A 19-year-old woman was brought to the emergency department (ED) by her parents, who reported, "Her panic attacks have gotten out of control." The patient described a 2-year history of "panicky feelings coming out of nowhere," accompanied by an uncontrollable urge to "run out of the house." Usually these episodes lasted "a few minutes" and were accompanied by sudden onset of dizziness, palpitations, and "a feeling like things aren't real." The episodes had increased over the past month from 2 to 3 per week to 2 per day.
The results of a general medical and neurological examination by her primary care physician at the onset of symptoms had been "completely normal," as had the findings on routine laboratory tests. Antianxiety medication initially reduced the episode frequency but was no longer effective. A brief mental status examination was administered in the ED; the patient was oriented in all spheres, had normal cognitive functions (short-term memory, calculation, serial 7s), and showed no evidence of psychotic process.
The obvious initial diagnosis is panic disorder (PD), although I suspect there are some twists to still learn. Certainly, the age at onset is consistent with PD, which typically begins in late adolescence or early adulthood. Given the roughly 2:1 female predominance in PD, the case is also consistent with this diagnosis. Underlying medical and neurological causes need to be ruled out, including hyperthyroidism, pheochromocytoma, hypoglycemia, and epilepsy. But, given the normal medical, neurological, and laboratory examinations performed by the patient's primary care physician, I have to assume that such organic causes are less likely than PD.
Still, there are reasons to be skeptical. The increase in attack frequency and reduced effectiveness of antianxiety medication make me wonder whether some underlying physical process has worsened. It is also possible that recent psychosocial stressors are increasing the frequency of attacks, or that the patient has developed a tolerance to the medication. At this point, I would like to hear more about the patient's developmental and childhood history, personal and family psychiatric history, any known substance abuse, and recent psychosocial stressors. I would also like more details on the phenomenology of the panic episodes, such as whether they are associated with any alteration in level of consciousness or neurological symptoms. I also would like to hear more about the initial workup and treatment of the patient's attacks.
The patient's parents reported that their daughter had a "perfectly normal" birth and early developmental history, meeting all major neurodevelopmental milestones. There was no history of head trauma, seizures, or abnormal behavior. The patient did exhibit "a little school phobia" when she was in kindergarten, but this resolved spontaneously over a few months. Family history was negative for mood or anxiety disorders, schizophrenia, and other major psychiatric disorders. Although the patient and her parents denied any major recent stressors, the patient acknowledged "some bad arguments with my boyfriend in the past couple of months." The patient denied use of alcohol or illicit drugs, which was confirmed by her parents.
With respect to the attacks, the patient reported sometimes feeling "numb all over" while experiencing dizziness and palpitations. There was no history of pounding headaches or precipitation of symptoms with squatting. During her panic episodes, she had initially not shown any alteration in level of consciousness, automatisms, or stereotypies. However, over the past 2 months, her mother reported that the patient "seemed to space out a few minutes after she feels panicky . . . she has a blank stare and moves her hands in a funny way."
The patient was evaluated about 22 months ago by her family physician who—as noted earlier—found no abnormalities in general medical or neurological examinations. Vital signs at that time were within normal limits. Results of laboratory studies, including complete blood cell count; measurement of electrolyte, blood urea nitrogen, creatinine, fasting glucose, calcium, and thyroid-stimulating hormone levels; and liver function tests had all been within normal limits. Her doctor diagnosed "panic attacks" and started the patient on a combination regimen of sertraline (Zoloft), 25 mg/d, and clonazepam (Klonopin), 0.5 mg twice daily.
Within 30 days, the patient's panic episodes had decreased from 2 per week to 1 or 2 per month. The primary care physician nevertheless referred the patient to a consulting neurologist, who reported a "nonfocal" neurological examination. Findings on a routine waking electroencephalogram (EEG) (without special leads) were normal. No further neurological tests were recommended at that time. An increase in the patient's clonazepam dosage to 1 mg twice daily led to stabilization of the panic episodes at a frequency of about 1 per month. This pattern persisted until about 2 months ago.
That is a lot of information, but where does it leave the diagnosis of PD? First, the history of so-called school phobia—really, separation anxiety—is interesting. There is a well-established correlation between PD and childhood separation anxiety disorder. In fact, the pres- ence of the latter tends to predict early onset of PD.1 Perhaps the fights with her boyfriend have even reawakened fears of separation, leading to increased panic episodes. On the other hand, the absence of any familial history of anxiety gives pause since PD does tend to run in families.
As for the episodes, feeling "numb all over" is consistent with PD. The lack of pounding headaches, hypertension, and postural exacerbation argue against pheochromocytoma. The lack of altera- tion in consciousness—at least initially —argues against temporal lobe epilep- sy as a cause for these episodes, as does the normal waking EEG. The normal neurological examination also makes me more confident that I am not missing any major neurological problems.
However, the subsequent evolution of the patient's episodes is worrisome. It seems that recently there has been alteration in level of consciousness (described as spacing out or a blank stare), perhaps accompanied by stereotypies of some sort. I would still consider complex partial seizures (CPS), probably related to temporal lobe epilepsy, in the differential diagnosis. At this point I would like to do a repeat neurological examination and get a CT scan of the brain, or preferably, an MRI scan. A repeat EEG, perhaps with nasopharyngeal leads or sleep deprivation would also be useful.
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