Placebo-controlled procedural trials for neurological conditions

Neurological disease has been a central focus in the ongoing ethical debate over the use of invasive placebo controls, especially sham surgery. The risk to research subjects and necessary use of deception involved in these procedures must be balanced against the methodological need to control for bias and the placebo effect. We review a framework formulated for the ethical assessment of sham surgery in the context of research evaluating novel procedures for neurological conditions. Special issues raised include the growing evidence of expectation and conditioning effects in a number of neurological diseases, the escalating scale of risk from different types of invasive placebo interventions, and the increasing use of cross-over designs, which allow a switch from placebo to active intervention without additional procedures.     

Burden of neurological conditions in Canada

Neurological conditions are among the leading causes of disability in the Canadian population and are associated with a large public health burden. An increase in life expectancy and a declining birth rate has resulted in an aging Canadian population, and the proportion of age-adjusted mortality due to non-communicable diseases has been steadily increasing. These conditions are frequently associated with chronic disability and an increasing burden of care for patients, their families and caregivers. The National Population Health Study of Neurological Conditions (NPHSNC) aims to improve knowledge about neurological conditions and their impacts on individuals, their families, caregivers and health care system. The Systematic Review of Determinants of Neurological Conditions, a specific objective within the NPHSNC, is a compendium of systematic reviews on risk factors affecting onset and progression of the following 14 priority neurological conditions: Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), brain tumours (BT), cerebral palsy (CP), dystonia, epilepsy, Huntington’s disease (HD), hydrocephalus, multiple sclerosis (MS), muscular dystrophies (MD), neurotrauma, Parkinson’s disease (PD), spina bifida (SB), and Tourette’s syndrome (TS). The burden of neurological disease is expected to increase as the population ages, and this trend is presented in greater detail for Alzheimer’s and Parkinson’s disease because the incidence of these two common neurological diseases increases significantly with age over 65 years. This article provides an overview of burden of neurological diseases in Canada to set the stage for the in-depth systematic reviews of the 14 priority neurological conditions presented in subsequent articles in this issue.     

A database of genetically determined neurological conditions for clinicians.

Progress is reported in the establishment of a database of genetically determined neurological conditions. There are now 1,300 conditions and 3,400 references store on the hard disk of a microcomputer. The database is searched, and a differential diagnosis obtained, by choosing a small number of signs and symptoms from a comprehensive list of cardinal features.     

Sleep apnea in pediatric neurological conditions

Sleep apnea in neurologically compromised children is common but underrecognized. It can be secondary to diseases at all locations on the neuroaxis and may independently alter their presentation, severity, and course. As a primary and secondary illness, it is associated with significant neurological morbidities. In its severe manifestation, it can cause life-threatening short- and long-term systemic morbidities. The authors review the most recent and relevant literature and provide the pediatric neurologist with a framework with which to identify children at risk.     

Effect of dynamic orthoses on gait: a retrospective control study in children with hemiplegia

Several positive influences of orthoses on gait in children with cerebral palsy have been documented, as well as some detrimental effects. Most importantly, push-off is decreased in orthoses, compromising a physiological third ankle rocker. The aim of this study was to evaluate the effect of three types of orthosis on gait in a homogeneous group of children. All orthoses aimed at improving push-off and normalizing the pathological plantarflexion-knee extension couple. Thirty-seven children (22 females, 15 males) with hemiplegia, aged 4 to 10 years (30 Gross Motor Function Classification System [GMFCS] Level I, six GMFCS Level II), walked barefoot and with orthoses being either Orteams (orthoses with the dorsal part containing 11 sleeves), posterior leafsprings (PLS), or Dual Carbon Fibre Spring ankle foot orthosis (AFOs; CFO: carbon fibre at the dorsal part of the orthosis). All orthoses were expected to prevent plantarflexion and allow dorsiflexion, thus improving first, second, and third rocker. The orthoses were compared through objective gait analysis, including 3D kinematics and kinetics. All orthoses successfully improved the gait pattern and only small differences were noted between the configurations of the different orthoses. The CFO, however, allowed a more physiological third ankle rocker compared with the Orteam/PLS. Although the PLS ensured the highest correction at the ankle around initial contact, the CFO created a significantly higher maximal hip flexion moment in stance. In general, the results of this study indicated a substantial functional flexibility of the CFO.     

The misdiagnosis of functional disorders as other neurological conditions

Journal of Neurology - Several studies have shown that when patients with functional neurological disorders are followed up, it is rare to find another neurological condition that better explains...     

Rethinking the neurological examination II: dynamic balance assessment

The authors propose that the neurological exam needs reevaluation with respect to the dynamic balance test (walking). Validated tests such as: preferred and maximum gait speed, dynamic gait index, five-times-sit-to-stand test, timed up & go cognitive and manual, should be part of the neurological examination routine. In the neurological exam of older patients, these same bedside tests bring the plus of evaluation the risk of occasional falling.     

General view of orthoses

Braces and/or orthoses are one of the useful tools for treating stroke patients. Orthoses work to substitute for mechanical and/or functional impairments. This article discusses what orthoses are, what the purposes of orthoses are, how the orthoses are made, how long it takes to make the braces, and who makes them. Although braces and orthoses are heavier and tighter than usual shoes and clothing, they help patients a great deal in performing activities of daily living.     

Gold and its relationship to neurological/glandular conditions

Despite increasing sales of gold supplements, and claims of benefits for neurological and glandular conditions, gold has received little attention in modern medical literature except as a drug for rheumatoid arthritis. Historically, however, gold had a reputation as a "nervine," a therapy for nervous disorders. A review of the historical literature shows gold in use during the 19th century for conditions including depression, epilepsy, migraine, and glandular problems such as amenorrhea and impotence. The most notable use of gold was in a treatment for alcoholism developed by Keeley (1897). In the modern medical literature, gold-containing medicines for rheumatoid arthritis are known to have occasional neurotoxic adverse effects. There are also a few studies suggesting a role for gold as a naturally occurring trace element in the reproductive glands. One small recent study demonstrated a possible positive effect of gold on cognitive ability. There is a need for more experimental and clinical research of the neuropharmacology and neurochemistry of gold, and for the exploration of gold's possible role as a trace element.     

New aspects of two old neurological problems

Psychiatric Quarterly -     

New systems for delivery of drugs to the brain in neurological disease

The restricted or regulated entry of most blood-borne substances into the brain has been recognised for more than a century. The blood-brain barrier (BBB)-shielding function provided by endothelial cells is important in the treatment of neurological diseases because this exclusion of foreign substances also restricts entry of many potentially therapeutic agents into the brain. The recent identification of several neuroactive proteins of potential therapeutic value has highlighted the crucial need for effective and safe transcapillary delivery methods to the brain. One promising method is delivery through brain capillaries by augmentation of pinocytotic vesicles delivery systems that use this cellular mechanism are in development. Recent investigations in animal models show that large molecules of neurotherapeutic potential can be conjugated to peptidomimetic ligands, which bind to selected peptide receptors, and are then internalised and transported in small vesicles across the cytoplasmic brain capillary barrier. These conjugates have been shown to remain functionally active and effective in animal models of neurological disease.     

免疫抑制治疗对36例神经系统副肿瘤综合征相关抗体定量的动态影响

目的 探讨免疫抑制治疗对神经系统副肿瘤综合征(PNS)相关抗体定量的动态影响。方法 对36例神经系统副肿瘤综合征进行规范化的免疫抑制治疗(包括糖皮质激素或环磷酰胺),在治疗前及治疗开始后1周、4周、治疗后1周,结束后3月分别对患者血清抗-Hu抗体、抗-Yo抗体、 抗-Ri抗体进行定量检测(酶联免疫吸附试验,ELISA),对比治疗前后相关抗体滴度的动态变化情况。结果 血清抗-Hu抗体:治疗开始后1周抗体滴度即开始持续下降(P<0.01),但在治疗后3月,抗体滴度反弹升高,与治疗前比较没有明显差异(P>0.05)。抗-Yo抗体及抗-RI抗体在治疗开始后抗体滴度同样呈持续下降趋势,其中抗-Yo抗体治疗开始后1周下降有明显差异(P<0.01),抗-RI抗体在治疗后4周明显下降(P<0.01),但治疗结束后1周、3月抗体滴度有所上升,但与治疗前比较仍显著下降(P<0.01)。结论 免疫抑制治疗在治疗期间能够一定程度上有效抑制PNS相关抗体的滴度,但对于血清抗-Hu抗体远期抑制效果欠佳。     

Complementary and alternative medicine use among US adults with common neurological conditions

Our objective was to determine patterns, reasons for, and correlates of complementary and alternative medicine (CAM) use in US adults with common neurological conditions. We compared CAM use between adults with and without common neurological conditions (regular headaches, migraines, back pain with sciatica, strokes, dementia, seizures, or memory loss) using the 2007 National Health Interview Survey of 23,393 sampled US adults. Adults with common neurological conditions used CAM more frequently than those without (44.1 vs. 32.6%, p < 0.0001); differences persisted after adjustment. For each CAM modality, adults with common neurological conditions were more likely to use CAM than those without these conditions. Nearly half of adults with back pain with sciatica, memory loss, and migraines reported use of CAM. Mind/body therapies were used the most; alternative medical systems were used the least. Over 50% of adults with common neurological conditions who used CAM had not discussed their use with their health care provider. Those with neurological conditions used CAM more often than those without because of provider recommendation, or because conventional treatments were perceived ineffective or too costly. Significant correlates of CAM use among adults with common neurological conditions include higher than high school education, anxiety in the prior year, living in the west, being a former smoker, and light alcohol use. CAM is used more frequently among adults with common neurological conditions than those without. More research on the efficacy of CAM use for common neurological conditions is warranted.     

CSF hypocretin/orexin levels in narcolepsy and other neurological conditions.

OBJECTIVE: To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders. METHODS: A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years). RESULTS: As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS. CONCLUSIONS: Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.