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The causes and treatment of pseudobulbar affect in ischemic stroke

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Opinion statement

Pseudobulbar affect (PBA) is a disorder of emotional regulation characterized by uncontrollable outbursts of laughing and/or crying that are disproportionate to the emotions being experienced. The pathophysiology of PBA is currently unknown, although the disorder is thought to occur exclusively in the setting of neurologic disease, including stroke. The most influential theory on PBA posits that emotional outbursts are being generated in the brainstem autonomously due to loss of regulatory control by the frontal lobes. Although rarely life threatening, PBA can have significant impact on patients’ quality of life and thus merits treatment. Although currently there are no treatments approved by the Food and Drug Administration (FDA) for PBA, tricyclic antidepressants and selective serotonin reuptake inhibitors are commonly used. Both these treatments are inexpensive and relatively low risk, although the quality of the available data on their efficacy is not optimal. Recently, a new agent containing dextromethorphan and quinidine (DM/Q) demonstrated efficacy in treating PBA in two large clinical trials—one in patients with multiple sclerosis and the other in patients with amyotrophic lateral sclerosis. Further studies are being conducted. If DM/Q is approved for PBA treatment, it will be the first agent approved by the FDA for this purpose. The choice of whether to use DM/Q in this setting will likely depend on individual patient factors. Currently, the antidepressants are probably the most attractive pharmacologic options for treating PBA. Although nonpharmacologic therapies have not been studied systematically, they should be explored in cognitively intact patients.

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References and Recommended Reading

  1. Lawson IR, MacLeod RD: The use of imipramine (“Tofranil”) and other psychotropic drugs in organic emotionalism. Br J Psychiatry 1969, 115:281–285.

    PubMed  CAS  Google Scholar 

  2. House A, Dennis M, Molyneux A, et al.: Emotionalism after stroke. BMJ 1989, 298:991–994.

    PubMed  CAS  Google Scholar 

  3. Dark FL, McGrath JJ, Ron MA: Pathological laughing and crying. Aust N Z J Psychiatry 1996, 30:472–479.

    Article  PubMed  CAS  Google Scholar 

  4. Lieberman A, Benson DF: Control of emotional expression in pseudobulbar palsy. A personal experience. Arch Neurol 1977, 34:717–719.

    PubMed  CAS  Google Scholar 

  5. Darwin C: The Expression of Emotions in Man and Animals. New York: Appleton and Company; 1872.

    Google Scholar 

  6. Wilson SAK: Some problems in neurology: no. 2 pathological laughing and crying. J Neurol Psychopathol 1924, 4:299–333.

    Google Scholar 

  7. Gallagher JP: Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand 1989, 80:114–117.

    PubMed  CAS  Google Scholar 

  8. Zeilig G, Drubach DA, Katz-Zeilig M, Karatinos J: Pathological laughter and crying in patients with closed traumatic brain injury. Brain Inj 1996, 10:591–597.

    Article  PubMed  CAS  Google Scholar 

  9. Schiffer R, Pope LE: Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci 2005, 17:447–454.

    PubMed  CAS  Google Scholar 

  10. Kim JS, Choi S, Kwon SU, Seo YS: Inability to control anger or aggression after stroke. Neurology 2002, 58:1106–1108.

    PubMed  CAS  Google Scholar 

  11. Poeck K: Pathophysiology of emotional disorders associated with brain damage. In Handbook of Clinical Neurology. Edited by Vinken PJ, Bruyn GW. Amsterdam: North Holland Publishing; 1969:343–367.

    Google Scholar 

  12. Kim JS, Choi-Kwon S: Poststroke depression and emotional incontinence: correlation with lesion location. Neurology 2000, 54:1805–1810.

    PubMed  CAS  Google Scholar 

  13. Andersen G, Ingeman-Nielsen M, Vestergaard K, Riis JO: Pathoanatomic correlation between poststroke pathological crying and damage to brain areas involved in serotonergic neurotransmission. Stroke 1994, 25:1050–1052.

    PubMed  CAS  Google Scholar 

  14. Achari AN, Colover J: Posterior fossa tumors with pathological laughter. JAMA 1976, 235:1469–1471.

    Article  PubMed  CAS  Google Scholar 

  15. Wisoff JH, Epstein FJ: Pseudobulbar palsy after posterior fossa operation in children. Neurosurgery 1984, 15:707–709.

    Article  PubMed  CAS  Google Scholar 

  16. Tei H, Sakamoto Y: Pontine infarction due to basilar artery stenosis presenting as pathological laughter. Neuroradiology 1997, 39:190–191.

    Article  PubMed  CAS  Google Scholar 

  17. Bhatjiwale MG, Nadkarni TD, Desai KI, Goel A: Pathological laughter as a presenting symptom of massive trigeminal neuromas: report of four cases. Neurosurgery 2000, 47:469–471; discussion 471–472.

    Article  PubMed  CAS  Google Scholar 

  18. Parvizi J, Anderson SW, Martin CO, et al.: Pathological laughter and crying: a link to the cerebellum. Brain 2001, 124(Pt 9):1708–1719.

    Article  PubMed  CAS  Google Scholar 

  19. Arciniegas DB, Lauterbach EC, Anderson KE, et al.: The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Proceedings of a roundtable meeting. CNS Spectr 2005, 10:1–14; quiz 15–16.

    PubMed  Google Scholar 

  20. Moore SR, Gresham LS, Bromberg MB, et al.: A self report measure of affective lability. J Neurol Neurosurg Psychiatry 1997, 63:89–93.

    PubMed  CAS  Google Scholar 

  21. Nahas Z, Arlinghaus KA, Kotrla KJ, et al.: Rapid response of emotional incontinence to selective serotonin reuptake inhibitors. J Neuropsychiatry Clin Neurosci 1998, 10:453–455.

    PubMed  CAS  Google Scholar 

  22. Allman P, Hope RA, Fairburn CG: Emotionalism following brain damage: a complex phenomenon. Postgrad Med J 1990, 66:818–821.

    Article  PubMed  CAS  Google Scholar 

  23. Cummings JL, Arciniegas DB, Brooks BR, et al.: Defining and diagnosing involuntary emotional expression disorder. CNS Spectr 2006, 11(Suppl 6):1–7.

    PubMed  Google Scholar 

  24. Kim SW, Shin IS, Kim JM, et al.: Mirtazapine treatment for pathological laughing and crying after stroke. Clin Neuropharmacol 2005, 28:249–251.

    Article  PubMed  CAS  Google Scholar 

  25. Udaka F, Yamao S, Nagata H, et al.: Pathologic laughing and crying treated with levodopa. Arch Neurol 1984, 41:1095–1096.

    PubMed  CAS  Google Scholar 

  26. Wolf JK, Santana HB, Thorpy M: Treatment of “emotional incontinence” with levodopa. Neurology 1979, 29:1435–1436.

    PubMed  CAS  Google Scholar 

  27. Ramasubbu R: Lamotrigine treatment for post-stroke pathological laughing and crying. Clin Neuropharmacol 2003, 26:233–235.

    Article  PubMed  CAS  Google Scholar 

  28. Schiffer RB, Herndon RM, Rudick RA: Treatment of pathologic laughing and weeping with amitriptyline. N Engl J Med 1985, 312:1480–1482.

    PubMed  CAS  Google Scholar 

  29. Robinson RG, Parikh RM, Lipsey JR, et al.: Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Am J Psychiatry 1993, 150:286–293.

    PubMed  CAS  Google Scholar 

  30. Murai T, Barthel H, Berrouschot J, et al.: Neuroimaging of serotonin transporters in post-stroke pathological crying. Psychiatry Res 2003, 123:207–211.

    Article  PubMed  CAS  Google Scholar 

  31. Seliger GM, Hornstein A, Flax J, et al.: Fluoxetine improves emotional incontinence. Brain Inj 1992, 6:267–270.

    Article  PubMed  CAS  Google Scholar 

  32. Andersen G, Vestergaard K, Riis JO: Citalopram for poststroke pathological crying. Lancet 1993, 342:837–839.

    Article  PubMed  CAS  Google Scholar 

  33. Burns A, Russell E, Stratton-Powell H, et al.: Sertraline in stroke-associated lability of mood. Int J Geriatr Psychiatry 1999, 14:681–685.

    Article  PubMed  CAS  Google Scholar 

  34. Brooks BR, Thisted RA, Appel SH, et al.: Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004, 63:1364–1370.

    PubMed  CAS  Google Scholar 

  35. Panitch HS, Thisted RA, Smith RA, et al.: Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. Ann Neurol 2006, 59:780–787.

    Article  PubMed  CAS  Google Scholar 

  36. Palmer GC: Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies. Curr Drug Targets 2001, 2:241–271.

    Article  PubMed  CAS  Google Scholar 

  37. Su TP, Hayashi T: Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction. Curr Med Chem 2003, 10:2073–2080.

    Article  PubMed  CAS  Google Scholar 

  38. Kamei H, Kameyama T, Nabeshima T: Effects of sigma receptor ligands on conditioned fear stress. Methods Find Exp Clin Pharmacol 1998, 20:613–618.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Memory and Aging Center, University of California, San Francisco, 350 Parnassus Avenue, Box 1207, Suite 706, San Francisco, CA, 94143, USA

    Howard Rosen

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  1. Preethi Balakrishnan
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  2. Howard Rosen
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Correspondence to Howard Rosen.

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Balakrishnan, P., Rosen, H. The causes and treatment of pseudobulbar affect in ischemic stroke. Curr Treat Options Cardio Med 10, 216–222 (2008). https://doi.org/10.1007/s11936-008-0023-z

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