Adan, Guleed 
ORCID: 0000-0001-7340-4207
(2025)
Recurrence after a first unprovoked seizure
PhD thesis, University of Liverpool.
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Abstract
Background Epilepsy is defined as two or more unprovoked seizures occurring over 24 hours apart. Accurate prognostic estimates following a single unprovoked seizure are crucial for guiding clinical decisions on the risks of further seizures and epilepsy. Risk stratification after a first unprovoked seizure is essential to counsel patients on recurrence risks, affecting driving, employment, and treatment. The International League Against Epilepsy's diagnosis allows epilepsy diagnosis after a single unprovoked seizure based on recurrence risk, requiring precise prediction methods. Advanced imaging techniques have shown potential in diagnosing and predicting seizure outcomes in established epilepsy, but their utility after a first unprovoked seizure (FUS) is underexplored. This thesis investigates recurrence risks, prognostic factors, and advanced imaging biomarkers associated with FUS. Methods Firstly, a systematic review and meta-analysis were conducted, searching databases like the Cochrane Register, MEDLINE, SCOPUS, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. The aim was to estimate seizure recurrence and identify prognostic factors for recurrence and mortality after a first unprovoked seizure. Inclusion criteria were population and hospital cohorts with first unprovoked seizures of any semiology, aged over one month, with at least six months follow-up and a minimum of 30 participants per study. Data were extracted and analysed using a random-effects, generic inverse variance model to account for heterogeneity. The GRADE framework assessed evidence quality. Secondly, an observational cohort MRI study recruited 40 FUS patients and 60 healthy controls. MRI scans were performed using a 3T Siemens Prisma system, capturing 3D T1-weighted and Diffusion Kurtosis images. Data analysis involved generalised q-sampling imaging and statistical comparisons between patients and controls, considering variables like age, sex, and intracranial volume. Results The meta-analysis included 58 studies with 12,160 participants, revealing a seizure recurrence rate of 27% at six months, 36% at one year, and 43% at two years. From 1979 records, 23 studies (5918 participants) met the inclusion criteria. Cohort sizes had a median of 134 participants. Most were cohort studies (15 prospective, 7 retrospective) with one randomised controlled trial. Follow-up periods ranged from six to 283 months. Seven studies involved participants initiated on anti seizure medication (ASM) after a first seizure, while 16 did not. Eight studies had adult cohorts, twelve paediatric, and three included both. Moderate-quality evidence linked abnormal EEG with higher recurrence risk. Other factors showed low-quality evidence, including focal neurological deficit, Todd's paresis, status epilepticus, family history of epilepsy, male sex, initial focal seizures, seizures occurring from sleep, and age under 16. Abnormal imaging and febrile seizures showed a trend towards increased recurrence risk, but evidence quality was very low. In the observational cohort study, MRI abnormalities were found in 60% of patients and 33.3% of controls, with 50% of patients experiencing seizure recurrence within 24 months. Recurrence was more common in those with abnormal MRIs (75% vs. 45%, p = 0.0053). Advanced imaging techniques revealed significant right-sided inward deformation of the thalamus and outward deformation of the amygdala in patients compared to controls. Additionally, atrophy was observed in several thalamic nuclei. Lower quantitative anisotropy (QA) was observed in multiple white matter tracts in patients with FUS, with even lower QA in those experiencing recurrent seizures. Conclusions This thesis provides crucial insights into recurrence risks and prognostic factors following a first unprovoked seizure. Despite evidence limitations and heterogeneity, clinical data can aid risk stratification. Findings suggest MRI can detect abnormalities in many FUS patients, aiding diagnosis and prognosis. Advanced imaging techniques revealed structural changes in thalamic structures and the amygdala, potentially serving as biomarkers for seizure recurrence. Lower QA in white matter tracts indicates network disruptions in FUS patients, which may be causal or consequential. High-quality, prospective longitudinal studies are needed to confirm these findings and optimise advanced imaging for early diagnosis and prognostication in epilepsy. This research underscores the importance of standardised protocols and developing international core outcome sets for future seizure studies. Identifying high-risk cohorts will enhance trials for disease-modifying therapies, potentially altering the disease course.
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Aug 2025 15:22 |
| Last Modified: | 18 Aug 2025 15:23 |
| DOI: | 10.17638/03189523 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3189523 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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