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New-Onset Panic Disorder After Right Thalamic Infarct

Received October 27, 1997; accepted November 6, 1997. From the Department of Psychiatry, University of Iowa, and the Veterans Affairs Medical Center (VAMC), Iowa City, Iowa. Address reprint requests to Dr. Woodman, University of Iowa, Department of Psychiatry and VAMC, 200 Hawkins Drive, Iowa City, IA 52242.

Key Words: Case Report • New-Onset Panic Disorder • Stroke • Infarction • Panic Disorder

Disturbances in affect have been recognized as part of the poststroke sequelae. Over the past 15 years, numerous studies have shown that depression is common in poststroke patients.^1–6 More recently, generalized anxiety has been identified as a frequently overlooked complication of stroke, most commonly in the acute poststroke period, but in some cases persisting over a 2- to 3-year follow-up period.^7–9 Anxiety and depression that occur after a cerebral vascular event are responsive to pharmacotherapy. Untreated anxiety and depression can have significant morbidity and may interfere with poststroke rehabilitation.^l0 In addition, the occurrence of a specific psychiatric disorder secondary to a discrete anatomical lesion can contribute to understanding the pathophysiology of the disorder. The following case illustrates a new-onset panic disorder following a right-sided thalamic infarct.

Case Report

Mr. T., a 69-year-old, married, Caucasian, right-handed man with no prior medical or psychiatric illness, presented to the hospital with mild left-sided weakness and new-onset visuospatial neglect of the left side. Light touch and tactile localization were diminished on the left side as compared with the right, but no additional motor or sensory deficits were found on physical examination. A head computed tomography (CT) revealed a less than 1 cm infarct in the right-posterior thalamus. The motor weakness resolved within several hours of hospitalization. The patient's sensory symptoms were stable during his hospitalization, and he was discharged to home 1 week after admission. He returned 1 month later complaining of new-onset episodes of tachycardia, shortness of breath, dizziness, nausea, and overwhelming fear of dying. The attacks had a sudden onset and occurred at unpredictable times. They lasted 5–10 minutes and resulted in a period of derealization for up to 2 hours after each episode. The patient experienced the attacks several times a day (range: 0–7, average: 3). The attacks had differing intensities and a variable number of symptoms. The patient did not develop any phobic avoidance. Family history of psychiatric illness was only remarkable for probable major depressive disorder in the patient's mother. The patient was diagnosed with panic disorder without agoraphobia, and treatment with a selective serotonin reuptake inhibitor (SSRI), 20 mg of fluoxetine a day, was initiated. The patient was given Xanax (0.25 mg/day), as needed, for anxiety for the first 2 weeks, and then the benzodiazepines were discontinued. The patient had an excellent response to fluoxetine, with a decreased number of attacks and fewer symptoms per attack at Week 2 and almost complete remission of symptoms at Week 4.

The patient was rehospitalized secondary to unrelated gastrointestinal symptoms 7 months after his stroke. Fluoxetine was not continued by the inpatient medical team, and the patient was discharged to home without it. Two weeks after discontinuation of fluoxetine, the panic attacks returned. Fluoxetine was restarted, with amelioration of attacks after 3 weeks of resumed treatment. He remained virtually panic-free on fluoxetine at the 1-year poststroke follow-up point.

Discussion

This case of panic disorder presenting after a right, nondominant, posterior thalamic infarct is unusual and may contribute to an understanding of the neuropathology of panic disorder.

The location of the patient's stroke on head CT as well as the clinical symptoms suggest the involvement of the ventral posterior nucleus of the thalamus. The ventral posterior nucleus is the largest primary somatic sensory-relay nucleus of the thalamus and is composed of two major divisions, the ventral posteromedial nucleus (VML) and the ventralposterolateral nucleus (VPL).¹¹ Results from a number of single-unit recording studies in the ventral posterior nucleus have shown somatotopic features in which the contralateral limbs and trunk are represented in the VPL and the head, face, and intraoral structures in the VML.^12–14 Also, the clinical finding of neglect is associated with a lateral location for the infarct. Kumral et al. evaluated 100 consecutive patients with thalamic hemorrhages and found that the symptom of neglect was associated with strokes of the anterolateral or posterolateral thalamus 77% of the time that it occurred.¹⁵ The patients' symptoms suggest involvement of the VPL, as contralateral neglect of the trunk and limbs are the major residual symptom.

Knowledge of the chemical architecture of the thalamus is limited but increasing. The presence of gamma-aminobutyric acid (GABA)-producing neurons occur in virtually all thalamic nuclei. The nuclei in the posterior group have GABA-immunoreactive neurons uniformly distributed in relative abundance. The thalamus receives substantial monoaminergic innervation as well, principally from the noradrenergic neurons of the locus ceruleus and from the serotonergic neurons of the dorsal raphe nucleus. The midbrain dopaminergic neurons do not contribute significantly to the innervation of the thalamus.^16,17 Norepinephrine fibers enter the thalamus through the reticular nucleus and then go anteriorly. Therefore, few noradrenergic fibers occur in the ventral posterior nuclei. However, the serotonergic innervation of the thalamus is substantial.¹⁹ It derives from extrinsic fibers arising mostly from the midbrain raphe nuclei, collecting into a major bundle that sweeps dorsoventrally. The innervation of lateral nuclear group is dense with serotonergic receptors, particularly the 5HT-1 subtype. Neuroactive peptides, including the brain-gut peptide cholecystekinin, are present in the thalamus, but their distribution and density are not well known, and they are not thought to be plentiful.²⁰

All of the neurotransmitters that ennervate the thalamus have been implicated in the etiology of panic disorder, including GABA and serotonin, which have been consistently found in moderate-to-high density in the VPL of primates. Animal studies have generally found that increasing 5HT function is anxiogenic.²¹ The opposite occurred in this case, where the stroke would be expected to decrease the serotonin in the thalamus, and by this model would be associated with no change in anxiety. The human challenge studies, with 5HT-2a/2c and 5HT-3 function increased, have by and large been in keeping with the animal data.²² However, treatment studies hint at the reverse, that SSRIs, which increase serotonin, are effective in panic disorder.²³ Therefore, another neurotransmitter system is most likely involved in panic disorder. The GABAergic system has also been implicated in panic disorder. Nutt et al. have suggested that panic disorder patients may have an abnormal benzodiazepine receptor sensitivity.²⁴ Recent studies have provided evidence that the GABA and 5HT systems are functionally intertwined, suggesting that benzodiazepines may exert their anxiolytic effects by indirectly affecting 5HT function through their facilitations of GABA.^25,26

Norepinephrine and cholecystekinin have been implicated in the etiology of panic disorder, but the density of these transmitters in the thalamus as a whole and in the VPL specifically is not felt to be high.

This case illustrates new-onset panic disorder following a nondominant posterior thalamic stroke. We hypothesize that the stroke includes the ventral posterolateral nucleus, based on clinical data and CT evidence. Neurotransmitters that are found in the thalamus, particularly serotonin (5HT-1) and GABA in the VPL, have been associated with panic disorder. A relationship between GABA dysfunction and its effect on the serotonin system may play a role in the etiology of panic disorder in this patient. The patient's excellent response to a SSRI supports this hypothesis. Panic disorder is probably a heterogeneous disorder, and the role of the thalamus in the etiology of some types of anxiety and panic attacks needs further study.

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