ORIGINAL CONTRIBUTION Skew Deviation as the Initial Manifestation of Left Paramedian Thalamic Infarction Edward Margolin, MD, FRCS (C), Dana Hanifan, MA, CCC, Mary K. Berger, MS, CCC, Omar R. Ahmad, MD, Jonathan D. Trobe, MD, and Stephen S. Gebarski, MD Abstract: We describe a 73-year-old man who developed diplopia as the initial manifestation of a left thalamic infarction. By the time he reached the emergency department, clouded consciousness precluded localization of the lesion. Results of brain MRI were initially interpreted as negative. Ophthalmologic examination several hours later disclosed a small vertical ocular misalignment attributed to skew deviation. This finding led to careful scrutiny of the upper brainstem on MRI. Comparison of the diffusion, apparent diffusion coefficient, and exponential apparent diffusion coefficient MRI studies allowed a diagnosis of subtle left thalamic infarction. The recognition of skew deviation in this setting is important because it may be the most specific indicator of a brainstem lesion. (J Neuro-Ophthalmol 2008;28:283–286) T he clinical manifestations of thalamic infarction depend principally on the region that has been injured (1). The thalamus is traditionally divided into four regions based on its arterial supply: anterior, paramedian, inferolateral, and posterior (2). The two most common infarcts involve the inferolateral thalamus, supplied by the inferolateral artery, and the paramedian thalamus, supplied by the paramedian (thalamosubthalamic) artery, a branch of the first segment of the posterior cerebral artery (P1). Less common are infarcts of the anterior thalamus supplied by the tuberothalamic artery and posterior thalamus supplied by the posterior choroidal arteries (2). The principal clinical features of infarcts involving the paramedian thalamus—consisting of the medial dorsal nucleus, internal medullary lamina, and intralaminar nuclei—are decreased arousal, altered social skills and Departments of Ophthalmology (EM, ORA, JDT), Speech and Language (DH, MKB), and Radiology (SSG), University of Michigan Health System, Ann Arbor, Michigan. Address correspondence to Jonathan Trobe, MD, Kellogg Eye Center, 100 Wall Street, Ann Arbor, MI 48105; E-mail: edwardma@ med.umich.edu J Neuro-Ophthalmol, Vol. 28, No. 4, 2008 personality, short-term memory loss (amnesia), aphasia (with lesions on the left) or spatial deficits (with lesions on the right), vertical gaze paresis, impaired convergence, and skew deviation (2,3). We describe a patient with infarction of the left paramedian thalamus who presented with vertical diplopia and later developed aphasia and amnesia. We emphasize that the paramedian thalamus is the only brain region in which a single lesion will produce this combination of deficits. The detection of skew deviation was challenging because of impaired consciousness but critical to early localization because the imaging abnormality was subtle. CASE REPORT A 73-year-old bilingual Japanese automotive executive who had resided in the United States for 20 years noticed vertical double vision upon awakening. He became progressively drowsy. The patient’s medical history included supraventricular tachycardia, tachy-brady syndrome, benign prostatic hypertrophy, amebiasis, and peptic ulcer disease. Medications included fexofenadine (Allegra) and tamsulosin (Flomax). He was known to speak fluent English and had no history of hearing loss. In the initial neurologic examinations in the emergency department 4 hours after symptom onset, examiners noted drowsiness without any focal neurologic deficits. Impaired consciousness precluded detailed neurologic examination. Results of brain CT (Fig. 1) and CT angiography were normal. Because of the report of diplopia, an ophthalmologic consultation was requested. Eight hours after symptom onset, the patient was sufficiently arousable to allow detection of a 4 prism-diopter right hypertropia with normal ocular ductions. There were no other ophthalmic abnormalities. Thirteen hours after symptom onset, results of brain MRI were initially interpreted as normal. With the information that skew deviation had been detected, increased scrutiny of the upper brainstem region on MRI disclosed an area of restricted diffusion in the left paramedian thalamus, particularly when the diffusion, apparent diffusion, and exponential diffuse images were compared. The T2 and 283 J Neuro-Ophthalmol, Vol. 28, No. 4, 2008 FIG. 1. Noncontrast axial CT performed 8 hours after symptom onset shows no abnormalities. FLAIR MRI images through the equivalent section did not disclose any clear signal abnormality (Fig. 2). Two days after hospital admission, he still had a 4 prism-diopter right hypertropia in primary gaze position. Consciousness had improved enough to permit ascertainment that he was disoriented to time and place. Speech-language evaluation disclosed that he was hypophonic but able to follow verbal single-step commands and repeat sentences such as ‘‘I got home from work.’’ He could not name visually displayed common objects such as a clock. He made frequent word substitutions with verbal paraphasic errors (‘‘watch’’ for ‘‘clock’’) more frequently than literal paraphasic errors Margolin et al (‘‘buffon’’ for ‘‘button’’). He could not complete automatic sequences, such as counting or carry out written commands, and his handwriting was small (micrographic). On the fourth hospital day, he was fully awake. He could now verbalize automatic speech sequences, such as counting. On the sixth hospital day, his motor speech, auditory comprehension for two-step directions, and ability to repeat longer sentences had improved, but he had persisting wordfinding and reading comprehension deficits. He was discharged home with a therapeutic regimen of aspirin and atorvastatin. On the eighth day after the stroke, a comprehensive outpatient speech and language evaluation was completed using portions of the Boston Diagnostic Aphasia Examination (BDAE) (4) and the Boston Naming Test (BNT) (5). The BNT specifically assesses visual confrontation naming and the ability to benefit from various probes. On these tests, he showed further improvement in motor speech production, the ability to follow verbal one-step and twostep commands, and intact sentence repetition, but scored only 8 of 60 on the BNT, more than 4 SD below the mean. He still had reading comprehension deficits at the singleword level but was responding to cueing. Fourteen days after stroke onset, the hypertropia was restricted to up-and-right gaze. There were no other neurologic deficits except disorientation to time and a lingering aphasia. Twenty-one days after stroke onset, he still had deficits in word-finding. As his language skills resolved, it became apparent that he had difficulties in short-term memory and in executive dysfunction, including impaired awareness of his deficits and reduced ability to set goals and to plan and organize his professional tasks (Table 1). One year after the stroke, he still had lingering hypertropia, but informal examination of mental status and language disclosed no deficits. He had returned to work and acknowledged no memory or other cognitive deficits. FIG. 2. MRI performed 13 hours after the initial onset of symptoms. A. Axial diffusion image through the paramedian thalamus shows subtle high signal (arrow). B. Axial apparent diffusion coefficient map through this level shows low signal in the same location (arrow), consistent with restricted diffusion. C. Axial exponential apparent diffusion coefficient map shows corresponding high signal (arrow), making this focus of restricted diffusion quite conspicuous. D. T2 axial image through the paramedian thalamus shows no definite focal signal alteration (arrow). E. Axial FLAIR image through the paramedian thalamus shows subtle signal inhomogeneity but no definite focal signal alteration (arrow). 284 q 2008 Lippincott Williams & Wilkins Skew Deviation J Neuro-Ophthalmol, Vol. 28, No. 4, 2008 TABLE 1. Evolution of aphasic deficits in our patient Hypophonia Auditory Comprehension Sentence Repetition Limited to high probability sentences Limited to high and some low probability sentences Intact Day 2 Moderate-severe One-step verbal commands Day 6 Mild One- and two-step verbal commands Day 8 Very mild Day 21 None Two-step verbal commands Intact Intact DISCUSSION Our patient presented with acutely impaired consciousness, vertical ocular misalignment, aphasia, and amnesia caused by left paramedian thalamic infarction. CT results were negative, and MRI showed only a subtle area of restricted diffusion that was initially overlooked. The report of diplopia as the initial symptom called forth an ophthalmologic examination, which led to the detection of a small vertical ocular misalignment attributed to skew deviation. That finding directed attention to the brainstem, which led to a reevaluation of the MRI. Once the diffusion images were studied carefully and matched with apparent diffusion coefficient (ADC) and exponential apparent diffusion coefficient (eADC) maps, the small paramedian thalamic infarction was recognized. It was only after consciousness improved that language and memory deficits characteristic of lesions in this region were recognized. Skew deviation has been reported in thalamic infarction (3,6–10), but not as often as vertical gaze paresis (1–3,7,11–14). Our patient is unusual in having reported diplopia as an early symptom and in having skew deviation without other ocular motor abnormalities. Skew deviation rather than vertical gaze paresis probably occurs when the infarct is relatively small and the peri-infarct edema extends minimally into the rostral midbrain tegmentum in the territory of the medial longitudinal fasciculus and the interstitial nucleus of Cajal (6,15). Skew deviation was described by Dieterich and Brandt (6) in 8 of 14 patients with unilateral paramedian thalamic infarction. In addition to vertical ocular misalignment, these patients had a head tilt opposite to the side of the lesion, ocular torsion, and subjective visual vertical tilt. We did not assess these features in our patient because head tilt was not present. Among 40 patients with thalamic infarction, Bogousslavsky et al (7) listed skew deviation in only 1, Spontaneity of Verbal Oral Expression Paraphasias Jargon Speech Word-Finding Impairment Severely nonfluent Frequent None Severe Moderately nonfluent Occasional None Moderate Mildly nonfluent Fluent Rare None Moderate Rare None Mild a patient who had a unilateral paramedian lesion. No further details of ocular alignment testing were provided. A report of 2 patients with combined polar-paramedian thalamic infarcts (one on the left and one bilateral) mentioned skew deviation as a feature in both, but no details of the neuroophthalmic examination were included (3). A single case report of bilateral paramedian infarction confined to the thalamus described an ocular tilt reaction as the only manifestation (9). The authors reported hypertropia and ocular torsion present on fundus photography. Transient vertical diplopia without ocular ductional deficits was reported in a patient with unilateral ventrolateral thalamic infarction; nystagmus was the only other finding (10). Skew deviation also occurs in thalamic hemorrhage. In a prospective study of 100 patients with thalamic hemorrhage (16), the authors reported skew deviation in 17 (31%) of the 55 patients in whom the lesion was posterolateral. A case report of bilateral thalamic hemorrhage described a patient with tetraplegia and skew deviation but no details of the ophthalmic examination were provided (17). Transient skew deviation in thalamic infarction and hemorrhage may be more common than reported, considering that impaired consciousness could interfere with its detection (8,18,19). During the period of reduced consciousness, language deficits are often noted, as in our patient. There is debate as to whether these language deficits represent a true aphasia or whether they are caused by impaired arousal, attention, and motivation. In our patient, however, the language deficits appeared to meet the criteria for a limited aphasia (20–23). They included word-finding errors, frequent word substitution, and paraphasias (related-word substitutions) with minimally impaired repetition and no auditory comprehension deficits. These deficits resemble transcortical motor aphasia but are distinctive in having more frequent paraphasic errors (24), rapid resolution of speech and language deficits, and lingering executive 285 J Neuro-Ophthalmol, Vol. 28, No. 4, 2008 cognitive and short-term memory loss (3). The similarity between thalamic and transcortical motor aphasias suggests that the linguistic role of the thalamus is related to its connections to the frontal lobe anterior to Broca’s area and to the temporo-parietal-occipital junction posterior to Wernicke’s area (25). As expected, our patient showed relatively rapid recovery of consciousness and language skills (3). As consciousness and language improved, significant lingering deficits in memory and executive function became evident (26–28). These deficits may be explained by the fact that thalamic nuclei have extensive reciprocal connections with the cerebral cortex, particularly between the frontal lobes and dorsal medial thalamus (28,29). That such deficits may have more long-term adverse effects than the language problems was borne out in our patient, who had protracted difficulty resuming his position as an automotive company executive. Our patient demonstrates the fact that small thalamic infarcts may have potent neurologic effects yet subtle imaging findings. Although CT is very helpful in the emergency imaging evaluation of suspected brain infarction because of its rapid image acquisition and its sensitivity in the detection of acute hemorrhage, nonhemorrhagic infarcts often do not show detectable differences in attenuation until many hours after the event. MRI is much more sensitive in the detection of ischemic or infarcted brain tissue, especially when diffusion imaging is performed (30). By isolating the diffusion coefficient, it is possible to obtain an idea of the properties of diffusion occurring within a particular voxel. 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