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Title: To identify the patho-physiology of neurological deficits after aneurysmal subarachnoid haemorrhage, explore their interrelationship and identify tools which best measure these deficits
Author: Bhargava, Deepti
ISNI:       0000 0004 5370 3754
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2014
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Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a neurological catastrophe with 30R40% survival, 30% survivors left with moderate to severe disability and 66% survivors suffering functional or cognitive deficits compromising return to premorbid performance status. Delayed neurological deficit (DIND) is the most common cause of morbidity and mortality affecting the hospitalized aSAH patient. Although many theories have been proposed, we do not fully understand the pathoRphysiology of DIND or the nature of resultant cognitive and functional disability. Thereby, even with advances in overall patient care, the outcome of the patients afflicted with DIND remains suboptimal. Aim: The aims of this work are: 1. To elucidate physiological variables during course of delayed neurological deficit to explore DIND pathophysiology 2. To explore functional and cognitive deficits after aSAH by administering a battery of patient reported outcome scales, thereby better understand the correlation between different components of health status in aSAH patients and to derive a set of tools that will help easy, uniform and early identification of subtle but clinically significant neuroRpsychoRsocial deficits in this patient group to guide appropriate management and rehabilitation. Methods: A prospective observational pilot study with a sample size of 16 patients was undertaken to investigate DIND pathophysiology. Eligible participants underwent invasive monitoring of regional cerebral blood flow, tissue oxygen concentration, energy metabolism and tissue ionic changes to cover the time epochs prior to development of DIND, during its onset, and with administration of TripleRH therapy. Descriptive analysis of the parameters over time was undertaken to compare patients who did / did not develop symptoms of DIND. A questionnaire based survey was carried out with a sample size of 200 SAH patients using AKC short sentences test, The Dysexecutive Questionnaire, The Everyday Memory Questionnaire, Stroke Symptom CheckRlist, Wimbledon SelfRreport Scale and Stroke QOL to assess functional and cognitive deficits after aSAH. Descriptive analysis was done to identify patterns of deficits and identify tools that best help to pickRup these deficits. Logistic regression and structural equation modelling was done to pick interactions thereof. 5 Results: In the pathophysiology study, 7 patients developed DIND. Large interRsubject baseline variations were observed in tissue perfusion and oxygenation in all patients. Changes in perfusion and oxygenation were not linked to symptoms. A trend was observed in energy metabolism with simultaneous escalation in both lactate and pyruvate between day 4R7 (coinciding with symptoms), in 6 patients with DIND and only 1 patient without DIND. The extracellular potassium ion concentration paralleled metabolic changes in 4/6 patients where ionic monitoring was undertaken. The ionic/metabolic changes were not related to change in perfusion or oxygenation. TripleRH therapy, particularly raised mean arterial pressure, improved symptoms. It led to improvement in cerebral perfusion and oxygenation but, did not lead to any changes in metabolic profile. The questionnaire survey witnessed a 57% response rate. 76% of these patients experienced functional and cognitive difficulties. Nearly half returned to economic productivity. Even a third of patients with good Modified Rankin Score (MRS) at discharge failed to return to work. Cognitive disability and mood disorder explained 26% of the variance in patients’ perceived MRS at follow up. Cognitive disability had a direct as well as indirect effect on MRS by affecting the patient's mood. Conclusion: Invasive neuromonitoring is well tolerated and safely provides valuable and timely information regarding DIND even in awake patients. This work provides baseline neurophysiology data to guide future studies. It questions current hypothesis for DIND pathophysiology and argues that besides ischaemia, DIND is related to increased metabolic demand outstripping the available supply, at least partly secondary to rising extracellular potassium concentration which drives sodiumRpotassium pump for maintenance of cellular homeostasis. Triple H therapy acts by restoring the balance. Besides physical disability, a significant proportion of SAH patients are left with cognitive, speech, memory and affect deficits compromising return to social productivity. Mood plays a significant role in determining perceived well being and is in turn affected by cognitive ability. Mood and cognition are thus targets for holistic followRup and rehabilitation, especially in good grade (i.e. with minimal physical disability) individuals. Patient reported outcome measures are easily administered, cheap and useful source of detailed outcome information regarding these parameters in this patient group.
Supervisor: Ross, Stuart ; Quinn, Audrey Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available