Sensitivity of Magnetic Resonance Imaging of the Medial Longitudinal Fasciculus in Internuclear Ophthalmoplegia.

BACKGROUND: Internuclear ophthalmoplegia (INO) is a result of insult to the medial longitudinal fasciculus (MLF). Clinicoradiological correlation in patients with INO has been reported to be poor; however, prior studies have used low resolution MRI imaging techniques and included patients with subclinical INO. We aimed to determine the sensitivity of modern MRI interpreted by a specialist neuroradiologist to detect clinically evident INO. METHODS: A retrospective chart review of patients in 2 tertiary University-affiliated neuro-ophthalmology practices with the diagnosis of INO. MRI scans of all patients were reviewed and interpreted by a fellowship-trained neuroradiologist for the presence of lesion in MLF and concordance with the original imaging report. RESULTS: Forty-five patients were included in the study: 33 with demyelinating disease, 11 with stroke, and 1 with intracranial mass. A visible MLF lesion was present in 25/33 demyelinating cases and 7/11 ischemic cases. Lesions in 2 cases in each group were identified only after review by a fellowship-trained neuroradiologist. In demyelinating INO, patients with a visible MLF lesion were more likely to show other brainstem (72%) and supratentorial (51%) white matter lesions. CONCLUSIONS: In 25% of patients with demyelinating INO and 33% of patients with ischemic INO, no visible lesion was identified on current high-quality MRI imaging. Review of imaging by a neuroradiologist increased the possibility of lesion been identified.

Lesion follows function: video-oculography compared with MRI to diagnose internuclear ophthalmoplegia in patients with multiple sclerosis.

BACKGROUND: Video-oculography (VOG) is used to quantify functional deficits in internuclear ophthalmoplegia (INO), whereas MRI can detect the corresponding structural lesions in the medial longitudinal fasciculus (MLF). This study investigates the diagnostic agreement of MRI compared to VOG measurements. METHODS: We prospectively compared structural MRI findings and functional VOG measures of 63 MS patients to assess their diagnostic agreement for INO. RESULTS: MRI detected 12 true-positive and 92 true-negative MLF lesions for INO compared to VOG (12 true-positive and 38 true-negative patients) but identified one-third of the MLF lesions on the wrong side. MRI ratings were specific (92.0%) to detect MLF lesions but not sensitive (46.2%) for diagnosing INO (86.4% and 63.2% by patient). Accordingly, MRI has a high positive likelihood ratio of 5.77 but a modest negative likelihood ratio of 0.59 for the probability of INO (4.63 and 0.43) with an accuracy of 82.5% (79.4%). CONCLUSION: MRI assessments are highly specific but not sensitive for detecting INO compared to VOG. While MRI identifies MLF lesions in INO, VOG quantifies the deficit. As a simple, quick, and non-invasive test for diagnosing and tracking functional INO deficits, it will hopefully find its place in the diagnostic and therapeutic pathways of MS.

Internuclear Ophthalmoplegia as an Isolated Symptom of Brainstem Wake-up Stroke Responsive to Intravenous Thrombolysis: Evidence from MRI.

BACKGROUND: Internuclear ophthalmoplegia (INO) is a disorder of eye movements caused by a lesion involving the medial longitudinal fasciculus (MLF) within the brainstem, and it is characterized by adduction impairment combined with contralateral dissociated abduction nystagmus. The frequency of acute ischemic stroke (AIS) presenting with INO as a predominant symptom is very low, and many patients suffering from this brainstem AIS are precluded from intravenous thrombolysis (IVT). OBJECTIVE: To provide for the first time a magnetic resonance imaging (MRI) evidence of response to the IVT in brainstem wake-up stroke presenting with INO as an isolated symptom. METHODS: Here, we described a rare case of pons AIS presenting with INO as a unique symptom of awakening. In order to differentiate an ischemic stroke from other stroke mimics, and to determine whether the patient was within the therapeutic window for IVT (wake-up stroke), brain MRI including DWI and FLAIR sequences was acquired. RESULTS: A left paramedian pontine DWI/FLAIR mismatch was detected and the patient was considered eligible for IVT. After IVT, the patient made a full recovery with complete resolution of INO. Follow-up MRI at 1 month demonstrates the absence of ischemic lesions. CONCLUSION: Our case provides neuroradiological evidence of IVT efficacy in brainstem stroke, and it should prompt clinicians to rapidly perform MRI in wake-up onset INO and to just as quickly administer IVT, since INO is a functionally disabling deficit. Finally, this case demonstrates the value of MRI in diagnostic, prognostic, and therapeutic workup of posterior circulation wake-up stroke.

Oftalmoplejía internuclear bilateral (WEBINO) en un paciente pediátrico con Lupus Eritematoso Sistémico / Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) in a pediatric patient with Systemic Lupus Erythematosus

Resumen El síndrome de WEBINO (wall-eyed bilateral internuclear ophthalmoplegia), se presenta por una lesión del tegmento pontino (incluye área pontina paramediana, fascículo longitudinal medial y núcleo del abducens). Presenta limitación bilateral en la aducción y exotropía en la posición de la mirada primaria, nistagmo del ojo que abduce e incapacidad para la convergencia. Reporte de caso: Presentamos el caso de una paciente de 14 años con antecedente de Lupus Eritematoso Sistémico que debutó con diplopía horizontal de inicio súbito. El diagnóstico de WEBINO fue clínico y asociado con hallazgos de lesión isquémico pontomesencefálica en Resonancia Nuclear Magnética y angioresonancia cerebral. Se administró tratamiento con Metilprednisolona y presentó resolución gradual de los síntomas, sin embargo una semana después falleció por criptococosis sistémica. Conclusiones: Hacer el diagnostico de WEBINO se hace desafiante por su rareza y por la precisión de su localización neuroanatómica. Se debe realizar una exploración detallada para definir la causa probable y establecer el tratamiento oportuno que favorezca el pronóstico neurológico.

Background: Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is presented by a lesion of the pontine tegment (includes paramedian pontine area, medial longitudinal fascicle and nuclei of the abducens). It presents bilateral limitation in adduction and exotropia in the position of the primary gaze, abducting eye nystagmus and inability to converge. Case report: We present the case of a 14-year-old patient with a history of Systemic Lupus Erythematosus who debuted with sudden onset horizontal diplopia. WEBINO's diagnosis was clinical and associated with findings of ponto-mesencephalic ischemic injury in magnetic resonance imaging and magnetic resonance angiography. Treatment with Methylprednisolone was administered and she presented gradual resolution of the symptoms, however, one week later she died of systemic cryptococcosis. Conclusions: Making the WEBINO diagnosis is challenging due to its rarity and the precision of its neuroanatomical location. A detailed examination should be performed to define the probable cause and establish the appropriate treatment that favors the neurological prognosis.

MRI topography of lesions related to internuclear ophthalmoplegia in patients with multiple sclerosis or ischemic stroke.

BACKGROUND AND PURPOSE: Internuclear ophthalmoplegia is a dysfunction of conjugate eye movements, caused by lesions affecting the medial longitudinal fasciculus (MLF). Multiple sclerosis (MS) and ischemic stroke represent the most common pathophysiologies. While magnetic resonance imaging (MRI) allows for localizing lesions affecting the MLF, comprehensive comparative studies exploring potential different spatial characteristics of lesions affecting the MLF are missing until now. METHODS: We retrospectively investigated MRI examinations of 82 patients (40 patients with MS and 42 patients with ischemic stroke). For lesion localization, the brainstem was segmented into (1) ponto-medullary junction, (2) mid pons, (3) upper pons, and (4) mesencephalon. RESULTS: Corresponding lesions affecting the MLF were observed in 29/40 (72.5%) MS and 38/42 (90.5%) stroke patients. Compared to stroke patients, MS patients had significantly more lesions in multiple locations (P < .001). Stroke patients showed more lesions at the level of the mesencephalon (P < .001), while lesions at the level of the ponto-medullary junction, mid, and upper pons did not statistically differ between the groups. CONCLUSION: Our results demonstrate that multiple lesions affecting the MLF make inflammatory-demyelination due to MS more likely, while lesion localization at the level of the mesencephalon favors ischemia.

A model for interrogating the clinico-radiological paradox in multiple sclerosis: Internuclear ophthalmoplegia.

BACKGROUND AND PURPOSE: The clinico-radiological paradox in multiple sclerosis (MS) is well recognized, relevant and yet poorly understood. The suitability of an in vivo model for the clinico-radiological paradox was tested, using internuclear ophthalmoplegia (INO) and the medial longitudinal fasciculus (MLF). METHODS: In this cross-sectional study lesions of the MLF were rated by an experienced MS neuroradiologist blinded to all other information. The presence of an INO was objectively determined by a validated infrared oculography protocol (DEMoNS). Clinical information, including the National Eye Institute Visual Function Questionnaire, was obtained. RESULTS: This study included 202 patients with MS. The clinico-radiological paradox occurred in 50 patients (25%). This consisted of 45 patients having an INO without an MLF lesion and five patients with an MLF lesion but without an INO. The visual function overall score was related to the presence of an INO (p = 0.016), but not to MLF lesions seen on magnetic resonance imaging (MRI) (p = 0.207). A consensus list of potential causes for the clinico-radiological paradox was compiled and the MRI images were deposited in a repository. CONCLUSION: This study provides an objective and quantitative model to investigate the clinico-radiological paradox. Our data suggest that pathology of the MLF is more frequently detected and more clinically relevant by infrared oculography than by MLF lesion rating on MRI.

Neuro-Ophthalmologic Features and Outcomes of Thalamic Infarction: A Single-Institutional 10-Year Experience.

BACKGROUND: Neuro-ophthalmologic deficit after thalamic infarction has been of great concern to ophthalmologists because of its debilitating impacts on patients' daily living. We aimed to describe the visual and oculomotor features of thalamic infarction and to delineate clinical outcomes and prognostic factors of the oculomotor deficits from an ophthalmologic point of view. METHODS: Clinical and neuroimaging data of all participants were retrospectively reviewed. Among the 12,755 patients with first-ever ischemic stroke, who were registered in our Stroke Data Bank between January 2009 and December 2018, 342 were found to have acute thalamic infarcts on MRI, from whom we identified the patients exhibiting neuro-ophthalmologic manifestations including visual, oculomotor, pupillary, and eyelid anomalies. RESULTS: Forty (11.7%) of the 342 patients with thalamic infarction demonstrated neuro-ophthalmologic manifestations, consisting of vertical gaze palsy (n = 19), skew deviation with an invariable hypotropia of the contralesional eye (n = 18), third nerve palsy (n = 11), pseudoabducens palsy (n = 9), visual field defects (n = 7), and other anomalies such as isolated ptosis and miosis (n = 7). Paramedian infarct was the most predominant lesion of neuro-ophthalmologic significance, accounting for 84.8% (n = 28) of all patients sharing the oculomotor features. Although most of the patients with oculomotor abnormalities rapidly improved without sequelae, 6 (18.2%) patients showed permanent oculomotor deficits. Common clinical features of patients with permanent oculomotor deficits included the following: no improvement within 3 months, combined upgaze and downgaze palsy, and the involvement of the paramedian tegmentum of the rostral midbrain. CONCLUSIONS: Thalamic infarction, especially in paramedian territory, can cause a wide variety of neuro-ophthalmologic manifestations, including vertical gaze palsy, skew deviation, and third nerve palsy. Although most oculomotor abnormalities resolve spontaneously within a few months, some may persist for years when the deficits remain unimproved for more than 3 months after stroke.

Caudal paramedian midbrain infarction: a clinical study of imaging, clinical features and stroke mechanisms.

Caudal paramedian midbrain infarction (CPMI) is an extremely rare form of ischemic stroke and related clinical studies are scarce. Our aim is to investigate the clinical features, neuroradiological findings and stroke etiology of CPMI. We conducted a retrospective study of 12 patients with CPMI, confirmed by diffusion-weighted MRI from 6820 cerebral infarction patients at our stroke center from January 2012 to August 2018. Experienced neurologists evaluated the clinical manifestations, neuroimaging findings and stroke mechanisms. Twelve patients (11 men, 1 woman) aged 42-81 years old met the study inclusion criteria. Seven patients had a unilateral infarction (two right-sided, five left-sided) and five had bilateral infarctions. Sagittal image showed a backward oblique sign in the lower level of the midbrain. Significantly, the bilateral CPMIs presented with a characteristic "V-shaped" appearance in the axial MRI. All patients presented with bilateral cerebellar dysfunction which included dysarthric speech, truncal or gait ataxia and four-limb ataxia. In addition, diplopia and internuclear ophthalmoplegia were frequently encountered in CPMI. Five (41.7%) patients were classified with large artery atherosclerosis, four (33.3%) with small vessel disease, two (16.7%) with cardiogenic embolism, and one (8.3%) with undetermined etiology. CPMI is a rare cerebrovascular disease that destroys the Wernekink commissure, medial longitudinal fasciculi and other adjacent structures. It is characterized by bilateral cerebellar ataxia and eye movement disorders, mainly internuclear ophthalmoplegia. A distinct "V-shaped" radiological feature can be seen in bilateral CPMI patients. The primary mechanisms of unilateral CPMI involve small vessel disease. The underlying stroke mechanisms of bilateral CPMI are either large artery atherosclerosis disease or cardiac embolism.

The Clinical and Imaging Profile of Skew Deviation: A Study of 157 Cases.

BACKGROUND: Skew deviation, a vertical misalignment of the eyes caused by a lesion in the vestibulo-ocular pathway, is a common manifestation of brainstem dysfunction, yet comprehensive information about its clinical profile is lacking. The aim of this study was to document presenting symptoms, causes, ocular alignment features, accompanying neurologic signs, pertinent brain imaging abnormalities, and measures used to relieve diplopia. METHODS: We searched the electronic medical records text from 2000 to 2018 for "skew" or "skew deviation" at a tertiary care academic center, including only patients diagnosed under supervision of faculty neuro-ophthalmologists. After excluding patients with features suggesting an imitator of skew deviation, we collected data useful in answering the selected clinical issues. RESULTS: In a cohort of 157 patients, vertical misalignment ranged between 1 and 30 prism diopters (PD) (median 5 PD) and was comitant in 100 (64%) patients. Diplopia was reported by 87% and blurred vision by 11% of patients. Blurred vision was more common when vertical misalignment was less than 3 PD. At least one accompanying neurologic sign was present in 133 (85%) patients, most often nystagmus, followed by gaze paresis, ataxia, saccadic pursuit, and internuclear ophthalmoplegia. Stroke affecting the thalamus, brainstem, or cerebellum accounted for 82 (52%) of cases. Stroke was usually ischemic, mostly unprovoked, but also occurring after intracranial or extracranial surgical procedures. Brainstem tumor and operative injury caused most of the remaining cases. A subgroup of 17 (11%) patients had skew deviation as the only new clinical sign and had no pertinent brain imaging abnormalities. Resolution of skew deviation, documented in 58 (42%) of 137 patients who had at least one follow-up visit, usually occurred within 3 months, but sometimes not until after 12 months. Of 110 patients who still had diplopia on follow-up examinations, the diplopia was successfully relieved with prism spectacles in 68 (62%). The cause of the skew deviation, amount of vertical misalignment, and degree of incomitance did not predict the success in relieving diplopia. Accompanying neurologic signs, including ataxia, endured in 44% of patients and were often more debilitating than the diplopia of skew deviation. CONCLUSIONS: The amplitude of misalignment in skew deviation varies widely but is generally 5 PD or less. When misalignment is 3 PD or less, patients report blurred vision rather than diplopia. Skew deviation is usually accompanied by other neurologic signs reflecting brainstem dysfunction. Yet there is a small subgroup in which vertical misalignment is an isolated sign, and there are no supporting brain imaging abnormalities. The main cause of skew deviation is ischemic stroke, which affects not only the brainstem but also the thalamus. Diplopia from skew deviation frequently persists, in which case prism spectacles may be successful in palliating it. Accompanying neurologic signs, especially ataxia, may outlast skew deviation and be more debilitating.

Bringing prevost's sign into the third dimension: Artificial intelligence estimation of conjugate gaze adjusted length (CGAL) and correlation with acute ischemic stroke.

Conjugate gaze deviation is associated with acute ischemic stroke (AIS), although previously only measured on a 2D plane. The current study evaluates 3D imaging efficacy to assess conjugate gaze deviation and correlate direction and strength of deviation to neuro-clinical findings.A retrospective analysis of 519 patients who had CT scans for suspected AIS at our institution. Direction and angle of eye deviation were calculated based on 2D axial images. Volumetric reconstruction of CT scans allowed for calculation of 3D conjugate gaze adjusted length (CGAL). Angle, direction, and vector strength of both 2D and 3D scans were calculated by an artificial intelligence algorithm and tested for agreement with hemispheric ischemia location. CGAL measurements were correlated to NIHSS scores. Follow up MRI data was used to evaluate the sensitivity and specificity of CGAL in the identification of AIS.The final analysis included 122 patients. A strong agreement was found between 3D gaze direction and hemispheric ischemia location. CGAL measurements were highly correlated with NIHSS score (r = .72, P = .01). A CGAL >0.25, >0.28, and >0.35 exhibited a sensitivity of 91%, 86%, and 82% and specificity of 66%, 89%, and 89%, respectively, in AIS identification. A CGAL >0.28 has the best sensitivity-specificity balance in the identification of AIS. A CGAL >0.25 has the highest sensitivity.Given CED's correlation with NIHSS score a 1/4 deviation in the ipsilateral direction is a sensitive ancillary radiographic sign to assist radiologists in making a correct diagnosis even when not presented with full clinical data.

Single Muscle Transposition in the Management of Monocular Elevation Deficiency.

Monocular elevation deficiency is characterized by the inability to elevate one eye in abduction, adduction, and primary gaze. To date, various operations, including Knapp's procedure, have been used in the management of hypotropia associated with this condition. However, single muscle transposition has only recently been described as a feasible alternative, offering a number of advantages over other techniques. In particular, it reduces the risk of anterior segment ischemia and allows for an inferior rectus recession to occur simultaneously as is often required, thus avoiding the need for staged operations. It also facilitates a wider range of management options to correct for associated horizontal deviation. We present a case detailing the use of single muscle transposition in the management of monocular elevation deficiency and in doing so confirm the utility of this novel technique.

Ocular Dyskinesia and Hemifacial Spasm Secondary to Fourth Ventricular Tumor: Report of 4 Cases and Review of the Literature.

In clinical pediatric neurosurgery practice, fourth ventricle and cerebellar tumors are not rare. However, reports of secondary refractory hemifacial spasm are very rare. No report is currently available on the treatment of hemifacial spasm secondary to fourth ventricle and cerebellar tumors in China. Zamponi et al. [Childs Nerv Syst 2011 Jun;27(6):1001-5] reported that these lesions can occur in neonates and infants, and surgical resection is effective.

Magnetic resonance imaging findings in Parinaud's syndrome: comparing pineal mass findings to other etiologies.

PURPOSE: In a recent study, it was found that, although intrinsic midbrain signal abnormality (IMSA) on MRI is associated with Parinaud's syndrome (PS) in patients with pineal gland masses (PM), it had no predictive value with respect to resolution of PS. We sought to compare the PM and non-pineal etiologies (NPE) of PS by reviewing imaging features of PS and whether or not they are predictive of resolution of symptoms. METHODS: We reviewed electronic medical records from 1980 to 2017 and identified 71 patients with PS from any etiology who had MR imaging: 26 with PM and 45 with NPE. We subdivided the 45 NPE patients into those with intrinsic midbrain lesions (IMBL) (n = 23) and those with extrinsic midbrain lesions (EMBL) (n = 22). PS resolution and hydrocephalus data were collected. Imaging studies were reviewed for the presence of IMSA and hydrocephalus. RESULTS: PS patients with EMBL were less likely to have IMSA than those with PM or IMBL (p ≤0.001). PS resolution occurred more commonly with PM than IMBL and NPE (p = 0.03, p = 0.01). For all NPE patients, resolution of PS occurred with equal frequency in patients with and without IMSA (p = 1.00). Hydrocephalus occurred more frequently in patients with PM and EMBL than IMBL (p = 0.01, p = 0.03). CONCLUSIONS: IMSA is present more often in patients with PS from PM or IMBL than in patients with EMBL. EMBL, including PM, have an increased likelihood for PS resolution. There is no predictive value of IMSA with respect to resolution of PS in NPE as well as PM.