Aging accelerates brain abnormalities in childhood onset epilepsy patients
New research confirms that childhood onset temporal lobe epilepsy has a significant impact on brain aging. Study findings published in Epilepsia, a peer-reviewed journal of the International League Against Epilepsy (ILAE), show age-accelerated ventricular expansion outside the normal range in this patient population.
According to the Centers for Disease Control and Prevention (CDC), epilepsy affects nearly 2 million Americans. Temporal lobe epilepsy is the most common form of partial epilepsy, with 60% of all patients having this form of the disease. Previous evidence suggests that patients with childhood onset epilepsy have significant cognitive and developmental deficiencies, which continue into adulthood, particularly in those resistant to antiepileptic drugs.
Prior imaging studies of patients with temporal lobe epilepsy have shown abnormalities in brain structure in hippocampus, in thalamus and other subcortical structures, and also in cortical and white matter volume. However, there is limited knowledge of the effects of aging on these structural changes.
To characterize differences in brain structure and patterns of age-related change, Dr. Bruce Hermann and colleagues from the University of Wisconsin-Madison recruited 55 patients with chronic temporal lobe epilepsy and 53 healthy controls for their study. Participants were between the ages of 14 and 60, with patients having mean age of onset of epilepsy in childhood/adolescence. Magnetic resonance imaging (MRI) was used to measure cortical thickness, area and volume in the brains of all subjects.
In participants with epilepsy, there were extensive abnormalities in brain structure, involving subcortical regions, cerebellum and cortical gray matter thickness and volume in the temporal and extratemporal lobes. Furthermore, researchers found that increasing chronological age was associated with progressive changes in cortical, subcortical and cerebellar regions for both epilepsy subjects and healthy controls. The pattern of change was similar for both groups, but epilepsy patients always showed more extensive abnormalities. In particular, epilepsy patients displayed age-accelerated expansion of the lateral and third ventricles. “The anatomic abnormalities in patients with epilepsy indicate a significant neurodevelopmental impact,” said Dr. Hermann.
“Patients with epilepsy are burdened with significant neurodevelopmental challenges due to these cumulative brain abnormalities,” concludes Dr. Hermann. “The consequences of these anatomical changes for epilepsy patients as they progress into elder years remain unknown and further study of the adverse effects in those of older chronological age is needed.”
Childhood-Onset Epilepsy Triples Risk for Death
Epilepsy has been defined as a “condition characterized by recurrent unprovoked seizures,” but it is really much more than that. People with epilepsy may experience significant economic, medical, personal, and societal burdens. Even children with absence epilepsy, previously thought to be a “benign” condition, have an increased risk for poor psychosocial outcome, including alcohol abuse, inadvertent pregnancy, low employment skills, school failure, and psychiatric disorders. In addition, new data emphasize that epilepsy is a condition with increased mortality.
New High-Quality Data
A recent long-term population-based, prospective study revealed that the death rate for children with epilepsy was triple that expected for the general population.[4] This study’s 40-year follow-up and high autopsy rate (70%-80%) offer extraordinarily high-quality information. Nearly half (48%) of the patients with uncontrolled seizures died. Children with symptomatic epilepsy had significantly higher mortality rates (11.1/1000 person years) compared with those who had idiopathic or cryptogenic epilepsy (3.2/1000 person years, P < .001). Children whose epilepsy was in 5-year remission on medications had lower mortality (5/35,14%), and children with controlled seizures who were off medications for 5 years fared even better - only 4/103 (4%) in this category died.
Although some children with epilepsy do indeed “outgrow” their seizures, those who do not face continued risks to their health. This study emphasizes the potential lethality of childhood epilepsy, which is perhaps underappreciated by many physicians and others who provide care for people with epilepsy.
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This study is published in Epilepsia. Media wishing to receive a PDF of this article may contact .(JavaScript must be enabled to view this email address).
Some recent studies (Sillanpää M, Shinnar S) seem to indicate most data that evaluate future mortality after onset of epilepsy in childhood are derived from retrospective assessments of adults or by following childhood cohorts for periods generally less than 10 years. These data report outcomes from a group of 245 patients with childhood-onset epilepsy (at least 2 unprovoked seizures) who were followed for 40 years in Finland. The patients were all younger than 16 years old in 1964 when enrolled in the cohort. Most patients (61%) had onset of epilepsy during an active study conducted from 1961-1964, and the remaining children experienced onset of epilepsy prior to 1961. The patients had follow-up examinations every 5 years through 2002, and the investigators identified deaths that occurred between these 5-year intervals. The median time of follow-up for the cohort was 40 years. The investigators also compared patients against the Finnish death registry. An autopsy was performed in 70% of the patients who died to rule out nonepileptic causes of death. The investigators defined sudden unexpected death as a sudden death with no other identified cause and no evidence that a seizure occurred. In the cohort, 122 patients (49.7%) had idiopathic or cryptogenic epilepsy, with the remainder having epilepsy due to a remote cause. Long-term remission was defined as 5 years without seizures.
At the last follow up (or death), 45% of the patients were in remission and did not require medications, 11% were in remission but required antiepileptic medication, and 44% were not in remission. Overall, 24% (n = 60) of the patients died. Of the 60 patients who died, 15 had idiopathic or cryptogenic epilepsy whereas 45 had epilepsy due to a remote cause. Of the patients who died, 33 (55%) were believed to have epilepsy-related death (60% of the deaths in patients with cryptogenic epilepsy and 53% of the deaths in those with remote cause epilepsy). The death rate was highest in patients who were not in remission (15.9 deaths per 1000 person-years), followed by those in remission but on medication (11.8 deaths per 1000 person-years), and lowest in those in remission and off medication (1.5 deaths per 1000 person-years). Death was 3 times more common in those with remote cause epilepsy compared with either cryptogenic or idiopathic epilepsy. Sudden, unexplained death occurred in 18 patients (30% of deaths). Put another way, during the 40 years of follow-up, the risk for sudden, unexplained death in all patients was 7%. The only significant risk factor for death, in multivariable analyses, was not being in remission. The investigators concluded that childhood-onset epilepsy was associated with increased risk for death related to epilepsy and sudden, unexplained death, and the risk was highest in patients who were not in remission.
Full citation:“Brain Structure and Aging in Chronic Temporal Lobe Epilepsy.” Kevin Dabbs, Tara Becker, Jana Jones, Paul Rutecki, Michael Seidenberg, and Bruce Hermann. Epilepsia; April 2, 2012 (DOI:10.1111/j.1528-1167.2012.03447.x).
URL upon publication:10.1111/j.1528-1167.2012.03447.x
Epilepsia is the leading, most authoritative source for current clinical and research results on all aspects of epilepsy. As the journal of the International League Against Epilepsy, subscribers every month will review scientific evidence and clinical methodology in: clinical neurology, neurophysiology, molecular biology, neuroimaging, neurochemistry, neurosurgery, pharmacology, neuroepidemiology, and therapeutic trials. For more information, please visit http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1528-1167.
The International League Against Epilepsy (ILAE) is the world’s preeminent association of physicians and health professionals working toward a world where no person’s life is limited by epilepsy. Since 1909 the ILAE has provided educational and research resources that are essential in understanding, diagnosing and treating persons with epilepsy. The ILAE supports health professionals, patients, and their care providers, governments, and the general public worldwide by advancing knowledge of epilepsy.
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Dawn Peters
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