The trial of David Ferrier, November 1881: Context, proceedings, and aftermath.

In November 1881, the eminent physiologist and physician David Ferrier was prosecuted under the Cruelty to Animals Act 1876. The prosecution was raised by the Victoria Street Society, formerly known as the Society for the Protection of Animals Liable to Vivisection, through its activist founder, Frances Power Cobbe. This article examines the legislative context prior to Ferrier's trial, the personalities involved in the prosecution, and its course and outcome. The resultant impact, both personal, on Cobbe and Ferrier, and professional, on experimental neurophysiology, is discussed, in particular the foundation of the Association for the Advancement of Medicine by Research (AAMR) and the provision of legal support for medical practitioners subject to litigation.

The advent of epilepsy directed neurosurgery: The early pioneers and who was first.

Efforts to treat epileptic seizures likely date back to primitive, manmade skull openings or trephinations at the site of previous scalp or skull injuries. The purpose may have been the release of "evil spirits," removal of "cerebral excitement," and "restoral of bodily and intellectual functions." With progressive discoveries in brain function over the past 100 to 300 years, the cerebral cortical locations enabling voluntary movements, sensation, and speech have been well delineated. The locations of these functions have become surgical targets for the amelioration of disease processes. Disease entities in particular cerebral-cortical areas may predispose to the onset of focal and or generalized seizures, which secondarily interfere with normal cortical functioning. Modern neuroimaging and electroencephalography usually delineate the location of seizures and often the type of structural pathology. If noneloquent brain regions are involved, open surgical biopsy or removal of only abnormal tissue may be undertaken successfully. A number of the early neurosurgical pioneers in the development of epilepsy surgery are credited and discussed in this article.

Religion, spirituality, and epilepsy.

This review provides responses to four questions on epilepsy, religion, and spirituality. Firstly, have early religious beliefs and writings stigmatized and discriminated against epilepsy and if so, what has been done to correct this? We provide textual evidence suggesting an affirmative response. Secondly, which religious luminaries, gods, saints, and religious symbols have connections with epilepsy? We argue that the evidence to suggest that St Paul, Joan of Arc, the Prophet Mohammed, and others had epilepsy is weak and emphasizes the limitations of imposing contemporary neurological frameworks upon them. Furthermore, we discuss how different faith traditions identify Divine figures, as associated with epilepsy, and the use of religious symbols in healing. Thirdly, why is religiosity associated with having epilepsy? We review empirical studies focusing upon the epileptic personality, religiosity, mysticism, and religious conversion and find that, while some studies suggest that religious experience may be associated with epilepsy, this cannot be taken as proven. Fourthly, in what ways has religion been a force for good for those with epilepsy? We discuss the role of Christian social reform in caring for individuals with epilepsy and that of religion in coping with the condition. We conclude by arguing that the relationship between religion and epilepsy has been overstated in the academic literature.

Implementation of a stroke thrombolysis service within a tertiary neurosciences centre in the United Kingdom.

BACKGROUND: Intravenous alteplase is licensed for treatment of ischaemic stroke within 3 h of onset. Up to one-third of patients in the UK present to hospital within this time window but few are treated. AIMS: To examine the effect of a stroke thrombolysis protocol on service provision for an acute stroke service in the UK, jointly run by Neurology and Medicine for the Elderly providing a comprehensive stroke service to a local population of 370,000. DESIGN: Prospective observational study. METHODS: Data collected prospectively for all thrombolysis referrals over a 12-month period beginning July 2004. RESULTS: One hundred and eighty-eight patients were referred for potential thrombolysis, 129 transferred, 102 had an ischaemic stroke and 49 received intravenous thrombolysis. Referral rates from primary care and accident and emergency increased after guideline dissemination. Forty-three percent of the 49 patients treated with intravenous rt-PA achieved independence (modified Rankin Scale score 0-2) at 3months. CONCLUSION: A high proportion of ischaemic stroke patients can be treated with alteplase within 3 h of onset with organized hospital services and dissemination of a simple referral protocol to local primary and secondary care services.

Non-lateralised deficits of drawing production in hemispatial neglect.

Spatially lateralised deficits that typically define the hemispatial neglect syndrome have been shown to co-occur with other non-lateralised deficits of attention, memory, and drawing. However even a simple graphic task involves multiple planning components, including the specification of drawing start position and drawing direction. In order to investigate the influence of these factors in neglect we presented patients with a circle-copying task, and specified the drawing start point. The ability to draw from the instructed location was strongly related to tests that measure constructional abilities, but not related to start point laterality. In contrast, the direction in which patients drew the circle was affected by start point laterality: patients with neglect were less likely to draw in a typical direction when the cue was on the affected side of space and this was strongly related to severity of the neglect. Patients with neglect consistently produced circles that were smaller than the model; however, the scaling was not affected by the laterality of the start point, nor was the proportion of drawings correctly started at the cue. These findings demonstrate the complex relationship between neglect and even the simplest test for the syndrome.

Single gene disorders causing ischaemic stroke.

Stroke is the third most common cause of death and the leading cause of long-term neurological disability in the world. Conventional vascular risk factors for stroke contribute approximately to only forty to fifty percent of stroke risk. Genetic factors may therefore contribute to a significant proportion of stroke and may be polygenic, monogenic or multi-factorial. Monogenic (single gene) disorders may potentially account for approximately one percent of all ischaemic stroke. Monogenic stroke disorders include conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) and hereditary endotheliopathy, retinopathy, nephropathy and stroke (HERNS). In addition, other monogenic conditions such as sickle cell and Fabry disease also lead to stroke. These monogenic disorders cause either small vessel or large vessel stroke (or a combination of both) and serve as useful models for understanding and studying conventional stroke and cerebrovascular disease and its accompaniments such as vascular dementia.

Suboptimal medication adherence in Parkinson's disease.

Patients take less medication than prescribed in many disease areas but evidence for suboptimal therapy adherence in Parkinson's disease (PD) is limited. A single-center observational study of antiparkinsonian medication was undertaken using electronic monitoring (MEMS; Aardex, Zug, Switzerland) over 3 months. Of 68 patients approached, 6 declined and 8 dropped out, leaving 54 patients (taking 117 preparations) with available data. Poorer compliance was associated significantly with younger age, with taking more antiparkinsonian tablets per day, with higher depression scores, and with poorer quality of life. Of the 54 evaluable patients, 11 (20%) had average total compliance of under 80% (underusers) and 43 (80%) had average total compliance of over 80% (satisfactory adherence). Underusers had median total compliance of 65% (interquartile range, 37-74) versus 98% (interquartile range, 93-102) in the satisfactory adherence group. Timing compliance (number of doses taken in the correct time interval) was poor in both underusers (median, 11%; interquartile range, 2-20) and those with satisfactory adherence (median, 25%; interquartile range, 11-73). In conclusion, poorer compliance is associated with younger age, depression, and more tablets per day, and one-fifth of PD patients underuse medication. Consideration of drug therapy adherence has implications in the management of PD.

Reliability of the modified Rankin Scale across multiple raters: benefits of a structured interview.

BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) is widely used to assess global outcome after stroke. The aim of the study was to examine rater variability in assessing functional outcomes using the conventional mRS, and to investigate whether use of a structured interview (mRS-SI) reduced this variability. METHODS: Inter-rater agreement was studied among raters from 3 stroke centers. Fifteen raters were recruited who were experienced in stroke care but came from a variety of professional backgrounds. Patients at least 6 months after stroke were first assessed using conventional mRS definitions. After completion of initial mRS assessments, raters underwent training in the use of a structured interview, and patients were re-assessed. In a separate component of the study, intrarater variability was studied using 2 raters who performed repeat assessments using the mRS and the mRS-SI. The design of the latter part of the study also allowed investigation of possible improvement in rater agreement caused by repetition of the assessments. Agreement was measured using the kappa statistic (unweighted and weighted using quadratic weights). RESULTS: Inter-rater reliability: Pairs of raters assessed a total of 113 patients on the mRS and mRS-SI. For the mRS, overall agreement between raters was 43% (kappa=0.25, kappa(w)=0.71), and for the structured interview overall agreement was 81% (kappa=0.74, kappa(w)=0.91). Agreement between raters was significantly greater on the mRS-SI than the mRS (P<0.001). Intrarater reliability: Repeatability of both the mRS and mRS-SI was excellent (kappa=0.81, kappa(w) > or =0.94). CONCLUSIONS: Although individual raters are consistent in their use of the mRS, inter-rater variability is nonetheless substantial. Rater variability on the mRS is thus particularly problematic for studies involving multiple raters. There was no evidence that improvement in inter-rater agreement occurred simply with repetition of the assessment. Use of a structured interview improves agreement between raters in the assessment of global outcome after stroke.

Basilar artery occlusion.

Basilar artery occlusion is assumed to carry a grave prognosis, with mortality rates of up to 90%. Diagnosis is often delayed, or even missed, as a result of the variety of clinical presentations seen with this condition. The pathogenesis of occlusion can be secondary to both local atherothrombosis or cardioembolism. The use of noninvasive imaging such as magnetic resonance imaging and computed tomography angiography has improved recognition of clinical syndromes associated with occlusion. Although no randomized studies have been performed, recanalization of the vascular occlusion, particularly with thrombolytic agents, appears to result in improved outcomes in selected patients. However, the optimum timing for therapy is unclear, and reperfusion therapy may need to be combined with definitive vascular treatment of underlying vascular stenosis. Increasing awareness of this condition may reveal the natural history to be more diverse than previously recognized.

Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale.

BACKGROUND AND PURPOSE: The modified Rankin Scale is widely used to assess changes in activity and lifestyle after stroke, but it has been criticized for its subjectivity. The purpose of the present study was to compare conventional assessment on the modified Rankin Scale with assessment through a structured interview. METHODS: Sixty-three patients with stroke 6 to 24 months previously were interviewed and graded independently on the modified Rankin Scale by 2 observers. These observers then underwent training in use of a structured interview for the scale that covered 5 areas of everyday function. Eight weeks after the first assessment, the same observers reassessed 58 of these patients using the structured interview. RESULTS: Interrater reliability was measured with the kappa statistic (weighted with quadratic weights). For the scale applied conventionally, overall agreement between the 2 raters was 57% (kappa(w)=0.78); 1 rater assigned significantly lower grades than the other (P=0.048). On the structured interview, the overall agreement between raters was 78% (kappa(w)=0.93), and there was no overall difference between raters in grades assigned (P=0.17). Rankin grades from the conventional assessment and the structured interview were highly correlated, but there was significantly less disagreement between raters when the structured interview was used (P=0.004). CONCLUSIONS: Variability and bias between raters in assigning patients to Rankin grades may be reduced by use of a structured interview. Use of a structured interview for the scale could potentially improve the quality of results from clinical studies in stroke.