Panic disorder and hyperventilation syndrome (HVS) are frequently underrecognized conditions that are easily mistaken for epileptic seizures. This chapter highlights practical diagnostic strategies for distinguishing these disorders. We explore etiologies of HVS and conclude with a discussion of the effects of hyperventilation on seizures and the EEG because these issues may arise in the context of the evaluation of hyperventilation symptoms. Potential areas of commonality in the pathogenesis of panic disorder and epilepsy are discussed in Chapter 206.

A 28-year-old woman had undergone a subtotal resection of a right temporal ganglioglioma at 11 years of age. This had presented with complex partial seizures associated with déjà-vu sensation followed by altered responsiveness. She was seizure free until 8 years later, when typical seizures recurred, but now with secondary generalization. A further resection of a large part of the right temporal lobe was undertaken. This resulted in significant improvement in the epilepsy, but the patient continued to have occasional complex partial seizures with a rising epigastric aura, déjà-vu sensations, and complex motor automatisms.

She subsequently developed new episodes, different from her typical complex partial seizures. These began with a sense of shortness of breath and a choking feeling. She experienced nausea that was distinct from the earlier rising epigastric aura. The episodes also included dizziness and a perception that things were unreal around her. She also had an overwhelming feeling that she was going to die. With great concern about these episodes, the husband gave up his job to be constantly by her side.

Video-electroencephalographic (EEG) monitoring demonstrated that, although the patient has had ongoing epileptiform discharges and slow waves over the right temporal region, the new episodes were unassociated with electrographic correlate. A diagnosis of panic attacks was rendered. The patient has undergone a process of psychoeducation, reassurance, and discussion with the appropriate neurosurgeons. She began to articulate her fear of dying from her tumor. Panic attacks improved significantly with this treatment but occasionally recurred without clear provocation. Her husband was trained to be observant but not overindulgent in response to the episodes, and he ultimately returned to work.

One of the most common episodic symptoms that can be confused with a seizure is a panic attack. Numerous series attest to the common misdiagnosis of seizures in patients with panic attacks^26,38 and the erroneous diagnosis of panic attacks among patients with seizures.^1,14,51,78 Recurrent unexpected panic attacks define the condition termed panic disorder.⁶⁶ Diagnostic criteria for panic attacks and panic disorder are listed in Table 1. Significant morbidity associated with epilepsy or panic disorder and with the failure to allocate appropriate treatment makes the need to distinguish these two disorders especially crucial.

Epilepsy has a lifetime prevalence of 3% to 4%,³⁶ and panic disorder has a lifetime prevalence of 1% to 2%.⁶⁴ Although there is a fairly equal overall rate of epilepsy in men and women, panic disorder is twice as likely in women.

According to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV),³ a panic attack is a “discrete period of intense fear or discomfort” in which four or more of the symptoms listed in Table 1 “develop abruptly and reach a peak within 10 minutes.” Many of the symptoms of panic attacks are reminiscent of symptoms that may appear during some types of epileptic seizures. Differences between panic attacks and seizures are highlighted in Table 2 and elaborated on in the following discussion.

Fear is a commonly encountered component of partial seizures and is the most common ictal psychiatric symp-tom.^13,81 The importance of the temporal lobe as a site of localization for fear auras is validated by electrical stimulation of mesial temporal structures such as the amygdala, which produces many of the symptoms reminiscent of panic attacks (intense fear, dizziness, nausea, tachycardia, chest pain, and depersonalization).²⁹ Gloor argued that “the aura of fear in a temporal lobe seizure may take exactly the form of a typical panic attack.”²⁹ He further contended that this “situation is further compounded in those patients with epilepsy who also have panic attacks that may provoke their epileptic seizures, either by hyperventilation or by some direct effect of the CNS arousal.”²⁹

The fear aura tends to be associated more with a typical rising epigastric aura, whereas panic attacks are associated more with a spreading abdominal discomfort. The aura tends to be described as if it has a “harder,” more organic feel. Williams⁸¹ described ictal fear as unnatural rather than seeming more reality based. The intensity of ictal fear sensation is mild to moderate and rarely reaches the intensity of a panic attack.

Anxiety symptoms in panic attacks vary in nature among different individuals. Some experience a nonspecific sensation of “impending doom,” whereas others may experience a fear of having incurred a devastating medical problem such as a heart attack or stroke. Sometimes, the anxiety is less prominent than the other features, such as palpitations or chest discomfort, noted in Table 1. It is thus of little wonder that most patients with a panic attack present initially to an emergency room or a nonpsychiatric medical clinician rather than to a psychiatrist.³⁴

In panic attacks, autonomic symptoms and other bodily symptoms appear such as palpitations, sweating paresthesias, dizziness, nausea, feeling faint, and a sense of abdominal or central chest discomfort, and it is not uncommon for patients experiencing a panic attack to be thought of as having an acute
coronary attack or a stroke. Autonomic symptomatology is also common in seizures, but these are of lesser “subjective” intensity than in panic attacks. Of note, paroxysmal salivation is a typical autonomic symptom in seizures of mesial temporal or insular origin and not of panic attacks. Salivation may often be copious and associated with nausea and vomiting.

Subjective dyspnea often experienced during a panic attack led to the earlier confusion and often mislabeling of panic attacks as hyperventilation syndrome, although some might argue that they are intimately related (see later discussion).²⁸ Alteration in breathing pattern is very common to both seizures and panic attacks, so that the documentation of hyperventilation has limited distinguishing value. If hyperventilation is severe, tetany may occur, which could be confused with seizures associated with tonic activity.

In contrast to complex partial seizures, distinct confusion or loss of consciousness is unusual in a panic attack, although patients may become completely absorbed by the panic experience to the point at which they are unable to report what is going on around them. A panic attack associated with profound hyperventilation could also conceivably lead to a “subjective perception” of loss of consciousness. Symptoms of derealization, depersonalization, and déjà-vu may occur in both conditions.⁷³ The patient with panic attacks associated with these symptoms could end up undergoing an extraordinarily extensive testing if panic is not considered in the differential diagnosis by the medical clinician. Because of dissociation during panic attacks and subsequent claims of amnesia for the episodes, the patient may never make it to a psychiatrist for treatment (M. Trimble, personal communication). Distortion of perception should raise additional suspicion for partial seizures.

“Reported” preservation of awareness of surroundings and responsiveness during the ictus are usually interpreted as supportive evidence of a panic attack. It is important to remember, however, that in seizures of nondominant mesial temporal origin, patients may continue to follow commands and interact with the examiner or other interlocutors during the ictus, giving the appearance of “intact” consciousness.²³ Careful testing of these patients, however, after the event reveals that they do not recall what happened during it. In such cases, recording of these events with video-EEG may be the only way of establishing a correct diagnosis.

Ictal fear usually lasts <30 seconds and is usually more stereotyped than panic attacks. A partial complex seizure during which ictal fear may occur usually lasts only 2 minutes. However, partial complex status epilepticus associated with isolated fear has been reported.⁶² In contrast, panic attacks usually last from 5 to 20 minutes and have a longer buildup of anxieties.

Postictal symptoms of panic and symptoms of primary panic disorder can often lead to confusion. For example, in a study of 100 patients with refractory epilepsy, Kanner et al.⁴⁴ found that 10% of patients experienced postictal symptoms of panic after >50% of their seizures. The median duration of these symptoms was 24 hours. A careful history of the context in which symptoms occur as well as a review of other clues (Table 2) should help to avoid militate against this potential confusion.

Seizures can begin at any age, although certain forms of seizures, such as absence seizures, are much likelier to begin in childhood. Panic disorder usually begins in late adolescence or early adulthood, although onset in the 30s and even 40s can occur.⁶⁴ Symptoms suggestive of panic attacks that begin in older age groups should be vigorously investigated for the possibility of a seizure disorder.

The value of performing a detailed history (including contacting witnesses of an episode) when distinguishing seizures from panic attacks cannot be overemphasized. Anecdotal experience and review of case series of seizures⁷⁹ mistaken to be panic attacks often reveals some evidence of associated classic ictal phenomenology during some of the attacks such as automatisms or motor activity suggestive of spread of seizure activity. Patients often fail to recognize or report such associated symptoms such as transient confusion or subtle automatisms, and therefore it behooves the clinician to search for these clues. Sometimes, a frank 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.

Panic attacks tend to be somewhat less stereotyped than seizures, although this is best documented on video-EEG because historical accounts of observers may not necessarily emphasize the obvious replicability of ictal episodes.

Although some panic attacks may be linked to specific situations, panic disorder comprises at least two spontaneous panic attacks, at least one of which is associated with worry about subsequent attacks or avoidance behavior. Controversy
exists whether agoraphobia (a common comorbid condition consisting of fear related to places from which escape may be difficult)^48,64,76 is a component of panic disorder or represents an independent condition that may be provoked by a panic attack. Similar to epilepsy, anticipatory anxiety may become so severe that the individual begins to restrict travel and activity for fear of finding himself or herself in the midst of an attack. Social phobias are common in panic disorder, but agoraphobia may also occur in epilepsy.

Although sleep can be provocative for many types of seizures, it is worth remembering that two thirds of patients with panic attacks have had one or more events at night. Polysomnography has demonstrated panic attacks occurring at sleep onset during stage 2 sleep or slow-wave sleep, but most commonly after awakening.^10,53,61,63

The EEG may be helpful in suggesting an epileptic disorder both interictally, if epileptiform abnormalities or other focal cerebral abnormalities are found, or ictally, if an episode is caught during an episode while the EEG is running. Not uncommonly, the epileptologist is consulted to help to distinguish a seizure disorder from panic disorder and extended EEG monitoring such as video-EEG is ordered. Video-EEG has the advantage of permitting a detailed review of recorded clinical behavior in addition to detailed EEG analysis. Experienced electroencephalographers are aware, however, of the limitations of the EEG, in that simple partial and sometimes even complex partial seizures may not reveal an obvious correlate on scalp EEG¹⁴ and that, therefore, the absence of an obvious electrographic seizure during an episode does not necessarily exclude seizures.¹⁸ Supplementation of routine EEG recording
with meticulously placed sphenoidal electrodes may enhance the yield on EEG.⁴³ Elevated serum prolactin levels 15 to 20 minutes after an episode may help to point to a seizure as the etiology, even when there is no obvious change on the surface EEG recording.⁹

It has been suggested that lactate infusion could be used as a diagnostic tool to provoke panic if it is present, but this is rarely necessary or even feasible.^57,70 Hyperventilation may provoke a panic attack in those prone to panic disorder, but evidence suggests that such provoked attacks are subjectively different from natural panic attacks.³¹ It is generally considered that both these procedures have their effects by causing alterations in pCO₂ and pH.⁶⁶