Voltage-gated potassium channel complex
antibodies, particularly those directed against
leucine-rich
glioma inactivated 1, are associated with a common form of
limbic encephalitis that presents with
cognitive impairment and
seizures. Faciobrachial dystonic
seizures have recently been reported as
immunotherapy-responsive, brief, frequent events that often
predate the
cognitive impairment associated with this
limbic encephalitis. However, these observations were made from a retrospective study without serial cognitive assessments. Here, we undertook the first prospective study of faciobrachial dystonic
seizures with serial assessments of seizure frequencies, cognition and
antibodies in 10 cases identified over 20 months. We hypothesized that (i) faciobrachial dystonic
seizures would show a differential response to anti-epileptic drugs and
immunotherapy; and that (ii) effective treatment of faciobrachial dystonic
seizures would accelerate recovery and prevent the development of
cognitive impairment. The 10 cases expand both the known age at onset (28 to 92 years, median 68) and clinical features, with events of longer duration, simultaneously bilateral events, prominent automatisms, sensory
aura, and post-ictal fear and speech arrest. Ictal epileptiform electroencephalographic changes were present in three cases. All 10 cases were positive for
voltage-gated potassium channel-complex
antibodies (346-4515 pM): nine showed specificity for
leucine-rich
glioma inactivated 1. Seven cases had normal clinical magnetic resonance imaging, and the cerebrospinal fluid examination was unremarkable in all seven tested. Faciobrachial dystonic
seizures were controlled more effectively with
immunotherapy than anti-epileptic drugs (P = 0.006). Strikingly, in the nine cases who remained anti-epileptic
drug refractory for a median of 30 days (range 11-200), the addition of
corticosteroids was associated with cessation of faciobrachial dystonic
seizures within 1 week in three and within 2 months in six cases.
Voltage-gated potassium channel-complex
antibodies persisted in the four cases with relapses of faciobrachial dystonic
seizures during
corticosteroid withdrawal. Time to recovery of baseline function was positively correlated with time to
immunotherapy (r = 0.74; P = 0.03) but not time to anti-epileptic
drug administration (r = 0.55; P = 0.10). Of 10 cases, the eight cases who received anti-epileptic drugs (n = 3) or no treatment (n = 5) all developed
cognitive impairment. By contrast, the two who did not develop
cognitive impairment received
immunotherapy to treat their faciobrachial dystonic
seizures (P = 0.02). In eight cases without clinical magnetic resonance imaging evidence of hippocampal signal change, cross-sectional volumetric magnetic resonance imaging post-recovery, after accounting for age and head size, revealed cases (n = 8) had smaller brain volumes than healthy controls (n = 13) (P < 0.001). In conclusion, faciobrachial dystonic
seizures can be prospectively identified as a form of
epilepsy with an expanding phenotype.
Immunotherapy is associated with excellent control of the frequently anti-epileptic
drug refractory
seizures, hastens time to recovery, and may prevent the subsequent development of
cognitive impairment observed in this study.