Stuart Jamieson

The validity of using the mini mental state examination in NICE dementia guidelines.

The mini mental state examination (MMSE) is widely used as a rapid means of quantifying cognitive function.1 The National Institute for Clinical Excellence (NICE) guidelines concerning the use of cholinesterase inhibitors (CI) in Alzheimer’s disease recommend using the MMSE as quantifiable measure to inform decisions regarding initiation and continuation of drug treatment.2 Our study questions whether poor interrater reliability of the MMSE makes it an inappropriate tool for monitoring drug response. A postal survey evaluating the MMSE section termed “attention and calculation” was conducted among all consultant neurologists in the UK. The original instructions regarding this section involve asking the patient to count backwards in sevens from 100 for five subtractions, or, if the patient “cannot or will not perform this task” to spell “WORLD” backwards, scoring the number of letters in the correct order.1 Of the 407 questionnaires sent, there were 234 (58%) …

Cognitive impairment in Parkinson's disease

Cognitive impairment is a significant non-motor symptom of Parkinsons disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinsons disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinsons disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimers related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential.

Migration of intraocular silicone oil into the brain

A 74-year-old woman gave a 6-month history of predominately right-sided parietal headaches, often worse on waking. Her history included left phthisis bulbi (atrophy and calcification of the eye), resulting from multiple attempted surgical repairs for retinal detachment 20 years previously. She wore a coloured contact lens over her left eye for cosmetic purposes. Neurological examination was normal. An unenhanced CT brain scan of her head demonstrated a high-attenuation abnormality in the left vitreous cavity with posterior extension along the optic nerve. There were further foci of high attenuation in the suprasellar region and in the frontal horn of the right lateral ventricle (figures 1 …

Going through directional changes: evolving human movement classifiers using an event based encoding

Directional changes (DC) is an event based encoding for time series data that has become popular in financial analysis, particularly within the evolutionary algorithm community. In this paper, we apply DC to a medical analytics problem, using it to identify and summarise the periods of opposing directional trends present within a set of accelerometry time series recordings. The summarised time series data are then used to train classifiers that can discriminate between different kinds of movement. As a case study, we consider the problem of discriminating the movements of Parkinsons disease patients when they are experiencing a common effect of medication called levodopa-induced dyskinesia. Our results suggest that a DC encoding is competitive against the window-based segmentation and frequency domain encodings that are often used when solving this kind of problem, but offers added benefits in the form of faster training and increased interpretability.

A New Evolutionary Algorithm-Based Home Monitoring Device for Parkinson’s Dyskinesia

Parkinson’s disease (PD) is a neurodegenerative movement disorder. Although there is no cure, symptomatic treatments are available and can significantly improve quality of life. The motor, or movement, features of PD are caused by reduced production of the neurotransmitter dopamine. Dopamine deficiency is most often treated using dopamine replacement therapy. However, this therapy can itself lead to further motor abnormalities referred to as dyskinesia. Dyskinesia consists of involuntary jerking movements and muscle spasms, which can often be violent. To minimise dyskinesia, it is necessary to accurately titrate the amount of medication given and monitor a patient’s movements. In this paper, we describe a new home monitoring device that allows dyskinesia to be measured as a patient goes about their daily activities, providing information that can assist clinicians when making changes to medication regimens. The device uses a predictive model of dyskinesia that was trained by an evolutionary algorithm, and achieves AUC>0.9 when discriminating clinically significant dyskinesia.

When myopathy breaks the rules: a late-onset distal presentation

Myopathies typically present with proximal or generalised muscle weakness, but it is important for clinicians to recognise they may also have other distributions. This paper describes a case of distal myopathy that was confirmed genetically as ZASP (Z-band alternatively spliced PDZ motif-containing protein) myofibrillar myopathy (MFM). MFMs are particularly topical because the genetic basis of several have recently been established, enabling diagnosis of conditions previously labelled ‘idiopathic myopathy’, and shedding new light on their pathophysiology. This paper describes a purely distal lower limb phenotype of ZASP MFM, the pathophysiology of ZASP and other MFMs, and the differential diagnosis of late-onset distal symmetrical weakness. The case includes several learning points: ZASP MFM is a new diagnosis; it should be included in differential diagnoses for late-onset myopathy, especially if there is a distal pattern or autosomal dominant inheritance; testing for cardiomyopathy is recommended, and a genetic test is now available.

Objective Assessment of Cognitive Impairment in Parkinson’s Disease Using Evolutionary Algorithm

Parkinson’s disease (PD) is a common and disabling condition without cure. An early and accurate diagnosis is important for monitoring the disease and managing symptoms. Over time, the majority of patients with PD develop cognitive impairment, which is diagnosed using global tests of cognitive function or more detailed neuropsychological assessment. This paper presents an approach to detect PD and to discriminate different degrees of PD cognitive impairment in an objective way, considering a simple and non-invasive “reach and grasp” task performed with the patient wearing sensor-enabled data gloves recording movements in real-time. The PD patients comprised three subgroups: 22 PD patients with normal cognition (PD-NC), 23 PD patients with mild cognitive impairment (PD-MCI) and 10 PD patients with dementia (PDD). In addition, 30 age-matched healthy subjects (Controls) were also measured. From the experimental data, 25 kinematic features were extracted with the aim of generating a classifier that is able to discriminate not only between Controls and PD patients, but also between the PD cognitive subgroups. The technique used to find the best classifier was an Evolutionary Algorithm - Cartesian Genetic Programming (CGP), and this is compared with Support Vector Machine (SVM) and Artificial Neural Network (ANN). In all cases, the CGP classifiers were comparable with SVM and ANN, and in some cases performed better. The results are promising and show both the potential of the computed features and of CGP in aiding PD diagnosis.

Exploring diagnostic models of Parkinson's disease with multi-objective regression

Parkinsons disease is a progressive neurodegenerative disorder. The biggest risk factor for developing Parkinsons disease is age and so prevalence is increasing in countries where the average age of the population is rising. Cognitive problems are common in Parkinsons disease and identifying those with the condition who are most at risk of developing such issues is an important area of research. In this work, we explore the potential for using objective, automated methods based around a simple figure copying exercise administered on a graphics tablet to people with Parkinsons disease. In particular, we use a multi-objective evolutionary algorithm to explore a space of regression models, where each model represents a combination of features extracted from a patients digitised drawing. The objectives are to accurately predict clinical measures of the patients motor and cognitive deficit. Our results show that both of these can be predicted, to a degree, and that certain sub-sets of features are particularly relevant in each case.

Using epigenetic networks for the analysis of movement associated with levodopa therapy for Parkinson's disease.

Levodopa is a drug that is commonly used to treat movement disorders associated with Parkinsons disease. Its dosage requires careful monitoring, since the required amount changes over time, and excess dosage can lead to muscle spasms known as levodopa-induced dyskinesia. In this work, we investigate the potential for using epiNet, a novel artificial gene regulatory network, as a classifier for monitoring accelerometry time series data collected from patients undergoing levodopa therapy. We also consider how dynamical analysis of epiNet classifiers and their transitions between different states can highlight clinically useful information which is not available through more conventional data mining techniques. The results show that epiNet is capable of discriminating between different movement patterns which are indicative of either insufficient or excessive levodopa.

Holocord syrinx associated with haemangioblastoma

A 50-year-old man gave a 6-year history of muscle wasting and weakness of both legs. He had noticed marked muscle loss across his chest and back and ‘spasms’ of his legs at night, often induced by coughing or sneezing. There were no sensory symptoms or problems with sphincters, speech or swallowing. On examination, there was muscle wasting in both legs and in the pectoral muscles, but no fasciculations. There was increased tone in all four limbs, with several beats of clonus in the legs. His strength was normal when examined on the couch, although he was adamant that he was not as strong as he used to be. Reflexes were brisk bilaterally in all four limbs and both plantars were upgoing. Sensations to fine touch and to joint-position sense were normal; vibration sense …