Pathological Laughing As a Manifestation in a Clinically Isolated Brainstem Syndrome: A Case Report Belgin Kocer, MD, Yusuf Oner, MD, Hale Batur, MD, Bijen Nazliel, MD, Bulent Cengiz, MD, Turgut Tali, MD From the Department of Neurology, Gazi University School of Medicine, C¸ankaya-Ankara, Turkey (BK, HB, BN, BC); and Department of Radiology, Gazi University School of Medicine, C¸ ankaya-Ankara, Turkey (YO, TT). Keywords: Multiple sclerosis, clinically isolated syndromes, pathological laugh- ing, pathophysiology, treatment. Acceptance: Received February 7, 2008, and in revised form April 20, 2008. Accepted for publication May 19, 2008. Correspondence: Address correspon- dence to Dr. Belgin Kocer, Sedat Simavi sokak 17/32 B Block, C¸ ankaya-Ankara, Turkey. E-mail: ebkocer@yahoo.com. J Neuroimaging 2009;19:291-294. DOI: 10.1111/j.1552-6569.2008.00281.x ABSTRACT The prevalence of pathological laughing and crying in multiple sclerosis (MS) is 10%. It has been speculated that the anatomical lesion responsible for the pathological laughing is located in the pontine base, prefrontal cortex, and cerebellum. We report an 18-year-old male patient presenting with pathological laughing and hypomania. In his neurological examination, he had a euphoric effect with ataxic walking and dysarthria speech. He had a bilateral conjugated gaze limitation, with a prominent bilateral horizontal nystagmus on left gaze, dysmetria, dysdiadokokinesia, and remarkable dysfunction in a heel-to-shin test on the left. The IgG index in cerebrospinal fluid was normal with an oligoclonal band was present. In cranial MRI, there was a lesion on central pons which was hypointense in T1 images with contrast enhancement and hyperintense in T2 and flair images. Also another lesion in right brachium pontis which did not contrast enhancement but was hyperintense on T2 and flair images was present. There was an elevation of myoinositol/creatine ratio and choline and a reduction of NAA in proton MR spectroscopy. MR spectroscopic evalua- tion of the patient demonstrated the demyelination process. There has been no report of patients in whom pathological laughter was the presenting symptom of clinically isolated brainstem syndrome. Introduction In 85% of young adults with multiple sclerosis (MS), onset is a subacute clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. CIS presents 10% with a brainstem syndrome. Only 35% of patients with clinically iso- lated brainstem syndrome develop clinically definite MS inside 37 months. 1 Psychiatric disorders have been described in MS, including symptoms of depression, bipolar disorder, euphoria, patholog- ical laughter and crying, and psychosis as well as maladaptive personality traits. 2 The prevalence of pathological laughing and crying in MS is 10%. 3 Pathological laughter and crying has also rarely been reported in association with brainstem stroke involving the basis pontis or the cerebral peduncles, pontine glioma, and cerebellar vermian ependymoma. 4-6 We describe a patient in whom pathological laughing was the symptom of clin- ically isolated brainstem syndrome. Case An 18-year-old male patient was admitted to our clinic with unmeaningful laughing, paresthesia in the oral area, diplopia, ataxia in walking, inappropriate jugularity and in the fifth day of acute sinusitis. He frequently laughed in response to stimuli that normally would not trigger laughter. Nothing was remark- able in his past medical history. In his physical examination, blood pressure was 110/80 mmHg with a heart rate of 96 /min. He had no fever, and rest of his physical examination was normal. In his neurological examination, he had a euphoric effect with ataxic walking and dysarthric speech. He had a bi- lateral conjugated gaze limitation and a prominent bilateral hor- izontal nystagmus on left gaze, dysmetria, dysdiadokokinesia, and remarkable dysfunction in a heel-to-shin test remarkable on the left. The rest of his neurological examination test was normal. In his laboratory evaluation, CBC, blood chemistry, sed- imentation rate, ferritin, VitB12, folate, thyroid function test, ASO, C-reactive proteine, romatoid factor, lupus anticoagu- lant, ANA, anti-DNA, anticardiolipin antibodies IgM and IgG, pANCA, cANCA, and patergie test were negative, and protein C, protein S, antitrombin III activities were within in normal limits. Factor V Leiden mutation (1691 G > A) and MTHFR (C677T) heterozygoty and protrombin gene mutation normal was present. In his lumber puncture, cerebrospinal fluid glucose was 88 mg/dL, protein was 22.9 mg/dL, clor was 125 meq/L, and no cells were present. The IgG index in cerebrospinal fluid was normal with an oligoclonal band present. Serum and cere- brospinal fluid brucella agglutination, VDRL, TORCH IgM and IgG, HSV1 and HSV2 PCR were negative. In an elec- troencephalogram (EEG), right and left pattern visual-evoked potential (pVEP) and posterior tibial somatosensorial-evoked potential (SEP), brainstem auditory-evoked potential (BAEP), and electroneuromyographic (ENMG) evaluation were normal. In cranial MRI, in T1 images there was a hypointense lesion on central pons showing contrast enhancement. This lesion was hyperintense on T2 and flair images. Also another lesion which did not contrast enhancement in right brachium pontis, and hy- perintense on T2 and flair images was present (Fig 1A–D). MR spectroscopic evaluation revealed an increase in the myoinos- itol/creatine ratio, with an increase in coline and a decrease in N-asetil aspartate (NAA), which was in accordance with a demyelinative process (Fig 2). Copyright ◦ C 2008 by the American Society of Neuroimaging 291