Up Against the Wall
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.
The findings from the new neurological examination were again essentially within normal limits, except for a "questionable left visual field defect." However, the neurologist noted a peculiarity when the patient was asked to copy a standard clock face placed in front of her: she copied only the numbers 12 to 6, which were crowded into the right half of her drawing. The left side of the clock face (with numbers 7 to 11) was blank.
That is very worrisome. This is likely to be an example of hemispatial neglect. A person who has damage to the right parietal lobe will not attend to things in the left visual field. For example, a person may not shave the left side of his face. Or, a patient with a right parietal stroke may bump into things on the left side when walking. I now believe the EEG and the MRI findings will be especially important.
Findings from a repeated waking EEG with nasopharyngeal leads was again normal. However, prolonged (72 hour) 16-channel ambulatory EEG monitoring coincided with one of the patient's typical panic episodes, which evolved into a period of altered consciousness. This coincided with abnormal spike discharges in the right parietal region, without accompanying discharges in mesial temporal regions.
T2-weighted imaging on the MRI scan showed a 2.1 3 2.3-cm mass in the right parietal lobe. Subtotal resection and pathological examination revealed a low-grade astrocytoma. The patient's subsequent 3-month course showed a near-total disappearance of panic episodes and altered level of consciousness.
The association between panic symptoms and CPS has been known for many years, but the precise nature of this association is complex.2,3 On the one hand, CPS, usually originating in the temporal lobe, may produce symptoms that closely mimic those of a panic episode, such as paresthesias, anxiety, and tachycardia.
Indeed, a wide range of psychiatric symptoms are associated with CPS, including poor impulse control, rage episodes, suicide attempts, rapid mood swings, depression, and psychotic episodes.3 On the other hand, patients whose panic episodes lead to severe hyperventilation may actually develop neurological symptoms, such as paresthesias and altered levels of consciousness.4
The differential diagnosis of these two conditions can be difficult, and some patients may meet criteria for both PD and CPS. Although CPS-related anxiety is commonly associated with seizure foci in the temporal lobes, evidence suggests that parietal lobe seizures (PLS) may present with panic episodes. At least two cases of PLS- related panic episodes due to underlying parietal lobe tumors have been reported.5 Strikingly, results of the neurological examinations in both cases were reported as "unremarkable," as were initial standard lead EEG recordings.
In the composite case described here, an important (although long-delayed) clue was the presence of hemispatial neglect-a hallmark of right parietal lobe pathology.6 It is intriguing that some patients with right parietal seizure foci can present a transient neglect phenomenon in the postictal period, even in the absence of overt clinical neglect signs.7
Although late age at onset of panic episodes (after age 45) may help point to the presence of a structural/neurological cause, age of onset was clearly not helpful in this case. However, the alteration in level of consciousness-not seen in most patients with PD-was an important clue.
Aside from the specific pathology in this case, there are cautionary take-home lessons for all psychiatrists. First, a neurological examination may be unremarkable or nonfocal, even in the presence of structural brain disease. Second, routine EEGs may also be normal, even when epilepsy is present. (Repeated EEGs with nasopharyngeal leads or prolonged ambulatory monitoring is often necessary to "catch" the seizure.) Third, a favorable response to psychotropic medication (at least initially) is not unequivocal evidence of a psychogenic cause; on the contrary, a favorable response may also be seen when the psychopathology is due to underlying structural brain disease or epilepsy. Finally, psychiatrists must always look beyond DSM-IV criteria and scrutinize the longitudinal course and evolution of a psychiatric disorder-for example, noting that alteration in consciousness was not an early feature in this case, but developed, presumably, as the underlying tumor expanded.
The title of this column-"Up Against the Wall"-is derived from the word "parietal," ie, from the Latin "parietalis," meaning "belonging to the wall." The idea is that the parietal lobe rests directly against the "wall" of the skull; hence, expansion of a parietal tumor can go on just so long before the patient begins to suffer.
Battaglia M, Bertella S, Politi E, et al. Age at onset of panic disorder: influence of familial liability to the disease and of childhood separation anxiety disorder.
Am J Psychiatry
Thompson SA, Duncan JS, Smith SJ. Partial seizures presenting as panic attacks.
Stern TA, Murray GB. Complex partial seizures presenting as a psychiatric illness
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Perkin GD, Joseph R. Neurological manifestations of the hyperventilation syndrome.
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Alemayehu S, Bergey GK, Barry E, et al. Panic attacks as ictal manifestations of parietal lobe seizures.
Marotta JJ, McKeeff TJ, Behrmann M. Hemispatial neglect: its effects on visual perception and visually guided grasping.
Prilipko O, Seeck M, Mermillod B, et al. Postictal but not interictal hemispatial neglect in patients with seizures of lateralized onset.