Changing Trends in Life Expectancy in Intellectual Disability over Time

Decreased life expectancy (LE) has historically been found among people with intellectual disability (ID) compared to the general population. Several recent studies have looked into ageing and cause of death in ID. Results of many of these studies suggest that, although LE in ID remains lower than the general population, it has increased across many Western societies in recent decades. Increases in LE in the general and ID populations appear to follow similar trends. Some major causes of mortality in ID are similar to the general population, and therefore may be amenable to similar preventative healthcare interventions. In this article, we have outlined possible reasons for improved LE in ID, and potential areas that may require further intervention. However, more detailed studies on mortality in ID may provide more accurate insight into areas requiring intervention in ID populations.

Per-protocol investigation of a best practice exercise referral scheme.

OBJECTIVES: To investigate the effects of an exercise referral scheme (ERS) aligned to the UK best practice guidelines on a range of outcomes including those associated with key health concerns of the Scottish population. STUDY DESIGN: A longitudinal design with data collection at three time points (baseline, midway and post) during a 12-week ERS intervention was employed. METHODS: Health-related physical fitness was assessed through measurement of resting heart rate, blood pressure, FEV1:FEV6 (ratio of forced expiratory volume over one [FEV1] and six [FEV6] seconds), body mass and peak oxygen uptake (VO2 peak), whilst functional capacity was assessed through the five times sit to stand test. Psychosocial well-being and quality of life were measured using the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and the Profile of Mood State questionnaires. Growth curve analyses were used to model each outcome variable across the three time periods. RESULTS: A range of effects were obtained with significant linear improvements in physical performance tests (P < 0.001) and psychosocial assessments (P ≤ 0.002). Additionally, significant quadratic effects of time were obtained for body composition variables and physical activity levels (P < 0.001) with the greatest improvements obtained between baseline and midway assessments. CONCLUSIONS: An ERS aligned to the UK best practice guidelines can positively influence a range of health outcomes including those associated with lung function and cardiovascular fitness which are prevalent medical conditions in Scotland. In addition, results indicate that ERS can positively affect outcomes related to functional capacity as well as mental well-being and perceptions of health. The findings of the study identify the need for further investigation including consideration of the initial health status of referred clients.

Falls and fractures 2 years after acute stroke: the North Dublin Population Stroke Study.

BACKGROUND: Stroke patients are at increased risk of falls and fractures. The aim of this study was to determine the rate, predictors and consequences of falls within 2 years after stroke in a prospective population-based study in North Dublin, Ireland. DESIGN: Prospective population-based cohort study. SUBJECTS: 567 adults aged >18 years from the North Dublin Population Stroke Study. METHODS: Participants were enrolled from an Irish urban population of 294,592 individuals, according to recommended criteria. Patients were followed for 2 years. Outcome measures included death, modified Rankin Scale (mRS), fall and fracture rate. RESULTS: At 2 years, 23.5% (124/522) had fallen at least once since their stroke, 14.2% (74/522) had 2 or more falls and 5.4% (28/522) had a fracture. Of 332 survivors at 2 years, 107 (32.2%) had fallen, of whom 60.7% (65/107) had 2 or more falls and 23.4% (25/107) had fractured. In a multivariable model controlling for age and gender, independent risk factors for falling within the first 2 years of stroke included use of alpha-blocker medications for treatment of hypertension (P = 0.02). When mobility measured at Day 90 was included in the model, patients who were mobility impaired (mRS 2-3) were at the highest risk of falling within 2 years of stroke [odds ratio (OR) 2.30, P = 0.003] and those functionally dependent (mRS 4-5) displayed intermediate risk (OR 2.02, P = 0.03) when compared with independently mobile patients. CONCLUSION: Greater attention to falls risk, fall prevention strategies and bone health in the stroke population are required.

Endovascular treatment for acute ischaemic stroke with large vessel occlusion: the experience of a regional stroke service.

AIM: To report the experience of a regional stroke referral service with endovascular treatment for patients with acute ischaemic stroke (AIS) and large vessel occlusion. MATERIALS AND METHODS: A prospective review was undertaken of 93 consecutive cases receiving endovascular treatment for AIS over a 42-month period (January 2010 to June 2013). The National Institutes of Health Stroke Scale (NIHSS), location of large vessel occlusion, details of endovascular procedure, and degree of reperfusion achieved (Thrombolysis In Cerebral Infarction [TICI] score) were recorded. Mortality and functional outcome (modified Rankin Scale [mRS]) were measured at 90 days. RESULTS: The mean patient age was 62 years (range 26-87 years). The mean NIHSS at presentation was 16 (range 6-29). All patients had confirmed proximal large-artery occlusion on computed tomography (CT) angiography: 87 in the anterior circulation, six in the posterior circulation. Of the 93 patients treated, 64 (69%) received intravenous thrombolysis. Successful reperfusion (TICI grade 2a to 3) was achieved in 80 (86%) cases. There were 13 (14%) cases of failed vessel recanalisation (TICI grade 0). Good functional outcome (mRS ≤2) was achieved in 51 (55%) cases. The 90-day mortality was 20 (22%) cases. Fifty-seven (61%) cases were transferred from outside centres. There was no significant increase in morbidity or mortality for transferred patients. CONCLUSION: Successful endovascular recanalisation can result in good functional outcomes for patients with AIS and large vessel occlusion. Our interventional neuroradiology service provides endovascular treatment as part of a regional stroke service without increase in morbidity or mortality for patients transferred from outside institutions.

Inflammatory cytokines, high-sensitivity C-reactive protein, and risk of one-year vascular events, death, and poor functional outcome after stroke and transient ischemic attack.

BACKGROUND: Inflammation driven by pro-inflammatory cytokines is a new therapeutic target in coronary disease. Few data exist on the association of key upstream cytokines and post-stroke recurrence. In a prospective cohort study, we investigated the association between pivotal cytokines, high-sensitivity C-reactive protein (hsCRP) and one-year outcomes. METHODS: BIO-STROKETIA is a multi-center prospective cohort study of non-severe ischemic stroke (modified Rankin score ≤ 3) and transient ischemic attack. Controls were patients with transient symptoms attending transient ischemic attack clinics with non-ischemic final diagnosis. Exclusion criteria were severe stroke, infection, and other pro-inflammatory disease; hsCRP and cytokines (interleukin (IL) 6, IL-1ß, IL-8, IL-10, IL-12, interferon-γ (IFN-γ), tumor-necrosis factor-α (TNF-α)) were measured. The primary outcome was one-year recurrent stroke/coronary events (fatal and non-fatal). RESULTS: In this study, 680 patients (439 stroke, 241 transient ischemic attack) and 68 controls were included. IL-6, IL-1ß, IL-8, IFN-γ, TNF-α, and hsCRP were higher in stroke/transient ischemic attack cases (p ≤ 0.01 for all). On multivariable Cox regression, IL-6, IL-8, and hsCRP independently predicted one-year recurrent vascular events (adjusted hazard ratios (aHR) per-quartile increase IL-6 1.31, confidence interval (CI) 1.02-1.68, p = 0.03; IL-8 1.47, CI 1.15-1.89, p = 0.002; hsCRP 1.28, CI 1.01-1.62, p = 0.04). IL-6 (aHR 1.98, CI 1.26-3.14, p = 0.003) and hsCRP (aHR 1.81, CI 1.20-2.74, p = 0.005) independently predicted one-year fatality. IL-6 and hsCRP (adjusted odds ratio per-unit increase 1.02, CI 1.01-1.04) predicted poor functional outcome, with a trend for IL-1ß (p = 0.054). CONCLUSION: Baseline inflammatory cytokines independently predicted late recurrence, supporting a rationale for randomized trials of anti-inflammatory agents for prevention after stroke and suggesting that targeted therapy to high-risk patients with high baseline inflammation may be beneficial.

The influence of acute exercise on bone biomarkers: protocol for a systematic review with meta-analysis.

BACKGROUND: Bone is a plastic tissue that is responsive to its physical environment. As a result, exercise interventions represent a potential means to influence the bone. However, little is currently known about how various exercise and participant characteristics interact to influence bone metabolism. Acute, controlled, interventions provide an in vivo model through which the acute bone response to exercise can be investigated, typically by monitoring circulating bone biomarkers. Currently, substantial heterogeneity in factors such as study design, quality, exercise, and participant characteristics render it difficult to synthesize and evaluate the available evidence. Using a systematic review and meta-analytic approach, the aim of this investigation is to quantify the effect of an acute exercise bout on circulating bone biomarkers as well as examine the potential factors that may moderate this response, e.g., variation in participant, exercise, and sampling characteristics. METHODS: This protocol was designed in accordance with the PRISMA-P guidelines. Seven databases (MEDLINE, Embase, Sport Discus, Cochrane CENTRAL, PEDro, LILACS, and Ibec) will be systematically searched and supplemented by a secondary screening of the reference lists of all included articles. The PICOS (Population, Intervention, Comparator, Outcomes and Study Design) approach was used to guide the determination of the eligibility criteria. Participants of any age, sex, training, or health status will be considered for inclusion. We will select studies that have measured the bone biomarker response before and after an acute exercise session. All biomarkers considered to represent the bone metabolism will be considered for inclusion, and sensitivity analyses will be conducted using reference biomarkers for the measurement of bone resorption and formation (namely ß-CTX-1 and P1NP). Multi-level, meta-regression models within a Bayesian framework will be used to explore the main effect of acute exercise on bone biomarkers as well as potential moderating factors. The risk of bias for each individual study will be evaluated using a modified version of the Downs and Black checklist while certainty in resultant outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: A better understanding of the bone metabolic response to an acute bout of exercise has the potential to advance our understanding of the mechanisms through which this stimulus impacts bone metabolism, including factors that may moderate this response. Additionally, we will identify current gaps in the evidence base and provide recommendations to inform future research. SYSTEMATIC REVIEW REGISTRATION: This protocol was prospectively registered in the Open Science Framework Registry ( https://osf.io/6f8dz ).

An actuatable soft reservoir modulates host foreign body response.

The performance of indwelling medical devices that depend on an interface with soft tissue is plagued by complex, unpredictable foreign body responses. Such devices-including breast implants, biosensors, and drug delivery devices-are often subject to a collection of biological host responses, including fibrosis, which can impair device functionality. This work describes a milliscale dynamic soft reservoir (DSR) that actively modulates the biomechanics of the biotic-abiotic interface by altering strain, fluid flow, and cellular activity in the peri-implant tissue. We performed cyclical actuation of the DSR in a preclinical rodent model. Evaluation of the resulting host response showed a significant reduction in fibrous capsule thickness (P = 0.0005) in the actuated DSR compared with non-actuated controls, whereas the collagen density and orientation were not changed. We also show a significant reduction in myofibroblasts (P = 0.0036) in the actuated group and propose that actuation-mediated strain reduces differentiation and proliferation of myofibroblasts and therefore extracellular matrix production. Computational models quantified the effect of actuation on the reservoir and surrounding fluid. By adding a porous membrane and a therapy reservoir to the DSR, we demonstrate that, with actuation, we could (i) increase transport of a therapy analog and (ii) enhance pharmacokinetics and time to functional effect of an inotropic agent. The dynamic reservoirs presented here may act as a versatile tool to further understand, and ultimately to ameliorate, the host response to implantable biomaterials.

A Comparative Study of Hummingbirds and Chickens Provides Mechanistic Insight on the Histidine Containing Dipeptide Role in Skeletal Muscle Metabolism.

Histidine containing dipeptides (HCDs) have numerous ergogenic and therapeutic properties, but their primary role in skeletal muscle remains unclear. Potential functions include pH regulation, protection against reactive oxygen/nitrogen species, or Ca2+ regulation. In recognition of the challenge of isolating physiological processes in-vivo, we employed a comparative physiology approach to investigate the primary mechanism of HCD action in skeletal muscle. We selected two avian species (i.e., hummingbirds and chickens), who represented the extremes of the physiological processes in which HCDs are likely to function. Our findings indicate that HCDs are non-essential to the development of highly oxidative and contractile muscle, given their very low content in hummingbird skeletal tissue. In contrast, their abundance in the glycolytic chicken muscle, indicate that they are important in anaerobic bioenergetics as pH regulators. This evidence provides new insights on the HCD role in skeletal muscle, which could inform widespread interventions, from health to elite performance.

Nitrate-rich beetroot juice selectively lowers ambulatory pressures and LDL cholesterol in uncontrolled but not controlled hypertension: a pilot study.

BACKGROUND: Dietary nitrate has been shown to increase nitrate/nitrite levels in multiple populations, with potential blood pressure lowering effects. However, there are few reports among hypertensives. AIMS: We aimed to assess the effect of daily nitrate in subjects with controlled hypertension vs. uncontrolled hypertension. METHODS: On day 0, hypertensives wore an ambulatory BP monitor (ABPM) for 24 h and fasting blood was taken. Subjects then consumed concentrated beetroot juice (12.9 mmol nitrate) for 14 consecutive days. On day 14 subjects consumed their last nitrate dose after fasting blood was drawn and again had an ABPM for 24 h. RESULTS: According to baseline ABPM, 11 subjects had controlled BP while 8 had uncontrolled BP. There were similar, significant increases in serum nitrate/nitrite in both groups. We observed little change in BP variables among controlled hypertensives. However, there were reductions in BP variables in uncontrolled hypertensives where decreases in nighttime DBP (-6 ± 4.8 mmHg), arterial stiffness (-0.08 ± 0.03 ambulatory arterial stiffness index) and LDL (-0.36 ± 0.42 mmol/L) reached significance (p = 003, 0.05 and 0.046, respectively). CONCLUSIONS: Our results support the existing data suggesting an anti-hypertensive effect of nitrate-containing beetroot juice, but only among those with uncontrolled hypertension.

Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9-aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N-nitrosourea, and busulfan, but they were sensitive to the other agents. Both D-245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA alkyltransferase activity, and their levels of glutathione and glutathione-S-transferase were similar. D-245 MG xenografts expressed the human mismatch repair proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.

Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: recommendations for saturation divers.

Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised.

Colleagues as Change Agents: How Department Networks and Opinion Leaders Influence Teaching at a Single Research University.

Relationships with colleagues have the potential to be a source of support for faculty to make meaningful change in how they teach, but the impact of these relationships is poorly understood. We used a mixed-methods approach to investigate the characteristics of faculty who provide colleagues with teaching resources and facilitate change in teaching, how faculty influence one another. Our exploratory investigation was informed by social network theory and research on the impact of opinion leaders within organizations. We used surveys and interviews to examine collegial interactions about undergraduate teaching in life sciences departments at one research university. Each department included discipline-based education researchers (DBERs). Quantitative and qualitative analyses indicate that DBERs promote changes in teaching to a greater degree than other departmental colleagues. The influence of DBERs derives, at least partly, from a perception that they have unique professional expertise in education. DBERs facilitated change through coteaching, offering ready and approachable access to education research, and providing teaching training and mentoring. Faculty who had participated in a team based-teaching professional development program were also credited with providing more support for teaching than nonparticipants. Further research will be necessary to determine whether these results generalize beyond the studied institution.

Flash-induced charge separation and dark recombination in a photosystem-II subchloroplast particle.

The decay time of flash-induced absorption changes in a Photosystem-II subchloroplast fragment is very temperature sensitive down to 210 K, below which it remains constant at 1.25 +/- 0.05 ms. The difference spectrum from the near-infra-red to the ultraviolet regions indicates that the monophasic decay represents charge recombination between P-680+ and the reduced primary acceptor. The charge recombination proceeds by electron tunneling. The P-680 concentration in the TSF-IIa fragment was estimated to be one in 30 +/- 5 total chlorophyll molecules.

Energy transfer from phycobiliproteins to photosystem I in vegetative cells and heterocysts of Anabaena variabilis.

The presence of phycobilins in heterocysts of Anabaena variabilis is established on the basis of absorption and fluorescence spectroscopy. At 77 K heterocysts exhibit fluorescence emission bands at 645 and 661 nm indicative of phycocyanin and allophycocyanin, respectively. Both allophycocyanin levels and fluorescence emission at 695 nm were low in heterocysts relative to whole filaments. In situ fluorescence microscopy confirmed the presence of phycobilins in individual heterocysts, but the pigment levels varied considerably among cells. Heterocysts exhibited Photosystem I activity, as evidenced by photooxidation of P-700, but no Photosystem II activity. The quantum efficiency of phycobilins in sensitizing P-700 photooxidation was 50-70% that of chlorophyll a. Phycoibins were also effective in promoting light-dependent reduction of acetylene to ethylene. The results are discussed in terms of the role of the heterocyst in nitrogen fixation and of the significance of energy transfer from phycobilins to Photosystem I in heterocysts.

Short-term blood pressure variability over 24 h and target organ damage in middle-aged men and women.

Blood pressure variability (BPV) has been associated with cardiovascular events; however, the prognostic significance of short-term BPV remains uncertain. As uncertainty also remains as to which measure of variability most accurately describes short-term BPV, this study explores different indices and investigates their relationship with subclinical target organ damage (TOD). We used data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47-73 years (n=2047). A subsample (1207) underwent 24-h ambulatory BP monitoring (ABPM). As measures of short-term BPV, we estimated the s.d., weighted s.d. (wSD), coefficient of variation (CV) and average real variability (ARV). TOD was documented by microalbuminuria and electrocardiogram (ECG) left ventricular hypertrophy (LVH). There was no association found between any measure of BPV and LVH in both unadjusted and fully adjusted logistic regression models. Similar analysis found that ARV (24 h, day and night), s.d. (day and night) and wSD were all univariately associated with microalbuminuria and remained associated after adjustment for age, gender, smoking, body mass index (BMI), diabetes and antihypertensive treatment. However, when the models were further adjusted for the mean BP the association did not persist for all indices. Our findings illustrate choosing the appropriate summary measure, which accurately captures that short-term BPV is difficult. Despite discrepancies in values between the different measures, there was no association between any indexes of variability with TOD measures after adjustment for the mean BP.

Mechanical stimulation of bone marrow in situ induces bone formation in trabecular explants.

Low magnitude high frequency (LMHF) loading has been shown to have an anabolic effect on trabecular bone in vivo. However, the precise mechanical signal imposed on the bone marrow cells by LMHF loading, which induces a cellular response, remains unclear. This study investigates the influence of LMHF loading, applied using a custom designed bioreactor, on bone adaptation in an explanted trabecular bone model, which isolated the bone and marrow. Bone adaptation was investigated by performing micro CT scans pre and post experimental LMHF loading, using image registration techniques. Computational fluids dynamic models were generated using the pre-experiment scans to characterise the mechanical stimuli imposed by the loading regime prior to adaptation. Results here demonstrate a significant increase in bone formation in the LMHF loaded group compared to static controls and media flow groups. The calculated shear stress in the marrow was between 0.575 and 0.7 Pa, which is within the range of stimuli known to induce osteogenesis by bone marrow mesenchymal stem cells in vitro. Interestingly, a correlation was found between the bone formation balance (bone formation/resorption), trabecular number, trabecular spacing, mineral resorption rate, bone resorption rate and mean shear stresses. The results of this study suggest that the magnitude of the shear stresses generated due to LMHF loading in the explanted bone cores has a contributory role in the formation of trabecular bone and improvement in bone architecture parameters.

Genetic transmission of tumoral calcinosis: autosomal dominant with variable clinical expressivity.

Tumoral calcinosis is a rare inherited metabolic disorder characterized by hyperphosphatemia, elevated serum 1,25-dihydroxyvitamin D levels and periarticular cystic and solid calcifications. Based on previous investigations, the inheritance of this disorder has been postulated to be autosomal recessive. This interpretation was based on finding clinically affected subjects in only single generations of kindreds. We investigated four generations of an affected kindred and found nine subjects with the disease. A unique dental lesion which is specific for this disorder and serves as a phenotypic marker was identified in two generations of the kindred. In all affected subjects, elevated serum 1,25-dihydroxyvitamin D levels were found, although each member did not have the classical clinical findings of tumoral calcinosis. The possibility that this disorder may be variably expressed and have multiple formes frustes has not been previously considered. Using the unique dental lesion as well as the classical clinical and biochemical abnormalities, we found that in this kindred, tumoral calcinosis is transmitted in an autosomal dominant mode, with variable clinical expressivity.

Influence of lovastatin on concentrations and composition of lipoprotein subfractions.

The effects of lovastatin therapy on concentrations and compositions of lipoproteins were examined in 14 patients with heterozygous familial hypercholesterolemia. The drug lowered plasma levels of cholesterol in total plasma, very low density + intermediate density lipoproteins (VLDL + IDL) and low density lipoproteins (LDL) by 25%, 41%, and 41%, respectively. Plasma total apo B was decreased by 35%. Three VLDL subfractions--VLDL-1, VLDL-2, and VLDL-3--of progressively higher density were examined. Lovastatin therapy reduced only the heaviest--VLDL-3. Concentrations of VLDL-1 and VLDL-2 were unchanged. Total VLDL-cholesterol/apo B was reduced significantly. Drug therapy also altered the composition of LDL as shown by decreasing the cholesterol/apo B. Finally, lovastatin significantly raised HDL-cholesterol concentrations. This study showed that lovastatin modifies the composition of the major apo B-containing lipoproteins as well as reducing their concentrations.

Sideways dislocation of the temporomandibular joint meniscus: the edge sign.

Seventy temporomandibular joint arthrograms of 49 patients with symptoms of internal joint derangement were reviewed. Twenty-three of these arthrograms (33%) were abnormal but atypical for anteriorly dislocated meniscus. The lower temporomandibular joint space had a well-defined edge located inferiorly, which was attributed to pressure from a sideways-dislocated meniscus. We called this appearance the "edge sign." Seven patients with radiologically apparent sideways dislocation were operated on. The meniscus was dislocated laterally in six and medially in one. The incidence of irreducibility and perforation was higher in sideways-dislocated than in anteriorly dislocated menisci.

Cerebrospinal fluid fistula secondary to ecchordosis physaliphora.

A patient with a large ecchordosis physaliphora extending from the sphenoid sinus into the subarachnoid space of the prepontine cistern and resulting in a cerebrospinal fluid fistula is described. Ecchordoses are most commonly asymptomatic and found only incidently at autopsy. This case report adds to the scant literature on symptomatic ecchordoses. The previously reported cases of symptomatic ecchordoses and intradural chordomas are briefly reviewed. Differentiation of chordoma and symptomatic ecchordosis may be difficult; however, the intradural location and relatively benign behavior of the latter are useful points. A discussion concerning the remnants of the notochord which persist in the adult and their role in the genesis of chordoma and ecchordosis physaliphora is also provided.