Antidepressant Treatment of Pathologic Laughing or Crying in Elderly Stroke Patients Michael J. Panzer, MD; Alan M. Mellow, MD, PhD
Abstract
Pathologic laughing or crying (PLC), a complication of many neurologic disorders, involves behavior that is either inappropriate to the context or to the patient’s subjective feeling state. It is due to a dysregulation of the motoric components of emotional experience. PLC is distinct from, but often associated with, major depression. The relatively few reports on treatment of PLC are primarily with tricyclic antidepressants. We report the effective treatment of PLC due to stroke in three patients with nortriptyline or fluoxetine. The cases also illustrate the broad spectrum of depressive symptoms (from none to a major depression) seen in patients with PLC. We discuss treatment implications and directions for future research.
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or over a century, numerous authors have described abnormal crying and, less frequently, laughing which are either inappropriate to the context or to the patient’s subjective feeling state. It is most commonly associated with stroke’ but is independent of poststroke depression.’It is also seen in a variety of other neurologic conditions (Table 1). A number of terms for this phenomenon have been employed. These include emotional l a b i l i t ~ ,emo~ tional incontinence,6 organic emotionalism,23 sham mirth,2:‘ involuntary laughter,” pathologic laughing and ~ e e p i n gand , ~ most frequently, pathologic laughWe recommend use of the term ing and pathological laughing or crying (PLC) because it is more specific, it is well recognized, and laughing and crying may or may not coexist. PLC also distinguishes the specific symptoms of pathologic laughing and crying from the wide range of other abnormal affects seen in many conditions. A key feature of PLC is its distinction from true mood disorders; it may or may not complicate a ma-
Received March 20, 1991. Received revised June 20, 1991. Accepted for publication Oct 18, 1991. . From the Department of Psychiatry, University of Michigan, Ann Arbor, MI. Address correspondence to Dr Alan M. Mellow, Geropsychiatry Program, Department of Psychiatry, University of Michigan Medical Center, 900 Wall Street, Ann Arbor, MI 48109-0722.
jor depressive episode. A partial or complete dissociation occurs between the subjective feeling state and the external display. Clinically, a spectrum is seen from patients with striking incongruity between laughing or crying and subjective feeling state (such as the man who experienced a laughing seizure at his father’s burialx) to those whose laughing or crying is simply an exaggeration of the subjective feeling state. While it is beyond the scope of this paper to discuss the pathophysiology of PLC,9,26it involves dysregulation of the motoric components of emotional expression, resulting from neurologic disease. PLC may occur in the context of pseudobulbar palsy, a syndrome of pathologic affect coupled with upper motor neuron signs and symptoms. These may include dysphagia, dysphasia, and hyperactive jaw and palatal reflexes. As the population ages, elderly patients will more commonly present to clinicians with PLC and other behavioral sequelae of stroke. Several treatments for PLC have been described. These include the antidepressants amitripty1ine,2,3,u,27*28imipramin2,23*27nortriptyline,z doxe ~ i n and , ~ desipramine.” Schiffer et a13 found that low-dose amitriptyline quickly and completely resolved both laughing and crying spells in eight of 12 nondepressed patients with multiple sclerosis. In a placebo-controlled study, Lawson and MacLeod’ successfully treated 11 stroke patients with imip-
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Panzer and Mellow TABLE 1 Conditions Associated With Pathologic Laughing or Crying Condition Source Stroke Hughes et all Multiple sclerosis Schiffer et Amyotrophic lateral Lieberman et al,’ Wolf et al‘ sclerosis Dottr7Ironside,’ Wilson,’ Brain tumors Achari & Colover,” Stevenson et a],” Cantu &Drew” Epilepsy Offen ct al,” Gascon & Lombr~so,’~ Sethi & Surya Rao,’’ Money & Hosta16 Primary lateral sclerosis Beal et all7 Progressive supranuclear Wolf et a16 palsy Huntington’s disease Caine et all’ Friedrich‘s ataxia Langworthy & Hesser” Temporal lobe infarction Swash2’ Prefrontal lobotomy KrameP Head trauma Ross & RushU Syringobulbia Langworthy & Hesser” Neurosyphilis Langworthy & Hesser”
ramine or amitriptyline. Ross and Rushz used an open design in effectively treating three patients with stroke or head trauma using imipramine, desipramine, or nortriptyline. Nortriptyline was found to be superior to placebo in stroke patients with PLC in a double-blind trial (RGRobinson, personal communication). Sandyk2’ reported a striking, rapid decrease in pathologic crying in a demented man treated with nomifensine. Jankovi? treated the pathologic crying of a patient with postencephalitic parkinsonism using methylphenidate. Wolf et a16 treated five patients (with amyotrophic lateral sclerosis, progressive supranuclear palsy, normal-pressure hydrocephalus, or stroke) in an open design with levodopa. Four of five patients had marked or total resolution of PLC. Udaka et a13’ performed the only known neurotransmitter metabolite study of PLC patients (primarily with stroke). They found that cerebrospinal fluid levels of the dopamine metabolite homovanillic acid (HVA) were significantly decreased in patients with either pathologic laughing or crying. No difference was found in the serotonin metabolite 5-hydroxyindoleaceticacid (5-HIAA) concentration. In addition, they treated 25 patients with levodopa; 15 had total or marked resolution of PLC symptoms within 2 to 5 days. Treatment response did not correlate with pretreatment HVA levels. Eight of the same patients were also treated with amantadine, four of whom showed substantial im-
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provement. Seliger and Hornstein2’ reported effective treatment of pathologic crying in a stroke patient first with 25 mg/day of amitriptyline then with 10 mg/day of fluoxetine. We report three cases of PLC due to stroke in geriatric patients, effectively treated with nortriptyline or fluoxetine. These cases illustrate that PLC can be associated with a spectrum of depressive syndromes ranging from the clear absence of a major depression, to some symptoms of a major depression but not meeting full criteria, to a full major depression. Case Reports
Case 1
Ms K. was an 80-year-old woman referred to the Geropsychiatry Program for evaluation of tearfulness. She had no psychiatric history prior to a stroke 4 years before evaluation. This resulted in right lower facial weakness, slurred speech, and dysphagia. Since the stroke, she also experienced several episodes a day of dramatic crying, with abrupt onset and resolution, lasting a few seconds. She felt sad and inadequate during these episodes but was euthymic and asymptomatic between them. Her tearfulness was more likely to occur when she was fatigued or frustrated by having difficulty with calculations or playing bridge. She did not laugh inappropriately. Her sleep, appetite, interest in activities, selfesteem, and mood between crying spells were normal. She denied thoughts of suicide or death. Four months prior to evaluation, her internist, in telephone consultation with one of the authors (A.M.M.), prescribed nortriptyline for presumptive PLC. The episodes of crying did not change at a dosage of 30 mg per day. Her other medications were trimethoprimsulfamethoxazole for prophylaxis of urinary tract infections, hydrochlorothiazide for hypertension, and aspirin to prevent recurrent stroke. On mental status testing, she was alert, pleasant, and well oriented. She did not appear sad except for approximately six times during a 90-minute interview when she Fried, each time for 10 to 14 seconds. There was no apparent relationship to the topic of discussion, and she did not understand why she cried. Speech and thought were normal, and there were no psychotic features. She scored 29 of 30 on the Mini-Mental State E ~ a m i n a t i o nPhysical .~~ examination showed an increased jaw jerk and a nor-
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ma1 gag reflex. Computed tomographic (CT) scan showed lesions of the left Sylvian fissure region and the right frontal lobe, consistent with infarction. Her dose of nortriptyline was increased to 40 mg daily. Within 2 days, the frequency of her crying spells decreased to about one per week. The improvement was still present at 3-month follow-up. She subsequently had another stroke, which did not affect the crying spells. Case 2 Ms J. was a 64-year-old woman referred for possible depression. The patient denied any problems, but her husband felt that over the prior year she had become withdrawn and less active, and she had begun taking naps in the evening. In addition, he described crying spells after totally innocuous statements by him. They occurred two to four times per week. Her mood was normal during these spells and neither of them could understand why she cried. She also laughed in the absence of anything funny about three times per week. She was uncertain whether she actually felt amused while laughing. * Ms J. denied prior psychiatric history. Her daughter was successfully treated for depression with fluoxetine. Medications included levothyroxine for hypothyroidism, and hydrochlorothiazide and lisinopril for hypertension. On mental status testing, she was alert and well oriented, with normal and reactive affect. Psychomotor activity was normal. There was no suicidal ideation, thought disorder, or psychosis. Her mood was euthymic. She scored 30 of 30 on the Mini-Mental State E ~ a m i n a t i o nCT . ~ ~scan of the head showed diffuse substance loss and reduced attenuation anterior to the frontal horn of the left lateral ventricle, consistent with ischemia. Neuropsychometric testing revealed subtle generalized cognitive deficits, as well as focal right hemisphere impairment. Although we did not feel she had a full major depressive syndrome, we prescribed 20 mglday of fluoxetine for her laughing and crying. On follow-up 1 month later, the frequency of her inappropriate laughing had decreased to twice in the previous month. She still cried up to three times weekly but only when her husband criticized her. When crying, she felt she was "not as good" as her husband would like yet did not feel sad per se. At subsequent follow-up her husband stated that she was making mistakes on addressing envelopes and with telephone numbers, although these problems were stable.
Case 3
Ms S. was a 64-year-old woman who suffered a right-sided frontotemporal stroke 2 years previously. This resulted in left facial and body weakness. Since then, she experienced episodes of crying during which she did not feel sad. There was no pathologic laughter. She had no psychiatric history before the stroke. When first seen by the authors she had taken fluoxetine 20 mglday for 10 weeks. The weekly frequency of her crying spells had not changed on fluoxetine. Only during the 3 weeks prior to evaluation had she felt depressed between crying spells. Her energy was chronically poor but had recently worsened. She complained of poor memory and at times got disoriented. Her sleep, interest, concentration, and appetite were normal, and she did not have suicidal ideation. She scored 29 of 30 on the MiniMental State E ~ a m i n a t i o nJaw . ~ ~ and palatal reflexes and speech were normal. Although we recommended increasing the dose of fluoxetine, she continued taking 20 mglday. Two months later, she was euthymic and her crying spells had decreased from once weekly to less than once per month. Within another 2 months, the frequency had increased to twice weekly, and her mood was again depressed. She felt a burden to her family, still had low energy and poor memory subjectively (with no change in cognition clinically). Her appetite was normal, and she denied suicidal ideation. She still did not feel dysphoric when crying, though she did feel sad the rest of the time. She met DSM-III-X33 criteria for a major depressive episode, whereas she had not previously. Overall, the patient felt that fluoxetine had decreased the frequency and duration of her crying spells. Discussion These cases illustrate the spectrum of depressive symptoms in patients who suffer from PLC. Case 1 is typical of pathologic crying secondary to bilateral cortical strokes,'.' in the absence of a depressive syndrome. The crying showed an impressive response to nortriptyline. The rapid response to increase in dosage (within 2 days) contrasts with the well-known delay of up to 6 weeks for the response of major depression to ant"ldepressants.31 This is consistent with other reports of rapid therapeutic response of PLC to antidepressant^.^#" The second patient may have had a very early dementing disorder, although she certainly did not meet DSM-III-R33criteria for dementia. While certain
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symptoms reported by her husband (which she denied) are often seen in depression, she also did not meet criteria for a major depression. The laughing occurred less frequently while taking fluoxetine, and the crying was less easily evoked, although its frequency did not change. Her symptoms of PLC were associated with a left frontal stroke. It is possible that she also had right-side disease detected only by neuropsychological testing. Case 3 represents pathologic crying .due to a right frontotemporal stroke. The frequency of crying episodes decreased while Ms S. took fluoxetine, but her delayed response to treatment may be unusual in this disorder. Her original PLC was due to a stroke without a major depression; the increase in frequency of crying spells when she did develop a major depression illustrates how symptoms of PLC may be exacerbated by a major depression. While the delay between fluoxetine initiation and improvement of PLC could also suggest another cause for the improvement, the stable -course for 2 years prior to fluoxetine treatment suggests a therapeutic response. Together, these cases illustrate several general aspects of PLC. It may occur with (case 1)or without (cases 2 and 3) pseudobulbar palsy.35 Laughing and crying may develop as a result of unilateral (cases 2 and 3) or bilateral (case 1)brain lesions (although bilateral lesions are more common'). PLC may be either independent of (case l), or exacerbated by (case 3), a major depression. Symptoms of laughing or crying may respond differentially to antidepressant treatment (case 2). Although these cases involved frontotemporal cortical strokes, subjective and objective emotional phenomenon are modulated at multiple cortical and subcortical levels. Hence, PLC may be seen in association with diffuse or localized lesions throughout the brain, including cortex, hypothalamus, limbic structures, basal ganglia, and brain stem. To our knowledge, there is only one other reported case of effective treatment of PLC with fluoxetine.*' Though its mechanism of action might suggest a serotoninergic role in the syndrome, Udaka et a131 found no difference between cerebrospinal fluid 5-HIAA levels in PLC patients and those of controls. The pathophysiology of PLC thus requires further study. Given the widespread use of fluoxetine in the treatment of depression and the increasing interest in the role of serotonin in dementia,36 we anticipate further reports on the use of this medication with PLC because the syndrome is often confused or coexistent with major depression and may complicate dementia.
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Previous reports on the effective treatment of PLC with dopaminergic agents6p31suggest a role for this neurotransmitter. Since tricyclic antidepressants are known to increase levels of brain d ~ p a m i n e , ~ ~ antidepressants may act through this mechanism. Other prodopaminergic agents that may prove to be useful in this disorder include br~mocriptine~' and b~propion.~~ One may reasonably choose kom among these agents in treating PLC, based 'largely on empirical data and some speculation on mechanism. The efficacy and dosage requirements of all these treatments require further investigation. Since patiqnts with PLC are seen in psychiatry, neurology, geriatrics, and general medicine settings, physicians in these specialties must be able to recognize the condition and understand its treatment and relationship to other disorders. References 1. Hughes W, Dodgson MCH, MacLennan DC: Chronic cerebral hypertensive disease. Lnncet 1954;2:770-774. 2. Robinson RG, Moms PL, Fedoroff JP: Depression and cerebrovascular disease. J Cliri Psychiatry 1990;51:26-31. 3. Schiffer RB, Herndon RM, Rudick RA: Treatment of pathologic laughing and weeping with amitriptyline. N EttglJ Med 1985;312:1480- 1482. 4. Schiffer RB, Cash J, Hemdon RM: Treatment of emotional lability with low-dosage tricyclic antidepressants. Psychosorriatics 1983;2411094- 1096. 5. Lieberman A, Benson F Control of emotional expression in pseudobulbar palsy. A personal experience. Arch Neurol 1977;34:717-719. 6. Wolf JK, Santana HB, Thorpy M: Treatment of "emotional incontinence" with levodopa, letter. Neurology 1979;29:14351436. 7. Dott NM: Sexual development and functional activity, in Clark WE Le Gros, Beattie J, Riddoch G, Dott NM (eds): The Hypothnlamus: Morphological, Functional, Clitiical arid Surgical Aspects. Edinburgh, Oliver and Boyd, 1938, p 180. 8. Ironside R: Disorders of laughter due to brain lesions. Brain 1956;79:589-609. 9. Wilson SAK Some problems in neurology. 11-Pathological laughing and crying. J Neurol Psychopnthol 1924;4:299333. 10. Achari AN, Colover J: Posterior fossa tumors with pathological laughter. JAMA 1976;235:1469-1471. 11. Stevenson GC, Stoney RJ, Perkins RK, A d a m JE: A transcervical transclival approach to the ventral surface of the brain stem for removal of a clivus chordoma. J Neurosirrg 1966;24:544-551. 12. Cantu RC, Drew JH: Pathological laughing and crying associated with a tumor ventral to the pons. Case report. J Nerrrosurg 1966;24:1024-1026. 13. Offen ML, Davidoff RA, Troost BT, Richey E T Dacrystic epilepsy. J Neurol Neurosurg Psychintry 1976;39:829-834. 14. Gascon GG, Lornbroso m. Epileptic (gelastic) laughter. Epil ~ s i a1971;12:63-76.
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17. Beal MF, Richardson E P Primary lateral sclerosis. A case report. Arch Neurol 1981;38:630-633. 18. Caine ED, Hunt RD, Weingartner H, Ebert MH: Huntington’s dementia. Clinical and neuropsychological features. Arch Gen Psychiatry 1978;35377-384. 19. Langworthy OR, Hesser FH: Syndrome of pseudobulbar palsy. An anatomic and physiologic analysis. Arch Intern Med 1940;65:106-121. 20. Swash M: Released involuntary laughter after temporal lobe infarction. ] Neurof 1972;35:108-113. 21. Kramer H C Laughing spells in patients, after lobotomy. ] Nerv Ment Dis 1954;119:517-522. 22. Ross ED, Rush AJ: Diagnosis and neuroanatomical correlates of depression in brain-damaged patients. Arch Gen Psychiatry 1981;38:1344- 1354. 23. Lawson IA, MacLeod RD: The use of imipramine and other psychotropic drugs in organic emotionalism. BY Psychiatry 1969;115:281-285. 24. Martin J P Fits of laughter (sham mirth) in organic cerebral disease. Brain 1950;73:453-464. 25. Zilgien H: Rire et pleurer spasmodiques. Epilepsie jacksoniennebccompagnee de crises de larmes et suivie d’aphasie et dhemiplegie gauche avec ramollissement de la zone corticale rnotrice droite. Rev Med Est 1906;38:1-12. 26. Poeck K: Pathophysiology of emotional disorders associated with brain damage, in Handbook of Clinical Neurology, vol 3. Amsterdam, North-Holland, 1969, pp 343-367. 27. Carosao JT, Cohen JA, Gudesblatt M: Amitriptyline in amyotrophic lateral sclerosis, letter. N Engf ] Med 1985; 313:1478.
28. Seliger GM, Homstein A: Serotonin, fluoxetine, and pseudobulbar affect. Neurology 1989;39:1400. 29. Sandyk R Nomifensine for ”emotional incontinence” of the pseudobulbar type. ] A m Geriatr Soc 1985;33:375. 30. Jankovic J: Amitriptyline in amyotrophic lateral sclerosis, letter. N Engl ] Med 1985;313:1478-1479. 31. Udaka F, Yamao S, Nagata H, et al: Pathologic laughing and crying treated with levodopa. Arch Neurol 1984;41: 1095- 1096. 32. Folstein MF, Folstein SE, McHugh P R Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. ] Psychiatr Res 1975;12:189-198. 33. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed, revised. Washington, DC, American Psychiatric Association, 1987. 34. Quitkin FM,Rabkin JG, Ross D, McGrath PJ: Duration of antidepressant drug treatment. What is an adequate trial? Arch Gen Psychiatry 1984;41:238-245. 35. Asfora WT, DeSalles AAF, Abe M, Kjellberg RN: Is the syndrome of pathological laughing and crying a manifestation of pseudobulbar palsy? J Neurol , Neurosurg Psychiatry 1989;52523-525. 36. Lawlor B A Serotonin and dementia. Psychiatr Ann 1990;20:567-570. 37. Andersen J, Aabro E, Gulmann N, et al: Anti-depressive treatment in .Parkinson‘s disease. Acta Neurol Scand 1980;62:210-219. 38. Cedarbaum JM, Schleifer LS: Drugs for Parkinson’s disease, spasticity, and acute muscle spasms, in Gilman AG, Rall TW, Nies AS, Taylor P (eds): The Phamcologiull Basis of Therapeu- tics, 8th ed. New York, Pergamon Press, 1990, p 474. 39. Maxwell RA, Mehta NB, Tucker WE, et al: Bupropion, in Goldberg ME (ed): Pharmacological and Biochemical Properties of Drug Substances, vol 3. Washington, DC, American Pharmaceutical Association, Academy of Pharmaceutical Sciences, 1981, p p 22-28.
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Abstract
Pathologic laughing or crying (PLC), a complication of many neurologic disorders, involves behavior that is either inappropriate to the context or to the patient’s subjective feeling state. It is due to a dysregulation of the motoric components of emotional experience. PLC is distinct from, but often associated with, major depression. The relatively few reports on treatment of PLC are primarily with tricyclic antidepressants. We report the effective treatment of PLC due to stroke in three patients with nortriptyline or fluoxetine. The cases also illustrate the broad spectrum of depressive symptoms (from none to a major depression) seen in patients with PLC. We discuss treatment implications and directions for future research.
u Gerintr Psychiatry Neurol 1992;4:195-199).
F
or over a century, numerous authors have described abnormal crying and, less frequently, laughing which are either inappropriate to the context or to the patient’s subjective feeling state. It is most commonly associated with stroke’ but is independent of poststroke depression.’It is also seen in a variety of other neurologic conditions (Table 1). A number of terms for this phenomenon have been employed. These include emotional l a b i l i t ~ ,emo~ tional incontinence,6 organic emotionalism,23 sham mirth,2:‘ involuntary laughter,” pathologic laughing and ~ e e p i n gand , ~ most frequently, pathologic laughWe recommend use of the term ing and pathological laughing or crying (PLC) because it is more specific, it is well recognized, and laughing and crying may or may not coexist. PLC also distinguishes the specific symptoms of pathologic laughing and crying from the wide range of other abnormal affects seen in many conditions. A key feature of PLC is its distinction from true mood disorders; it may or may not complicate a ma-
Received March 20, 1991. Received revised June 20, 1991. Accepted for publication Oct 18, 1991. . From the Department of Psychiatry, University of Michigan, Ann Arbor, MI. Address correspondence to Dr Alan M. Mellow, Geropsychiatry Program, Department of Psychiatry, University of Michigan Medical Center, 900 Wall Street, Ann Arbor, MI 48109-0722.
jor depressive episode. A partial or complete dissociation occurs between the subjective feeling state and the external display. Clinically, a spectrum is seen from patients with striking incongruity between laughing or crying and subjective feeling state (such as the man who experienced a laughing seizure at his father’s burialx) to those whose laughing or crying is simply an exaggeration of the subjective feeling state. While it is beyond the scope of this paper to discuss the pathophysiology of PLC,9,26it involves dysregulation of the motoric components of emotional expression, resulting from neurologic disease. PLC may occur in the context of pseudobulbar palsy, a syndrome of pathologic affect coupled with upper motor neuron signs and symptoms. These may include dysphagia, dysphasia, and hyperactive jaw and palatal reflexes. As the population ages, elderly patients will more commonly present to clinicians with PLC and other behavioral sequelae of stroke. Several treatments for PLC have been described. These include the antidepressants amitripty1ine,2,3,u,27*28imipramin2,23*27nortriptyline,z doxe ~ i n and , ~ desipramine.” Schiffer et a13 found that low-dose amitriptyline quickly and completely resolved both laughing and crying spells in eight of 12 nondepressed patients with multiple sclerosis. In a placebo-controlled study, Lawson and MacLeod’ successfully treated 11 stroke patients with imip-
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Panzer and Mellow TABLE 1 Conditions Associated With Pathologic Laughing or Crying Condition Source Stroke Hughes et all Multiple sclerosis Schiffer et Amyotrophic lateral Lieberman et al,’ Wolf et al‘ sclerosis Dottr7Ironside,’ Wilson,’ Brain tumors Achari & Colover,” Stevenson et a],” Cantu &Drew” Epilepsy Offen ct al,” Gascon & Lombr~so,’~ Sethi & Surya Rao,’’ Money & Hosta16 Primary lateral sclerosis Beal et all7 Progressive supranuclear Wolf et a16 palsy Huntington’s disease Caine et all’ Friedrich‘s ataxia Langworthy & Hesser” Temporal lobe infarction Swash2’ Prefrontal lobotomy KrameP Head trauma Ross & RushU Syringobulbia Langworthy & Hesser” Neurosyphilis Langworthy & Hesser”
ramine or amitriptyline. Ross and Rushz used an open design in effectively treating three patients with stroke or head trauma using imipramine, desipramine, or nortriptyline. Nortriptyline was found to be superior to placebo in stroke patients with PLC in a double-blind trial (RGRobinson, personal communication). Sandyk2’ reported a striking, rapid decrease in pathologic crying in a demented man treated with nomifensine. Jankovi? treated the pathologic crying of a patient with postencephalitic parkinsonism using methylphenidate. Wolf et a16 treated five patients (with amyotrophic lateral sclerosis, progressive supranuclear palsy, normal-pressure hydrocephalus, or stroke) in an open design with levodopa. Four of five patients had marked or total resolution of PLC. Udaka et a13’ performed the only known neurotransmitter metabolite study of PLC patients (primarily with stroke). They found that cerebrospinal fluid levels of the dopamine metabolite homovanillic acid (HVA) were significantly decreased in patients with either pathologic laughing or crying. No difference was found in the serotonin metabolite 5-hydroxyindoleaceticacid (5-HIAA) concentration. In addition, they treated 25 patients with levodopa; 15 had total or marked resolution of PLC symptoms within 2 to 5 days. Treatment response did not correlate with pretreatment HVA levels. Eight of the same patients were also treated with amantadine, four of whom showed substantial im-
196
provement. Seliger and Hornstein2’ reported effective treatment of pathologic crying in a stroke patient first with 25 mg/day of amitriptyline then with 10 mg/day of fluoxetine. We report three cases of PLC due to stroke in geriatric patients, effectively treated with nortriptyline or fluoxetine. These cases illustrate that PLC can be associated with a spectrum of depressive syndromes ranging from the clear absence of a major depression, to some symptoms of a major depression but not meeting full criteria, to a full major depression. Case Reports
Case 1
Ms K. was an 80-year-old woman referred to the Geropsychiatry Program for evaluation of tearfulness. She had no psychiatric history prior to a stroke 4 years before evaluation. This resulted in right lower facial weakness, slurred speech, and dysphagia. Since the stroke, she also experienced several episodes a day of dramatic crying, with abrupt onset and resolution, lasting a few seconds. She felt sad and inadequate during these episodes but was euthymic and asymptomatic between them. Her tearfulness was more likely to occur when she was fatigued or frustrated by having difficulty with calculations or playing bridge. She did not laugh inappropriately. Her sleep, appetite, interest in activities, selfesteem, and mood between crying spells were normal. She denied thoughts of suicide or death. Four months prior to evaluation, her internist, in telephone consultation with one of the authors (A.M.M.), prescribed nortriptyline for presumptive PLC. The episodes of crying did not change at a dosage of 30 mg per day. Her other medications were trimethoprimsulfamethoxazole for prophylaxis of urinary tract infections, hydrochlorothiazide for hypertension, and aspirin to prevent recurrent stroke. On mental status testing, she was alert, pleasant, and well oriented. She did not appear sad except for approximately six times during a 90-minute interview when she Fried, each time for 10 to 14 seconds. There was no apparent relationship to the topic of discussion, and she did not understand why she cried. Speech and thought were normal, and there were no psychotic features. She scored 29 of 30 on the Mini-Mental State E ~ a m i n a t i o nPhysical .~~ examination showed an increased jaw jerk and a nor-
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ma1 gag reflex. Computed tomographic (CT) scan showed lesions of the left Sylvian fissure region and the right frontal lobe, consistent with infarction. Her dose of nortriptyline was increased to 40 mg daily. Within 2 days, the frequency of her crying spells decreased to about one per week. The improvement was still present at 3-month follow-up. She subsequently had another stroke, which did not affect the crying spells. Case 2 Ms J. was a 64-year-old woman referred for possible depression. The patient denied any problems, but her husband felt that over the prior year she had become withdrawn and less active, and she had begun taking naps in the evening. In addition, he described crying spells after totally innocuous statements by him. They occurred two to four times per week. Her mood was normal during these spells and neither of them could understand why she cried. She also laughed in the absence of anything funny about three times per week. She was uncertain whether she actually felt amused while laughing. * Ms J. denied prior psychiatric history. Her daughter was successfully treated for depression with fluoxetine. Medications included levothyroxine for hypothyroidism, and hydrochlorothiazide and lisinopril for hypertension. On mental status testing, she was alert and well oriented, with normal and reactive affect. Psychomotor activity was normal. There was no suicidal ideation, thought disorder, or psychosis. Her mood was euthymic. She scored 30 of 30 on the Mini-Mental State E ~ a m i n a t i o nCT . ~ ~scan of the head showed diffuse substance loss and reduced attenuation anterior to the frontal horn of the left lateral ventricle, consistent with ischemia. Neuropsychometric testing revealed subtle generalized cognitive deficits, as well as focal right hemisphere impairment. Although we did not feel she had a full major depressive syndrome, we prescribed 20 mglday of fluoxetine for her laughing and crying. On follow-up 1 month later, the frequency of her inappropriate laughing had decreased to twice in the previous month. She still cried up to three times weekly but only when her husband criticized her. When crying, she felt she was "not as good" as her husband would like yet did not feel sad per se. At subsequent follow-up her husband stated that she was making mistakes on addressing envelopes and with telephone numbers, although these problems were stable.
Case 3
Ms S. was a 64-year-old woman who suffered a right-sided frontotemporal stroke 2 years previously. This resulted in left facial and body weakness. Since then, she experienced episodes of crying during which she did not feel sad. There was no pathologic laughter. She had no psychiatric history before the stroke. When first seen by the authors she had taken fluoxetine 20 mglday for 10 weeks. The weekly frequency of her crying spells had not changed on fluoxetine. Only during the 3 weeks prior to evaluation had she felt depressed between crying spells. Her energy was chronically poor but had recently worsened. She complained of poor memory and at times got disoriented. Her sleep, interest, concentration, and appetite were normal, and she did not have suicidal ideation. She scored 29 of 30 on the MiniMental State E ~ a m i n a t i o nJaw . ~ ~ and palatal reflexes and speech were normal. Although we recommended increasing the dose of fluoxetine, she continued taking 20 mglday. Two months later, she was euthymic and her crying spells had decreased from once weekly to less than once per month. Within another 2 months, the frequency had increased to twice weekly, and her mood was again depressed. She felt a burden to her family, still had low energy and poor memory subjectively (with no change in cognition clinically). Her appetite was normal, and she denied suicidal ideation. She still did not feel dysphoric when crying, though she did feel sad the rest of the time. She met DSM-III-X33 criteria for a major depressive episode, whereas she had not previously. Overall, the patient felt that fluoxetine had decreased the frequency and duration of her crying spells. Discussion These cases illustrate the spectrum of depressive symptoms in patients who suffer from PLC. Case 1 is typical of pathologic crying secondary to bilateral cortical strokes,'.' in the absence of a depressive syndrome. The crying showed an impressive response to nortriptyline. The rapid response to increase in dosage (within 2 days) contrasts with the well-known delay of up to 6 weeks for the response of major depression to ant"ldepressants.31 This is consistent with other reports of rapid therapeutic response of PLC to antidepressant^.^#" The second patient may have had a very early dementing disorder, although she certainly did not meet DSM-III-R33criteria for dementia. While certain
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symptoms reported by her husband (which she denied) are often seen in depression, she also did not meet criteria for a major depression. The laughing occurred less frequently while taking fluoxetine, and the crying was less easily evoked, although its frequency did not change. Her symptoms of PLC were associated with a left frontal stroke. It is possible that she also had right-side disease detected only by neuropsychological testing. Case 3 represents pathologic crying .due to a right frontotemporal stroke. The frequency of crying episodes decreased while Ms S. took fluoxetine, but her delayed response to treatment may be unusual in this disorder. Her original PLC was due to a stroke without a major depression; the increase in frequency of crying spells when she did develop a major depression illustrates how symptoms of PLC may be exacerbated by a major depression. While the delay between fluoxetine initiation and improvement of PLC could also suggest another cause for the improvement, the stable -course for 2 years prior to fluoxetine treatment suggests a therapeutic response. Together, these cases illustrate several general aspects of PLC. It may occur with (case 1)or without (cases 2 and 3) pseudobulbar palsy.35 Laughing and crying may develop as a result of unilateral (cases 2 and 3) or bilateral (case 1)brain lesions (although bilateral lesions are more common'). PLC may be either independent of (case l), or exacerbated by (case 3), a major depression. Symptoms of laughing or crying may respond differentially to antidepressant treatment (case 2). Although these cases involved frontotemporal cortical strokes, subjective and objective emotional phenomenon are modulated at multiple cortical and subcortical levels. Hence, PLC may be seen in association with diffuse or localized lesions throughout the brain, including cortex, hypothalamus, limbic structures, basal ganglia, and brain stem. To our knowledge, there is only one other reported case of effective treatment of PLC with fluoxetine.*' Though its mechanism of action might suggest a serotoninergic role in the syndrome, Udaka et a131 found no difference between cerebrospinal fluid 5-HIAA levels in PLC patients and those of controls. The pathophysiology of PLC thus requires further study. Given the widespread use of fluoxetine in the treatment of depression and the increasing interest in the role of serotonin in dementia,36 we anticipate further reports on the use of this medication with PLC because the syndrome is often confused or coexistent with major depression and may complicate dementia.
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Previous reports on the effective treatment of PLC with dopaminergic agents6p31suggest a role for this neurotransmitter. Since tricyclic antidepressants are known to increase levels of brain d ~ p a m i n e , ~ ~ antidepressants may act through this mechanism. Other prodopaminergic agents that may prove to be useful in this disorder include br~mocriptine~' and b~propion.~~ One may reasonably choose kom among these agents in treating PLC, based 'largely on empirical data and some speculation on mechanism. The efficacy and dosage requirements of all these treatments require further investigation. Since patiqnts with PLC are seen in psychiatry, neurology, geriatrics, and general medicine settings, physicians in these specialties must be able to recognize the condition and understand its treatment and relationship to other disorders. References 1. Hughes W, Dodgson MCH, MacLennan DC: Chronic cerebral hypertensive disease. Lnncet 1954;2:770-774. 2. Robinson RG, Moms PL, Fedoroff JP: Depression and cerebrovascular disease. J Cliri Psychiatry 1990;51:26-31. 3. Schiffer RB, Herndon RM, Rudick RA: Treatment of pathologic laughing and weeping with amitriptyline. N EttglJ Med 1985;312:1480- 1482. 4. Schiffer RB, Cash J, Hemdon RM: Treatment of emotional lability with low-dosage tricyclic antidepressants. Psychosorriatics 1983;2411094- 1096. 5. Lieberman A, Benson F Control of emotional expression in pseudobulbar palsy. A personal experience. Arch Neurol 1977;34:717-719. 6. Wolf JK, Santana HB, Thorpy M: Treatment of "emotional incontinence" with levodopa, letter. Neurology 1979;29:14351436. 7. Dott NM: Sexual development and functional activity, in Clark WE Le Gros, Beattie J, Riddoch G, Dott NM (eds): The Hypothnlamus: Morphological, Functional, Clitiical arid Surgical Aspects. Edinburgh, Oliver and Boyd, 1938, p 180. 8. Ironside R: Disorders of laughter due to brain lesions. Brain 1956;79:589-609. 9. Wilson SAK Some problems in neurology. 11-Pathological laughing and crying. J Neurol Psychopnthol 1924;4:299333. 10. Achari AN, Colover J: Posterior fossa tumors with pathological laughter. JAMA 1976;235:1469-1471. 11. Stevenson GC, Stoney RJ, Perkins RK, A d a m JE: A transcervical transclival approach to the ventral surface of the brain stem for removal of a clivus chordoma. J Neurosirrg 1966;24:544-551. 12. Cantu RC, Drew JH: Pathological laughing and crying associated with a tumor ventral to the pons. Case report. J Nerrrosurg 1966;24:1024-1026. 13. Offen ML, Davidoff RA, Troost BT, Richey E T Dacrystic epilepsy. J Neurol Neurosurg Psychintry 1976;39:829-834. 14. Gascon GG, Lornbroso m. Epileptic (gelastic) laughter. Epil ~ s i a1971;12:63-76.
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Laughing or Crying 15. Sethi PK, Surya Rao T Gelastic, quiritarian, and cursive epilepsy. A clinicopathological appraisal. ] Neurol Neurosurg Psychiatry 1976;39:823-828. 16. Money J, Hosta G: Laughing seizures with sexual precocity: Report of two cases. Johns Hopkins Med ] 1967;120326336.
17. Beal MF, Richardson E P Primary lateral sclerosis. A case report. Arch Neurol 1981;38:630-633. 18. Caine ED, Hunt RD, Weingartner H, Ebert MH: Huntington’s dementia. Clinical and neuropsychological features. Arch Gen Psychiatry 1978;35377-384. 19. Langworthy OR, Hesser FH: Syndrome of pseudobulbar palsy. An anatomic and physiologic analysis. Arch Intern Med 1940;65:106-121. 20. Swash M: Released involuntary laughter after temporal lobe infarction. ] Neurof 1972;35:108-113. 21. Kramer H C Laughing spells in patients, after lobotomy. ] Nerv Ment Dis 1954;119:517-522. 22. Ross ED, Rush AJ: Diagnosis and neuroanatomical correlates of depression in brain-damaged patients. Arch Gen Psychiatry 1981;38:1344- 1354. 23. Lawson IA, MacLeod RD: The use of imipramine and other psychotropic drugs in organic emotionalism. BY Psychiatry 1969;115:281-285. 24. Martin J P Fits of laughter (sham mirth) in organic cerebral disease. Brain 1950;73:453-464. 25. Zilgien H: Rire et pleurer spasmodiques. Epilepsie jacksoniennebccompagnee de crises de larmes et suivie d’aphasie et dhemiplegie gauche avec ramollissement de la zone corticale rnotrice droite. Rev Med Est 1906;38:1-12. 26. Poeck K: Pathophysiology of emotional disorders associated with brain damage, in Handbook of Clinical Neurology, vol 3. Amsterdam, North-Holland, 1969, pp 343-367. 27. Carosao JT, Cohen JA, Gudesblatt M: Amitriptyline in amyotrophic lateral sclerosis, letter. N Engf ] Med 1985; 313:1478.
28. Seliger GM, Homstein A: Serotonin, fluoxetine, and pseudobulbar affect. Neurology 1989;39:1400. 29. Sandyk R Nomifensine for ”emotional incontinence” of the pseudobulbar type. ] A m Geriatr Soc 1985;33:375. 30. Jankovic J: Amitriptyline in amyotrophic lateral sclerosis, letter. N Engl ] Med 1985;313:1478-1479. 31. Udaka F, Yamao S, Nagata H, et al: Pathologic laughing and crying treated with levodopa. Arch Neurol 1984;41: 1095- 1096. 32. Folstein MF, Folstein SE, McHugh P R Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. ] Psychiatr Res 1975;12:189-198. 33. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed, revised. Washington, DC, American Psychiatric Association, 1987. 34. Quitkin FM,Rabkin JG, Ross D, McGrath PJ: Duration of antidepressant drug treatment. What is an adequate trial? Arch Gen Psychiatry 1984;41:238-245. 35. Asfora WT, DeSalles AAF, Abe M, Kjellberg RN: Is the syndrome of pathological laughing and crying a manifestation of pseudobulbar palsy? J Neurol , Neurosurg Psychiatry 1989;52523-525. 36. Lawlor B A Serotonin and dementia. Psychiatr Ann 1990;20:567-570. 37. Andersen J, Aabro E, Gulmann N, et al: Anti-depressive treatment in .Parkinson‘s disease. Acta Neurol Scand 1980;62:210-219. 38. Cedarbaum JM, Schleifer LS: Drugs for Parkinson’s disease, spasticity, and acute muscle spasms, in Gilman AG, Rall TW, Nies AS, Taylor P (eds): The Phamcologiull Basis of Therapeu- tics, 8th ed. New York, Pergamon Press, 1990, p 474. 39. Maxwell RA, Mehta NB, Tucker WE, et al: Bupropion, in Goldberg ME (ed): Pharmacological and Biochemical Properties of Drug Substances, vol 3. Washington, DC, American Pharmaceutical Association, Academy of Pharmaceutical Sciences, 1981, p p 22-28.
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