized by specific links strength profiles, which are altered with PD, indicating disruption in the synchronous activity and network communication among brain waves and muscle rhythms. Our findings demonstrate the presence of previously unrecognized functional networks and basic principles of brain control of locomotion, with potential clinical implications for novel network-based biomarkers for early detection of Parkinson's and neurodegenerative disorders, movement, and sleep disorders.

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.

A case of parasympathetic hyperactivity and associated Parry-Romberg syndrome.

This case report describes a 46-year-old female with a history of multiple endocrine neoplasia type 1 syndrome status post-parathyroidectomy, thymectomy via robotic video-assisted thoracoscopic surgery, and pituitary adenoma resection presenting with parasympathetic hyperactivity and Parry-Romberg syndrome. Parry-Romberg syndrome is a rare disorder that manifests as facial hemiatrophy. Reported symptoms include cognitive dysfunction, olfactory hallucinations, and parasympathetic hyperactivity: miosis of the right eye, anhidrosis, diarrhea, urinary incontinence, bowel incontinence, and orthostatic hypotension. Previous reports have noted associations between Parry-Romberg syndrome and sympathetic hyperactivity and dysregulation. This case report focuses on an association between Parry-Romberg syndrome and unopposed parasympathetic activity.

Bilateral Paragangliomas in the Setting of Autonomic Dysfunction: A Case Report.

In 2018, a 59-year-old female patient presented with hoarseness in her voice, headache, intermittent pain in her right side, difficulty of right arm movement, left side neck pain, difficulty controlling hypertension of unknown etiology, and a large mass on the upper left side of her neck with a smaller mass on the right side. MRI of the neck revealed masses at each carotid bifurcation. These were determined to be bilateral paragangliomas. Paragangliomas are rare tumors, and bilateral ones tremendously so. The patient underwent radiation over 2 years, resulting in the successful shrinking and stabilization of both masses. Since completing radiation, the patient reported improvement in her memory, and her blood pressure has stabilized with medication.

Acute occlusion of the fetal posterior cerebral artery: diagnosis and management paradigms.

BACKGROUND AND PURPOSE: The diagnosis and management of acute fetal posterior cerebral artery occlusion are challenging. While endovascular treatment is established for anterior circulation large vessel occlusion stroke, little is known about the course of acute fetal posterior cerebral artery occlusions. We report the clinical course, radiological findings and management considerations of acute fetal posterior cerebral artery occlusion stroke. METHODS: We performed a retrospective review of consecutive patients presenting with acute large vessel occlusion who underwent cerebral angiogram and/or mechanical thrombectomy between January 2015 and January 2021. Patients diagnosed with fetal posterior cerebral artery occlusion were included. Demographic data, clinical presentation, imaging findings and management strategies were reviewed. RESULTS: Between January 2015 and January 2021, three patients with fetal posterior cerebral artery occlusion were identified from 400 patients who underwent angiogram and/or mechanical thrombectomy for acute stroke (0.75%). The first patient presented with concomitant fetal posterior cerebral artery and middle cerebral artery occlusions. Thrombectomy was performed with recanalisation of the fetal posterior cerebral artery but the patient died from malignant oedema. The second patient presented with isolated fetal posterior cerebral artery occlusion. No endovascular intervention was performed and the patient was disabled from malignant posterior cerebral artery infarct. The third patient presented with carotid occlusion and was found to have fetal posterior cerebral artery occlusion after internal carotid artery recanalisation. No further intervention was performed. The patient was left with residual contralateral homonymous hemianopia and mild left sided weakness. CONCLUSION: Fetal posterior cerebral artery occlusion is a rare, but potentially disabling, cause of ischaemic stroke. Endovascular treatment is feasible. Further investigation is needed to compare the efficacy of medical versus endovascular management strategies.

Dry Eye Syndrome and Sicca Complex are Commonly Found in Patients with Postural Orthostatic Tachycardia Syndrome.

PURPOSE: Patients with postural orthostatic tachycardia syndrome (POTS) present to outpatient dysautonomia clinics endorsing a wide range of symptoms. Dry eyes and mouth, or sicca complex are frequently reported. This retrospective study investigates the incidence and quantifies the severity of dry eye syndrome (DES) in patients with POTS. PATIENTS AND METHODS: This retrospective study compiles survey results, and dry eye clinical data from twenty-three POTS patients (22 females, average age 34.9 and st dev 14.0 years) surveyed during their initial or follow-up appointments. Patient's medication lists were documented to account for anticholinergics, antihistamines, and anticholinesterase use. Patients endorsing dry eye symptoms were tested with Schirmer's test strips to identify clinically dry eyes and stratified for severity. RESULTS: Sixty-five percent of patients endorsed dry eye symptoms (15/23). Seventy-four percent of patients endorsed dry mouth symptoms (17/23). Among patients endorsing dry eyes, 81% of eyes had decreased tear production with Schirmer's strip wetting less than 10 mm/5 min (13/16). CONCLUSION: DES is an additional and significant disease burden for the POTS patient population. Dry eye and exocrine gland function should be evaluated as part of the dysautonomia work up with referral to ophthalmology as appropriate. Patients with clinically dry eyes who report additional autonomic dysfunction should be further evaluated for widespread autonomic dysfunction.

Long thoracic neuropathy caused by an apical pulmonary tumor.

Long thoracic nerve palsy has been reported to have traumatic, iatrogenic, and idiopathic causes. The authors describe the case of a 62-year-old man who presented with progressively worsening right shoulder pain, winging of the scapula, and Horner syndrome. A chest CT scan revealed an apical pulmonary mass. To the authors' knowledge, this is the first report of a long thoracic nerve palsy caused by an apical pulmonary tumor.

A quality improvement curriculum for the neurology clerkship: A practice-based approach to discharge education.

In the Neurology Clerkship at our institution, we introduced a medical education curriculum to increase student competency in providing discharge education to patients with neurologic disease, and to increase knowledge of QI principles. The curriculum was peer-based, in that it was developed by medical students, experienced by medical student clerks, and modified over time with their feedback, which was tracked using exit surveys. Patients counseled were predominantly male (67%) and white (55%), with stroke or TIA together representing the most common diagnoses (58%). A high proportion of students (>85%) agreed that the clerkship project was effective in teaching discharge education, the risk factors for readmission, and increased confidence in providing discharge education. We conclude that medical students are poised to learn QI principals through practice-based curricula, and through practice may improve the quality and safety of care for patients with neurologic disease. This curriculum can be implemented within other services, and with different learners.

Self-Reported Exercise Trends in Parkinson's Disease Patients.

OBJECTIVE: To examine trends in type, frequency, and effectiveness of different modes of exercise in patients with Parkinson's Disease (PD). BACKGROUND: Exercise has been shown to improve symptoms in PD patients. Recent studies suggest that dance may be a particularly helpful exercise option. However, it remains unclear how the benefits of various forms of exercise compare to dance and to each other. Information on these trends can help inform future exercise programs for PD patients. METHOD: 55 PD patients completed a survey on their exercise frequency, the impact of exercise on their symptoms, and whether they exercise alone or in groups. 9 PD patients who attend dance therapy classes completed an extended survey with additional questions comparing the benefit of dance therapy to traditional forms of exercise. RESULTS: Of the 64 patients surveyed, 67% of patients exercised at least twice a week for at least 30 minutes at a time, and 28% of patients exercised alone only. Walking was most commonly reported (77%), followed by stretching (52%), and weights (28%). 97% of patients who exercised noted mitigation of their PD symptoms. Additionally, a significantly greater percentage of patients who exercised in groups reported symptomatic improvements compared to patients who only exercised alone (p = 0.03). CONCLUSION: More patients who participated in group exercise reported symptomatic improvement compared to those who exercised strictly alone. This suggests that the psychosocial and cognitive component of group therapy, such as dance, may confer additional benefits to PD patients.

Education Research: A framework for global health curricula for neurology trainees.

As the global burden of neurologic disease increases, educating future neurologists about the principles of global health through global health curricula is of utmost importance. However, few neurology residency training programs have developed and implemented comprehensive global health curricula. This report outlines the design, implementation, and evaluation of the University of Massachusetts Medical School neurology residency global health curriculum. Using accepted curriculum development methods and incorporating an innovative use of technology, we created a global health curriculum focused on neurology to engage trainees. The implementation of curricula and organization of elective opportunities also incorporates learning objectives and an evaluation process. The University of Massachusetts Medical School neurology global health curriculum can be used as a framework for other residency programs developing global health programs. Global health education increases young neurologists' awareness of the growing burden of neurologic disease and, subsequently, may motivate them to address the need for neurologic expertise around the world.

Neurology Residents as Comprehensive Educators (Neuro RACE).

Residents are expected to be educators often without any formal schooling, and many continue a career in academic medicine where they play a pivotal role in education. However, few resident curricula have been published to include instruction in teaching, particularly in the field of Neurology. To guide Neurology residents as they take on their role as a clinician-educator, we developed a 1-year curriculum (Neurology Residents as Comprehensive Educators "Neuro RACE") with monthly sessions divided into didactics, small group discussions, and interactive kinetic learning. A postcurriculum survey was used to evaluate the residents' response to this curriculum. Residents reported an overall improvement in their comfort and confidence in their teaching abilities. As an integral part of academic training, residents-as-teachers curricula should take a prominent role in Neurology training programs.

Alcohol use and hospital readmissions following stroke: A safety net hospital experience.

OBJECTIVE: The purpose of this study is to identify predictors of stroke-related readmissions at 30days on a safety net hospital level and suggest interventions to reduce the number of readmissions. BACKGROUND: Hospital readmissions are an important measure of the quality of health care services. Readmissions indicate unresolved problems from the index admission, inadequate post-hospitalization care, or a mixture of these factors. Additionally, hospital readmissions are associated with a substantial economic burden on the health care system. The study's purpose is to identify predictors of stroke-related readmissions within 30days on a hospital level and suggest interventions to reduce the number of readmissions. METHODS: We conducted a single-center retrospective study of patients admitted to Boston Medical Center (BMC) and diagnosed with ischemic and hemorrhagic stroke. Unadjusted and adjusted logistic regressions were used to evaluate possible predictors of stroke related readmissions. RESULTS: Of 352 patients admitted with a diagnosis of ischemic or hemorrhagic stroke at BMC during the study period, 44 (12.5%) patients were readmitted to BMC within 30days. Current alcohol abuse was significantly associated with readmission (OR 95% CI 1.03-5.62). Discharge against medical advice was also associated, though the sample size was small. CONCLUSIONS: These results suggest that early inpatient and post-hospitalization interventions to address alcohol abuse during the index hospital admission may reduce the rate of hospital readmission within 30days. The results have prompted interventions on the stroke service such as early inpatient social work and addiction medicine involvement for patients with risk factors of alcohol abuse.

The role of the neurologist in cases of abuse and neglect.

OBJECTIVE: The objective of this article is to define abuse and neglect and underscore the importance of their assessment in the practice of neurology. REVIEW STUDY: This review outlines the medical and psychologic consequences of abuse and neglect and their impact on individuals and family units. It highlights specific neurologic repercussions of abuse and neglect and provides clinical scenarios that a neurologist may encounter. CONCLUSIONS: Abuse and neglect impact neurology patients. By assessing and referring our patients to the appropriate resources, we may improve their outcomes and help to break the cycle of abuse.