Hypoxic-Ischemic Encephalopathy With Clinical and Imaging Abnormalities Limited to Occipital Lobe

In multiple sclerosis (MS), even in the absence of a clinical episode of optic neuritis (ON), the optic nerve and retinal nerve fiber layer (RNFL) may be damaged leading to dyschromatopsia. Subclinical dyschromatopsia has been described in MS associated with lower motor and cognitive performances.; ; To set the prevalence of dyschromatopsia in eyes of MS patients without a history of ON, to compare its prevalence in patients with and without ON history, and to explore the association between dyschromatopsia and disease duration, average peripapillary RNFL thickness, macular volume, and cognitive and motor performances.; ; An observational cross-sectional study was conducted at multiple medical centers. Data were collected after single neurological and ophthalmological evaluations. Dyschromatopsia was defined by the presence of at least 1 error using Hardy-Rand-Rittler plates.; ; In our population of 125 patients, 79 patients (63.2%) never had ON and 35 (28.8%) had unilateral ON. The prevalence of dyschromatopsia in eyes of patients without ON was 25.7%. Patients with dyschromatopsia had a statistically significant lower RNFL thickness (P = 0.004 and P = 0.040, right and left eyes, respectively) and worse performance in symbol digit modalities test (P = 0.012). No differences were found in macular volume or motor function tasks.; ; Dyschromatopsia occurs frequently in MS patients. It may be associated with a worse disease status and possibly serve as a marker for the detection of subclinical disease progression since it was detected even in the absence of ON. It correlated with thinner peripapillary RNFL thickness and inferior cognitive performance.

Original Contribution Hypoxic-Ischemic Encephalopathy With Clinical and Imaging Abnormalities Limited to Occipital Lobe Hemant A. Parmar, MD, Jonathan D. Trobe, MD Background: The vulnerable brain areas in hypoxic-ischemic encephalopathy (HIE) following systemic hypotension are typically the neocortex, deep cerebral gray nuclei, hippocampus, cerebellum, and the parieto-occipital arterial border zone region. The visual cortex is not commonly recognized as a target in this setting. Methods: Single-institution review from 2007 to 2015 of patients who suffered cortical visual loss as an isolated clinical manifestation following systemic hypotension and whose brain imaging showed abnormalities limited to the occipital lobe. Results: Nine patients met inclusion criteria. Visual loss at outset ranged from hand movements to 20/20, but all patients had homonymous field loss at best. In 1 patient, imaging was initially normal but 4 months later showed encephalomalacia. In 2 patients, imaging was initially subtle enough to be recognized as abnormal only when radiologists were advised that cortical visual loss was present. Conclusions: The occipital lobe may be an isolated target in HIE with cortical visual loss as the only clinical manifestation. Imaging performed in the acute period may appear normal or disclose abnormalities subtle enough to be overlooked. Radiologists informed of the clinical manifestations may be more attune to these abnormalities, which will become more apparent months later when occipital volume loss develops. Journal of Neuro-Ophthalmology 2016;36:264-269 doi: 10.1097/WNO.0000000000000380 © 2016 by North American Neuro-Ophthalmology Society H ypoxic-ischemic encephalopathy (HIE) results from hypoperfusion or hypoxia of the central nervous system. In adults, the common causes are cardiac arrest, severe hypotension, trauma, and drowning (1-5). In children, the Departments of Radiology (HAP), Ophthalmology and Visual Sciences (JDT), and Neurology (JDT), University of Michigan, Ann Arbor, Michigan. Some of the imaging and clinical findings were presented at the 49th American Society of Neuroradiology (ASNR) Meeting, April 12-14, 2012, New York, NY. The authors report no conflicts of interest. Address correspondence to Hemant A. Parmar, MD, Department of Radiology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109; E-mail: [e-mail] 264 common causes are dehydration, neonatal anoxia, and abusive head trauma. At any age, the principal targets are the cerebral cortex, corpus striatum, hippocampus, and cerebellar Purkinje cells (6,7). In the cerebral hemispheres, the regions that lie between the domains of the anterior, middle, posterior cerebral arteries (the "watershed" or "border zone" regions) are known to be particularly vulnerable (8). Lying outside the traditional watershed regions, the primary visual cortex is not commonly considered a target in HIE. Yet some patients rarely may have cortical vision loss as the only clinical and neuroimaging manifestation of HIE, as reported in 2 single-case reports in this journal (9,10). We report 7 patients who sustained persistent cortical visual loss and who had magnetic resonance imaging (MRI) abnormalities limited to the occipital lobes. In 3 of these patients, the initial imaging was either normal or incorrectly interpreted as normal because the signs were subtle. METHODS We obtained institutional review board approval for a retrospective evaluation of the radiologic and neuroophthalmologic electronic medical records from 2007 to 2015 for evidence of cardiac arrest or systemic hypotension immediately followed by cortical vision loss attributed to HIE. Patients were included only if there were no confounding clinical features that would suggest an alternative cause of stroke. One of the authors (H.A.P.), a neuroradiologist, analyzed the brain computed tomography (CT) and MRI studies to ascertain that imaging abnormalities were confined to the occipital lobe. We also documented the interpretation of the patients' initial CT and MRI studies by other neuroradiologists. We recorded the age, gender, nature of the precipitating event, interval before the initial neuroimaging study, and clinical and imaging findings in all patients. We expressed the delay between the precipitating event and the initial brain imaging as hyperacute (up to 1 Parmar and Trobe: J Neuro-Ophthalmol 2016; 36: 264-269 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution day after the precipitating event), acute (1-7 days), subacute (8-21 days), or chronic (more than 21 days). RESULTS Patient Cohort Nine patients met inclusion criteria (Table 1). Two patients (Cases 5 and 3) had been previously reported (9,10), but we included them in the cohort to display the full spectrum of clinical and imaging findings in a larger context. There were 6 men and 3 women, ranging in age between 13 and 70 years. Six patients had cardiac arrest (spontaneous, 2; motor vehicle accident, 2; electrocution, 1; and pneumonia, 1). Three patients had documented systemic hypotension from other causes (cardiac surgery, 1; chest gunshot wound, 1; and epidural anesthesia, 1). Neuroimaging Abnormalities Seven patients had undergone MRI and 2 patients had undergone only CT because MRI was contraindicated because of gunshot injury or pacemaker device (Table 2). Initial brain imaging occurred less than 1 day of the precipitating event (hyperacute) in 1 patient, within 1-7 days (acute) in 3 patients, within 8-21 days (subacute) in 2 patients, and after 22 days (chronic) in 3 patients. Occipital lobe imaging abnormalities were bilateral and symmetric in 4 patients and bilateral but asymmetric in 5 patients. Among 4 patients who had undergone imaging within 7 days, 3 had abnormalities readily identified on diffusionweighted and fluid-attenuated inversion recovery image (FLAIR) sequences (Cases 1, 3, and 4). In Case 4, the abnormality was initially interpreted as posterior reversible encephalopathy syndrome (PRES), although the clinical setting was hypotension and not hypertension (Fig. 1). The fourth patient (Case 2) showed no abnormality on the initial MRI but developed subtle FLAIR high signal and encephalomalacia on an MRI study performed 4 months later (Fig. 2). Of the 2 patients who received intravenous contrast (Cases 3 and 4), only 1 (Case 4) showed enhancement in the involved areas. Of the 2 patients imaged between 8 and 21 days, 1 (Case 6) had only CT, which showed a hypodensity restricted to the occipital lobe. In the other patient (Case 5), MRI performed 11 days after the precipitating event was initially interpreted as normal. Follow-up MRI 5 months later showed subtle volume loss in both occipital lobes. In retrospect, subtle cortical enhancement was visible on the initial MRI examination (9). Of 3 patients imaged after 22 days (Cases 7, 8, and 9), 2 MRI studies showed encephalomalacia characterized by T2 signal prolongation, volume loss, sulcal prominence, and ex vacuo enlargement of the ipsilateral occipital horn. In 1 of these patients (Case 8), the initial MRI, performed 4 months after the precipitating event, was interpreted as normal. On a thinner section MRI, performed 8 months after the precipitating event, subtle high FLAIR signal was evident in the visual cortex. In retrospect, subtle occipital cortical laminar necrosis had been overlooked on the initial study (Fig. 3). The third patient (Case 7), imaged with CT only, showed encephalomalacia in both occipital lobes (Fig. 4). Thus, in 3 of the 9 patients, imaging abnormalities were either overlooked or the imaging was normal. In 2 of them TABLE 1. Demographic and clinical findings in patients with occipital lobe hypoxic-ischemic encephalopathy Cause Case 1 M/13 Hypoplastic left heart repair Case 2 M/45 Spontaneous cardiac arrest Case 3 M/28 Electrocution, cardiac arrest Case 4 F/54 Spontaneous cardiac arrest Case 5 M/22 Motor vehicle accident, cardiac arrest Case 6 M/60 Chest gunshot wound Case 7 Case 8 M/56 F/42 Case 9 F/70 Lumbar epidural anesthesia Motor vehicle accident, systemic hypotension from cardiac arrest Pneumonia, cardiac arrest Parmar and Trobe: J Neuro-Ophthalmol 2016; 36: 264-269 Visual Manifestations Normal visual acuity but initially constricted visual fields bilaterally that resolved completely Initially hand movements vision, both eyes, improving to 20/25, both eyes, with full visual fields Initially hand movements vision, both eyes, improving to 20/25, both eyes, with persistent bilateral homonymous hemianopias Visual acuity 20/20, both eyes; persistent right homonymous inferior quadrantanopia Hand movements vision both eyes, recovering to 20/20 but persistently constricted visual fields Visual acuity 20/20, both eyes; persistent left homonymous inferior quadrantanopia No light perception in both eyes persistently Persistently reduced visual acuity of 20/50 both eyes; formal visual fields unreliable Visual acuity 20/20, both eyes; persistent bilateral inferior altitudinal visual field defects 265 Copyright © North American Neuro-Ophthalmology Society. 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FLAIR Signal Intensity Parmar and Trobe: J Neuro-Ophthalmol 2016; 36: 264-269 Precontrast T1 Signal Intensity Postcontrast T1 Enhancement Case 1 Low Not done High Pos Not done Abnormal Study not done Case 2 Normal Not done Normal Neg Not done Normal Volume loss, high FLAIR Case 3 Low No enhancement High Pos Not done Abnormal Study not done Case 4 Low Enhancement High Pos Not done Abnormal Case 5 Normal Enhancement Normal Neg Not done Normal Volume loss, high FLAIR Volume loss Case 6 MRI not done MRI not done Not done Not done Occipital hypodensities Abnormal Unchanged Case 7 MRI not done MRI not done MRI not done MRI not Occipital done hypodensities Abnormal Study not done Case 8 High Not done High Neg Not done Normal Unchanged Case 9 Low Not done High Neg Not done Abnormal Study not done DWI CT Initial Imaging Interpretation Follow-up MRI Findings Comments MRI performed within 1 d of event showed mild DWI and FLAIR changes in occipital gyri Initial MRI was normal; MRI performed 4 mo later showed subtle FLAIR cortical signal and encephalomalacia in occipital lobes (Fig. 2) MRI performed within 5 d of event showed florid DWI abnormality with high FLAIR signal isolated to occipital lobes MRI performed within 6 d of event mistakenly interpreted as PRES (Fig. 1) Initial MRI interpreted as normal; visual loss considered of psychogenic origin until MRI 5 mo later showed subtle occipital encephalomalacia No MRI due to gunshot wound; bilateral occipital hypodensities visible in subacute stage No MRI because of pacemaker; CT showed chronic encephalomalacia confined to occipital lobes (Fig. 4) Initial MRI performed 4 mo after event interpreted as normal; visual field loss was considered psychogenic until patient was reimaged 4 mo later when thinner slices showed subtle FLAIR signal in occipital gyri; review of earlier MRI showed subtle abnormalities (Fig. 3) MRI performed greater than 6 mo after cardiac arrest showed encephalomalacia in occipital lobes CT, computed tomography; DWI, diffusion-weighted; FLAIR, fluid-attenuated inversion recovery image; MRI, magnetic resonance imaging; Neg, negative; Pos, positive; PRES, posterior reversible encephalopathy syndrome. Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution 266 TABLE 2. Neuroimaging in patients with occipital lobe hypoxic-ischemic encephalopathy Original Contribution FIG. 1. Case 4. A 54-year-old woman had a spontaneous cardiac arrest. She had normal visual acuity but persistent right homonymous inferior quadrantanopia without other clinical neurologic deficits. Magnetic resonance imaging performed 6 days after the event (A) shows high signal on diffusion-weighted imaging (arrows) and corresponding low signal (arrows) on apparent diffusion coefficient map in both occipital lobes (B), and also increased fluid-attenuated inversion recovery image signal in those regions (C). (Cases 5 and 8), the imaging findings were overlooked on the initial interpretation but identified on review when the cortical visual loss was emphasized to the radiologist. In a third patient (Case 2), the occipital lobe abnormalities were considered normal on the initial interpretation and on review. Imaging abnormalities appeared only on an MRI study performed 4 months later (Fig. 2). Ophthalmic Abnormalities All 9 patients had impaired visual acuity or visual fields at the initial examination conducted within days to weeks of the precipitating event (Table 1). At that examination, visual acuity was markedly depressed in 4 patients (Cases 2, 3, 6, and 7), moderately depressed in 1 patient (Case 8), and normal in 4 patients (Cases 1, 4, 5, and 9). Among those 4 patients with markedly depressed visual acuity at outset, visual acuity improved to 20/25 or better in 3 patients (Cases 2, 3, and 6) and remained no light perception in 1 patient (Case 7). The patient with moderately depressed visual acuity at outset did not improve (Case 8). Three patients (Cases 4, 5, and 9) retained normal visual acuity but had persistent dense unilateral (Cases 4 and 5) or bilateral (Case 9) inferior homonymous quadrantic visual field defects, reflecting predominant damage to the superior occipital lobe. Two patients (Cases 3 and 6) with markedly depressed vision at outset had recovery of visual acuity but retained bilateral homonymous FIG. 2. Case 2. A 45-year-old man experienced a spontaneous cardiac arrest and had hand movements vision in both eyes without other neurologic deficits. Magnetic resonance imaging (MRI) performed 5 days after the cardiac arrest shows no abnormality on diffusion-weighted (A), apparent diffusion coefficient (B), or fluid-attenuated inversion recovery image (FLAIR) (C) sequences. MRI performed 4 months later (D) shows volume loss in both occipital lobes with very subtle FLAIR hyperintensities in both occipital cortices (arrows) and underlying white matter. Visual acuity at that time had improved to 20/25 in both eyes and visual fields were full. Parmar and Trobe: J Neuro-Ophthalmol 2016; 36: 264-269 267 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 3. Case 8. A 42-year-old woman who had a cardiac arrest after a motor vehicle accident. She had visual acuity of 20/50 in each eye with impaired visual fields but no other neurologic deficits. Magnetic resonance imaging (MRI) performed 3 months later with 5-mm slice thickness was interpreted as normal. In retrospect, it shows a subtle area of fluid-attenuated inversion recovery image hyperintensity in both occipital lobes (A), with minimal precontrast T1 gyriform hyperintensity (arrows, B). MRI performed 7 months after the cardiac arrest with 3-mm slice thickness accentuates these abnormalities (arrows) and shows mild occipital encephalomalacia (C). hemianopias involving upper and lower quadrants. The patient (Case 9) who had bilateral inferior homonymous quadrantanopias showed evidence of visuospatial dysfunction, a feature often associated with occipitoparietal border zone infarction. Visuospatial dysfunction was not identified in any other patient with adequate vision. In 3 patients (Case 2, 5, and 8), the visual loss was at first considered to be of psychogenic origin because the initial MRI was normal (Case 2) or because subtle abnormalities were overlooked (Cases 5 and 8). DISCUSSION Our study is notable for demonstrating hypoxic-ischemic damage to the primary visual cortex and MRI abnormalities confined to the occipital lobe. Recognition of this phenomenon was delayed in 3 patients because the MRI signs were either normal (Case 2) or subtle enough to be overlooked (Cases 5 and 8). In a fourth patient (Case 4), the restricted diffusion was misinterpreted as having been caused by PRES, although the clinical setting was systemic hypotension. We surmise that the interpreting radiologist considered the occipital lobe a more likely target for PRES than for HIE. Although not traditionally acknowledged as a vulnerable region in HIE, the primary visual cortex has features that could make it susceptible to damage in this condition. It lies at a remote region of arterial blood supply-the terminus of the posterior cerebral artery (11). Under hypotensive conditions, perfusion may not be adequate. Another possible explanation for isolated occipital damage is that the granular cells FIG. 4. Case 7. A 56-year-old man developed systemic hypotension after epidural anesthesia. He lost all vision in both eyes without recovery. Magnetic resonance imaging could not be performed because of a cardiac pacemaker. Brain computed tomography (CT) performed 3 months after the event shows volume loss and hypodensities in both occipital lobes (A). CT section at higher level (B) reveals no abnormality in the occipital-parietal border ("watershed") zone considered most vulnerable to ischemia in systemic hypotension. 268 Parmar and Trobe: J Neuro-Ophthalmol 2016; 36: 264-269 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution in the occipital striate cortex may be less resistant to hypoxia (12). Preferential involvement of the occipital lobes is also seen in patients with severe neonatal hypoglycemia (12). The traditional posterior watershed area is said to involve the parieto-occipital region and to produce visuospatial, attentional, and ocular motor deficits-the Balint-Holmes syndrome (13,14). But only one patient in our series (Case 9) had features suggestive of this syndrome. Although primary visual cortex is not commonly an isolated target in HIE, our series further documents that this phenomenon may not be rare. 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