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. 2017;60(1):211-223.
doi: 10.3233/JAD-170031.

Relative Incidence of Seizures and Myoclonus in Alzheimer's Disease, Dementia with Lewy Bodies, and Frontotemporal Dementia

Alexander J Beagle  1 , Sonja M Darwish  1 , Kamalini G Ranasinghe  1 , Alice L La  1 , Elissaios Karageorgiou  1   2 , Keith A Vossel  1   3
Affiliations

Relative Incidence of Seizures and Myoclonus in Alzheimer's Disease, Dementia with Lewy Bodies, and Frontotemporal Dementia

Alexander J Beagle et al. J Alzheimers Dis. 2017.

Abstract

Background: Patients with Alzheimer's disease (AD) are more prone to seizures and myoclonus, but relative risk of these symptoms among other dementia types is unknown.

Objective: To determine incidence of seizures and myoclonus in the three most common neurodegenerative dementias: AD, dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).

Methods: Our institution's medical records were reviewed for new-onset unprovoked seizures and myoclonus in patients meeting criteria for AD (n = 1,320), DLB (n = 178), and FTD (n = 348). Cumulative probabilities of developing seizures and myoclonus were compared between diagnostic groups, whereas age-stratified incidence rates were determined relative to control populations.

Results: The cumulative probability of developing seizures after disease onset was 11.5% overall, highest in AD (13.4%) and DLB (14.7%) and lowest in FTD (3.0%). The cumulative probability of developing myoclonus was 42.1% overall, highest in DLB (58.1%). The seizure incidence rates, relative to control populations, were nearly 10-fold in AD and DLB, and 6-fold in FTD. Relative seizure rates increased with earlier age-at-onset in AD (age <50, 127-fold; 50-69, 21-fold; 70+, 2-fold) and FTD (age <50, 53-fold; 50-69, 9-fold), and relative myoclonus rates increased with earlier age-at-onset in all groups. Seizures began an average of 3.9 years after the onset of cognitive or motor decline, and myoclonus began 5.4 years after onset.

Conclusions: Seizures and myoclonus occur with greater incidence in patients with AD, DLB, and FTD than in the general population, but rates vary with diagnosis, suggesting varied pathomechanisms of network hyperexcitability. Patients often experience these symptoms early in disease, suggesting hyperexcitability could be an important target for interventions.

Keywords: Alzheimer’s disease; dementia with Lewy bodies; epilepsy; frontotemporal dementia.

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Conflict of interest statement

COMPETING INTERESTS

The authors have no conflict of interest to report.

Figures

Figure 1
Figure 1
Cumulative probability curves of new-onset seizures and myoclonus. (A) Cumulative probability curves for all patients. (B and C) Cumulative probability curves of new-onset seizures (B) and myoclonus (C), by diagnostic cohort (panel B, p=0.005 and panel C, p<0.0001, age-at-diagnosis-stratified log-rank test comparing the three groups). Curves become dotted at the point where 80% of patients are censored.
Figure 2
Figure 2
Age-stratified incidence rate ratios (IRR), the ratios of incidence rates in dementia groups to incidence rates in age-matched control populations, and raw incidence rates for new-onset seizures and myoclonus, by diagnostic cohort. (A and B) IRR for new-onset seizures (A) and myoclonus (B) (panel A, seizure IRR increased with earlier age in AD, p<0.0001, and FTD, p=0.012, Χ2 test, and panel B, myoclonus IRR increased with earlier age in AD, p<0.0001, DLB, p=0.022, and FTD, p=0.033, Χ2 test). The IRR values and 95% confidence intervals are provided in Supplementary Table 2. (C and D) Component incidence rates from patients and control data in epidemiological studies[46, 47] for seizures (C) and myoclonus (D). No patients with DLB were seen in the stratum of 30 – 49 years of age.
Figure 3
Figure 3
Onset of seizures and myoclonus in relation to onset of cognitive or motor decline, by diagnostic cohort. (A) Occurrence of new-onset seizures in relation to age-at-onset of cognitive or motor decline. (B) Occurrence of myoclonus in relation to age-at-onset of cognitive or motor decline.
See this image and copyright information in PMC

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