Splenial Restricted Diffusion as MRI Correlate of Diaschisis in a Blind Infant With Unilateral Posterior Cerebral Artery Stroke

A 3-month-old male infant appeared on multiple clinical examinations to have acutely developed bilateral retrogeniculate blindness. Electroencephalography showed focal status epilepticus confined to the left posterior cerebral hemisphere. MRI demonstrated restricted diffusion in the domain of the left posterior cerebral artery consistent with acute stroke. Notably, the restricted diffusion extended across the midline in the splenium of the corpus callosum. This splenial sign may be the imaging correlate of cerebral diaschisis, a well-described phenomenon in which patients with new brain lesions develop acutely impaired neurologic function in related but nonlesioned brain regions. Diaschisis has been posited as the explanation for the temporary bilateral blindness in adult patients suffering from unilateral occipital infarctions.

Photo Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Splenial Restricted Diffusion as MRI Correlate of Diaschisis in a Blind Infant With Unilateral Posterior Cerebral Artery Stroke Emily A. Eton, MD, Tapan P. Patel, MD, PhD, Ashok Srinivasan, MD, Toshio Moritani, MD, Jonathan D. Trobe, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 05/04/2022 FIG. 1. Trace diffusion-weighted imaging in coronal (A) and axial (B) projections shows a high signal in the territory of the left posterior cerebral artery, indicating acute ischemia. Notably, the high signal extends across the splenium of the corpus callosum (arrows). Apparent diffusion coefficient map (C) shows a corresponding hypointense signal in the splenium, confirming restricted diffusion. The left posterior cerebral hemispheric restricted diffusion could account for homonymous hemianopia, but not for the complete blindness apparent on clinical examination. The restricted diffusion in the splenium may therefore be the MRI correlate of diaschisis, defined as acutely impaired neurologic function in an unlesioned brain region remotely connected to a recently lesioned brain region. Abstract: A 3-month-old male infant appeared on multiple clinical examinations to have acutely developed bilateral retrogeniculate blindness. Electroencephalography showed focal status epilepticus confined to the left posterior cerebral hemisphere. MRI demonstrated restricted diffusion in the domain of the left posterior cerebral artery consistent with acute stroke. Notably, the restricted diffusion extended across the midline in the splenium of the corpus callosum. This splenial sign may be the imaging correlate of cerebral diaschisis, a well-described phenomenon in which patients with new brain lesions develop acutely impaired neurologic function in related but nonlesioned brain regions. Diaschisis has been posited as the explanation for the temporary Department of Ophthalmology and Visual Sciences (EAE, TPP, JDT), Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan; Department of Radiology (Neuroradiology) (AS, TM), University of Michigan, Ann Arbor, Michigan; and Department of Neurology (JDT), University of Michigan, Ann Arbor, Michigan The authors report no conflicts of interest. Address correspondence to Jonathan D. Trobe, MD, University of Michigan, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105; E-mail: [e-mail] Eton et al: J Neuro-Ophthalmol 2021; 41: e119-e121 bilateral blindness in adult patients suffering from unilateral occipital infarctions. Journal of Neuro-Ophthalmology 2021;41:e119–121 doi: 10.1097/WNO.0000000000000954 © 2020 by North American Neuro-Ophthalmology Society S even days after an episode of shallow breathing, lip smacking, eye twitching, and rhythmic jerking of the right foot, a 3-month-old boy showed spontaneous conjugate eye movements, but no fixation or following movements, no blink to light or confrontation in either eye, no optokinetic nystagmus, normally constricting pupils, clear media, and a normal fundus examination. These findings were replicated on neuro-ophthalmic examination several weeks later. At the time of our examinations, the child was not requiring a ventilatory support, was interactive, and was described by a pediatric neurologist as “easily arousable, cooing, and responding to stimulation of all extremities.” The infant had been born at 35 weeks of gestation. A prenatal ultrasound anatomic scan at 20 weeks had e119 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay demonstrated bilaterally enlarged polycystic kidneys. Genetic testing confirmed a diagnosis of autosomal recessive polycystic kidney disease, for which he had undergone bilateral nephrectomy at 5 days of age, followed by continuous peritoneal dialysis. He had been in the neonatal intensive care unit since delivery for the management of respiratory failure. Diffusion-weighted MRI (DWI) at the time of apparent cerebral blindness showed a large area of restricted diffusion in the distribution of the left posterior cerebral artery, consistent with acute infarction. The diffusion restriction extended across the midline along the splenium of the corpus callosum (Fig. 1A, B). An apparent diffusion coefficient (ADC) map showed a corresponding area of hypointense signal confirming low ADC (Fig. 1C). A 24-h electroencephalogram (EEG) showed frequent ictal activity ranging from 10 seconds to 5 minutes, limited to the left posterior cerebral hemisphere. Episodes began with medium amplitude rhythmic 3–4 Hz discharges with embedded spikes, transitioning to higher amplitude spike and wave activity. This activity was indicative of focal status epilepticus. There was interictal hemispheric asymmetry with attenuated amplitudes and fewer fast frequencies over the left cerebral hemisphere but no EEG abnormalities over the right posterior cerebral hemisphere or anywhere else in the brain. Ten months after the ischemic event, neuro-ophthalmologic evaluation showed an alert child with no focal neurologic impairments apart from those in the visual domain. He could fix and follow small targets with either eye occluded. With both eyes open, he showed rapid conjugate gaze toward targets displayed first in the right hemifield and then in the left hemifield. But when targets were displayed simultaneously in the right and left hemifields, he consistently gazed only toward the target displayed in the left hemifield. In other words, he demonstrated extinction to double simultaneous visual stimulation, a sign of either a subtle right homonymous hemianopia or hemispatial neglect. Because he did not display consistent leftward orientation toward auditory stimuli placed simultaneously on the right and left sides beyond the perimeter of the visual field, we presumed that his behavior suggested hemianopia rather than neglect. The region of cerebral infarction is sufficient to account for a right homonymous hemianopia, but not the degree of vision impairment suggested by our initial clinical examination. The restricted diffusion in the splenium prompted us to postulate that the child’s early blindness might be explained by diaschisis, a process in which the disruption of neuronal activity occurs at a site distant from the original lesion due in part to altered functional connectivity between remote brain regions (1,2). One plausible mechanism for the observed neurophysiological changes occurring remote from the site of brain injury is astrocyte-mediated neuromodulation. In addie120 tion to providing structural and physiological support of neurons, astrocytes actively participate in the modulation of neuronal synaptic transmission by releasing neuroactive substances, such as adenosine and glutamate (3). Astrocytes in the cortex are extensively coupled through gap junctions into a syncytium. Animal models of focal mechanical brain injury have shown intercellular calcium waves within the astrocyte network that propagate to distant regions and influence neuronal activity (4). Dysfunctional astrocyte calcium signaling in the distant brain regions may also contribute to excitotoxicity and an alteration in the blood–brain barrier, resulting in cytotoxic edema that displays hyperintensity on DWI. Neonatal brains are especially susceptible to excitotoxic injury, with several reports showing diffusion restriction in the splenium of the corpus callosum of neonates suffering from hypoxic-ischemic injury or acute ischemic stroke (5–7). Such a reported pattern of diffusion restriction mirrors that of our patient. The disrupted neuronal electrophysiologic function that may underlie diaschisis can be a transient phenomenon without resultant permanent neuronal cell death (8). Thereafter, the recovery of neuronal function can occur by synaptic remodeling and may explain improvement from blindness to a hemianopic defect in our patient. Imaging correlates of diaschisis have been previously reported with MRI arterial spin labeling (9), tractography (10), volume measures (11), single-photon emission computerized tomographic imaging (SPECT) (12), positron emission tomography (13), and computed tomography perfusion studies (14). But diaschisis has not been shown with DWI in cortical blindness. A study of 19 children with unilateral middle cerebral artery (MCA) distribution infarctions (15) found that 8 children showed diffusion restriction in an area anatomically connected to the infarcted region but in a separate vascular territory. Six patients had diffusion restriction that extended across the corpus callosum, as in our case. This imaging correlate of diaschisis tended to follow known anatomic connections, with posterior MCA strokes showing restricted diffusion across the splenium of the corpus callosum and anterior strokes showing restricted diffusion across the genu. The patients with additional regions of diffusion restriction showed worse motor and cognitive outcomes than those with diffusion restriction confined to the MCA territory. In an adult with a right occipital lobe hemorrhage and bilateral cortical blindness, SPECT imaging showed decreased perfusion in both parieto-occipital regions. The hypoperfusion in the nonlesioned hemisphere was attributed to diaschisis (16). MRI was not reported in that case, but we wonder whether it might have shown abnormalities similar to those of our patient. STATEMENT OF AUTHORSHIP Eton et al: J Neuro-Ophthalmol 2021; 41: e119-e121 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay Category 1: a. Conception and design: E.A. Eton and J.D. Trobe; b. Acquisition of data: E.A. Eton and J.D. Trobe; c. Analysis and interpretation of data: E.A. Eton, A. Srinivasan, and J.D. Trobe. Category 2: a. Drafting the manuscript: E.A. Eton, T.P. Patel, and J.D. Trobe; b. Revising it for intellectual content: E.A. Eton, T.P. Patel, A. Srinivasan, T. Moritani, and J.D. Trobe. Category 3: a. Final approval of the completed manuscript: E.A. Eton, T.P. Patel, A. Srinivasan, T. Moritani, and J.D. Trobe. REFERENCES 1. Bivard A, Stanwell P, Parsons M. Stroke and cerebral ischemia. In: Stagg C, Rothman D, eds. Magnetic Resonance Spectroscopy: Tools for Neuroscience Research and Emerging Clinical Applications. San Diego, CA: Academic Press, 2014:183–195. 2. Carrera E, Tononi G. Diaschisis: past, present, future. Brain. 2014;137:2408–2422. 3. Araque A, Parpura V, Sanzgiri RP, Haydon PG. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci. 1999;22:208–215. 4. Choo AM, Miller WJ, Chen YC, Nibley P, Patel TP, Goletiani C, Morrison B III, Kutzing MK, Firestein BL, Sul JY, Haydon PG, Meaney DF. Antagonism of purinergic signalling improves recovery from traumatic brain injury. Brain. 2013;136:65–80. 5. 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