304 research outputs found
The development of a questionnaire to assess the attitudes of older people to end-of-life issues (AEOLI)
Objectives: To develop an end-of-life attitudes questionnaire for use in a large community-based sample of older people. Design: Nominal groups and standardization of questions. Participants: Eighteen older people, ten academics and five specialist palliative care health professionals were involved in nominal groups. Thirty older people took part in initial pilot work and a further 50 were involved in reliability testing. Results: A 27-item attitudes of older people to end-of-life issues (AEOLI) questionnaire. Discussion: In modern times, death and dying predominantly occurs among older people and yet we know very little about older people's attitudes to end-of-life care. The AEOLI questionnaire can be used in large scale surveys to elicit attitudes on end-of life issues considered important by older people and health care professionals
Psychiatric manifestations of coeliac disease, a systematic review and meta-analysis
Background: Coeliac disease (CD) is increasingly prevalent and is associated with both gastrointestinal (GI) and extra-intestinal manifestations. Psychiatric disorders are amongst extra-intestinal manifestations proposed. The relationship between CD and such psychiatric disorders is not well recognised or understood. Aim: The aim of this systematic review and meta-analysis was to provide a greater understanding of the existing evidence and theories surrounding psychiatric manifestations of CD. Methodology: An online literature search using PubMed was conducted, the prevalence data for both CD and psychiatric disorders was extracted from eligible articles. Meta analyses on odds ratios were also performed. Results: A total of 37 articles were included in this review. A significant increase in risk was detected for autistic spectrum disorder (OR 1.53, 95% CI 1.24–1.88, p < 0.0001), attention deficit hyperactivity disorder (OR 1.39, 95% CI 1.18–1.63, p < 0.0001), depression (OR 2.17, 95% CI 2.17–11.15, p < 0.0001), anxiety (OR 6.03, 95% CI 2.22–16.35, p < 0.0001), and eating disorders (OR 1.62, 95% CI 1.37–1.91, p < 0.00001) amongst the CD population compared to healthy controls. No significant differences were found for bipolar disorder (OR 2.35, 95% CI 2.29–19.21, p = 0.43) or schizophrenia (OR 0.46, 95% CI 0.02–10.18, p = 0.62). Conclusion: CD is associated with an increased risk of depression, anxiety, eating disorders as well as ASD and ADHD. More research is required to investigate specific biological explanations as well as any effect of gluten free diet
Cerebellar ataxia with sensory ganglionopathy; does autoimmunity have a role to play?
Background and purpose: Cerebellar ataxia with sensory ganglionopathy (SG) is a disabling combination of neurological dysfunction usually seen as part of some hereditary ataxias. However, patients may present with this combination without a genetic cause. Methods: We reviewed records of all patients that have been referred to the Sheffield Ataxia Centre who had neurophysiological and imaging data suggestive of SG and cerebellar ataxia respectively. We excluded patients with Friedreich's ataxia, a common cause of this combination. All patients were screened for genetic causes and underwent extensive investigations. Results: We identified 40 patients (45% males, mean age at symptom onset 53.7 ± 14.7 years) with combined cerebellar ataxia and SG. The majority of patients (40%) were initially diagnosed with cerebellar dysfunction and 30% were initially diagnosed with SG. For 30% the two diagnoses were made at the same time. The mean latency between the two diagnoses was 6.5 ± 8.9 years (range 0-44). The commonest initial manifestation was unsteadiness (77.5%) followed by patchy sensory loss (17.5%) and peripheral neuropathic pain (5%).Nineteen patients (47.5%) had gluten sensitivity, of whom 3 patients (7.5%) had biopsy proven coeliac disease. Other abnormal immunological tests were present in another 15 patients. Six patients had malignancy, which was diagnosed within 5 years of the neurological symptoms. Only 3 patients (7.5%) were classified as having a truly idiopathic combination of cerebellar ataxia with SG. Conclusion: Our case series highlights that amongst patients with the unusual combination of cerebellar ataxia and SG, immune pathogenesis plays a significant role
Headache associated with coeliac disease: a systematic review and meta-analysis
OBJECTIVE: The aim of this systematic review was to explore the relationship between coeliac disease (CD) and headache. The objectives were to establish the prevalence of each entity amongst the other, to explore the role of gluten free diet (GFD), and to describe the imaging findings in those affected by headaches associated with CD. METHODOLOGY: A systematic computer-based literature search was conducted on the PubMed database. Information regarding study type, population size, the age group included, prevalence of CD amongst those with headache and vice versa, imaging results, the nature of headache, and response to GFD. RESULTS: In total, 40 articles published between 1987 and 2017 qualified for inclusion in this review. The mean pooled prevalence of headache amongst those with CD was 26% (95% CI 19.5⁻33.9%) in adult populations and 18.3% (95% CI 10.4⁻30.2%) in paediatric populations. The headaches are most often migraine-like. In children with idiopathic headache, the prevalence of CD is 2.4% (95% CI 1.5⁻3.7%), whereas data for adult populations is presently unavailable. Brain imaging can be normal, although, cerebral calcifications on CT, white matter abnormalities on MRI and deranged regional cerebral blood flow on SPECT can be present. GFD appears to be an effective management for headache in the context of CD, leading to total resolution of headaches in up to 75% of patients. CONCLUSIONS: There is an increased prevalence of CD amongst idiopathic headache and vice versa. Therefore, patients with headache of unknown origin should be screened for CD, as such patients may symptomatically benefit from a GFD
Safety, tolerability, and nocebo phenomena during transcranial magnetic stimulation: a systematic review and meta‐analysis of placebo‐controlled clinical trials
Background
The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta‐analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied.
Methods
After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups.
Results
Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%‐3.2%) and 2.7% (95% CI 2.0%‐3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%‐22.6%) and 13.6% (95% CI 11.6%‐15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75‐3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness.
Secondary meta‐analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14‐7.40) and 2.93 times higher (95% CI 1.41‐6.07), respectively, in the active treatment groups compared to placebo.
Conclusions
TMS is a safe and well‐tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice
Psychogenic non-epileptic seizures (PNES) in the context of concurrent epilepsy – making the right diagnosis
Epilepsy is a risk factor for the development of psychogenic non-epileptic seizures (PNES) and comorbid epilepsy is recognized as a comorbidity in about 10–30% of patients with PNES. The combination of epileptic and nonepileptic seizures poses a particular diagnostic challenge. In patients with epilepsy, additional PNES may be suspected on the basis of their typical semiology. The possibility of additional PNES should also be considered if seizures fail to respond to antiepileptic drug treatment, in patients with frequent emergency admissions with seizures and in those who develop new types of seizures. The description of semiological details by patients and witnesses can suggest additional PNES. Home video recordings can support an initial diagnosis, however, especially in patients with mixed seizure disorders it is advisable to seek further diagnostic confirmation by capturing all habitual seizure types with video-EEG. The clinical features of PNES associated with epilepsy are similar to those in isolated PNES disorders and include longer duration, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movement, persistently closed eyes and mouth, ictal crying, recall of ictal experiences and absence of postictal confusion. PNES can also present as syncope-like episodes with unresponsiveness and reduced muscle tone. There is no unique epileptological or brain pathology profile putting patients with epilepsy at risk of additional PNES. However, patients with epilepsy and PNES typically have lower educational achievements and higher levels of psychiatric comorbidities than patients with epilepsy alone. Psychological trauma, including sexual abuse, appears to be a less relevant aetiological factor in patients with mixed seizure disorders than those with isolated PNES, and the gender imbalance (i.e. the greater prevalence in women) is less marked in patients with PNES and additional epilepsy than those with PNES alone. PNES sometimes develop after epilepsy surgery. A diagnosis of ‘known epilepsy’ should never be accepted without (at least brief) critical review. This narrative review summarises clinical, electrophysiological and historical features that can help identify patients with epilepsy and additional PNES
Oxidative Stress and Memory Decline in Adults with Down Syndrome: Longitudinal Study
By the age of 40, virtually all patients with Down syndrome (DS) have neuropathological changes characteristic of Alzheimer's disease (AD). The aim of our study was to investigate whether the levels of superoxide dismutase enzymes (SOD), glutathione peroxidase (GPx), or their ratio could predict cognitive decline in people with DS over a 4-year period. Thirty-two adults with DS participated in a longitudinal study with SOD and GPx assays at baseline. Informants rated their functional ability and memory function at baseline and at 4 years follow-up. The more able adults with DS also completed assessments of language skills and memory, at two different time points 4 years apart. Twenty-six individuals with DS completed assessments of memory (Modified Memory Object Task, MOMT), adaptive behavior (ABAS), and receptive vocabulary (British Picture vocabulary, BPVS) at both time-points. SOD positively correlated with change on the MOMT score (r = 0.578, p = 0.015). There were no significant correlations between GPx level or SOD/GPx ratio and temporal changes in ABAS, BPVS, or MOMT scores. Our results suggest that SOD predicts memory decline over time and that these antioxidant enzymes could be a potential target for prevention of memory deterioration in adults with DS. Further research is required to test whether supplements which improve SOD function can also prevent cognitive decline. These findings may also have implications for prevention of cognitive decline in other groups which are at high risk of developing dementia, such as adults with familial AD or mild cognitive impairment
Chronic idiopathic axonal polyneuropathy: Prevalence of pain and impact on quality of life
BACKGROUND AND AIM: Chronic idiopathic axonal polyneuropathy (CIAP) is a term describing axonal neuropathies of insidious onset, with slow or no progression of the disease over at least 6 months and with no etiology being identified despite appropriate investigations. We aimed to establish the prevalence of pain in patients with CIAP and investigate the impact of pain on quality of life (QoL). METHODS: All consecutive patients with CIAP attending a specialist neuropathy clinic were invited to participate. Pain was assessed via the DN4 questionnaire and the visual analogue scale (VAS). Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The SF-36 questionnaire was used to measure participants' quality of life. RESULTS: Fifty-five patients with CIAP were recruited (63.6% male, mean age 73.4 ± 8.7 years). Based on the DN4 questionnaire, peripheral neuropathic pain was present in 33 patients (60.0%). After having adjusted for age, gender and disease severity pain showed significant negative correlations with the energy/fatigue domain of QoL (β = -0.259, p = 0.049), with the emotional well-being domain (β = -0.368, p = 0.007) and the general health perception domain (β = -0.356, p = 0.007). CONCLUSION: Pain is very prevalent in CIAP and is associated with poorer emotional well-being, worse general health perception, and increased fatigue
Stiff person syndrome and gluten sensitivity
Stiff person syndrome (SPS) is a rare autoimmune disease characterised by axial stiffness and episodic painful spasms. It is associated with additional autoimmune diseases and cerebellar ataxia. Most patients with SPS have high levels of glutamic acid decarboxylase (GAD) antibodies. The aetiology of SPS remains unclear but autoimmunity is thought to play a major part. We have previously demonstrated overlap between anti-GAD ataxia and gluten sensitivity. We have also demonstrated the beneficial effect of a gluten-free diet (GFD) in patients with anti-GAD ataxia. Here, we describe our experience in the management of 20 patients with SPS. The mean age at symptom onset was 52 years. Additional autoimmune diseases were seen in 15/20. Nineteen of the 20 patients had serological evidence of gluten sensitivity and 6 had coeliac disease. Fourteen of the 15 patients who had brain imaging had evidence of cerebellar involvement. Twelve patients improved on GFD and in seven GFD alone was the only treatment required long term. Twelve patients had immunosuppression but only three remained on such medication. Gluten sensitivity plays an important part in the pathogenesis of SPS and GFD is an effective therapeutic intervention
Ionic lanthanum passage across cerebral endothelium exposed to hyperosmotic arabinose
Hyperosmotic media infused into the cerebral circulation open the blood-brain barrier to protein and colloid. The mechanism whereby such substances cross the affected vessels is still disputed. We describe here the transendothelial route taken by ionic lanthanum (La 3+ ), a small electron-dense tracer which, unlike colloidal lanthanum, can be administered to the living animal. In adult rats, 2.9 ml of hyperosmotic (1.4 M) arabinose was infused into the internal carotid artery as a 30-s bolus, followed by 5 mM LaCl 3 . To find the extravasated La 3+ , which is invisible by light microscopy, horseradish peroxidase (HRP) was injected simultaneously into the femoral vein. The hyperosmotic treatment resulted in exudation of both HRP and La 3+ primarily around cerebral arterioles. The La 3+ crossed arterioles through successive tight junctions between endothelial cells. Although the tight junctions were not discernibly opened, they must have become permeable because the extracellular pools between successive tight junctions were penetrated by the La 3+ . These pools are normally inaccessible to La 3+ . Luminal and abluminal pits and cytoplasmic vesicles, some of them containing La 3+ , formed intraendothelial clusters. Their role, if any, in the transfer of ion remains remains uncertain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47227/1/401_2004_Article_BF00685347.pd
- …