Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work.

Epidemiology of paediatric injuries in Rwanda using a prospective trauma registry.

BACKGROUND: Child survival initiatives historically prioritized efforts to reduce child morbidity and mortality from infectious diseases and maternal conditions. Little attention has been devoted to paediatric injuries in resource-limited settings. This study aimed to evaluate the demographics and outcomes of paediatric injury in a sub-Saharan African country in an effort to improve prevention and treatment. METHODS: A prospective trauma registry was established at the two university teaching campuses of the University of Rwanda to record systematically patient demographics, prehospital care, initial physiology and patient outcomes from May 2011 to July 2015. Univariable analysis was performed for demographic characteristics, injury mechanisms, geographical location and outcomes. Multivariable analysis was performed for mortality estimates. RESULTS: Of 11 036 patients in the registry, 3010 (27·3 per cent) were under 18 years of age. Paediatric patients were predominantly boys (69·9 per cent) and the median age was 8 years. The mortality rate was 4·8 per cent. Falls were the most common injury (45·3 per cent), followed by road traffic accidents (30·9 per cent), burns (10·7 per cent) and blunt force/assault (7·5 per cent). Patients treated in the capital city, Kigali, had a higher incidence of head injury (7·6 per cent versus 2·0 per cent in a rural town, P < 0·001; odds ratio (OR) 4·08, 95 per cent c.i. 2·61 to 6·38) and a higher overall injury-related mortality rate (adjusted OR 3·00, 1·50 to 6·01; P = 0·019). Pedestrians had higher overall injury-related mortality compared with other road users (adjusted OR 3·26, 1·37 to 7·73; P = 0·007). CONCLUSION: Paediatric injury is a significant contributor to morbidity and mortality. Delineating trauma demographics is important when planning resource utilization and capacity-building efforts to address paediatric injury in low-resource settings and identify vulnerable populations.

ANTECEDENTES: Históricamente, las iniciativas relativas a la supervivencia pediátrica han priorizado los esfuerzos para reducir la morbilidad y la mortalidad debida a enfermedades infecciosas y patología materna. Se ha prestado escasa atención a los traumatismos en pediatría en entornos de recursos limitados. El objetivo de este estudio ha sido evaluar la demografía y los resultados de los traumatismos pediátricos en un país del África subsahariana en un intento para mejorar la prevención y el tratamiento. MÉTODOS: Se estableció un registro prospectivo de traumatismos en dos campus universitarios de Ruanda para recoger sistemáticamente las características demográficas, atención pre-hospitalaria, fisiología inicial y resultados, de mayo de 2011 a julio de 2015. Se efectuó un análisis univariado para los datos demográficos, mecanismos del traumatismo, localización geográfica y resultados. Para las estimaciones de mortalidad se llevó a cabo un análisis multivariable. RESULTADOS: De un total de 11.036 pacientes incluidos en el registro, 3.010 (27,3%) tenían menos de 18 años. Los pacientes pediátricos eran predominantemente varones (69,9%) con una edad media de 8,3 años. Las caídas fueron la causa más frecuente del traumatismo (45,3%) seguidas de los accidentes de tráfico (30,9%), quemaduras (10,7%) y traumatismo cerrado/asalto (7,5%). Los pacientes tratados en la capital presentaban una incidencia más elevada de traumatismos craneales (7,5% versus 2,0%, P < 0,0001, razón de oportunidades, odds ratio, OR 4,08, i.c. del 95% 2,6-6,4) y una mayor mortalidad global relacionada con el traumatismo (P = 0,019, OR ajustado 3,00, i.c. del 95% 1,5-6,0). Los peatones presentaron una mortalidad global relacionada con el traumatismo más alta en comparación con otros usuarios de la carretera (P = 0,0074, OR ajustado 3,26, i.c. del 95% 1,37-7,73). CONCLUSIÓN: Los traumatismos pediátricos contribuyen significativamente a la morbilidad y mortalidad. Delinear la demografía de los traumatismos es importante a la hora de planificar el uso de recursos y el desarrollo de capacidades dirigidas al esfuerzo para abordar los traumatismos pediátricos en entornos de bajos recursos e identificar poblaciones vulnerables.

The outcomes of the elderly in acute care general surgery.

INTRODUCTION: Elderly patients form a growing subset of the acute care surgery (ACS) population. Older age may be associated with poorer outcomes for some elective procedures, but there are few studies focusing on outcomes for the elderly ACS population. Our objective is to characterize differences in mortality and morbidity for acute care surgery patients >80 years old. METHODS: A retrospective review of all ACS admissions at a large teaching hospital over 1 year was conducted. Patients were classified into non-elderly (<80 years old) and elderly (≥80 years old). In addition to demographic differences, outcomes including care efficiency, mortality, postoperative complications, and length of stay were studied. Data analysis was completed with the Student's t test for continuous variables and Fisher's exact test for categorical variables using STATA 12 (College Station, TX, USA). RESULTS: We identified 467 non-elderly and 60 elderly patients with a mean age-adjusted Charlson score of 3.2 and 7.2, respectively (p < 0.001) and a mortality risk of 1.9 and 11.7 %, respectively (p < 0.001). The elderly were at risk of longer duration (>4 days) hospital stay (p = 0.05), increased postoperative complications (p = 0.002), admission to the ICU (p = 0.002), and were more likely to receive a non-operative procedure (p = 0.003). No difference was found (p = NS) for patient flow factors such as time to consult general surgery, time to see consult by general surgery, and time to operative management and disposition. CONCLUSIONS: Compared to younger patients admitted to an acute care surgery service, patients over 80 years old have a higher risk of complications, are more likely to require ICU admission, and stay longer in the hospital.

Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group.

OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

Predictors of poor outcome in patients with a spontaneous cerebellar hematoma.

BACKGROUND AND PURPOSE: The authors studied the clinical and neuroimaging features of cerebellar hematomas to predict poor outcome using comprehensive statistical models. METHODS: We retrospectively reviewed clinical and neuroimaging features in 94 patients with spontaneous cerebellar hematomas to identify predictive features for a poor neurologic outcome, defined as death or dismissal to long-term care facility. Data were analyzed using chi square and Fisher's exact test with calculation of odd's ratios together with 95% confidence intervals. RESULTS: Clinical and neuroradiologic predictors for a poor outcome at p < 0.05 were admission systolic blood pressure > 200 mm Hg, hematoma size > 3 cm, visible brain stem distortion, and acute hydrocephalus. Presenting findings predicting subsequent death at p < 0.05 were abnormal corneal and oculocephalic responses, Glasgow coma sum score less than 8, motor response less than localization to pain, acute hydrocephalus and intraventricular hemorrhage. CONCLUSION: A tree-based analysis model using binary recursive partitioning showed that cornea reflex, hydrocephalus, doll's eyes, age, and size were the most important discriminating factors. Absent corneal reflexes on admission highly predicts poor outcome (86 percent, confidence limits 67-96 percent). When a cornea reflex is present, acute hydrocephalus predicts poor outcome but only when doll's eyes are additionally absent.

Clinician's biases toward surgery in cerebellar hematomas: an analysis of decision-making in 94 patients.

BACKGROUND AND PURPOSE: No studies have examined clinical decision-making in cerebellar hemorrhages. Clinical and CT features may influence surgery in patients with a spontaneous cerebellar hematoma. One commonly accepted adage is to remove a clot when 3 cm or larger in axial diameter on presentation CT scan. It is possible that certain preferences impact on outcome. METHODS: We analyzed 94 patients with spontaneous cerebellar hematomas between the years of 1973-1993. Thirty-one patients underwent suboccipital craniectomy and clot removal with or without ventriculostomy. Deterioration denoted worsening of consciousness, new brainstem signs, or presentation in coma. Statistical analysis was performed utilizing a tree-based model fitted by binary recursive partitioning. Ninety-five percent confidence intervals (CI) were calculated. RESULTS: The overall probability of surgical intervention was 33% (CI 23-43%). The chance of surgery in stable patients was 7% (CI 2-20%). Neurologic deterioration was seen in 54 patients (57%) and increased the prospects of a surgical procedure (52%, CI 38-66%). Surgery was performed in all deteriorating patients with small hematomas (size <3 cm), but large clots (size >3 cm) did not substantially influence surgical decision-making (45%, CI 30-60%) except in patients younger than 70 years old (57%, CI 41-82%). CONCLUSIONS: Clinicians at our institution usually wait for clinical deterioration to unfold prior to operating on patients with cerebellar hematomas. After deterioration occurs, they prefer small hematomas but will operate on large hematomas when patients are younger than 70, generally withholding surgery from older patients. These attitudes may impact on outcome and should be considered in future treatment trials.

Predicting deterioration in patients with lobar haemorrhages.

OBJECTIVE: To study the clinical course and determine predictors of deterioration in patients with lobar haemorrhages). METHODS: A comprehensive review of 61 consecutive patients with lobar haemorrhages was performed. Neurological deterioration was defined as (1) decrease in Glasgow coma sum score by 2 points, (2) new neurological deficit, or (3) clinical signs of brain herniation. A univariate logistic regression was performed and expressed in odds ratios. RESULTS: Sixteen of 61 (26%) patients with lobar haemorrhages deteriorated after admission. In a univariate analysis, only a Glasgow coma score <14 predicted deterioration (75% of deteriorators v 24% who did not deteriorate; p<0.0001). Initial CT characteristics predictive of deterioration included haemorrhage volume >60 ml (63% v 16%, p< 0.0001), shift of the septum pellucidum (75% v 36%, p<0.01), effacement of the contralateral ambient cistern (33% v 0%, p<0.0001), and widening of the contralateral temporal horn (50% v 0%, p<0.0001). Patients presenting and deteriorating within 12 hours of ictus declined due to enlargement of the haemorrhage. Those who deteriorated more than 12 hours after initial neurological symptoms, showed increased mass effect secondary to oedema. CONCLUSION-Patients with lobar haemorrhages presenting immediately after ictus are at risk for deterioration from enlargement of the haemorrhage and predictors of deterioration may be absent. Patients with large volume lobar haemorrhages presenting to the emergency department with decreased level of consciousness and shift on CT are at risk for further deterioration from worsening oedema. These patients require close observation and early aggressive management may be warranted.

Musical tradition, insurrection, and resurrection: the life and legacy of composer/bassist Charles Mingus.

Charles Mingus was perhaps the foremost straight-ahead jazz upright bassist and composer of his generation, blending the inspirational influences of gospel, jazz improvisation, and art music leanings into a unique style all his own. His demise from amyotrophic lateral sclerosis (ALS) in his fifth decade robbed the world of one of the great creative voices of American music. Aspects of Mingus' life, his career as a bassist, bandleader, and composer, and his neuromuscular illness are discussed, emphasizing his legacy for the disparate fields of jazz and neurology.

Predicting neurologic deterioration in patients with cerebellar hematomas.

BACKGROUND: Patients with cerebellar hematomas may appear stable but may worsen suddenly. Whether certain clinical or CT scan findings predict worsening is not known. METHODS: We reviewed clinical and neuroimaging data in 72 patients with cerebellar hematomas at the Mayo Clinic from 1973 through 1993 to identify predictive features for neurologic deterioration. Patients presenting in coma and patients with vascular malformations or malignancies were excluded. Data were analyzed using chi-square or Fisher's exact test, with calculation of odds ratios with 95% confidence intervals. Multivariate logistic regression analysis was performed on appropriate variables. RESULTS: Thirty-three patients (46%) deteriorated, with a decrease in level of consciousness, new brainstem signs, or worsened motor response on the Glasgow Coma Scale. Clinical and neuroradiologic predictors for neurologic deterioration at p < 0.05 were admission systolic blood pressure greater than 200 mm Hg, pinpoint pupils and abnormal corneal or oculocephalic reflexes, hemorrhage extending into the vermis, hematoma size more than 3 cm in diameter, brainstem distortion, intraventricular hemorrhage, upward herniation, and acute hydrocephalus. Multivariate analysis demonstrated that hemorrhage located in the vermis (p = 0.03) and acute hydrocephalus (p = 0.0006) on admission CT scanning independently predicted deterioration. CONCLUSION: Patients with a cerebellar vermian hematoma or acute hydrocephalus are at high risk for neurologic deterioration. These patients should be carefully monitored and are more likely to require consideration for neurosurgical intervention.

Clinical profiles predictive of outcome in pontine hemorrhage.

We reviewed predictive factors of poor outcome in pontine hemorrhage in 38 patients admitted to the neurological-neurosurgical intensive care unit. Twenty-one patients died within days of admission (55%). Nine patients were severely or moderately disabled and dependent on others for daily care (24%). Eight patients made a good recovery (21%). Death was significantly more common in patients with a history of hypertension, coma on admission, absent motor response, absent corneal reflex or oculocephalic responses. However, clinical and CT features observed only in patients who died were hyperthermia (core temperature > 39 degrees C), tachycardia (> 110 beat/min), CT evidence of extension into the midbrain and thalamus, and acute hydrocephalus on admission. Good recovery only occurred in patients who were alert on admission and had small unilateral pontine hemorrhages. These clinical profiles should be useful in determining the level of care and future resuscitative efforts.

Steroid interactions affecting metabolic activities of a T-lymphocyte line.

A glucocorticoid sensitive T-lymphocyte cell line (CEM) was used to study in vitro interaction effects of steroidal compounds on their metabolic activity. Mixtures of steroidal hormones and related substances were added to the cells and assessed in short-term culture experiments by the incorporation of 3H dTr. Dose ranges were selected to include the linear portion of the dose-response curve of each of the potentially interactive substances. Evidence for synergy, additivism or antagonism was obtained for each of the various steroid combinations studied using algebraic and geometric calculations.

Potential for inter-observer and intra-observer variability in x-ray review to establish stone-free rates after lithotripsy.

The potential for variability among observers interpreting diagnostic tests is well known but has not been well established for radiological imaging of urolithiasis. We measured the inter-observer and intra-observer variability in the reporting of plain abdominal films and tomograms from patients who had undergone extracorporeal shock wave lithotripsy (ESWL). Unlabeled copies of the plain abdominal films and tomograms for 58 patients were individually submitted to 3 different radiologists. Selected films from 25 patients were resubmitted to the same radiologists. We found differences among radiologists reporting plain abdominal films alone 52% of the time and even by the same radiologist rereading the films 24% of the time. Tomograms alone decreased the uncertainty but differences still occurred among radiologists 24% of the time and with themselves 16% of the time. When plain abdominal films and tomograms were read together there were differences among radiologists 28% of the time and with themselves 7% of the time but these were usually minor. We concluded from this study that the plain abdominal film alone was frequently difficult to interpret, resulting in uncertainty about the presence or absence of residual stone fragments. Tomograms alone or a plain abdominal film plus tomograms is superior to a plain abdominal film alone. Finally, radiological assessment with all modalities probably overestimates stone-free rates after ESWL even without consideration of the potential for reporting variability among observers.

Immune reactivity in aging-autologous mixed lymphocyte responses.

The level of activity in the autologous mixed lymphocyte reaction (AMLR) was studied in populations of young and old subjects. AMLR activity was reduced in the older age group. A subpopulation of the older age group who had Alzheimer's disease was shown to have the lowest AMLR values. Within this group, those with a history indicating a more rapid development of CNS-related disability from senescence showed the weakest AMLR responses. The AMLR values correlated neither with sex, nutritional status nor history of infections. This impairment of a central regulating immune reaction may be a significant variable in manifestations of the aging process.