□ CASE REPORT □ Divergence Paralysis Caused by Acute Midbrain Infarction Hiromasa Tsuda 1, Yukiko Shinozaki 1, Kozue Tanaka 1 and Kazuteru Ohashi 2 Abstract A 41-year-old woman with idiopathic thrombocytopenic purpura and dyslipidemia abruptly developed vertigo, truncal ataxia and divergence paralysis. Cranial magnetic resonance imaging demonstrated the presence of infarction in the left superior paramedian mesencephalic artery involving the vicinity of the periaqueductal gray matter. The symptoms rapidly resolved under the administration of anti-platelet agents. The precise location of the hypothetical divergence center of the ocular motor system remains unclear because the lesions responsible for divergence paralysis are rarely identified on neuroimaging. We emphasize that this is a first reported case of DP caused by acute midbrain infarction and speculate that the mesencephalic reticular formation may be partially involved. Key words: divergence center, horizontal diplopia, idiopathic thrombocytopenic purpura, ophthalmoplegia, periaqueductal gray matter (mesencephalic central gray) (Intern Med 51: 3169-3171, 2012) (DOI: 10.2169/internalmedicine.51.8443) Introduction Divergence paralysis (DP) is characterized by uncrossed horizontal diplopia at far distances with no or minimal deviation at near distances (1-6). In addition, despite the absence of restricted ocular movement, concomitant esotropia in all fields of gaze has been observed (1-6). However, the precise location of the hypothetical divergence center of the ocular motor system (DC) remains uncertain because only six cases of localized lesions responsible for DP identified on neuroimaging have been reported in the English language literature (1-5) Among these cases, Tsuda et al. (1, 2) recently reported two cases of DP caused by old infarctions in the vicinity of the periaqueductal gray matter (PAG) that were detected on magnetic resonance (MR) imaging. We herein describe an additional case of DP secondary to an acute midbrain infarction. Case Report A 41-year-old Japanese woman with dyslipidemia, idiopathic thrombocytopenic purpura (ITP) and a smoking habit abruptly developed vertigo, gait disturbance and hori- zontal diplopia only at far viewing distances in March 2012. The corrected visual acuities were 1.5 in both eyes. The funduscopic findings did not demonstrate any abnormalities in either eye. The patient’s pupil diameter was 3 mm bilaterally in the lightened room. Pupil responses to light and near distances were prompt in both eyes. The palpebral aperture measured 9 mm bilaterally. In the primary position, a 5.5 prism diopter (PD) of esotropia at 0.5 m and a 10 PD of esotropia at 5 m were observed. Despite the absence of any restriction of ocular movements (Fig. 1), the red glass test demonstrated concomitant esotropia in all fields of gaze. The Maddox rod test demonstrated normal ocular torsion. Based on these results, the patient was diagnosed as having DP. Furthermore, truncal ataxia with the patient primarily falling backward was observed, although no limb ataxia, dysarthria or nystagmus were noted. There were no other neurological abnormalities, except for DP and truncal ataxia. A complete blood cell count revealed a decreased platelet count of 71,000/μL. Blood chemistry demonstrated dyslipidemia. The patient’s thyroid function was within normal ranges. Electrocardiogram, chest radiography and carotid ultrasound imaging demonstrated normal findings. On cranial magnetic resonance (MR) imaging, normal findings were observed on diffusion-weighted images; however, fluid at- 1 Department of Neurology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Japan and 2Department of Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Japan Received for publication June 21, 2012; Accepted for publication August 20, 2012 Correspondence to Dr. Hiromasa Tsuda, hiromasatsuda@cick.jp 3169 Intern Med 51: 3169-3171, 2012 Figure 1. stricted. DOI: 10.2169/internalmedicine.51.8443 In the primary position, slight esotropia was observed. Ocular movement was not re- Figure 2. Cranial magnetic resonance imaging on fluid-attenuated inversion recovery images demonstrated the presence of a high-intensity lesion in the territory of the left superior paramedian mesencephalic artery (A, white arrow) that involved the left-sided region of the periaqueductal gray matter (B, black arrow). tenuating inversion recovery images demonstrated the presence of a high-intensity lesion in the territory of the left superior paramedian mesencephalic artery involving the PAG (Fig. 2). Orbital MR imaging and cranial MR angiography demonstrated normal findings. Thereafter, following the administration of intravenous sodium ozagrel (anti-platelet agent) at a dose of 160 mg/day, the vertigo and truncal ataxia disappeared within one day and the DP disappeared within three days. Three months later, cranial MR imaging demonstrated no abnormalities in the brainstem. Discussion A cerebral infarction is a rare, recognized complication of ITP, although its precise etiology remains unknown (7). Lepore (6) has reported cases of DP secondary to brainstem infarctions and stated that DP might be a nonlocalizing symptom of brainstem damage because no lesions responsible for DP have been identified. On the other hand, Stern et al. (3) described a case of DP associated with left abducens nerve palsy secondary to a hematoma in the caudal pons close to the floor of the fourth ventricle. Lee et al. (4) noted a case of isolated DP caused by a localized hematoma in the upper pontine tegmentum extending to the midbrain. Moreover, Tsuda et al. (5) noted cranial MR imaging findings in two cases of isolated DP secondary to multiple sclerosis and acute pontine infarction, respectively, and concluded that the nucleus reticularis tegmenti pontis might be responsible for divergence of the eyes. In contrast, based on a postmortem examination, Bender et al. (8) noted that a small cavernous hemangioma was detected as a lesion responsible for DP in the right-sided region of the PAG at the level between the superior and inferior colliculi. Furthermore, based on the results of stereotactic surgery to destroy the dorsolateral tegmentum extending laterally from the midbrain aqueduct to the lateral border of the midbrain, Nashold et al. (9) wrote that the neurophysiological mechanism responsible for the divergence of the eyes might be located in the midbrain tegmentum. Recently, based on two cases of DP caused by old infarctions, Tsuda et al. (1, 2) speculated 3170 Intern Med 51: 3169-3171, 2012 DOI: 10.2169/internalmedicine.51.8443 that the DC might be located in the vicinity of the PAG. In both cases, the old infarct lesions were located in the leftsided and posterior regions of the PAG (1, 2). However, in reported human cases (1, 2, 8, 9), the etiology of DP secondary to midbrain tegmentum involvement has not yet been discussed in detail. Based on a primate (rhesus monkeys) study, Mays (10) reported that both convergence and divergence neurons are intermixed in the mesencephalic reticular formation just dorsal or dorsolateral to the oculomotor nucleus. In our present case, DP was observed and a high-intensity lesion located in the left-sided region of the PAG was detected on MR imaging. Three months later, the midbrain lesion was not observed on MR imaging. Therefore, we considered the possibility that the lesion was an area of edema that developed secondary to brainstem ischemia. We believe that the mesencephalic reticular formation may be associated with divergence of the eyes, not only in rhesus monkeys (10), but also in humans. Consequently, in our present case and in previously reported cases (1, 2), we speculated that the mesencephalic reticular formation might be partially involved in addition to the PAG. On the other hand, truncal ataxia is not an unusual symptom in cases of midbrain infarction, although its precise responsible region remains unclear (11, 12). In conclusion, we emphasize that this is a first reported case of DP caused by acute midbrain infarction. The authors state that they have no Conflict of Interest (COI). References 1. Tsuda H, Sekiya R, Kozue T, Kishida S. Isolated divergence paralysis due to midbrain tegmentum infarction. Intern Med 50: 1131, 2011. 2. Tsuda H, Kamata K, Tanaka K, Kishida S. Magnetic resonance imaging finding in divergence paralysis. Neuroophthalmology 36: 52-53, 2012. 3. Stern RM, Tomsak RL. Magnetic resonance images in a case of “divergence paralysis”. Surv Ophthalmol 30: 397-401, 1986. 4. Lee SA, Sunwoo IN, Kim KW. Divergence paralysis due to a small hematoma in the tegmentum of the brainstem. Yonsei Med J 28: 326-328, 1987. 5. Tsuda H, Ishikawa H, Koga N, Ishikawa H, Miki K, Mizutani T. Magnetic resonance imaging findings in divergence paralysis. Neuroophthalmology 30: 59-62, 2006. 6. Lepore FE. Divergence paresis: a nonlocalizing cause of diplopia. J Neuroophthalmol 19: 242-245, 1999. 7. Mahawish K, Pocock N, Mangarai S, Sharma A. Cerebral infarction in idiopathic thrombocytopenic purpura: a case report. BMJ Case Rep 2009: 1748, 2009. 8. Bender MB, Savitsky N. Paralysis of divergence. Arch Ophthalmol 23: 1046-1051, 1940. 9. Nashold BS Jr, Seaber JH. Defects of ocular motility after stereotactic midbrain lesions in man. Arch Ophthalmol 88: 245-248, 1972. 10. Mays LE. Neural control of vergence eye movements: convergence and divergence neurons in midbrain. J Neuroophthalmol 51: 1091-1108, 1984. 11. Kim JS, Kim J. Pure midbrain infarction: Clinical, radiologic, and pathophysiologic findings. Neurology 64: 1227-1232, 2005. 12. Mathout GM, Bhidayasiri R. Midbrain ataxia: an introduction to the mesencephalic locomotor region and the pedunculopontine nucleus. AJR Am J Roentgenol 184: 953-956, 2005. Ⓒ 2012 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html 3171