The case described above illustrates the common confusion between panic attacks resulting from a panic disorder and ictal fear or ictal panic, which is the expression of simple (and complex) partial seizures that typically originate in mesial temporal structures. In this chapter, we review the clinical differences between these two conditions, their relatively frequent comorbidity, and the involvement of common neurobiological mechanisms and neuroanatomical structures that explain such comorbidity.
Panic disorder is a neuropsychiatric disorder that presents with recurrent panic attacks.1 According to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV),2 the criteria of panic attacks include a discrete period of intense fear or discomfort, in which four or more of the following symptoms develop abruptly and reach a peak within 10 min: (1) cardiopulmonary symptoms that can present as chest pain or discomfort, sensations of shortness of breath or smothering, palpitations, pounding heart, or accelerated heart rate; (2) neurologic symptoms, including trembling or shaking, paresthesias (numbness or tingling sensation), dizziness, unsteady gait, light-headedness, or faintness; (3) psychiatric symptoms, including feelings of derealization (feelings of unreality) or depersonalization (being detached from oneself), fear of losing control or going crazy, and fear of dying; (4) autonomic symptoms, such as sweating, chills, or hot flushes, and gastrointestinal symptoms, such as feeling of choking, nausea, or abdominal distress.
Case Study
A 34-year-old woman was taken to the emergency room after being witnessed as having a generalized tonic-clonic (GTC) seizure. The patient had been in good health until the time of this seizure, with the exception of self-described panic attacks, which she had been experiencing for the previous 6 years. She described the attacks as a “panicky” feeling associated with a sensation of déjà vu and of “butterflies” in her stomach going up to her neck, often accompanied by a nauseous feeling, which at times was followed by copious salivation. The episodes lasted between 15 and 30 sec and occurred both in an awake state and out of sleep. Their average frequency had initially been two to five per month, with an increased frequency during the 2 days preceding her menstrual periods, at which time she could have up to three attacks in 1 day. In those days she typically complained of feeling tired and having problems with concentration and completing complex cognitive tasks. During the past year, the frequency of her attacks had increased to 6 to 10 per month, and on the day of her GTC, she had experienced 6 attacks.
She had been treated initially with alprazolam and then with various selective serotonin reuptake inhibitors (SSRIs) without remission of her attacks. In the past year, she had decided to stop all psychotropic medication.
Following the GTC, a brain computed tomography (CT) scan with and without contrast was done; it was reported to be unremarkable. An electroencephalography (EEG) study done with awake and sleep recordings was also reported to be normal. The patient was advised that because this had been her first seizure, no pharmacologic treatment was indicated.
The patient continued to experience the episodes of panic with a frequency of two or three every 2 days. Three weeks after the first GTC, she had a second GTC, which resulted in an inpatient hospitalization. Brain magnetic resonance imaging (MRI) revealed a lesion in the left mesial temporal region that did not enhance with contrast (Figure 19-1). The patient underwent a prolonged video-EEG monitoring study with scalp, anterotemporal, and sphenoidal electrodes placed under fluoroscopy. She had two episodes without any concurrent EEG changes (Figure 19-2). However, on the second day of monitoring, she had a complex partial seizure that was preceded by her typical “panicky” feeling and epigastric discomfort manifested by unresponsiveness. An ictal pattern of left anterotemporal origin was recorded (Figure 19-3). Of note, a period of 40 sec of unresponsiveness occurred without the patient’s subsequent awareness of the loss of responsiveness. The patient was diagnosed with complex partial seizures of left mesial temporal origin secondary to a left mesial temporal lesion, probably a dysembrioplastic neuroepithelioma.
According to the DSM-IV criteria, panic disorder consists of recurrent, unexpected panic attacks, where at least one of the attacks has been followed by 1 month or more of persistent concern about having additional attacks, worry about the implications of the attack or its consequences, and a significant change in behavior related to the attacks. Panic disorder can present with or without agoraphobia, defined as anxiety about being in places or situations in which escape might be difficult (or embarrassing) or in which help might not be available in the event of having a panic attack.
Ictal fear or ictal panic is the most frequent form of ictal psychiatric symptom.3–5 Its prevalence has been estimated at ∼60% of auras presenting with “psychiatric” symptoms.3 Patients may report experiencing the “panicky” sensation associated with other symptoms, including epigastric discomfort, nausea, salivation, feelings of derealization or depersonalization, déjà vu, and jamais vu. The ictal fear can evolve into a complex partial or secondarily GTC seizure.
Ictal fear or panic is brief (<30 s in duration); if it evolves into a complex partial seizure, the event may last up to 2 min. Rarely, partial complex status epilepticus associated with isolated fear has been reported.6
Panic attacks have a significantly longer duration that can typically range from 5 to 20 min and at times may persist for several hours.
Ictal fear is stereotypical, occurs out of context to concurrent events, and is associated with other ictal phenomena, such as periods of confusion of variable duration and subtle or overt automatisms. The intensity of the sensation of fear is mild to moderate and rarely reaches the intensity of a panic attack. In fact, Williams described ictal fear as unnatural, rather than seeming more reality-based.7
Panic attacks tend to be somewhat less stereotyped than seizures; the feeling of fear or panic is very intense and is often referred as a feeling of impending doom. It is not infrequent for patients to become extremely apprehensive about experiencing another panic attack that may then lead to the development of a full-blown agoraphobia.
Ictal fear occurs independently of stressful situations, although some patients have identified an association with nonspecific stressors.
In patients with panic attacks and associated phobic disorders, panic attacks can often be triggered when facing the phobic stimulus (height, closed environments, etc.).
Ictal fear may occur during awake and sleep states. Although panic attacks can occur out of sleep, this is a relatively rare occurrence. Polysomnography has demonstrated panic attacks occurring at sleep onset, during stage 2 or slow-wave non-rapid eye movement (REM) sleep, but most commonly after awakening.8–11
Partial seizures of mesial temporal lobe origin that can present with ictal fear can begin at any age, although they are more likely to occur after late childhood/early adolescence. Panic disorder usually begins in late adolescence or early adulthood, but onset in the 30s and even 40s is common.12 In fact, panic disorder in childhood presents as school phobia.13 Symptoms suggestive of panic attacks that begin in older age groups should be vigorously investigated for the possibility of a seizure disorder.
Table 19-1 outlines the chief clinical differences between panic attacks and ictal fear.
| Symptom | Panic Attack | Ictal Fear |
|---|---|---|
| Consciousness | Preserved | Often impaired |
| Description of fearful sensation | Impending doom. “I feel like I am dying” | Fearful sensation, but often not intense |
| Duration | 5 to 20 min | <60 s (typically <30 s) |
| Anticipatory anxiety | Common | Uncommon |
| Agoraphobia | Common | Uncommon |
| Associated automatisms | Very rare | Common |
| Epileptiform activity on interictal EEG recordings | Absent | Present, but often sphenoidal electrodes may be necessary |
| Response to SSRI | Common | Negative |
| Response to AEDs | Rare | Common |
Clearly, a careful history is pivotal in suspecting and ultimately reaching the correct diagnosis. Although panic attacks and ictal fear may have similar symptoms, these may differ in their intensity and qualitative characteristics. Anecdotal experience and a review of case series of seizures mistaken to be panic attacks often reveal some evidence of associated classic ictal phenomenology during some of the attacks, such as automatisms, or motor activity suggestive of spread of seizure activity.14 Patients will often fail to recognize or report such associated symptoms as transient confusion or subtle automatisms; therefore, it behooves the clinician to search for these clues. Sometimes, as in the case illustrated above, a convulsion following fear symptomatology clinches the epileptic diagnosis. Identifying a past medical history of febrile seizures or other risk factors for spontaneous seizures provides additional diagnostic clues. In addition, a detailed analysis of the reported symptoms can be helpful. The following sections illustrate typical symptoms.
Autonomic and cardiovascular symptoms are part of panic attacks and ictal panic. Yet the intensity of these symptoms is greater to the point where the presence of chest discomfort and palpitations is often interpreted as the expression of an acute myocardial ischemia. A helpful sign is that of paroxysmal salivation, a typical autonomic symptom in seizures of mesial temporal or insular origin, but which is never reported in panic attacks.4 Salivation may often be copious and associated with nausea and vomiting.
Typically, patients with ictal panic may be aware of their surroundings, though at times they may notice that their concentration is affected after the event or that they must exert greater effort to achieve the same cognitive tasks. When ictal panic evolves to a complex partial seizure, patients become unaware of their surroundings. Yet it is not infrequent for responsiveness to be preserved in the course of a complex partial seizure of mesial temporal origin in the nondominant hemisphere.15 In fact, patients may continue interacting with others in a coherent manner during the ictus, but they are typically amnestic to the event when questioned postictally.
In the case of panic attacks, the patients’ awareness of their surroundings and responsiveness is expected to be preserved. Yet patients may become too absorbed by the panic to the point where they may not be able to report what is going on around them. In addition, a panic attack associated with profound hyperventilation could also conceivably lead to a “subjective perception” of loss of consciousness. Clearly, in such cases, the distinction with ictal panic is rendered more difficult.
The following symptoms may be less discriminating between ictal fear and panic attacks and can at times lead to confusion between the two conditions.
Hyperventilation is very common to both seizures and panic attacks; when severe, tetany may occur, which could be confused with seizures associated with tonic activity.
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