INTERESTING IMAGE Pathological Laughing Brain SPECT Findings David Morland, MD, MSc,* Valérie Wolff, MD, PhD,†‡ Cyrille Blondet, MD, MSc,*§ Christian Marescaux, MD,† and Izzie Jacques Namer, MD, PhD*§ Abstract: We present the case of a 40-year-old man consulting for uncontrollable episodes of laughing related to emotional lability and not systematically linked to feelings of happiness. Seven months earlier he had presented a pontine ischemic stroke related to an occlusion of the basilar and left vertebral arteries. No epileptic activity or new MRI brain lesions were found. Brain perfusion SPECT performed showed marked hypoperfusion in the right frontal inferior and temporoinsular regions, suggesting a diaschisis phenomenon caused by pontine lesions and highlighted laughing regulation pathways. The patient was successfully treated with a serotonergic reuptake inhibitor, fluoxetine. Key Words: pathological laughing, brain perfusion imaging, brain SPECT, diaschisis (Clin Nucl Med 2015;40: 734–736) Received for publication January 12, 2015; revision accepted March 11, 2015. From the *Service de Biophysique et Médecine Nucléaire and †Unité Neurovasculaire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; ‡Université de Strasbourg, EA 3072, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France; and §ICube, Université de Strasbourg/CNRS (UMR 7357), Strasbourg, France. David Morland present address: Service de Médecine Nucléaire, Institut Jean Godinot, Reims, France Conflicts of interest and sources of funding: none declared. Correspondence to: Izzie Jacques Namer, MD, PhD, Service de Biophysique et de Médecine Nucléaire, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre 1, avenue Molière, 67098 Strasbourg Cedex 09, France. E-mail: Izzie.Jacques.NAMER@chru-strasbourg.fr. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/15/4009–0734 DOI: 10.1097/RLU.0000000000000809 734 www.nuclearmed.com REFERENCES 1. Féré C. Le fou rire prodromique. Rev Neurol. 1903;11:353–358. 2. Assal F, Valenza N, Landis T. Clinico-anatomical correlates of fou rire prodromique in a pontine infraction. J Neurol Neurosurg Psychiatry. 2000; 69:697–698. 3. Couderq C, Drouineau J, Rosier MP, et al. « Fou rire prodromique » heralding a brainstem infarction. Favorable outcome after intraarterial thrombolysis. Rev Neurol. 2000;156:281–284. 4. Andersen G, Ingelman-Nielsen M, Vestergraard K, et al. Patho anatomic correlation between post stroke pathological crying and damage to brain areas involved in serotonergic neurotransmission. Stroke. 1994;25:1050–1052. 5. Arciniegas DB, Topkoff J. The neuropsychiatry of pathologic affect. An approach to evaluation and treatment. Semin Clin Neuropsychiatry. 2000;5: 290–306. 6. Mega MS, Cummings JL, Salloway S, et al. The limbic system: an anatomic, phylogenic and clinical perspective. J Neuropsychiatry Clin Neurosci. 1997; 9:315–330. 7. Wild B, Rodden FA, Grodd W, et al. Neural correlates of laughter and humour. Brain. 2003;126:2121–2138. 8. Coria F, Bahillo ME, Moral Blanco M, et al. Late onset isolated gelastic epilepsy secondary to entrapment of the right temporal horn. Neurologia. 2000; 15:204–207. 9. Parvizi J, Anderson SW, Martin CO, et al. Pathological laughter and crying: a link to the cerebellum. Brain. 2001;124:1708–1719. 10. Mukand J, Kaplan M, Senno R, et al. Pathological crying and laughing: treatment with sertraline. Arch Phys Med Rehabil. 1996;77:1309–1311. Clinical Nuclear Medicine • Volume 40, Number 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Clinical Nuclear Medicine • Volume 40, Number 9, September 2015 Pathological Laughing FIGURE 1. A 40-year-old man with a history of hypertension, dyslipidemia, chronic rejection of renal transplant, and ischemic pontine stroke 7 months earlier. On admission at the acute stage of stroke, neurological examination showed tetraparesis, bilateral facial palsy, dysarthria, deglutition problems, and bilateral cerebellar syndrome. The patient was treated with antithrombotic treatment associating aspirin and curative anticoagulation. The clinical outcome was highly favorable at 1 month, and the patient was symptom-free for the motor and the cerebellar symptoms. Sagittal T1-weighted (A) and three successive transverse T2-weighted MRIs (B) show ischemic lesions of the upper pons related to an occlusion of the basilar and left vertebral arteries (C, angio-MRI, time-of-flight sequence). © 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. www.nuclearmed.com 735 Morland et al Clinical Nuclear Medicine • Volume 40, Number 9, September 2015 FIGURE 2. The patient consulted for uncontrollable episodes of laughing related to an emotional lability, 7 months after the pontine stroke. During these episodes, the emotional sensations of the patient were highly variable and not systematically linked to feelings of happiness. Brain perfusion SPECT was performed in this period after intravenous injection of 740 MBq 99m Tc-ECD. Matched transverse slices (A, T2-weighted MRI; B, fused MRI-SPECT; C, SPECT) and 3D volume rendering SPECT (D) show pronounced hypoperfusion in right inferior frontal, insular, and temporal basal-polar-intern regions as well as right basal ganglia without any new lesion on MRI, suggesting a diaschisis phenomenon resulting from pontine lesions and highlight laughing regulation pathways. The patient was successfully treated with serotonergic reuptake inhibitor (fluoxetine 5 mg/day). The first case of pathological laughter was described in 1903 by Féré.1 This syndrome is most often related to a stroke in the vertebrobasilar territory.2,3 Patients with the most severe symptoms are those with bilateral pontine lesions.4 However, neural pathways involved in pathological laughter are not yet fully known and remain a matter of controversy.5,6 It has been hypothesized that pathological laughter was caused by a loss of regulation of a presumed “center for laughter” located in the brainstem connected to the facial and vagal nerve nucleus. Laughter seems to depend on 2 neuronal pathways: a voluntary system originating in the frontal cortex and an emotionally driven system receiving inputs from disparate regions of the brain (hypothalamus, orbitofrontal cortex, basal temporal cortex, basal ganglia, and thalamus).7 Interestingly, temporal poles have already been implicated in cases of gelastic epilepsy.8 The pons and cerebellum could modulate emotional responses.9 Hypoperfused areas demonstrated in this case are likely to be caused by a diaschisis phenomenon resulting from a pontine lesion because no corresponding abnormalities are seen on MRI. The neural pathways highlighted fit the laughter model described above. Pontine infarction could also damage raphe nuclei from the area where serotoninergic projections emerge. This hypothesis could explain the recovery from pathological laughing with a serotonergic reuptake inhibitor, confirmed in several studies.10 736 www.nuclearmed.com © 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.