|Year : 2015 | Volume
| Issue : 1 | Page : 46-49
A case report of hypertensive bleed presenting with pathological laughter: Focus on neurobiological correlates and pharmacological management
Sujita Kumar Kar1, Akhila Kumar Panda2
1 Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Consultant Neurologist, Amri Hospital, Bhubaneswar, Odisha, India
|Date of Web Publication||23-Jul-2015|
Dr. Sujita Kumar Kar
Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Pathological laughter and crying are episodes of either laughter or crying, which is intense and uncontrollable, usually lasting for brief periods and occurring in paroxysms. In the literature, pathological laughing and crying, emotionalism, pseudo-bulbar affect are synonymously used. Favorable evidences exist with regard to the use of antidepressants, mood stabilizers, and anti-glutaminergic agents for the management of pathological laughter and crying. In this case report, we highlight the clinical presentation of hypertensive bleed in the form of pathological laughter and its management with selective serotonin reuptake inhibitor - sertraline along with literature review regarding its neurobiological basis and pharmacological management.
Keywords: Pathological laughter, hypertensive bleed, sertraline
|How to cite this article:|
Kar SK, Panda AK. A case report of hypertensive bleed presenting with pathological laughter: Focus on neurobiological correlates and pharmacological management. J Geriatr Ment Health 2015;2:46-9
|How to cite this URL:|
Kar SK, Panda AK. A case report of hypertensive bleed presenting with pathological laughter: Focus on neurobiological correlates and pharmacological management. J Geriatr Ment Health [serial online] 2015 [cited 2019 Dec 16];2:46-9. Available from: http://www.jgmh.org/text.asp?2015/2/1/46/161383
| Introduction|| |
Laughter is a complex neuropsychiatric phenomenon regulated by cortical and sub-cortical neuronal structures. , Laughter involves complex motor activities of muscles of facial expression, phonation, and respiration, which are controlled by corresponding brainstem and spinal neurons (cranial and spinal nerves) and their regulatory cortical structures. , Cerebral cortex (frontal and temporal lobe), some important sub-cortical structures (thalamus, hypothalamus, sub-thalamus, amygdala) and brainstem regulate the process of laughter by either inhibitory or excitatory mechanism and cerebellum acts as a modulator of this complex process. , Wild et al. summarized the manifestation of laughter is driven by two biologically different neuronal pathways like: 
- Cortico-pontine network (frontoparietal cortex to ventral brainstem) [Figure 1].
|Figure 1: Two biologically different neuronal pathways explaining laughter is explained in the figure|
Click here to view
- Sub-cortical (amygdala-hypothalamus-peri-aqueductal gray-dorsal tegmentum) network [Figure 1].
The cortico-pontine network is under volitional control, whereas the sub-cortical network is independent of volition. ,
Pathological laughter and crying are episodes of laughter or cry, which is intense and uncontrollable, usually lasts brief and occurs in paroxysms.  In the literature, pathological laughing and crying, emotionalism, pseudo-bulbar affect (PBA) are synonymously used. Arias had described about two biological subtypes of pathological laughter as: 
- Pathological laughter due to unconcerned happiness with behavioral abnormalities - Seen in schizophrenia, mania, dementia, Angelman syndrome, hysteria, obsessive-compulsive disorder. ,
- Pathological laughter due to an imbalance in the inhibitory and excitatory mechanism - Seen in stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, brain tumors, gelastic epilepsy. ,,,,,,
Pathological laughter or crying causes a lot of social embarrassments. In several studies, it was found that selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, other antidepressants like mirtazapine and tricyclic antidepressants, mood stabilizers like lamotrigine, levodopa, and combination of dextromethorphan and quinidine in the treatment of pathological laughter and crying. ,,,,,,, Among the SSRIs, most reports and studies have used sertraline in the management of pathological laughter and crying. ,,, Sertraline is a safe and efficacious medication with minimum interaction with other drugs, which makes it a preferred drug along with escitalopram among the existing SSRIs. 
The Cochrane database systematic review (2010) had revealed that antidepressants are effective first-line management of pathological laughter and crying (or emotionalism) irrespective of antidepressant group. 
| Case Report|| |
A 65-year-old female was brought for psychiatric consultation with complaints of episodes of uncontrolled laughter, lasting for 30 min to 1 h, for previous 6 months. Family members reported that 3 months prior to the onset of these episodes of uncontrollable laughter, she had sudden onset (in February 2013) right-sided facial weakness and altered sensorium for which she was diagnosed to have hypertensive encephalopathy, hospitalized and treated conservatively. Over next 3-4 weeks, she had shown significant improvement and her facial weakness had also improved, however, she became nonadherent to treatment after 4 months. After 2 months of this incident (onset of hypertensive encephalopathy), her uncontrollable laughter episodes were started. The episodes were usually unprovoked and unanticipated. The episodes used to occur 2-3 times in a day. These episodes could not be stopped by voluntary effort and would cause embarrassment to the patient and her family members. There were no other complaints other than these episodes of loud laughter. She was used to do the activities of daily living without any difficulty. There was no episode of uncontrollable crying. There was no evidence of any depressive, anxiety, manic or psychotic symptoms. There was no evidence of any cognitive decline. She was a known hypertensive, but not taking any antihypertensive. She was detected to have hypertension in February 2013 and took antihypertensive for 4 months only. There was no past history or family history of psychiatric illness. Premorbidly, she was well-adjusted to life.
At the time of evaluation, her blood pressure was raised (170/120 mmHg) with pulse rate of 76/min. General physical examination and systemic examination did not reveal any abnormality other than right upper motor neuron facial weakness. Routine hemogram, renal function test, liver function test, blood sugar, lipid profile, and thyroid function test were found to be within normal limits. Magnetic resonance imaging of the brain revealed increased white matter signal intensity in the peri-ventricular region in frontoparietal parenchyma with ischemic demyelination changes [Figure 2].
|Figure 2: Magnetic resonance imaging of brain showing increased white matter signal intensity in the peri-ventricular region in frontoparietal parenchyma with ischemic demyelination changes|
Click here to view
The patient was prescribed SSRI sertraline 50 mg/day and antihypertensive amlodipine 5 mg/day. She was advised salt restricted diet and lifestyle modification. After 2 weeks, in follow-up, there was a significant improvement in her pathological laughter (both in frequency as well as duration) and her blood pressure had also come to the normal range. She was regularly in follow-up until November 2014. Her blood pressure was in normal range with no further episode of uncontrolled laughter in last 4 months. In follow-up, the patient had reported about the forgetfulness of day-to-day events though it was minimally impairing. Mini Mental Status Examination (MMSE) was done, and the score was found to be 25/30. In follow-up, patient's cognitive function was regularly checked in view of possible progression to dementia, but her MMSE score was maintained at that level without further deterioration.
| Discussion|| |
Our patient belonged to a low socioeconomic class of rural background who had never undergone evaluation for hypertension prior to the onset of facial weakness and altered sensorium. She might have had uncontrolled hypertension which was untreated and led to hypertensive encephalopathy and stroke. Again after management of hypertensive encephalopathy, she had become nonadherent to medications which was subsequently addressed during the psychiatric consultation.
The frontal cortex (motor and premotor cortex) has an inhibitory effect on laughter and the temporal lobe along with amygdala and hypothalamus has an excitatory effect on laughter.  In the index patient, lesions were involving the frontal cortex which explains that the frontal cortical inhibitory activity was lost and the unopposed excitatory activity of temporal cortex, amygdala, and hypothalamus led to development of pathological laughter.
As in several studies, SSRIs are found to be effective in the management of pathological laughter, ,,, in the index patient, sertraline (an SSRI) was prescribed in view of its better efficacy, tolerability, and minimum drug-drug interaction. 
Hypertensive encephalopathy usually results from chronic untreated hypertension. It may result in multiple micro-bleeds in the brain. Neurological deficits in patients with hypertensive encephalopathy range from minimal, nonspecific or focal deficits to a fully evolved stroke. Effective control of hypertension and addressing associated potential risk factors is the mainstay of treatment. Individuals who develop hypertensive encephalopathy are at risk to develop vascular dementia. In the index patient, MMSE score was 25/30, and there was minimal impairment in activities of daily living. Hence, the possibility of minimal cognitive impairment (MCI) was more likely than vascular dementia. However, in view of the risk of progression to vascular dementia, the patient was followed regularly with monitoring of cognitive functions.
The peri-aqueductal gray (PAG) activity is regulated through several receptors like - Glutaminergic NMDA receptor, muscarinic cholinergic receptors, GABA-A receptor, sigma-1 receptor, 5-HT 1 receptor, dopamine (D2) receptor, and norepinephrine (alpha) receptor.  As PAG is an important part of the involuntary system of emotional control, its activation and deactivation have a role on causation or management of pathological laughter. There is potential scope of utility of drugs acting through above-mentioned receptors for the management of pathological laughter. The recent focus is on the attribution of serotonin and glutamine imbalance to pathological laughter. , Dextromethorphan and quinidine combination is the first Food and Drug Administration-approved medication for treatment of pathological laughter (PBA) through its anti-glutaminergic action. 
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Arias M. Neurology of laughter and humour: Pathological laughing and crying. Rev Neurol 2011;53:415-21.
Wild B, Rodden FA, Grodd W, Ruch W. Neural correlates of laughter and humour. Brain 2003;126:2121-38.
Lauterbach EC, Cummings JL, Kuppuswamy PS. Toward a more precise, clinically - Informed pathophysiology of pathological laughing and crying. Neurosci Biobehav Rev 2013;37:1893-916.
Wortzel HS, Oster TJ, Anderson CA, Arciniegas DB. Pathological laughing and crying: Epidemiology, pathophysiology and treatment. CNS Drugs 2008;22:531-45.
Mendhekar DN. Pathological laughter as an obsessive-compulsive phenomenon. Psychopathology 2004;37:81-3.
Chahine LM, Chemali Z. Du Rire Aux Larmes: Pathological laughing and crying in patients with traumatic brain injury and treatment with lamotrigine. Epilepsy Behav 2006;8:610-5.
Takeuchi H, Iwamoto K, Mukai M, Fujita T, Tsujino H, Iwamoto Y. Effective use of sertraline for pathological laughing after severe vasospasm due to aneurysmal subarachnoid hemorrhage: Case report. Neurol Med Chir (Tokyo) 2014;54:231-5.
Ramasubbu R. Lamotrigine treatment for post-stroke pathological laughing and crying. Clin Neuropharmacol 2003;26:233-5.
Garg RK, Misra S, Verma R. Pathological laughter as heralding manifestation of left middle cerebral artery territory infarct: Case report and review of literature. Neurol India 2000;48: 388-90.
Ahmed A, Simmons Z. Pseudobulbar affect: Prevalence and management. Ther Clin Risk Manag 2013;9:483-9.
Kim SW, Shin IS, Kim JM, Lim SY, Yang SJ, Yoon JS. Mirtazapine treatment for pathological laughing and crying after stroke. Clin Neuropharmacol 2005;28:249-51.
Mukand J, Kaplan M, Senno RG, Bishop DS. Pathological crying and laughing: Treatment with sertraline. Arch Phys Med Rehabil 1996;77:1309-11.
Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, et al.
Comparative efficacy and acceptability of 12 new-generation antidepressants: A multiple-treatments meta-analysis. Lancet 2009;373:746-58.
Hackett ML, Yang M, Anderson CS, Horrocks JA, House A. Pharmaceutical interventions for emotionalism after stroke. Cochrane Database Syst Rev 2010;2:CD003690.
Miller A, Pratt H, Schiffer RB. Pseudobulbar affect: The spectrum of clinical presentations, etiologies and treatments. Expert Rev Neurother 2011;11:1077-88.
[Figure 1], [Figure 2]