Neuropsychiatric Symptoms of Epilepsy

54
C. Brandt
Introduction
Anxiety disorders constitute important, though for a long time, neglected comorbidities
of epilepsy [ 1 ]. They deserve attention, because they are frequent and negatively
impact the quality of life of persons with epilepsy. While stigma and social
consequences of epilepsy may lead to consecutive anxiety, there is also a bidirectional
relationship between both disorders. One aspect of this relationship is that an
anxiety disorder may also precede the onset of epilepsy. Animal models mirror the
relationship between both disorders.
Neurobiological Correlates of Anxiety
Activation of brain regions in anxiety in healthy subjects and in patients with different
anxiety disorders has been studied extensively by means of fMRI. Different areas have
been found to be involved in different subtypes of anxiety disorders: hyperactivity of
amygdala and insula in posttraumatic stress disorder (PTSD), social phobia and specific
phobia, hypoactivation in the dorsal and rostral anterior cingulate cortices, and
the ventromedial prefrontal cortex structures linked to the experience and regulation
of emotion in PTSD [ 2 ]. The serotonin system is crucially involved in the development
of anxiety, and PET studies showed decreased 5-HT1A binding in persons with
temporal lobe epilepsy (TLE), thus demonstrating that the serotonin system is disturbed
in persons with TLE [ 3 ]. The hippocampus plays an important role in re-experiencing
fear, and the mechanisms are similar to epileptic discharges [ 4 ]. Activation of
fear circuits is a major hypothesis for explaining symptoms in anxiety disorders, and
the reduction of an excessive output from these neurons may theoretically improve the
clinical picture [ 4 , 5 ]. GABAergic inhibition and modulation of Ca-channels work
antiepileptic and anxiolytic, which may be an explanation for the efficacy of some
antiepileptic drugs in anxiety disorders [ 6 ] that will be discussed below. Imbalances in
the GABAergic system have been found in brain specimens of operated patients with
refractory temporal lobe epilepsy and comorbid anxiety and/or depression [ 7 ].
Ictal, Postictal, and Interictal Anxiety
First of all, anxiety may be a seizure symptom, that is, a simple partial seizure may
present with anxiety as part of the seizure semiology. It is a key issue for the clinician
to clarify the differential diagnosis between ictal anxiety and an anxiety disorder.
Several features have been described as helpful: ictal psychiatric symptoms are
usually brief, stereotyped, occur out of the context, and are associated with other
seizure-related phenomena such as subtle or overt automatisms or postictal confusion
of variable duration [ 8 ].