Winners of the Undergraduate Prize 2015:
Clinical Case: Emeka Okonji
Research: Sanjeev Ramachandran
Audit: Lydia Silvester
Adult-onset Neuronal Ceroid Lipofuscinosis (Kufs Disease)
Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited lysosomal storage disorders – most commonly occurring in childhood – characterized by progressive, widespread neurodegeneration and intra-neuronal accumulation of autofluorescent lipopigments. Adult-onset NCL (also referred to as Kufs disease) is the rarest entity of this group, with an incidence of 1 in 1,000,000 worldwide.
The clinical presentation of Kufs disease involves any combination of progressive dementia, epilepsy, myoclonus, cerebellar and/or extrapyramidal signs. Behavioural changes are also common and visual loss is infrequent; however, the condition invariably leads to death within 15 years of the onset of symptoms.
The diagnostic challenges posed by patients with Kufs disease are two-fold. Firstly, their clinical presentation can mimic several other rare causes of progressive myoclonic epilepsy or dementia with motor deterioration. Secondly, unlike other forms of NCL, extra-neural accumulation of the hallmark lipopigments is unreliable for confirming a diagnosis of Kufs disease. This diagnosis is most reliably confirmed by invasive brain biopsy.
Mutations in the DNAJC5 gene, which has a key role in synaptic transmission, are a known cause of autosomal dominant Kufs disease. This gene encodes for cysteine string protein (CSP-α), which is located on pre-synaptic vesicles and enables the formation of SNARE-complexes – the key mediators of pre-synaptic vesicular fusion and exocytosis at the synaptic cleft. Causative mutations reduce synaptic levels of CSP-α, therefore impairing synaptic transmission.
This presentation will describe the clinical features and genetic analysis of a patient diagnosed with autosomal dominant Kufs disease in the UK.
The role of numerical cognition in social decision-making
Over the past decade there has been a surge of neuroscientific interest regarding the mechanisms that underpin human pro-social decision-making. However, the exact role played by numerical cognition in social decision-making remains unclear. This is surprising given the explicitly numerical nature of the dictator game task, which has been almost ubiquitously employed to examine the neural basis of pro-social behavior. We hypothesized that numerical magnitude allocation may play a critical role in the choices formulated during the dictator game task, and found that innate numerical biases and pro-social choices strongly correlated. Numerical magnitude biases towards lower numbers were associated with less favourable pro-social choices, whereas biases towards higher numbers were associated with greater pro-social choices. We proceeded to subliminally induce bi-directional modulation of numerical magnitude perception using a combined visuo-vestibular stimulation paradigm, and subsequently assessed dictator game performance. Strikingly, we found that altering numerical magnitude allocation led to corresponding changes upon an individual’s pro-social choices during the dictator game task. Taken together, these findings strongly suggest that tasks with an explicit numerical component, such as the dictator game, are directly dependent upon numerical biases. Our findings have significant implications for our understanding of performance on the standard dictator game paradigm and future studies investigating pro-social decision-making.
Bone Health in Parkinson’s disease; Evaluation and Recommendation, Salford Royal NHS Trust
INTRODUCTION: Parkinson’s Disease (PD) and atypical parkinsonism disorders are independent risk factors for increasing the likelihood of fracture. However, there are no national guidelines for the management of fracture risk within this group. This essay is part of a larger quality improvement project that estimated fracture risk of a cohort of patients from the Salford Royal NHS Foundation Trust using a validated fracture risk assessment tool, QFracture. Management was determined using newly published guidelines by Lyell et al (2014), and suggestions were made to improve practice.
METHODS: 257 sets of patient notes from clinic lists spanning the previous year were analysed using QFracture giving percentage risk of major osteoporotic and hip fracture over 5 and 10 years. The guidelines proposed by Lyell et al were then studied across the whole cohort.
RESULTS: The average fracture risks over ten years were 14.3% and 10.4% (PD) and 23.8% and 17% (atypical parkinsonism) for a major osteoporotic and hip fracture respectively.
DISCUSSION: 57% of the whole cohort was deemed to require treatment in consideration of the guidelines proposed by Lyell et al, where only 8% were receiving treatment. Recommendations of this project were to introduce thorough assessment of fracture risk into the clinical setting and ensure patients receive treatment when required. Since undertaking this work, changes to practice have taken place. They include improving documentation of patient heights and weights in order to assess them more thoroughly, as well as introducing the Lyell guidelines into regular practice and the planning of further work in this area.