Hammers, Alexander; (2002) PET investigations in focal epilepsy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Epilepsy is the most common serious disease of the brain. Positron Emission Tomography (PET) provides information on neurotransmitter systems and the pathophysiology of the epilepsies. Evaluation of PET together with anatomical information from high quality MRI correlates structure and function. Aims: o To develop methods to anatomically label neuroimaging datasets o To investigate and quantify GABAA receptor abnormalities in temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), malformations of cortical development (MCD) and patients with localisation-related epilepsy and normal MRI o To investigate and quantify abnormalities of opioid receptors in MCD Methods: Atlases of normal neuroanatomy were created from 21 high resolution MRI datasets. [¹¹C] flumazenil PET scans of 48 controls, 15 preoperative patients with IIS. 10 patients with MCD, 18 patients with TLE and normal MRI, and 44 patients with neocortical localisation-related epilepsy and normal MRI, as well as [¹¹C] diprenorphine PET scans of 20 controls and 15 patients with MCD, were analysed with statistical parametric mapping (SPM), a volume-of-interest (VOI) approach with partial volume effect correction (PVC), or both. Findings: A method for automatical anatomical labelling and a probabilistic anatomical atlas were developed. 8/15 patients with HS had abnormalities of [¹¹C] flumazenil binding outside the hippocampus. White matter (WM) binding correlated with neuron content. MCD patients showed abnormalities of [¹¹C] flumazenil binding within lesions and in the adjacent/overlying cortex. Patients with TLE and normal MRI had increased [¹¹C] flumazenil binding in the temporal lobe WM, indicating microdysgenesis, in addition to ipsilateral>contralateral hippocampal decreases. 33/44 patients with neocortical localisation-related epilepsy and normal MRI had abnormalities, often WM increases suggestive of migration disturbances. In some, the PET findings were surgically useful. More than three quarters of MCD patients had abnormalities of [¹¹C] diprenorphine binding, implying abnormalities of opioid neurotransmission which could be a novel target for pharmacological intervention.

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