Selective Unidirectional Horizontal Saccadic Paralysis From Acute Ipsilateral Pontine Stroke

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare and autosomal recessive syndrome. We describe 2 cases of HGPPS which are the first documented in patients of African ancestry from an isolated population in Cape Verde. They demonstrated typical findings on neuro-ophthalmic examination and brain magnetic resonance imaging. One patient had novel heterozymous mutations of the ROB0 3 gene.

Clinical Observation Selective Unidirectional Horizontal Saccadic Paralysis From Acute Ipsilateral Pontine Stroke Thong D. Pham, MD, Jonathan D. Trobe, MD Background: Impairment of unidirectional horizontal saccades with sparing of smooth pursuit has been described in human lesions in the dorsomedial pons. They have been too large to allow localization to the pontine paramedian reticular formation (PPRF). Methods: Single case report. Results: A patient with impaired rightward saccades but spared rightward pursuit eye movements had a brain MRI showing a discrete area of restricted diffusion in the region corresponding to the PPRF. Conclusions: This case provides support for the concept that PPRF lesions in humans may selectively impair unidirectional horizontal saccades. Journal of Neuro-Ophthalmology 2017;37:159-161 doi: 10.1097/WNO.0000000000000423 © 2016 by North American Neuro-Ophthalmology Society S elective loss of unilateral horizontal saccades with preservation of pursuit previously has been reported with computed tomographic abnormalities in the region of the pontine paramedian reticular formation (PPRF), caused by metastatic tumor (1), hemorrhage (2), and tuberculoma (3). But those lesions were large and not precisely localizing to the PPRF. Saccadic palsy of both vertical and horizontal gaze has been noted in a metastatic adenocarcinoma to the pons (4) and after cardiac surgery (5-8) secondary to injury to the PPRF and nucleus raphe interpositus (RIP) (7) and to the perineural network of cells supporting the omnipause and burst neurons (8). In one case, MRI of the brain performed 10 Departments of Ophthalmology and Visual Science (TDP, JDP) and Neurology (JDP), Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www. jneuro-ophthalmology.com). Address correspondence to Jonathan D. Trobe, MD, Departments of Ophthalmology and Visual Science, and Neurology, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105; E-mail: [e-mail] Pham and Trobe: J Neuro-Ophthalmol 2017; 37: 159-161 months after cardiac surgery demonstrated increased fluid-attenuated inversion recovery (FLAIR) signal in the right dorsomedial pons (5). We report a case of acute selective impairment of rightward saccades associated wit a discrete area of restricted diffusion in the region of the PPRF. CASE REPORT A 53-year-old woman experienced difficulty looking to the right, acute gait imbalance, and tingling in her left hand and foot. She had type 2 diabetes mellitus, hypothyroidism, and nonmetastatic pancreatic cancer, for which she had been treated 3 years earlier with surgery, chemotherapy, and radiation. She had remotely suffered a pulmonary embolism for which she had been placed on warfarin, which had been discontinued 2 months earlier. Two days after the onset of symptoms, her examination showed slowed conjugate saccades to the right, blinking that preceded all attempts at rightward gaze (see Supplemental Digital Content, Video, http://links.lww.com/WNO/A205) and moderate gait ataxia. When advised to stop blinking, she replied: "I cannot help it." She never blinked before initiating saccades in any other direction. Eyes were aligned and smooth pursuit was preserved in all directions. Contralaterally directed saccades (including those initiated in right gaze), vertical saccades, and convergence were intact. There was no nystagmus. We did not test the vestibulo-ocular reflex or optokinetic nystagmus and made no formal recordings of eye movements. Brain MRI showed a discrete area of restricted diffusion in the right dorsomedial pontine tegmentum with correlated hyperintensity on FLAIR, consistent with acute ischemic stroke in the region of the PPRF (Fig. 1). The center of the signal abnormality appeared to be slightly ventral to the expected region of the sixth nerve nucleus. There were numerous foci of high T2 and FLAIR signal within the periventricular, deep, and juxtacortical white matter of the cerebral hemispheres, brainstem, and 159 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 1. A. Axial diffusion-weighted imaging demonstrates a hyperintense area (arrow) in the right dorsomedial pons. B. Apparent diffusion coefficient map shows a corresponding hypointense area (arrow). C. FLAIR sequence at the same level shows a corresponding area of high signal (arrow). Left cerebellar and left temporal lobe hyperintense foci did not restrict diffusion. D. FLAIR sequence indicates the location of the relevant structures (rectangle = pontine paramedian reticular formation; triangle = medial longitudinal fasciculus; circle = sixth cranial nerve nucleus). cerebellum consistent with chronic small vessel ischemic disease. DISCUSSION Our patient displayed impaired rightward saccades with sparing of pursuit, a phenomenon that previously has been described, albeit rarely. The novel feature of this case is the association with restricted diffusion in the expected location of the PPRF, a neuroimaging finding not previously reported. The MRI signal abnormality appeared to lie ventral to the sixth cranial nerve nucleus, but we acknowledge the limitations of relating signal extent to lesion extent. Based on animal experiments and human clinical and pathological findings, the PPRF is believed to contain burst neurons involved in generating ipsilateral horizontal saccades (9). The RIP in the midline contains omnipause neurons that discharge tonically to inhibit burst neurons for horizontal saccades in the PPRF and vertical saccades located in the rostral interstitial nucleus of the medial longitudinal fasiculus (9). Omnipause neurons evidently also facilitate saccades, as lesions of the RIP cause slowing 160 of saccades in all directions. The proposed mechanism of this facilitation is loss of postinhibitory rebound needed to generate normal-velocity saccades (9). The functional areas of the PPRF have been established through electrolytic lesions in monkeys (10). Unilateral injection of kainic acid into the tegmental pons of macaque monkeys has caused ipsilateral horizontal saccadic palsy with intact pursuit and vestibular movements (11). Bilateral injection of kainic acid into the caudal PPRF area has caused bilateral horizontal saccadic palsy, whereas bilateral injection into the rostral PPRF area has caused loss of both vertical and horizontal saccades (11). Injection of ibotenic acid into macaque RIP has caused loss of horizontal and vertical saccades (12). Our patient blinked involuntarily before each attempt at generating rightward saccades. In patients with saccadic palsy of various etiologies, including multiple system atrophy-cerebellar type and oculomotor apraxia, blinking improves the speed of saccades by suppressing the activity of the omnipause neurons (9). The suppression of omnipause neuron activity by blinking may cause a more complete and synchronized inhibition, thus facilitating a faster saccade (9). Pham and Trobe: J Neuro-Ophthalmol 2017; 37: 159-161 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation Our report supports animal evidence that selective impairment of horizontal saccades may occur from a discrete caudal tegmental pontine lesion in a very tiny area. It also serves as a reminder that complete clinical evaluation of eye movements must extend beyond the assessment of pursuit. Without saccadic testing, the rightward gaze abnormality would have gone undetected. Had the abnormality been incomplete rather than merely slowed rightward saccades, we could have used the doll head maneuver to try to elicit ampler rightward gaze. If this occurred, we would have confirmed localization of the lesion to the PPRF rather than to the sixth nerve nucleus. 2. 3. 4. 5. 6. 7. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Thong D. Pham, MD, and Jonathan D. Trobe, MD; b. Acquisition of data: Thong D. Pham, MD and Jonathan D. Trobe, MD; c. Analysis and interpretation of data: Thong D. Pham, MD and Jonathan D. Trobe, MD. Category 2: a. Drafting the manuscript: Thong D. Pham, MD and Jonathan D. Trobe, MD; b. Revising it for intellectual content: Thong D. Pham, MD and Jonathan D. Trobe, MD. Category 3: a. Final approval of the completed manuscript: Thong D. Pham, MD and Jonathan D. Trobe, MD. 8. 9. 10. 11. REFERENCES 1. Pierrot-Deseilligny C, Chain F, Lhermitte F. Syndrome de la formation reticulaire pontique. Precisions physiopathologiques Pham and Trobe: J Neuro-Ophthalmol 2017; 37: 159-161 12. sur les anomalies des mouvements oculaires volontaires. Rev Neurol (Paris). 1982;138:517-532. Kommerell G, Henn V, Bach M, Lucking CH. Unilateral lesion of the paramedian pontine reticular formation. Neuro-ophthalmology. 1987;7:93-98. Masson C, Prier S, Masson M, Cambier J. [Unilateral paralysis of saccades caused by pontine tuberculoma] [in French]. Rev Neurol (Paris). 1989;145:652-655. Nishida T, Tychsen L, Corbett J. Resolution of saccadic palsy after treatment of brain-stem metastasis. Arch Neurol. 1986;43:1196-1197. 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