To the Editor: Vascular mania, in contrast to vascular depression, is an under-recognized condition and has mainly been reported in scattered case reports.1 Although there is no universally accepted definition or criteria for diagnosing vascular mania, it broadly encompasses a manic syndrome associated with evidence of cerebrovascular disease, including history of stroke or transient ischemic attack, focal neurologic signs, radiological changes on neuroimaging, or cognitive deficits.1,2 The age of onset of vascular mania, also called poststroke mania by some authors, is typically in the fifth or sixth decade.1—3 New-onset mania following cerebrovascular episodes in patients with a long-standing history of depression is an intriguing phenomenon, which has only rarely been cited in the literature.4 We describe a patient with a history of depression who, following a stroke, initially developed dementia and then presented with florid manic symptoms.
Mr. A, a 47-year-old white man, was diagnosed with major depressive disorder for about 12 years. He had no prior episodes of hypomania or mania and no family history of bipolar disorder. About a year and a half ago, he had a coronary artery bypass surgery and the postsurgical period was complicated by respiratory and renal failure and an ischemic stroke. The patient had a protracted recovery from the above events over a month. A head CT scan at that time showed an infarct in the left inferior frontal region. At that time, the patient was being treated with sertraline, 200 mg/day, and this was continued after his discharge from the hospital. Mr. A was subsequently switched to bupropion, sustained-release 300 mg/day in divided doses, and was taking this medication until his index admission to the psychiatric unit. A year after the stroke, the patient’s family noticed that he was having memory problems and would get confused about where he was. He would also get lost in his own home, would leave the stove burner on, and had difficulty finding words. About 5 months after the onset of the cognitive decline, and for a couple of weeks before admission, Mr. A was noted to be getting increasingly irritable. He displayed extreme mood swings wherein he would cry spontaneously or would be very angry. In addition to the mood lability, he was hyperactive and talkative, displayed flight of ideas, had decreased need for sleep, and had inflated self-esteem with grandiose plans to expand his business. He also developed psychotic symptoms and believed that his wife was cheating on him. His wife reported an episode where the patient was seeing objects on the wall. His admission to the psychiatric unit was precipitated after he threatened to hurt his family members.
During his admission, Mr. A had an extensive work-up done. His blood counts were normal. BUN was normal while serum creatinine was 1.38 mg/dl (normal range=0.70—1.20 mg/dl), which was at baseline because of prior history of renal insufficiency. His fasting blood glucose was elevated at 127 mg/dl (normal range=65—100 mg/dl), and he had been diagnosed with type 2 diabetes mellitus, which was being treated by diet. His liver function tests, TSH, B12 and folate levels were normal, and rapid plasma reagin was nonreactive. Urine drug screen was positive for benzodiazepine and opioids as the patient was prescribed temazepam and propoxyphene/acetaminophen, but the patient did not have any history of illicit drug or alcohol use. He scored 18/30 on the Montreal Cognitive Assessment,5 with deficits in the domains of visuospatial/executive functions, attention, verbal fluency, abstraction, and delayed recall. His orientation was intact. He scored 15/18 on the Frontal Assessment Battery6 and had deficits in conceptualization and lexical fluency. Mr. A’s brain MRI showed several foci of hyperintensities in the white matter and basal ganglia on T2-weighted images. An area of encephalomalacia 1 cm in diameter was seen in the region corresponding to the infarct seen on the previous head CT scan. The patient was diagnosed with vascular mania according to recently proposed criteria,1 along with vascular dementia (per DSM-IV-TR), and bupropion was discontinued. Ziprasidone and carbamazepine extended-release were started and increased to 80 mg b.i.d. with meals and 800 mg b.i.d., respectively. Donepezil was also started at 5 mg/day for symptoms of dementia. Over the next 2 weeks, the patient significantly improved in his presentation, and prior to discharge he did not display any overt manic or psychotic symptoms, although his cognitive deficits continued. Of note, the patient also showed a marked decrease in spontaneous crying spells.
The most notable facet of this case was the emergence of manic symptoms in a patient with chronic depression after vascular dementia set in. Delayed onset of manic symptoms following silent cerebral infarctions is more common than acute onset immediately after a stroke.7 Cerebrovascular disease has been found to be associated with late-life mania even when compared to age and sex-matched patients with depression.8 In the same vein, late-onset mania is associated with greater vascular risk factors, making some authors hypothesize that late-onset mania may be a distinct subtype of mania.3,9 Although there are anecdotal reports of new-onset mania following stroke, mania in a patient with vascular dementia with a prior history of depression has rarely been described.10 In these patients, the switch from unipolar depression to bipolar illness usually happens over several years in line with the appearance of cerebral changes.11 The role of antidepressants inducing manic symptoms in the index patient cannot be entirely excluded, but this may be less likely due to the chronic nature of treatment at the same dose of bupropion.
Studies of late-onset bipolar disorder show severe cognitive deficits in these subjects, with some falling in the demented range.12,13 In patients with history of stroke who develop mania, cognitive decline usually precedes the manic symptoms as with this patient.1,10 In a case report, a patient developed dementia 18 months after a cerebrovascular event and then developed mania 2 months after that.10 Neuroimaging studies show increased prevalence of white matter hyperintensities in bipolar patients, both young and elderly.14,15 In addition, silent cerebral infarctions are known to be associated with mood disorders in the elderly, but the patients with late-onset mania have more widespread areas of infarctions compared with those with late-onset depression.7 These observations concur with the brain MRI findings in our patient. Of note, the patient’s initial infarction was left-sided, which is in contrast with the traditional association of right-sided brain lesions with mania.16 However, poststroke mania has been reported in patients with left-sided lesions.17,18 The widespread nature of brain lesions in our patient may have resulted in the disruption of the frontolimbic circuits resulting in decreased prefrontal modulation of the anterior limbic network and mood dysregulation manifesting as manic symptoms.19
This patient exhibited spontaneous crying episodes which is reminiscent of pathological crying or the recently described involuntary emotional expression disorder.20 However, as this patient exhibited manic symptoms in addition to pathological crying, this combination of symptoms can be explained better within the rubric of disinhibition syndromes described with brain lesions.11 Finally, carbamazepine has been effective in treating poststroke mania in some case studies and deserves further attention.21,22