Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy

Abstract

The clinical implications of enlarged early cortical components of somatosensory evoked potentials in benign adult familial myoclonus epilepsy remain unknown. Somatosensory evoked potentials following electrical stimulation of the median nerve at the wrist were studied in 16 patients with a clinical diagnosis of benign adult familial myoclonus epilepsy (7 men and 9 women; mean age, 51 ± 18 years) and 19 age-matched apparently healthy control subjects (11 men and 8 women; mean age, 49 ± 18 years). Giant somatosensory evoked potentials were observed in 13 of the 16 patients. P25 and N35 amplitudes in the patient group were 11.4 ± 6.1 and 19.2 ± 11.5 μV, respectively, and both were significantly larger compared with those in control subjects (P = 0.008 for P25 and P < 0.0001 for N35). There was a significant positive relationship between age at somatosensory evoked potential examination and N20, P25, and N35 amplitudes, both in the patient and in the control groups (P < 0.05). The linear regression gradient of the N35 amplitude with respect to age was significantly larger in the patient group than in the control group (P = 0.04). Furthermore, regression analysis showed a significant positive relationship between the myoclonus rating scale and age at time of somatosensory evoked potential examination (R = 0.645, P = 0.007). Somatosensory evoked potential amplitude increased with age in patients with benign adult familial myoclonus epilepsy to a greater extent than in the control subjects, which suggests a progressive increase in cortical excitability based on progressive pathophysiology in benign adult familial myoclonus epilepsy.

Clinical anticipation in Japanese families of benign adult familial myoclonus epilepsy

“…1). One family (Family 2) was previously reported (Ikeda et al., 2005) and some of the patients were reported elsewhere (Hitomi et al., 2011). Diagnostic criteria for BAFME were adopted from the previous study (Hitomi et al., 2011).…”

“…The onset age of cortical tremor ranges between 11 and 50 years in Europe (Striano et al., 2009) and 10 and 70 years in Japan (Hitomi et al., 2011), and that of generalized seizure ranges between 12 and 67 years in Europe (Striano et al., 2009) and 17 and 73 years in Japan (Hitomi et al., 2011).…”

“…The term “benign” was designated for its non‐progressive course and rare occurrence of generalized seizures, and thus BAFME was distinguished from the various forms of progressive myoclonus epilepsy (PME). However, we recently reported increased cortical hyperexcitability and exaggerated myoclonus with aging in BAFME, which suggests that the pathophysiology of BAFME shows a slight but progressive tendency (Hitomi et al., 2011). Similarly, the clinical features have also been reported to progress in some European cases (Coppola et al., 2011).…”

Familial Cortical Myoclonic Tremor with Epilepsy and Cerebellar Changes: Description of a New Pathology Case and Review of the Literature

“…Presymptomatic electrophysiological abnormalities including a g-SEP have been reported in three of seven asymptomatic family members (9–18 years) of an Italian pedigree 10. Hitomi and colleagues25 observed increasing g-SEP amplitudes with aging. g-SEPs and long latency reflexes are not detected in all patients, and it has been reported that antiepileptic drugs (AEDs) can normalize these electrophysiological abnormalities 11, 17.…”

Autosomal dominant cortical tremor, myoclonus, and epilepsy: is the origin in the cerebellum? Editorial

“…Alternatively, decreased cortical inhibition may be caused by dysfunction of the cerebello-thalamo-cortical loop secondary to primary cerebellar pathology, especially at the level of the cerebellar cortex [14]. In addition, recent clinical studies suggest a correlation between clinical severity and patients' ages, indicating that the clinically evident progression of the disease reflects-at least in part-the effect of physiological aging [9,15].…”