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\begin{document}

\title{Pathological Laughing in a Patient with a Pontine Tumor}



\author[1]{Gopi Nepal}%
\author[2]{Pritam Gurung}%
\author[2]{Anik Jha}%
\author[2]{Durga Khadka}%
\author[2]{Resha Shrestha}%
\author[1]{Basant Pant}%
\affil[1]{Annapurna Neurological Institute and allied Sciences}%
\affil[2]{Annapurna Neurological Institute and Allied Sciences}%


\vspace{-1em}



  
  \date{April 23, 2024}


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\selectlanguage{english}
\begin{abstract}
An 18-year-old man presented with the complaints of occasional headache
and limb weakness associated with slurring of speech and purposeless
laughing. Magnetic resonance imaging showed a diffuse altered signal
intensity area involving the pons with asymmetrical expansion. The
patient underwent surgical resection. Histology revealed WHO grade IV
glioblastoma.%
\end{abstract}%



\sloppy


\textbf{Pathological Laughing in a Patient with a Pontine Tumor}

Gopi Nepal, M.B.B.S,\textsuperscript{1}, Pritam Gurung,
M.D.,Ph.D,\textsuperscript{1} Anik Jha, M.B.B.S., \textsuperscript{1}
Durga Khadka, M.D.,\textsuperscript{2} Resha Shrestha,
M.S.,\textsuperscript{1} and Basant Pant, M.D.,Ph.D. \textsuperscript{1}

\emph{\textsuperscript{1} Department of Neurosurgery, Annapurna
Neurological Institute and Allied Sciences, Maitighar, Kathmandu, Nepal}

\emph{\textsuperscript{2} Department of Psychiatry,} Annapurna
Neurological Institute and Allied Sciences\emph{, Maitighar, Kathmandu,
Nepal}

E-mail: gopinepal1000@gmail.com

\textbf{CONFLICT OF INTEREST}

None of the authors have potential conflicts of interest to be
disclosed.

\textbf{RUNNING TITLE}

Pathological laughter in a patient with a pontine lesion

ABSTRACT

An 18-year-old man presented with the complaints of occasional headache
and limb weakness associated with slurring of speech and purposeless
laughing. Magnetic resonance imaging showed a diffuse altered signal
intensity area involving the pons with asymmetrical expansion. The
patient underwent surgical resection. Histology was suggestive of a WHO
grade IV glioblastoma. Pathological laughing in a patient with a pontine
lesion is a very rare presentation. Evidence for a mechanism of action
underpinning how pontine lesions can cause such behavioral changes
through the disruption of a network of cerebro-ponto-cerebellar pathways
is discussed.

Keywords: Pathological laughing, Pons, tumor

\textbf{Introduction}

Pathological laughing and crying (PLC) can be described as
uncontrollable episodes of laughing or crying that are triggered by a
stimulus that would not normally cause either
response.\textsuperscript{1} Patients with a lesion in the pons mainly
present with features of motor deficits, and associated cranial nerve
palsies. However, pathological laughter in a patient with a pontine
lesion is a very rare presentation. The disruption of a network of
cerebro-ponto-cerebellar pathways has been considered to be a possible
mechanism for such behavior. We report a case of pathological laughing
in a patient with pontine tumor.

\textbf{Case report}

An 18 year-old man presented with a headache for 1 month and limb
weakness for 10 days. He also had slurring of speech and purposeless
laughing while talking over the same duration. On examination, motor
power in the lower limb was 4/5 in all limbs, with increased tone and
exaggerated deep tendon reflexes. Ankle clonus was present. Hand grip
was weak in both hands (Right \textgreater{} Left). A sensory exam
appeared to be intact.

Magnetic resonance imaging (MRI) showed diffuse altered signal intensity
area involving the pons with its asymetrical expansion predominantly on
the left aspect measuring 29 x 32 x 39 mm (Figure 1A-1B). The lesion was
causing dorsal displacement of the floor of the fourth ventricle, with
compression of the middle cerebellar peduncle. This was towards the left
side, was abutting both the basilar artery and its anterior displacement
with normal flow voids. The post contrast image showed thick, irregular,
and heterogeneous enhancement within the expanded pons (Figure 2 A-2B).
Magnetic resonace spectroscopy showed a decrease in NAA and an elevated
choline/ creatinine ratio. The patient was diagnosed with pontine tumor
and underwent a left retrosigmoid craniectomy, and gross total excision
of the tumor was achieved. Postoperative imaging showed complete
resection of the tumor. Histopathological examination was suggestive of
glioblastoma (Figure 3). A customized immunohistochemistry panel was
advised, which revealed immunoreactive Olig-2, Ki-67,ATRX, P53 and
H3K27M.

The patient's postoperative recovery was uneventful with mild
hemiparesis and facial palsy. The patient was discharged on tenth
postoperative day with satisfactory outcomes and a Karnofsky performance
score (KPS) of 50\%. Postoperatively, the patient was then scheduled for
referral to a cancer center for further treatment. However, he
unfortunately passed away in a local hospital while receiving treatment
for pneumonia.

\textbf{Discussion}

Pathological laughing has been reported across literature in cases of
tumor\textsuperscript{1,2}, infarction and abscess\textsuperscript{3}.
The exact mechanism is still poorly understood, with various
pathological proposals. Oppenheim, Siemerling, and Wilson suggested that
modulation is facilitated by direct corticobulbar pathways and in a
liner top-down model.\textsuperscript{4,5} They posited that PLC occurs
when the voluntary control of the emotional expression fails due to
bilateral lesions of the descending corticobulbar tracts. Parvizi et al,
suggested that an intact relationship between the cerebral cortex and
cerebellum is important for a normal regulation of emotional
expression.\textsuperscript{6} They propose therefore that problems with
an exaggerated or contextually inappropriate emotional response result
when the cerebellar modulation of these behaviors is impaired by a
lowered emotional threshold, or by a incorrect, contextually
inappropriate response. Wilson et al, suggested that a brainstem
faciorespiratory center could act as a mechanism of this
phenomenon.\textsuperscript{5} This center was presumed to be under the
control of higher centers, and pathological laughter was thought to
ensue when they were incapable of exerting their inhibitory influence on
the faciorespiratory center.

Structures such as the pre frontal cortex, anterior cingulated cortex,
internal capsule, thalamus, subthalamic nucleus, basis pontis, and
cerebellar white and gray matter have been implicated in PLC, as
revealed by many studies. The basis pontis stands out as the only
identified site where a discrete lesion can cause
PLC.\textsuperscript{7}

Functional imaging studies have proved helpful in discovering the neural
correlates for both pathological and normal regulation of emotional
expression.\textsuperscript{8} They used three types of fMRI experiment
tasks, including facial recognition,semantic decision, and motor
function to establish the response to non-specific stimuli. The patient
showed consistently abnormal pontine activation while performing all
tasks before treatment, which was not present for any of the controls.
However, the exaggerated pontine activation was normalized after
patients were treated with paroxetine, terminating the laughing
episodes. Thus, their study suggested that serotonergic replacement
decreases the aberrant activity in a circuit that involves the pons.

Various reports suggested that tricyclic antidepressants such as
amitriptyline and nortriptyline and selective serotonin reuptake
inhibitors (SSRIs) are effective in treating
PLC.\textsuperscript{9,10}Abnormal fMRI results disappearing with
clinical improvement after treatment with paroxetine also suggested some
SSRI efficacy in PLC.\textsuperscript{8}

Pathological laughing was the only feature shown by the case reported.
The patient's postoperative recovery was uneventful with mild
hemiparesis and facial palsy. He had no purposeless laughing after the
surgery. The patient was discharged with satisfactory outcome with a KPS
of 50\%. Postoperatively, the patient was scheduled for referral to a
cancer center for further treatment. However, he suffered from pneumonia
and passed away in another local hospital during the pneumonia treatment
process.

\textbf{Conclusion}

We have presented a very rare case of pathological laughing in a patient
with a pontine tumor. Patients with the features of PLC are often
underestimated. Therefore, these symptoms may serve as an early
indicator for disease progression. An understanding of the mechanisms
underlying these behavioral changes may help in providing both clinical
and psycho-social care.

\textbf{ACKNOWLEDGEMENTS}

The authors are also greatly indebted to Miss. Victoria Bennington from
California pacific Medical Center, san Francisco, USA for her
proofreading, which has profoundly improved this paper.

\textbf{CONFLICTS OF INTEREST}

None of the authors have potential conflicts of interest to be
disclosed.

\textbf{AUTHOR CONTRIBUTIONS}

Gopi Nepal was involved in the original draft, conceptualization,
review, and editing. Pritam Gurung involved in the review, editing, and
supervision. Anik Jha was involved in the review, and editing. Durga
Khadka and Resha Shrestha established the diagnosis and treated the
patient. Basant Pant involved in supervision.

\textbf{ETHICS APPROVAL AND CONSENT TO PARTICIPATE}

Ethical approval of the case report is not needed by the local ethical
guideline. Written informed consent was obtained from the patient to
include the clinical details.

\textbf{KEY CLINICAL MESSAGE}

Pathological laughing in a patient with a pontine lesion is a very rare
presentation. Patients with the features of PLC are often
underestimated. Therefore, these symptoms may serve as an early
indicator for disease progression.

\textbf{References}

1. Cantu RC, Drew JH. Pathological laughing and crying associated with a
tumor ventral to the pons. Case report. \emph{J Neurosurg} . 1966.
doi:10.3171/jns.1966.24.6.1024

2. Hargrave DR, Mabbott DJ, Bouffet E. Pathological laughter and
behavioural change in childhood pontine glioma. \emph{J Neurooncol} .
2006. doi:10.1007/s11060-005-9034-8

3. Elyas AE, Bulters DO, Sparrow OC. Pathological laughter and crying in
patients with pontine lesions: Case report. \emph{J Neurosurg Pediatr} .
2011. doi:10.3171/2011.8.PEDS11265

4. Text-Book of Nervous Diseases for Physicians and Students. By
Professor H. Oppenheim, of Berlin. Authorised translation by Alexander
Bruce, M.D., F.R.C.P.E., LL.D. Fifth enlarged and improved edition.
Edinburgh, 1911. 432 illustrations and 8 plates. Pric. \emph{J Ment Sci}
. 1911. doi:10.1192/bjp.57.237.376

5. Wilson SAK. Some Problems in Neurology: Pathological laughing and
crying. \emph{Psychopathol J Neurol} . 1924.

6. Parvizi J, Anderson SW, Martin CO, Damasio H, Damasio AR.
Pathological laughter and crying: A link to the cerebellum.\emph{Brain}
. 2001. doi:10.1093/brain/124.9.1708

7. Parvizi J, Coburn KL, Shillcutt SD, Coffey CE, Lauterbach EC, Mendez
MF. Neuroanatomy of pathological laughing and crying: A report of the
american neuropsychiatric association committee on research. \emph{J
Neuropsychiatry Clin Neurosci} . 2009. doi:10.1176/jnp.2009.21.1.75

8. Kosaka H, Omata N, Omori M, et al. Abnormal pontine activation in
pathological laughing as shown by functional magnetic resonance
imaging.\emph{J Neurol Neurosurg Psychiatry} . 2006.
doi:10.1136/jnnp.2005.073288

9. Schiffer RB, Herndon RM, Rudick RA. Treatment of Pathologic Laughing
and Weeping with Amitriptyline. \emph{N Engl J Med} . 1985.
doi:10.1056/nejm198506063122303

10. Burns A, Russell E, Stratton-Powell H, Tyrell P, O'Neill P, Baldwin
R. Sertraline in stroke-associated lability of mood. \emph{Int J Geriatr
Psychiatry} . 1999.
doi:10.1002/(SICI)1099-1166(199908)14:8\textless{}681::AID-GPS49\textgreater{}3.0.CO;2-Z

\textbf{Figure legend}

Figure 1

Magnetic resonance imaging (T1 axial and saggital) shows diffuse altered
signal intensity area involving the pons with its asymetrical expansion
predominantly on the left aspect measuring 29 x 32 x 39 mm. The lesion
is causing dorsal displacement of floor of the fourth ventricle with
compression of the middle cerebeller peduncle more on the left side, and
is abutting the basilar artery and its anterior displacement with normal
flow voids.

Figure 2

Magnetic resonance imaging contrast (T1 axial and coronal) shows thick
irregular and heterogeneous enhancement with in the expanded pons.

Figure 3

Histopathological examination showing increased cellularity and the
cells are arranged in diffuse pattern in a fibrillary background. The
cells are moderate to markedly pleomorphic and hyperchromatic with
abundant eosinophilic cytoplasm. The nuclei are round, oval and
elongated. Microvascular proliferation, few gemistocytes, necrosis in a
tiny focal area and hemorrhage are also seen. (Magnification 10 X)\selectlanguage{english}
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