Cerebral damage in epilepsy: A population-based longitudinal quantitative MRI study
Liu RS, Lemieux L, Bell GS, Sisodiya SM, Bartlett PA, Shorvon SD, et al.;
Commented by , 22 Nov 2005
It is unclear whether, and to what extent, structural brain abnormalities observed in patients with chronic epilepsy may reflect a progressive pathology, and what role seizures play in this pathology (ref. 1; ref. 2).
To investigate the effect of seizures on hippocampus, neocortex and cerebellum.
- Population-based prospective longitudinal study in 179 patients, aged 14-77 years, with temporal lobe epilepsy (TLE, n=66), extratemporal partial epilepsy (ETE, n=51) and generalized epilepsy (GE, n=62), and 90 age- and gender-matched healthy controls
- Quantitative MRI measurements were obtained about 3.5 years apart in each subject
- Patients with TLE had lower hippocampal volumes at baseline than ETE patients, GE patients and controls
- Reduction in hippocampal, cerebral and cerebellar volume over time was comparable in all epilepsy groups and controls, and was primarily determined by age
- Significant atrophy of hippocampus, neocortex and cerebellum occurred in 17% of epilepsy patients and 6% of controls
- A lower hippocampal and cerebellar volume, and an increased rate of cerebellar atrophy, correlated with a history of an initial precipitating insult
- In patients with ETE, changes in hippocampal, cerebral and grey matter volume correlated with convulsive seizure frequency
Professor Perucca's comments
Structural brain abnormalities, including hippocampal sclerosis, are common in patients with chronic refractory epilepsy, but whether epilepsy per se and/or seizures contribute to their pathogenesis is unclear.
Previous studies, mostly hospital-based, described a correlation between the frequency of partial and/or convulsive seizures and hippocampal volume loss in TLE patients (ref. 3; ref. 4; ref. 5; ref. 6), but this has not been a consistent finding (ref. 7; ref. 8; ref. 9; ref. 10).
Compared with previous work, this study has a number of advantages:
- it is the first prospective population-based study in this area
- it included a relatively large number of subjects
- it included different epilepsy syndromes, as well as matched healthy controls.
However, there are also important limitations:
- the epilepsy population was highly heterogenous with respect to syndrome, etiology and disease stage (only about one third of patients was newly diagnosed)
- incomplete information was given on some critical details, e.g. type of generalized epilepsies and changes in seizure frequency in each group
- seizures were largely well controlled with medication, possibly hampering ability to detect seizure-related brain damage
- sample size was insufficient for detailed subgroup analysis.
While these limitations should be kept in mind, the results indicate that across all syndromes investigated structural brain damage assessed by MRI measurements is not an inevitable consequence of epileptic seizures.
By contrast, a lower hippocampal and cerebellar volume and an increased rate of cerebellar atrophy appear to be closely related to a history of an initial precipitating insult, defined as a focal or prolonged febrile seizure, severe head trauma, previous meningitis or encephalitis, perinatal hypoxia or status epilepticus.
The data confirm that these insults can lead to significant brain damage – it is also possible that they make the brain more vulnerable to the effect of seizures (ref. 11).
A significant correlation between brain damage progression and frequency of convulsive seizures was only identified for ETE patients. No correlation was found between seizure frequency and hippocampal volume loss in TLE, indicating that regional damage associated with convulsive seizures may occur at sites remote from the epileptic focus.
In conclusion, while the study found that hippocampal, cerebral and cerebellar volume loss occurs more frequently in epilepsy patients than in controls, the difference appears to be mostly independent of seizure frequency and more related to processes triggered by initial precipitating insults.
Investigation of such processes may have important implications for the prevention of epilepsy and associated structural damage.
1. Pringle CE, Blume WT, Munoz DG, et al. Pathogenesis of mesial temporal sclerosis. Canadian Journal of Neurological Sciences 1993; 20; 184-193
2. Tasch E, Cendes F, Li LM, et al. Neuroimaging evidence of progressive neuronal loss and dysfunction in temporal lobe epilepsy. Annals of Neurology 1999; 45 (5); 568-576
3. Briellman RS, Berkovic SF, Syngeniotis A, et al. Seizure-associated hippocampal volume loss: A longitudinal magnetic resonance study of temporal lobe epilepsy. Annals of Neurology 2002; 51 (5); 641-644
4. Fuerst D, Shah J, Shah A, et al. Hippocampal sclerosis is a progressive disorder: A longitudinal volumetric MRI study. Annals of Neurology 2003; 53 (3); 413-416
5. Briellman RS, Newton MR, Wellard RM, et al. Hippocampal sclerosis following brief generalized seizures in adulthood. Neurology 2001;57 (2); 315-317
6. O'Brien TJ, So EL, Meyer FB, et al. Progressive hippocampal atrophy in chronic intractable temporal lobe epilepsy. Annals of Neurology 1999; 45 (4); 526-529
7. Holtkamp M, Schuchmann S, Gottschalk S, et al. Recurrent seizures do not cause hippocampal damage. Journal of Neurology 2004; 251 (4); 458-463
8. Van Paesschen W, Duncan JS, et al. Longitudinal quantitative hippocampal magnetic resonance imaging study of adults with newly diagnosed partial seizures: One-year follow-up results. Epilepsia 1998; 39 (6); 633-639
9. Liu RSN, Lemieux L, Bell GS, et al. The structural consequences of newly diagnosed seizures. Annals of Neurology 2002; 52 (5); 573-580
10. Salmenpera T, Kononen M, Roberts N, et al. Hippocampal damage in newly diagnosed focal epilepsy: A prospective MRI study. Neurology 2005; 64 (1); 62-68
11. Schmid R, Tandon P, Stafstrom CE, et al. Effects of neonatal seizures on subsequent seizure-induced brain injury. Neurology 1999; 53 (8); 1754-1761