Main findings
To the best of our knowledge, this is the first study examining the prevalence of well-validated diagnoses of epilepsy and other seizures disorders in patients admitted to acute psychiatric care. Noteworthy, we found a prevalence five to six times as high (3.9%) as reports from the general population (0.6-0.9% [
15,
16]). In addition, we found a history of acute symptomatic seizures and psychogenic non-epileptic seizures in 5.5 and 2.4% of the patients, respectively.
The total prevalence of seizure disorders in our cohort (10%) is comparable to a previous prevalence estimate of seizure disorders in acute psychiatric inpatients [
17]. Based on a retrospective chart review Boutros et al. reported that 9.5% of patients admitted to their acute psychiatric center had a diagnosis of epilepsy or “seizure”. However, the authors reported that the charts did not include information that allowed for an accurate diagnosis of epilepsy and noted that the tertiary nature of their facility probably gave inflated estimates.
We screened for epilepsy and seizures using two self-report questions and epilepsy diagnoses in local hospital records and the National Patient Registries. Noteworthy, the most precise screening tool for epilepsy was the self-report question ‘are you or have you ever been treated for epilepsy?” (Table
1). The small overestimation of epilepsy prevalence using this question (5.0% vs. 3.9%) may possibly be related to past or present use of antiseizure medications for psychiatric disorders. The sole use of ICD-9/10 diagnoses from hospital records and registries gave a large overestimation of epilepsy. In fact, only 14 out of 38 patients with a coded diagnosis of epilepsy were found to have true epilepsy on validation. During this validation process it was noted that contacts limited to EEG and clinical appointments for a suspected seizure disorder sometimes had been inappropriately coded as epilepsy. These observations underscore the limitations in solely using registry data as a measure of true epilepsy.
Differential diagnosis
The epileptic affliction of patients in this clinical sample spanned from a history of drug-resistant and debilitating chronic epilepsies, well-controlled epilepsy, epilepsy resolved (including self-limited childhood epilepsies), as well as recurrent acute symptomatic seizures. The high frequency of past or present epileptic seizures suggests that the brains of many of these people might harbor a shared susceptibility to both psychiatric and seizure disorders possibly by overlapping genetic variants and network abnormalities [
18‐
20].
Patients with psychogenic non-epileptic seizures exhibit a wide range of symptoms; the most common pattern consists of variable movements of limbs, head, and trunk, typically out of phase and often prolonged with preserved consciousness. These conversion symptoms are occasionally associated with self-harm behavior and may be caused by overwhelming and unspoken remote emotional traumas, sometimes related to uncontrolled epilepsy [
3,
12]. More than a quarter of patients presenting a seizure disorder was diagnosed with psychogenic non-epileptic seizures; two of which also had a history of epilepsy.
Along with psychogenic non-epileptic seizures, panic attacks with hyperventilation seemed to be the most common condition misinterpreted as an epileptic event. Dizziness and reduced consciousness with loss of control may occur, as well as peripheral sensory and even motor symptoms. The somatic symptoms may be explained by two independent mechanisms taking effect simultaneously, that is, biochemical changes due to lowered pH and cerebral vasoconstriction due to hypocapnia. A provocation test with hyperventilation is usually diagnostic. Hyperventilation may also be a puzzling part of psychogenic non-epileptic seizures [
3,
21], whereas conversive elements may be part of the hyperventilation syndrome. The borders between the two conditions may sometimes be blurred.
Seizure disorders and psychiatric disease
In the 2005 revised International League Against Epilepsy definition of epilepsy, the core elements of the diagnosis were extended beyond recurrent seizures to also include “the neurobiological, cognitive, psychological, and social consequences of the condition”. This definition encompasses a vulnerability to develop psychiatric disorders [
1]. The variable temporal relationships between epileptic and psychiatric symptoms in the present series support that these brain-behavior relationships may be bidirectional [
2], expressing that psychiatric comorbidity may be part of the epileptic disorder rather than only representing its consequences. Even long resolved self-limited epilepsies of childhood may be associated with poor psychosocial and neuropsychiatric outcome in adult life [
22‐
25], as interestingly was demonstrated in five patients reported here.
This complex patient series illustrates well the obstacles that may take place in the diagnosis, classification and management of seizure disorders in patients with psychiatric comorbidities. Various studies in patients with epilepsy have demonstrated a particular high prevalence of depressive and anxiety disorders substantially contributing to poor health-related quality of life, morbidity, and mortality [
26]. It is also well known that psychosis may accompany epilepsy in various ways. Postictal and interictal psychosis usually follow long-standing severe and uncontrolled epilepsy [
27]. Although the temporal relationship between psychiatric symptoms and seizure events was not exactly recorded in this study, elements of these complications may have been present in patients with drug-resistant epilepsy. So-called alternative psychoses may occur when seizures suddenly are suppressed by effective treatment. The relationship between epilepsy and interictal psychosis is bidirectional, but epilepsy antedating psychosis is far more common. In a cohort of consecutive patients with both epilepsy (meeting the ILAE diagnostic criteria) and psychosis unrelated to ictal symptoms, 6.8% of patients had developed psychosis prior to the development of epilepsy. Clinical characteristics did not differ in relation to the order of the onset of the two disorders, conceivably due to shared genetic vulnerabilities [
28].
Some antiseizure medications may cause various psychiatric adverse events. Moreover, a high load of antipsychotic medications may lower the seizure threshold. All these factors must be considered in patients with comorbid seizures and psychiatric disorders [
29]. It has further been hypothesized that various episodic psychiatric symptoms, including panic attacks and violent acts, occasionally may belong to a wider spectrum of epileptic disorders which falls outside the current criteria for epilepsy. Scalp EEGs may be unremarkable or ambiguous, but intracranial EEG may reveal signs of neuronal hyperexcitability, and some of these patients may respond to antiseizure medications [
30]. Interestingly, epileptiform and sharp elements in standard EEG recordings have been found to correlate with a higher frequency of hypomanic episodes in bipolar II disorder even in the absence of a history of seizures [
31].
Patients with substance use disorders are at high risk of developing seizures, both during the withdrawal phase (e.g. alcohol) and during intoxications (e.g. stimulants). These acute symptomatic seizures are provoked by systemic insults outside physiological limits and contrasts to the seizures precipitated by everyday circumstances in patients with epilepsy. Seizure occurrence may be dependent on the individual seizure threshold, either inherently [
20,
32] or facilitated by otherwise subclinical subtle brain lesions [
33] or influenced by prescribed psychotropic treatment, sleep deprivation and stress, particularly when these factors are combined. It has been reported that substance use disorders are considerably more common in patients with epilepsy as compared to the general population [
34]. However, the borders between epilepsy and acute symptomatic seizures may be blurred [
35], and epilepsy can easily be over-diagnosed. To complicate the picture even more, epilepsy and acute symptomatic seizures may occur in the same individual, as in five patients in this patient series. In these patients, acute symptomatic seizures differed from previous habitual seizures by the presence of evident withdrawal symptoms or intoxications with neurotoxic substances.
Noteworthy, inflammatory brain diseases should always be ruled out in patients presenting with acute psychiatric symptoms and epileptic seizures. Indeed, we advocate prompt diagnostic procedures for autoimmune or infectious encephalitis in such patients to ensure early appropriate treatment [
36,
37].
Strengths and limitations
A strength of the present study is that the study sites (the acute psychiatric department and neurological department) are the sole institutions providing acute psychiatric care and epilepsy management in the catchment area. The rather small sample size allowed for a detailed review of the entire medical record of each patient with a strict validation procedure using established definitions for epilepsy and other seizure disorders. Nevertheless, despite these efforts, the precision of exact diagnoses of seizure disorders might represent a problem in this type of retrospective study, as the differentiation between recurrent unprovoked seizures (epilepsy) and repeated acute symptomatic seizures may be challenging. Moreover, a large part of the self-reported seizure events was not addressed in the medical records. This might have led us to underestimate the number of patients with acute symptomatic seizures [
33]. The inclusion rate of 64.3% compares favorably to other studies in acute psychiatric settings [
38‐
40]. However, since patients with more severe acute psychiatric symptoms are more prone to decline study participation, this numbers may represent a selection bias.