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Fiber tractography (FT) has become an important noninvasive tool to ensure maximal safe tumor resection in eloquent glioma surgery. Intraoperatively applied FT is still predominantly based on diffusion tensor imaging (DTI). However, reconstruction schemes of high angular resolution diffusion imaging data for high-resolution FT (HRFT) are gaining increasing attention. The aim of this prospective study was to compare the accuracy of sophisticated HRFT models compared with DTI-FT.Ten patients with eloquent gliomas underwent surgery under awake craniotomy conditions. The localization of acquisition points, representing deteriorations during intraoperative electrostimulation (IOM) and neuropsychological mapping, were documented. The offsets of acquisition points to the respective fiber bundle were calculated. Probabilistic Q-ball imaging (QBI) and constrained spherical deconvolution (CSD)-FT were compared with DTI-FT for the major language-associated fiber bundles (superior longitudinal fasciculus [SLF] II-IV, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus/medial longitudinal fasciculus).Among 186 offset values, 46% were located closer than 10 mm to the estimated fiber bundle (CSD, 36%; DTI, 40% and QBI, 60%). Moreover, only 10 offsets were further away than 30 mm (5%). Lowest mean minimum offsets (SLF, 7.7 ± 7.9 mm; inferior fronto-occipital fasciculus, 12.7 ± 8.3 mm; inferior longitudinal fasciculus/medial longitudinal fasciculus, 17.7 ± 6.7 mm) were found for QBI, indicating a significant advantage compared with CSD or DTI (P0.001), respectively. No significant differences were found between CSD-FT and DTI-FT offsets (P = 0.105), albeit for the compound SLF exclusively (P0.001).Comparing HRFT techniques QBI and CSD with DTI, QBI delivered significantly better results with lowest offsets and good correlation to IOM results. Besides, QBI-FT was feasible for neurosurgical preoperative and intraoperative applications. Our findings suggest that a combined approach of QBI-FT and IOM under awake craniotomy is considerable for best preservation of neurological function in the presented setting. Overall, the implementation of selected HRFT models into neuronavigation systems seems to be a promising tool in glioma surgery.

The key to the diagnosis of ocular motor disorders is a systematic clinical examination of the different types of eye movements, including eye position, spontaneous nystagmus, range of eye movements, smooth pursuit, saccades, gaze-holding function, vergence, optokinetic nystagmus, as well as testing of the function of the vestibulo-ocular reflex (VOR) and visual fixation suppression of the VOR. This is like a window which allows you to look into the brain stem and cerebellum even if imaging is normal. Relevant anatomical structures are the midbrain, pons, medulla, cerebellum and rarely the cortex. There is a simple clinical rule: vertical and torsional eye movements are generated in the midbrain, horizontal eye movements in the pons. For example, isolated dysfunction of vertical eye movements is due to a midbrain lesion affecting the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), with impaired vertical saccades only or vertical gaze-evoked nystagmus due to dysfunction of the Interstitial nucleus of Cajal (INC). Lesions of the lateral medulla oblongata (Wallenberg syndrome) lead to typical findings: ocular tilt reaction, central fixation nystagmus and dysmetric saccades. The cerebellum is relevant for almost all types of eye movements; typical pathological findings are saccadic smooth pursuit, gaze-evoked nystagmus or dysmetric saccades. The time course of the development of symptoms and signs is important for the diagnosis of underlying diseases: acute: most likely stroke; subacute: inflammatory diseases, metabolic diseases like thiamine deficiencies; chronic progressive: inherited diseases like Niemann-Pick type C with typically initially vertical and then horizontal saccade palsy or degenerative diseases like progressive supranuclear palsy. Treatment depends on the underlying disease. In this article, we deal with central ocular motor disorders. In a second article, we focus on clinically relevant types of nystagmus such as downbeat, upbeat, fixation pendular, gaze-evoked, infantile or periodic alternating nystagmus. Therefore, these types of nystagmus will not be described here in detail.Der Schlüssel zur Diagnose von Augenbewegungsstörungen ist eine systematische klinische Untersuchung aller Arten von Augenbewegungen. Diese ist wie ein Fenster in Hirnstamm und Kleinhirn, selbst wenn die Bildgebung unauffällig ist. Die Untersuchung umfasst die folgenden Aspekte: Augenposition, Untersuchung auf einen Spontannystagmus, Motilität, Blickfolge, Blickhaltefunktion, Sakkaden, Vergenzreaktion, optokinetischer Nystagmus, Funktion des vestibulookulären Reflexes (VOR) sowie die Fixationssuppression des VOR. Anatomisch relevante Strukturen sind Mesenzephalon, Pons, Medulla oblongata, Zerebellum und sehr selten der Kortex. Topografisch-anatomisch gelten die folgenden einfachen klinischen Regeln: vertikale und torsionelle Augenbewegungen werden vorwiegend im Mesenzephalon (relevante Strukturen sind der rostrale interstitielle Kern des Fasciculus longitudinalis medialis und der interstitielle Nucleus Cajal) und horizontale Augenbewegungen im Pons (relevante Struktur ist z. B. die paramediane pontine Formatio reticularis) generiert. Somit finden sich z. B. bei Mittelhirnläsionen eine vertikale Sakkaden- oder Blickparese und ein isolierter vertikaler Blickrichtungsnystagmus und bei Läsionen im Bereich des Pons entsprechende horizontale Störungen sowie eine internukleäre Ophthalmoplegie. Läsionen der lateralen Medulla oblongata (Wallenberg-Syndrom) führen zu typischen Befunden mit Ocular Tilt Reaction, Fixationsnystagmus und Sakkadendysmetrie. Das Zerebellum spielt eine Rolle bei praktisch allen Augenbewegungen; typische klinische Zeichen sind eine allseitige Blickfolgesakkadierung, Blickrichtungsnystagmus oder dysmetrische Sakkaden. Wichtig für die Beurteilung der zugrunde liegenden Erkrankungen ist der Verlauf: akut bei Infarkten, subakut bei entzündlichen Erkrankungen, Thiaminmangel oder unerwünschter Medikamentenwirkung sowie chronisch progredient bei hereditären Erkrankungen wie Niemann-Pick Typ C mit typischer, zunächst vertikaler und dann horizontaler Sakkadenparese oder neurodegenerativen Erkrankungen wie der progressiven supranukleären Blickparese. Die Behandlung hängt von der zugrunde liegenden Erkrankung ab. Abschließend: in einem begleitenden Artikel werden in dieser Zeitschrift die häufigsten und klinisch relevanten Nystagmusformen wie z. B. Downbeat-, Upbeat-, Fixationspendelnystagmus, infantiler oder periodisch-alternierender Nystagmus und deren klinische Untersuchung dargestellt, sodass auf diese hier nicht detailliert eingegangen wird, wobei es bewusst Überlappungen gibt.

Vertical one-and-a-half syndrome (VOHS) is an uncommon presentation resulting from a unilateral thalamomesencephalic stroke with involvement of the rostral interstitial nucleus of the medial longitudinal fasciculus and posterior commissure. The artery of Percheron (aPe) is a branch of the posterior cerebral artery (PCA) and it is a variant that arises as a solitary trunk supplying both medial thalami and upper midbrain. A 78-year-old female patient, presented at the hospital emergency with approximately 12 hours of sudden onset of diplopia, associated with dizziness. Neurological exam revealed torsional nystagmus associated with bilateral upgaze palsy with limitation of infraduction on the left. We describe a rare case of VOHS associated with ischemic alterations at the MRI suggesting an aPe impairment. The conjugate gaze control lies anatomically at the midbrain at the central nervous system (CNS). This report describes a rare type of VOHS and brings a new insight on a possible aPe topography possibly causing this clinical presentation.

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.

Significance Ocular tilt reaction (OTR) is an abnormal eye-head postural reaction that consists of skew deviation, head tilt, and bilateral ocular torsion. Understanding of the pathway of the vestibulo-ocular reflex (VOR) is essential because this will help to localize the pathology. Purpose The aim of this study was to report a case of OTR with contralateral internuclear ophthalmoplegia (INO) and fifth and seventh cranial nerve palsies. Case report A 51-year-old gentleman with underlying diabetes mellitus presented with sudden onset of diplopia for 3 days. On examination, his visual acuity was 20/30 bilaterally without a relative afferent pupillary defect. He had a right OTR consisting of a right head tilt, a skew deviation with a left eye hypertropia, and bilateral ocular torsion (right excyclotorsion and left incyclotorsion) with nystagmus. He also had a left adduction deficit and right abduction nystagmus consistent with a left INO. Ocular examination revealed evidence of proliferative diabetic retinopathy bilaterally. Two days after the initial presentation, the patient developed left seventh and fifth cranial nerve palsies. MRI showed left pontine infarction and multiple chronic lacunar infarctions. There was an incidental finding of a vascular loop compression on cisternal portions of the left trigeminal, facial, and vestibulocochlear nerves. Antiplatelet treatment was started on top of a better diabetic control. The diplopia was gradually resolved with improved clinical signs. In this case, the left pontine infarction had likely affected the terminal decussated part of the vestibulocochlear nerve from the right VOR pathway, medial longitudinal fasciculus, and cranial nerve nuclei in the left pons. Conclusions The OTR can be ipsilateral to the lesion if the lesion is before the decussation of the VOR pathway in the pons, or it can be contralateral to the lesion if the lesion is after the decussation. In case of an OTR that is associated with contralateral INO and other contralateral cranial nerves palsy, a pathology in the pons that is contralateral to the OTR should be considered. Neuroimaging study can hence be targeted to identify the possible cause.

Introduction Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a rare variation of internuclear ophthalmoplegia associated with bilateral lesions of the medial longitudinal fasciculus. Case report In this case, the edematous lesions of the ipsilateral midbrain infarction appeared to compress the contralateral medial longitudinal fasciculus, resulting in WEBINO. Treatment of focal cerebral edema caused by ischemic stroke is still under debate. However, in this case, antiedema treatment was implemented to prevent the sequelae of the edematous lesion caused by a midbrain infarction, and a relatively rapid improvement of ocular symptoms was observed. Conclusion Herein, we report a rare case of WEBINO caused by a unilateral midbrain infarction in which the patient experienced edema-related neurological deficits. This case provides evidence that early antiedema therapy may benefit patients with similar presentations.

Introduction Medial longitudinal fasciculus infarction is rare in clinical practice and generally accompanied by brain tissue damage around the medial longitudinal fasciculus. Isolated medial longitudinal fasciculus midbrain infarction was seldom reported. Case report An 81-year-old man with hypertension was admitted to our hospital because of sudden onset diplopia. A neurological examination revealed right adduction paresis without abducting nystagmus in the left eye, whereas the convergence reflex was normal. Diffusion-weighted magnetic resonance imaging demonstrated a small acute lacunar medial longitudinal fasciculus infarction in the right midbrain at the level of the inferior colliculus. Diffusion-tensor imaging showed a reduction of the right medial longitudinal fasciculus. Medial longitudinal fasciculus infarction is rare and occurs most commonly in the pons. The authors report on a case of isolated medial longitudinal fasciculus infarction that was diagnosed because of sudden diplopia and manifested as simple internal rectus paralysis with no abducting nystagmus on the contralateral side of the lesion. Conclusion Isolated midbrain-medial longitudinal fasciculus infarction without contralateral abducting nystagmus is a rare occurrence. It can be differentiated from partial oculomotor palsy by assessing the convergence reflex, primary gaze, and diffusion-tensor imaging.

Parinaud’s syndrome involves dysfunction of the structures of the dorsal midbrain. We investigated the pathophysiology related to the signs and symptoms to better understand the symptoms of Parinaud’s syndrome: diplopia, blurred vision, visual field defects, ptosis, squint, and ataxia, and Parinaud’s main signs of upward gaze paralysis, upper eyelid retraction, convergence retraction nystagmus (CRN), and pseudo-Argyll Robertson pupils. In upward gaze palsy, three structures are disrupted: the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), interstitial nucleus of Cajal (iNC), and the posterior commissure. In CRN, there is a continuous discharge of the medial rectus muscle because of the lack of inhibition of supranuclear fibers. In Collier’s sign, the posterior commissure and the iNC are mainly involved. In the vicinity of the iNC, there are two essential groups of cells, the M-group cells and central caudal nuclear (CCN) group cells, which are important for vertical gaze, and eyelid control. Overstimulation of the M group of cells and increased firing rate of the CCN group causing eyelid retraction. External compression of the posterior commissure, and pretectal area causes pseudo-Argyll Robertson pupils. Pseudo-Argyll Robertson pupils constrict to accommodation and have a slight response to light (miosis) as opposed to Argyll Robertson pupils were there is no response to a light stimulus. In Parinaud’s syndrome patients conserve a slight response to light because an additional pathway to a pupillary light response that involves attention to a conscious bright/dark stimulus. Diplopia is mainly due to involvement of the trochlear nerve (IVth cranial nerve. Blurry vision is related to accommodation problems, while the visual field defects are a consequence of chronic papilledema that causes optic neuropathy. Ptosis in Parinaud’s syndrome is caused by damage to the oculomotor nerve, mainly the levator palpebrae portion. We did not find a reasonable explanation for squint. Finally, ataxia is caused by compression of the superior cerebellar peduncle.

There are no literature data on brainstem arachnoid cysts in humans.To describe the clinical case of brainstem (pontomesencephalic) arachnoid cyst and to analyze classification, pathogenesis, differential diagnosis and treatment of this pathology considering literature data and own experience.A 29-year-old patient with pontomesencephalic arachnoid cyst is reported. The disease manifested in childhood with a headache aggravated by bending and pushing. Later, syncope, vegetative-visceral paroxysms, mild oculomotor disturbances, transient paresthesia and numbness of the left half of the face occurred. Headaches became significantly more severe and resulted nausea and vomiting. Magnetic resonance imaging (MRI) revealed a two-chambered arachnoid cyst. A smaller chamber was localized in interpeduncular cistern, a larger one - in brainstem.Differential diagnosis included cystic glioma and Virchow-Robin space enlargement. Fenestration of the cyst wall within interpeduncular cistern was performed via right-sided pterional approach. The diagnosis was verified by histological examination. The follow-up period was 14 months. We observed postoperative cyst reduction confirmed by MR data and regression of all symptoms except for minimal signs of medial longitudinal fasciculus dysfunction.Correct surgical approach for brainstem arachnoid cyst complicated by progressive neurological deterioration is confirmed by postoperative regression of cyst and symptoms.Арахноидальные кисты ствола мозга у человека не описаны.Представить описание клинического случая внутристволовой (понтомезенцефальной) арахноидальной кисты и обсудить вопросы патогенеза, дифференциальной диагностики и лечения данной патологии.Приводится описание клинического случая пациентки 29 лет с арахноидальной кистой, расположенной в толще ствола головного мозга в области перехода среднего мозга в мост. Заболевание проявилось в детстве головной болью, усиливающейся при наклонах и натуживании, затем присоединились обморочные состояния, вегетовисцеральные пароксизмы, легкие глазодвигательные нарушения, преходящие парестезии и онемение левой половины лица; со временем головная боль значительно усилилась, стала сопровождаться тошнотой и рвотой. При магнитно-резонансной томографии (МРТ) выявлена двухкамерная арахноидальная киста с меньшей по размеру камерой в межножковой цистерне и большей — в толще ствола головного мозга.Дифференциальная диагностика проведена с кистозной глиомой и расширением пространств Вирхова—Робина. Операция заключалась в фенестрации стенки кисты, выходившей в межножковую цистерну, и выполнена из правостороннего птерионального доступа. Диагноз верифицирован при гистологическом исследовании биоптата. Катамнез прослежен на протяжении 14 мес. После операции отмечено значительное уменьшение размеров кисты по данным МРТ, регресс всех симптомов, кроме минимальных признаков дисфункции медиального продольного пучка.Правильность выбора хирургической тактики при арахноидальной кисте ствола головного мозга, вызывающей прогредиентное нарастание клинической симптоматики, подтверждается регрессом кисты и симптомов после операции.

Martin Lubow (1931–2015)1 is credited with coining the term ‘wall-eyed bilateral internuclear ophthalmoplegia’ (WEBINO).2 Most readers will be familiar with internuclear ophthalmoplegia (INO) and the fact that it can occur bilaterally. So why is WEBINO, as in the case presented by Chen3 in this issue of Practical Neurology , special? INO is caused by damage to the medial longitudinal fasciculus (MLF). This interrupts the nerve fibres connecting the sixth and third nerve nuclei, which facilitate conjugate horizontal eye movement. A unilateral INO causes slowing, or absence, of adduction of the ipsilateral eye and, usually, gaze-evoked nystagmus of the abducting, contralateral eye during attempted contralateral gaze. Interestingly, adduction is not infrequently preserved in the context of convergence.4 Because these are not the only fibres that travel in the MLF, there may be additional abnormalities due to interruption of the vestibular/otolithic pathways, such as skew deviation or vertical nystagmus. If the INO is bilateral, vertical nystagmus is very common and the vertical vestibulo-ocular reflex is demonstrably impaired.5 INO can result from many different underlying pathologies,5 6 though demyelinating disease is the most common cause of bilateral INO and stroke is the most common cause of unilateral INO.6 In spite of the impaired adduction, many patients with an INO are orthophoric in primary position, that is, their eyes point straight ahead. Some exotropia occurs in up to 60% of cases of unilateral INO4 but diplopia is often absent or surprisingly mild.7 A few patients are esotropic (convergent), particularly early on, possibly due to excessive convergence tone. The number of patients who are markedly exotropic (divergent) is surprisingly small, but many of these demonstrate large, wide-angle, exotropia. Bilateral INOs that show this divergence are labelled WEBINO. Of note, …

The aim of this study is to investigate the trajectory of medial longitudinal fasciculus (MLF) and explore its anatomical relationship with the oculomotor nerve using tractography technique. The MLF and oculomotor nerve were reconstructed at the same time with preset three region of interests (ROIs): one set at the area of rostral midbrain, one placed on the MLF area at the upper pons, and one placed at the cisternal part of the oculomotor nerve. This mapping protocol was tested in an HCP‐1065 template, 35 health subjects from Massachusetts General Hospital (MGH), 20 healthy adults and 6 brainstem cavernous malformation (BCM) patients with generalized q‐sampling imaging (GQI)‐based tractography. Finally, the 200 μm brainstem template from Center for In Vivo Microscopy, Duke University (Duke CIVM), was used to validate the trajectory of reconstructed MLF. The MLF and oculomotor nerve were reconstructed in the HCP‐1065 template, 35 MGH health subjects, 20 healthy adults and 6 BCM patients. The MLF was in conjunction with the ipsilateral mesencephalic part of the oculomotor nerve. The displacement of MLF was identified in all BCM patients. Decreased QA, RDI and FA were found in the MLF of lesion side, indicating axonal loss and/or edema of displaced MLF. The reconstructed MLF in Duke CIVM brainstem 200 μm template corresponded well with histological anatomy. The MLF and oculomotor nerve were visualized accurately with our protocol using GQI‐based fiber tracking. This GQI‐based tractography is an important tool in the reconstruction and evaluation of MLF., The mapping protocol of medial longitudinal fasciculus using the generalized q‐sampling imaging based tractography.

Stroke can present with unique neurologic symptoms, which can be used to help determine the location of the stroke. Internuclear ophthalmoparesis (INO), also known as internuclearophthalmoplegia, is a distinct gaze abnormality with impaired horizontal eye movements with compromised adduction of the affected eye, and abduction nystagmus of the contralateral eye. Infarcts involving the medial longitudinal fasciculus in either the pons or midbrain can result in INO. We present two cases of midbrain ischemic stroke, which presented as isolated INO. The midbrain has a unique and intricate vascular supply including branches from the basilar, superior cerebellar, posterior cerebral, posterior communicating, anterior choroidal, and posterior choroidal arteries, which is reviewed. Infarcts involving the paramedian midbrain, which is supplied by short circumferential arteries and penetrating branches arising from the posterior cerebral artery and superior cerebellar artery, can result in INO.

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome has previously been reported in only 2 patients with progressive supranuclear palsy (PSP). Herein, we report a third case of WEBINO syndrome with PSP. The patient was an 81-year-old man who had experienced gradually increasing gait disturbance and occasional falls since the age of 78 years. At 80 years of age, he presented with cognitive impairment, parkinsonism, and oculomotor abnormalities. The oculomotor abnormalities consisted of vertical gaze palsy and loss of eye convergence. Brain magnetic resonance imaging demonstrated marked atrophy of the midbrain. He was diagnosed with PSP. At the age of 81 years, he presented with alternating extropia in his forward gaze and adduction paresis and outward nystagmus of the abducted eye in his horizontal gaze, both of which were compatible with WEBINO syndrome. Previously, we reported the first case of PSP with WEBINO syndrome, and another group recently reported a second case. In light of the previous cases and the present case, WEBINO syndrome in PSP should not be considered extremely rare. Furthermore, WEBINO syndrome has not been reported in other neurodegenerative disorders, which suggests that it might be a useful and specific diagnostic finding in PSP.

The one and a half Fisher syndrome is produced by a unilateral lesion in the dorsal and inferior part of the pons located specifically in the pontine tegmentum. This is an area that contains the medial longitudinal fasciculus (LMF), the paramedian pontine reticular formation (PPRF) and the nucleus of the sixth cranial nerve, responsible for the horizontal movements of the gaze. Clinically it manifests with conjugate gaze palsy with internuclear ophthalmoplegia. The case is reported on a 60 year-old patient, who presented with binocular diplopia, ophthalmoplegia and paralysis of the gaze conjugated to the left. Imaging studies were performed that showed a hemi-protuberant hematoma secondary to a cavernoma. As expected, he presented with several episodes of re-bleeding with clinical worsening: headache, diplopia, tetraparesis, and hypoaesthesia in the right side of the face, as such that the microsurgical exeresis of the protuberant cavernoma was considered.

Impaired bilateral conjugate horizontal saccades can occur from bilateral abducens nuclear lesions,1 as seen in our patient with multiple sclerosis (Video 1 and Figure). Each abducens nucleus is a horizontal gaze center and innervates the ipsilateral lateral rectus through the abducens fascicle and the contralateral medial rectus via the medial longitudinal fasciculus (Figure). Thus, bilateral lesions of the abducens nuclei cause complete horizontal gaze paresis.

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., This study provides an objective and quantitative model to investigate the clinico‐radiological paradox, by comparing the presence of internuclear ophthalmoplegia and medial longitudinal fasciculus lesions on magnetic resonance imaging.

Damage to the corticospinal tract is a leading cause of motor disability, for example in stroke or spinal cord injury. Some function usually recovers, but whether plasticity of undamaged ipsilaterally descending corticospinal axons and/or brainstem pathways such as the reticulospinal tract contributes to recovery is unknown. Here, we examined the connectivity in these pathways to motor neurons after recovery from corticospinal lesions. Extensive unilateral lesions of the medullary corticospinal fibres in the pyramidal tract were made in three adult macaque monkeys. After an initial contralateral flaccid paralysis, motor function rapidly recovered, after which all animals were capable of climbing and supporting their weight by gripping the cage bars with the contralesional hand. In one animal where experimental testing was carried out, there was (as expected) no recovery of fine independent finger movements. Around 6 months post-lesion, intracellular recordings were made from 167 motor neurons innervating hand and forearm muscles. Synaptic responses evoked by stimulating the unlesioned ipsilateral pyramidal tract and the medial longitudinal fasciculus were recorded and compared with control responses in 207 motor neurons from six unlesioned animals. Input from the ipsilateral pyramidal tract was rare and weak in both lesioned and control animals, suggesting a limited role for this pathway in functional recovery. In contrast, mono- and disynaptic excitatory post-synaptic potentials elicited from the medial longitudinal fasciculus significantly increased in average size after recovery, but only in motor neurons innervating forearm flexor and intrinsic hand muscles, not in forearm extensor motor neurons. We conclude that reticulospinal systems sub-serve some of the functional recovery after corticospinal lesions. The imbalanced strengthening of connections to flexor, but not extensor, motor neurons mirrors the extensor weakness and flexor spasm which in neurological experience is a common limitation to recovery in stroke survivors.

Important anatomical structures in the pons participating in the control of eye movements include the abducens nucleus, paramedian pontine reticular formation (PPRF), medial longitudinal fasciculus (MLF), and the rostral portion of the vestibular nucleus. The compact organization of the pons makes it amenable to get significant clinical deficit despite small lesions such as lacunar infarcts. Medical manifestations of critical illness, such as malignant hypertension, can also result in pontine dysfunction. Lesions affecting each pontine nuclei themselves can cause specific clinical presentation; but sometimes (larger deficits) present with constellation of symptoms leading to specific syndromic entities. This chapter outlines the range of ocular motor deficits that are expected from the lesions affecting the pontine nuclei.

A projection by the superior colliculus to the supraoculomotor area (SOA) located dorsal to the oculomotor complex was first described in 1978. This projection’s targets have yet to be identified, although the initial study suggested that vertical gaze motoneuron dendrites might receive this input. Defining the tectal targets is complicated by the fact the SOA contains a number of different cell populations. In the present study, we used anterograde tracers to characterize collicular axonal arbors and retrograde tracers to label prospective SOA target populations in macaque monkeys. Close associations were not found with either superior or medial rectus motoneurons whose axons supply singly innervated muscle fibers. S-group motoneurons, which supply superior rectus multiply innervated muscle fibers, appeared to receive a very minor input, but C-group motoneurons, which supply medial rectus multiply innervated muscle fibers, received no input. A number of labeled boutons were observed in close association with SOA neurons projecting to the spinal cord, or the reticular formation in the pons and medulla. These descending output neurons are presumed to be peptidergic cells within the centrally projecting Edinger–Westphal population. It is possible the collicular input provides a signaling function for neurons in this population that serve roles in either stress responses, or in eating and drinking behavior. Finally, a number of close associations were observed between tectal terminals and levator palpebrae superioris motoneurons, suggesting the possibility that the superior colliculus provides a modest direct input for raising the eyelids during upward saccades.

Background and purpose The classic sign of a lesion in the medial longitudinal fasciculus is internuclear opthalmoplegia. However, clinical presentation may vary depending on the type of pathology and the lesion location. The purpose of this study was to identify and classify the different lesions of the medial longitudinal fasciculus on MRI and review their clinical presentations. We also offer an overview of the pertinent imaging anatomy of the medial longitudinal fasciculus. Materials and methods Patients with an abnormality affecting the medial longitudinal fasciculus were identified retrospectively using the keyword ‘medial longitudinal fasciculus’ included in radiology reports between 2010 and 2018 using the Nuance mPower software (Nuance Communications, Burlington, MA). The brain MRI examinations of these patients were reviewed by two neuroradiolgists. Detailed description of lesion location within the medial longitudinal fasciculus, pathology type, additional lesions, and clinical presentations were recorded along with pertinent demographic information. Results Five men and four women were identified with lesions in the medial longitudinal fasciculus on brain MRI. Five patients demonstrated demyelination in the medial longitudinal fasiculus and four patients demonstrated findings of an acute cerebrovascular accident. Two-thirds of medial longitudinal fasiculus lesions were located in the upper, mid, or lower pons with the remaining located in the midbrain. Of the patients presenting with a cerebrovascular accident, there was little to no additional evidence of acute stroke elsewhere in the brain. All patients were clinically symptomatic with 89% of patients demonstrating extraocular muscle dysfunction at presentation and 78% of patients experiencing dizziness. Additional symptoms included headache, weakness, and gait instability. Conclusions Lesions involving the medial longitudinal fasiculus may not always present with the classic sign of internuclear opthalmoplegia. Variations in lesion location may result in diplopia rather than internuclear opthalmoplegia, and additional brain lesions may produce clinical symptoms that confound extraocular muscle dysfunction. Lesions affecting the often-overlooked vestibular and otolithic reflexes, which run in the medial longitudinal fasiculus, may result in dizziness/weakness and mask the classic internuclear opthalmoplegia symptoms. The radiologist should carefully inspect the medial longitudinal fasiculus in all patients regardless of the supportive clinical history of extraocular muscle dysfunction since symptoms may be more general than classically described.

Background: The medial longitudinal fasciculus (MLF) interacts with eye movement control circuits involved in the adjustment of horizontal, vertical, and torsional eye movements. In this study, we attempted to identify and investigate the anatomical characteristics of the MLF in human brain, using probabilistic diffusion tensor imaging (DTI) tractography. Methods: We recruited 31 normal healthy adults and used a 1.5-T scanner for DTI. To reconstruct MLFs, a seed region of interest (ROI) was placed on the interstitial nucleus of Cajal at the midbrain level. A target ROI was located on the MLF of the medulla in the reticular formation of the medulla. Mean values of fractional anisotropy, mean diffusivity, and tract volumes of MLFs were measured. Results: The component of the MLF originated from the midbrain MLF, descended through the posterior side of the medial lemniscus (ML) and terminated on the MLF of medulla on the posterior side of the ML in the medulla midline. DTI parameters of right and left MLFs were not significantly different. Conclusion: The tract of the MLF in healthy brain was identified by probabilistic DTI tractography. We believe this study will provide basic data and aid future comparative research on lesion or age-induced MLF changes.

There are many named brainstem syndromic variants of medullary infarcts among which “eight-and-a-half” syndrome is a rare condition that involves ipsilateral abducens nucleus or paramedian pontine reticular formation, ipsilateral medial longitudinal fasciculus, and adjacent facial colliculus/facial nerve. Here, we describe a new variant of brainstem syndrome, which includes the clinical features of “eight-and-a-half syndrome” with associated hemiparesis. This patient is a known case of HIV illness since 6 years on antiretroviral therapy, presented with features of “Nine” syndrome.

Although there are a few studies of portions of the vestibular system such as the vestibulocerebellar tract and the neural connectivity of the vestibular nuclei (VN), no study of the ipsilateral vestibulothalamic tract (VTT) (originating from the VN and mainly connecting to the lateral thalami nuclei) has been reported. In the current study, using diffusion tensor tractography (DTT), we investigate the reconstruction method and characteristics of the ipsilateral VTT in normal subjects. Thirty-three subjects were recruited for this study. For the ipsilateral VTT, the seed region of interest (ROI) was placed on the VN, which was isolated on the FA map using adjacent structures as follows: the reticular formation (anterior boundary), posterior margin of medulla and pons (posterior boundary), medial lemniscus (medial boundary) and restiform body (lateral boundary). The target ROI was placed at the lateral thalamic nuclei using known anatomical locations. The DTT parameters of the ipsilateral VTT were measured. The ipsilateral VTTs that originated from the vestibular nuclei ascended postero-laterally to the upper pons and antero-medially to the upper midbrain via the medial longitudinal fasciculus, and terminated the lateral thalamic nuclei. No significant differences were observed in DTT parameters of the ipsilateral VTT between the right and left hemispheres (p > 0.05). Using DTT, we reconstructed the ipsilateral VTT and observed the anatomical characteristics of the ipsilateral VTT in normal subjects. We believe that the methodology and results in this study could be helpful to researchers and clinicians in this field.

Internuclear Ophthalmoplegia (INO) is a clinical syndrome which develops due to a lesion in the medial longitudinal fasciculus (MLF). It is a horizontal gaze disorder characterized by impaired adduction of eye on the side of the lesion of medial longitudinal fasciculus with dissociated nystagmus of the opposite abducting eye. This lesion is mostly caused by multiple sclerosis (usually bilateral lesion), stroke and tumours. A case with unilateral internuclear ophthalmoplegia due to vascular lesion was admitted in Anwer Khan Modern Medical College & Hospital on 27/05/2017.Anwer Khan Modern Medical College Journal Vol. 9, No. 1: Jan 2018, P 71-74

Purpose To describe the clinical symptoms, anatomical location of the injury and different etiologies of one-and-a-half syndrome and its variants. Observations A small lesion to the brainstem can cause complex syndromes that involve the disfunction of different nuclei and pathways. A 52-year-old man presented with sudden onset of diplopia characterized by horizontal gaze palsy and internuclear ophthalmoplegia (INO). With these clinical characteristics, the patient was diagnosed with the one-and-a-half syndrome. Neuroimaging revealed an acute/subacute ischemic lacunar event in the pontine tegmentum. The one-and-a-half syndrome is described as a horizontal gaze palsy in one direction (damage to the paramedian pontine reticular formation [PPRF] or the VI nerve nucleus) and an internuclear ophthalmoplegia in the other direction (damage to the medial longitudinal fasciculus). Along with the traditional description, the closed anatomical proximity with other nuclei and pathways makes possible the appearance of other more complex syndromes that have been grouped as the one-and-a-half syndrome and its variants. Conclusions and importance A detailed clinical neuro-ophthalmologic examination, along with a clear understanding of the neuroanatomical pathways, gives clinicians a good diagnostic opportunity to determine the precise location of injuries to the brainstem.

The head impulse test (HIT) is used to evaluate the vestibulo-ocular reflex (VOR) during a high-velocity head rotation. Corrective catch-up saccades that occur during or after the HITs usually indicate peripheral vestibular hypofunction, whereas in acute vestibular syndrome, normal clinical (bedside) HITs should prompt a search for a central lesion. However, recent quantitative studies that evaluated HITs using magnetic search coils or video-based techniques have demonstrated that specific patterns of HIT abnormalities are associated with central vestibular disorders. While normal clinical HITs are typical of central lesions, discrepancies have been observed between clinical and quantitative HITs. The horizontal head impulse VOR gains can be significantly reduced unilaterally or bilaterally (positive HITs) in lesions involving the vestibular nucleus, nucleus prepositus hypoglossi, or flocculus. In diffuse cerebellar lesions, the VOR gain during horizontal head impulses may increase (hyperactive) with corrective saccades directed the opposite way. The presence of cross-coupled vertical corrective saccades during horizontal HITs is also suggestive of diffuse cerebellar lesions. Lesions involving the vestibular nucleus, medial longitudinal fasciculus, and cerebellum may show decreased or increased gains of the VOR during vertical HITs. Defining the differences in patterns observed during abnormal HITs may help practitioners localize the responsible lesions in both central and peripheral vestibulopathy.

Lampreys, which represent the oldest group of living vertebrates (cyclostomes), show unique eye development. The lamprey larva has only eyespot-like immature eyes beneath a non-transparent skin, whereas after metamorphosis, the adult has well-developed image-forming camera eyes. To establish a functional visual system, well-organised visual centres as well as motor components (e.g. trunk muscles for locomotion) and interactions between them are needed. Here we review the available knowledge concerning the structure, function and development of the different parts of the lamprey visual system. The lamprey exhibits stepwise development of the visual system during its life cycle. In prolarvae and early larvae, the 'primary' retina does not have horizontal and amacrine cells, but does have photoreceptors, bipolar cells and ganglion cells. At this stage, the optic nerve projects mostly to the pretectum, where the dendrites of neurons in the nucleus of the medial longitudinal fasciculus (nMLF) appear to receive direct visual information and send motor outputs to the neck and trunk muscles. This simple neural circuit may generate negative phototaxis. Through the larval period, the lateral region of the retina grows again to form the 'secondary' retina and the topographic retinotectal projection of the optic nerve is formed, and at the same time, the extra-ocular muscles progressively develop. During metamorphosis, horizontal and amacrine cells differentiate for the first time, and the optic tectum expands and becomes laminated. The adult lamprey then has a sophisticated visual system for image-forming and visual decision-making. In the adult lamprey, the thalamic pathway (retina-thalamus-cortex/pallium) also transmits visual stimuli. Because the primary, simple light-detecting circuit in larval lamprey shares functional and developmental similarities with that of protochordates (amphioxus and tunicates), the visual development of the lamprey provides information regarding the evolutionary transition of the vertebrate visual system from the protochordate-type to the vertebrate-type.

A 24-year-old female patient presented to the casualty following coconut fall on the head a few hours back with acute-onset binocular diplopia maximum on the left gaze and also on looking to the left and downward. Clinical examination revealed no external injuries, focal neurological deficits, or features of raised intracranial pressure. Computed tomography imaging was within normal limits. Hence, she was referred to ophthalmology by the neurosurgeon as a case of suspected partial third nerve palsy. Ocular examination revealed best-corrected visual acuity of 6/6 BE. There was limitation of adduction in the right eye and nystagmus in the left eye on attempted laevoversion. Convergence was absent. Anterior segment and fundus of both eyes were normal. Diplopia charting showed crossed diplopia which was maximum on left gaze. A clinical diagnosis of right anterior internuclear ophthalmoplegia (type-1) was made. It was confirmed by magnetic resonance imaging which revealed acute infarcts in the region of superior pons near right medial longitudinal fasciculus. The patient was treated with occlusion glasses.

Internuclear ophthalmoplegia is characterised by restricted ocular motility in lateral gaze in which the affected eye shows impairment of adduction and it results from damage to medial longitudinal fasciculus (MLF). Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is an extremely rare neurological manifestation which has typical signs including primary gaze exotropia, vertical gaze palsy, ptosis, abducting nystagmus. The common and serious etiological factor is cerebrovascular accident involving the vessels supplying MLF and many cases have life threatening associated neurological impairment. In this case report we have discussed about a gentleman who presented with bilateral ptosis, primary gaze exotropia and headache. Patient found to have vertical gaze palsy and abducting nystagmus on examination. Computed tomography (CT) imaging shows infarct in pontine region and CT angiography revealed basilar artery occlusion supplying region of pons with involvement of posterior cerebral artery. Patient treated with antiplatelet and diplopia managed. Patient showed improvement on subsequent follow-up visits.

Objective:To determine the role of the medial longitudinal fasciculus (MLF) in conveying vestibular signals.Methods:In 10 patients with isolated acute unilateral internuclear ophthalmoplegia (INO) due to an acute stroke, we performed comprehensive vestibular evaluation using video-oculography, head impulse tests with a magnetic search coil technique, bithermal caloric tests, tests for the ocular tilt reaction, and measurements of subjective visual vertical and cervical and ocular vestibular evoked myogenic potentials (VEMPs).Results:The head impulse gain of the vestibulo-ocular reflex (VOR) was decreased invariably for the contralesional posterior canal (PC) (n = 9; 90%) and usually for the ipsilesional horizontal canal (n = 5; 50%). At least one component of contraversive ocular tilt reaction (n = 9) or contraversive tilt of the subjective visual vertical (n = 7) were common along with ipsitorsional nystagmus (n = 5). Cervical or ocular VEMPs were abnormal in 5 patients.Conclusions:The MLF serves as the main passage for the high-acceleration VOR from the contralateral PC. The associations and dissociations of the vestibular dysfunction in our patients indicate variable combinations of damage to the vestibular fibers ascending or descending in the MLF even in strokes causing isolated unilateral INO.

The medial longitudinal fasciculus (MLF) is the final common pathway for all conjugate adducting horizontal eye movements, as well as for the vertical–torsional vestibulo-ocular reflex (VOR). MLF lesion causes adduction paresis of ipsilesional (adducting) eye with dissociated nystagmus of contralesional (abducting) eye—the well-known clinical syndrome of internuclear ophthalmoplegia (INO). We measured the VOR stimulation and also any catch-up saccades, from individual semicircular canal (SCC) evoked by the head impulse test (HIT), using head and binocular 3-dimensional scleral search coils in 27 multiple sclerosis (MS) patients, 8 with unilateral, 19 with bilateral INO. In unilateral INO, VOR gain (normal >0.90) from ipsilesional lateral SCC stimulation was 0.48 for the adducting eye and 0.81 for the abducting eye; 0.61 from contralesional anterior SCC stimulation and only 0.29 from contralesional posterior SCC stimulation. In bilateral INO, there were VOR gain deficits from all six SCCs: lateral SCC gains were asymmetrically reduced to 0.45 in the adducting eye and 0.66 in the abducting eye; anterior SCC gain was 0.48 and posterior SCC gain was only 0.19. Horizontal VOR versional dysconjugacy between adducting and abducting eyes at 0.66 was less severe than horizontal catch-up saccade versional dysconjugacy (0.44); normal >0.80. Unexpected partial preservation of horizontal VOR with greater catch-up saccade impairment from the adducting than abducting eye suggests that the ascending tract of Deiters (ATD), an extra-MLF pathway, also mediates the horizontal VOR, but not adducting horizontal saccades. Vertical VOR deficits will produce vertical oscillopsia with any vertical head movement and measurement of the vertical VOR could help with the diagnosis and quantitative evaluation of MLF lesions in suspected MS. Horizontal VOR deficits and catch-up saccade versional dysconjugacy in INO will cause gaze instability and horizontal oscillopsia during active horizontal head movements.

Medial rectus motoneurons receive two main pontine inputs: abducens internuclear neurons, whose axons course through the medial longitudinal fasciculus (MLF), and neurons in the lateral vestibular nucleus, whose axons project through the ascending tract of Deiters (ATD). Abducens internuclear neurons are responsible for conjugate gaze in the horizontal plane, whereas ATD neurons provide medial rectus motoneurons with a vestibular input comprising mainly head velocity. To reveal the relative contribution of each input to the oculomotor physiology, single-unit recordings from medial rectus motoneurons were obtained in the control situation and after selective deafferentation from cats with unilateral transection of either the MLF or the ATD. Both MLF and ATD transection produced similar short-term alterations in medial rectus motoneuron firing pattern, which were more drastic in MLF of animals. However, long-term recordings revealed important differences between the two types of lesion. Thus, while the effects of the MLF section were permanent, 2 months after ATD lesioning all motoneuronal firing parameters were similar to the control. These findings indicated a more relevant role of the MLF pathway in driving motoneuronal firing and evidenced compensatory mechanisms following the ATD lesion. Confocal immunocytochemistry revealed that MLF transection produced also a higher loss of synaptic boutons, mainly at the dendritic level. Moreover, 2 months after ATD transection, we observed an increase in synaptic coverage around motoneuron cell bodies compared with short-term data, which is indicative of a synaptogenic compensatory mechanism of the abducens internuclear pathway that could lead to the observed firing and morphological recovery.SIGNIFICANCE STATEMENTEye movements rely on multiple neuronal circuits for appropriate performance. The abducens internuclear pathway through the medial longitudinal fascicle (MLF) and the vestibular neurons through the ascending tract of Deiters (ATD) are a dual system that supports the firing of medial rectus motoneurons. We report the effect of sectioning the MLF or the ATD pathway on the firing of medial rectus motoneurons, as well as the plastic mechanisms by which one input compensates for the lack of the other. This work shows that while the effects of MLF transection are permanent, the ATD section produces transitory effects. A mechanism based on axonal sprouting and occupancy of the vacant synaptic space due to deafferentation is the base for the mechanism of compensation on the medial rectus motoneuron.

The aim of the study is to identify characteristic features of pineal germinoma that enhance preoperative accuracy in differentiating germinoma from other pineal region tumors. Twenty-one consecutive patients with pineal region tumors were enrolled. In all patients, tumor resection was performed to verify the histology. Clinical records including upward gaze palsy of Parinaud's syndrome and neuroimaging were analyzed. In addition, we evaluated the relationship between magnetic resonance imaging (MRI) findings and tumor progression patterns in pineal germinoma. Among 21 patients, 15 patients were diagnosed with germ cell tumor, 4 with pineal parenchymal cell tumor, and 2 with meningioma. Upward gaze palsy was seen in 11 patients; nine had pure germinomas and two had mixed germ cell tumors. These tumors occupied the pineal region with extension to the area of the mesodiencephalic junction (MDJ) and the bi-epithalamic area between the bilateral pulvinar and the third ventricle. Tumor involvement of the former area could cause upward gaze palsy by insulting the rostral interstitial nucleus of the medial longitudinal fasciculus located in the MDJ area. Tumor invasion into the latter area is commonly seen as a cardioid-shaped tumor as the tumor image on the axial MRI view. Upward gaze palsy and a cardioid-shaped tumor image on the axial MRI views were demonstrated to be specific features of pineal pure germinoma. It is suggested that combination of both features may become useful tools to preoperatively differentiate germinoma from other pineal tumors, resulting in achievement of the optimum treatment of pineal region tumors.

A 73-year-old woman presented with acute impaired eye movements with preserved left eye abduction, right peripheral facial weakness (video 1), and left hemiparesis/hemihypesthesia. These deficits localized to the right pontine tegmentum involving the medial longitudinal fasciculus, facial nerve, abducens nucleus, medial lemniscus, and corticospinal tracts, as shown in figure 1. After tissue plasminogen activator, her left hemiparesis and hemihypesthesia resolved. Rosini et al.1 first described these deficits as 9 syndrome (7th nerve + 1.5 syndrome + 0.5 hemiparesis/hypesthesia = 9). Classically, 1-and-a-half syndrome consists of intranuclear ophthalmoplegia and conjugate horizontal gaze palsy; preserved abduction will be present in the contralateral eye. Our patient's right eye adduction was paretic and not plegic. Our patient was left with an “8-and-a-half syndrome” (figure 2). Infarct, hemorrhage, vasculitis, and demyelination are etiologies of 8-and-a-half syndromes reported in the literature.

A 48-year-old man developed lightheadedness and diplopia upon awakening 10 days prior. Since then, his double vision had been continuous and stable. Upon admission, neurologic examination revealed bilateral internuclear ophthalmoplegia, abducting nystagmus, and intact convergence reflex (video). His blood pressure was 155/100 mm Hg and HbA1c was 8.7%, suggesting a new diagnosis of diabetes mellitus type 2. CT angiography showed calcified plaques of bilateral cavernous internal carotid arteries. MRI showed a lesion with hyperintensity on T2 fluid-attenuated inversion recovery, contrast enhancement, and mild diffusion restriction ventral to the cerebral aqueduct in the pontomesencephalic junction (figure), which is supplied by interpeduncular perforating branches of posterior cerebral arteries.1 For this patient with hypertension and diabetes mellitus, the acute onset of symptoms and imaging findings suggest ischemic stroke due to arteriolosclerosis of perforating arteries, which should be differentiated from demyelinating diseases such as multiple sclerosis. Involvement of bilateral medial longitudinal fasciculus rather than oculomotor nucleus is a rare consequence of stroke.2

Introduction CNS cavernomas are a type of raspberry-shaped vascular malformations that are typically asymptomatic, but can result in haemorrhage, neurological injury, and seizures. Here, we present a rare case of a brainstem cavernoma that was surgically resected whereafter an upbeat nystagmus presented postoperatively. Case report A 42-year old man presented with sudden-onset nausea, vomiting, vertigo, blurred vision, marked imbalance and difficulty swallowing. Neurological evaluation showed bilateral ataxia, generalized hyperreflexia with left-sided predominance, predominantly horizontal gaze evoked nystagmus on right and left gaze, slight left labial asymmetry, uvula deviation to the right, and tongue deviation to the left. MRI demonstrated a 13-mm cavernoma with haemorrhage and oedema in the medulla oblongata. Surgery was performed via a minimal-invasive, midline approach. Complete excision was confirmed on postoperative MRI. The patient recovered well and became almost neurologically intact. However, he complained of mainly vertical oscillopsia. The videonystagmography revealed a new-onset spontaneous upbeat nystagmus in all gaze directions, not suppressed by fixation. An injury of the rarely described intercalatus nucleus/nucleus of Roller is thought to be the cause. Conclusion Upbeat nystagmus can be related to several lesions of the brainstem, including the medial longitudinal fasciculus, the pons, and the dorsal medulla. To our knowledge, this is the first case of an iatrogenic lesion of the nucleus intercalatus/nucleus of Roller resulting in an upbeat vertical nystagmus. For neurologists, it is important to be aware of the function of this nucleus for assessment of clinical manifestations due to lesions within this region.

Purpose: To report a case of myasthenia gravis presenting with a false localizing sign, a bilateral pseudo internuclear ophthalmoplegia. Observations: A 61 year-old male presented with a five-week history of painless binocular oblique diplopia that was associated with fatigue, vocal hoarseness and bilateral ptosis, the latter two of which worsened through the course of the day. Exam was remarkable for an apparent bilateral internuclear ophthalmoplegia (INO). MRI of the brain with and without contrast and MRA of the head and neck were within normal limits. Lab work was positive for anti-AChR binding, blocking, and modulating antibodies, as well as anti-striated muscle and anti-titin antibodies. The patient was initiated on therapy for myasthenia gravis. Conclusion and importance: Although myasthenia gravis often presents with ptosis or diplopia, rarely patients may develop pseudo-INO secondary to extraocular muscle weakness. True INO occurs with damage to the medial longitudinal fasciculus, a myelinated tract of fibers that controls yoked horizontal eye movements. Clinicians should be suspicious of the false localizing sign of a pseudo-INO associated with myasthenia gravis when more common causes of INO have been excluded. Keywords: Myasthenia gravis, Ocular myasthenia gravis, Pseudo internuclear ophthalmoplegia, False localizing signs

WEBINO (wall-eyed bilateral internuclear ophthalmoplegia) syndrome is characterized by bilateral adduction impairment, nystagmus of the abducting eye, and primary gaze exotropia. We present the case of a 68 year-old man who was initially attended in emergency department with sudden onset diplopia. Neurological exploration revealed WEBINO and gait ataxia. Relevant medical history included liver transplantation and subsequent tacrolimus prescription. Complementary exams revealed ischemic lesion in mesencephalic tegmentum, involving medial longitudinal fasciculus and pretectal area. WEBINO syndrome is unfrequent. Among its etiologies, ischemic and demyelinating are the most frequent. In our case, iatrogenic etiology was also considered. Clinical recognition of this syndrome is required to perform adequate exams in order to reach diagnosis.

The brainstem contains ocular motor and vestibular structures that, when damaged, produce specific eye movement disorders. In this review, we will discuss three brainstem syndromes with characteristic ocular motor and vestibular findings that can be highly localizing. First, we will discuss the lateral medullary (Wallenberg) syndrome, focusing on ocular lateropulsion, saccadic dysmetria, and the ocular tilt reaction. Second, we will review the medial longitudinal fasciculus syndrome including the ocular tilt reaction, nystagmus, and the vestibular-ocular reflex. Lastly, we will discuss hypertrophic olivary degeneration and oculopalatal tremor, which may develop weeks to months after a brainstem or cerebellar lesion. In these syndromes, the clinical ocular motor and vestibular examination is instrumental in localizing the lesion.

A 51-year-old woman with history of hypertension presented with left-sided weakness and diplopia. Imaging revealed a large hemorrhagic infarct involving the right thalamus and rostral midbrain with intraventricular extension (figure). Neuro-ophthalmic examination demonstrated bilateral upgaze palsy with limitation of infraduction on the right (video 1), overcome with a doll's head maneuver (video 2). Bilateral lid retraction was present with markedly reduced convergence along with convergence-retraction nystagmus. Vertical one-and-a half syndrome is an uncommon presentation resulting from a unilateral thalamomesencephalic stroke with involvement of the rostral interstitial nucleus of the medial longitudinal fasciculus and posterior commissure1 and was accompanied here by dorsal midbrain syndrome.

Trochlear nerve palsies and internuclear ophthalmoplegias are well documented neuro‐ophthalmological conditions.2017 However, cases of both of these conditions occurring together in the same patien...

Introduction We present a case of a gentleman with atypical headache symptoms clinically diagnosed as giant cell arteritis (GCA) and initiated on high dose oral steroids. He subsequently developed progressive neurological deficit including bilateral internuclear ophthalmoplegia (INO), as well as third cranial nerve involvement despite above treatment. He received IV methylprednisolone and demonstrated clinical response, temporal artery biopsy confirmed histological evidence of GCA. The nature of his presentation was atypical of cranial giant cell arteritis. Few reported cases describe INO in the context of GCA, with bilateral manifestation being rarer, especially with additional third cranial nerve involvement. Case description A 66-year-old gentleman presented with a 7-day history of bilateral temporal headaches. He noted prominence of both temporal arteries with mild tenderness during this period. He denied any visual changes, PMR symptoms, and jaw claudication or weight loss. He had been experiencing generalised fatigue and myalgia for the preceding 4 months. He was noted to have raised inflammatory markers (CRP 194, ESR 74) and due to the non-specific nature of headache, concern was for possible meningitis. CT head scan was unremarkable and lumbar puncture and CT-CAP did not demonstrate any abnormality including evidence of infection. He was assessed by the rheumatology team and a clinical diagnosis of GCA was made. He was initiated on prednisolone 60mg daily, and described clinical improvement of headaches over the subsequent day. Inflammatory markers also initially responded to treatment. After 2 days of oral therapy, he developed double vision as well as intermittent headache. CRP remained static at 40. He was seen with the neurology team and was found to have divergent gaze of the left eye with ptosis. Eye movements demonstrated bilateral internuclear opthalmoplegia with involvement of the left third cranial nerve. MRI head scan demonstrated small vessel ischaemic changes but no obvious focal pathology. Due to new visual involvement despite prednisolone 60mg, IV methylprednisolone was administered for a period of 3 days. Ophthalmological symptoms did not progress and CRP reduced to 8. Temporal artery biopsy reported findings consistent with GCA. He was re-established on prednisolone 60mg however intermittent headache recurred and CRP gradually increased. Decision was made to increase prednisolone to 80mg (1mg/kg). At this dose headache resolved and CRP decreased to normal range. Methotrexate was introduced at 20mg weekly in order to facilitate with prednisolone weaning. Within 3 weeks of initial IV methylprednisolone administration, ophthalmological symptoms slowly improved to complete resolution. Discussion Typical manifestion of cranial GCA consists of unilateral temporal headache. Patients can however exhibit other symptoms including bilateral involvement and features of systemic inflammation which may be non-specific. Cases of neurological involvement have also been described, with diplopia and cranial nerve involvement being widely reported. Few case reports have described bilateral internuclear ophthalmoplegia which is syndrome involving the medial longitudinal fasciculus of the brainstem. This is usually associated with multiple sclerosis however any pathology of this anatomical region can result in this clinical picture. This gentleman additionally demonstrated features of third nerve palsy of the left eye which would be in keeping with a more typical cranial nerve involvement in GCA. The hypothesis for his clinical picture would be of reversible localised ischaemia to the brain stem secondary to active inflammation of the supplying vessel. MRI imaging did not identify any focal pathology and as mentioned previously, following treatment, his clinical findings fully resolved in a gradual manner over a period of weeks. In regards to the management of his case, following exclusion of infection and in the absence of visual findings on presentation, he was started on prednisolone 60mg daily (40-60mg dose suggested within current BSR guidelines). He described improvement of his headache and CRP was seen to improve initially. Despite this treatment, he developed features of INO and third nerve palsy as described. Implementation of IV methylprednisolone therapy prevented further progression of his symptoms and subsequent resolution of raised CRP. However restarting prednisolone at 60mg after this appeared to demonstrate incomplete control of his condition, thus it was increased to 80mg. Decision to introduce methotrexate at an early stage was made in anticipation of likely difficulties in weaning prednisolone. He remains under close follow-up to monitor prednisolone weaning. He currently has not had any recurrence of his symptoms. Key learning points GCA can present in an atypical manner and should remain a differential in cases of unexplained headache with associated inflammation. A combination of INO and third nerve palsy is an atypical manifestation of this condition. Due to the nature of his presentation, our gentleman was seen by various specialties including the acute-medical team, rheumatologists and neurologists. Fortunately, a probable diagnosis of GCA was made early and appropriate treatment was initiated. However as this case demonstrates, response to treatment can vary and such adjustments were made to accommodate for this, potentially preventing long term disability. Conflicts of interest The authors have declared no conflicts of interest.

In this study, we used a novel imaging technique, DTI (diffusion tensor imaging)-driven tensor-based morphometry, to investigate brain anatomy in subjects diagnosed with Moebius syndrome (n = 21), other congenital facial weakness disorders (n = 9) and healthy controls (n = 15). First, we selected a subgroup of subjects who satisfied the minimum diagnostic criteria for Moebius syndrome with only mild additional neurological findings. Compared to controls, in this cohort, we found a small region of highly significant volumetric reduction in the paramedian pontine reticular formation and the medial longitudinal fasciculus, important structures for the initiation and coordination of conjugate horizontal gaze. Subsequently, we tested if volume measurements from this region could help differentiate individual subjects of the different cohorts that were included in our study. We found that this region allowed discriminating Moebius syndrome subjects from congenital facial weakness disorders and healthy controls with high sensitivity (94%) and specificity (89%). Interestingly, this region was normal in congenital facial weakness subjects with oculomotor deficits of myopathic origin, who would have been classified as Moebius on the basis of purely clinical diagnostic criteria, indicating a potential role for diffusion MRI morphometry for differential diagnosis in this condition. When the entire Moebius syndrome cohort was compared to healthy controls, in addition to this ‘landmark’ region, other areas of significantly reduced volume in the brainstem emerged, including the location of the nuclei and fibres of cranial nerve VI (abducens nerve), and fibres of cranial nerve VII (facial nerve), and a more rostral portion of the medial longitudinal fasciculus. The high sensitivity and specificity of DTI-driven tensor-based morphometry in reliably detecting very small areas of volumetric abnormality found in this study suggest broader applications of this analysis in personalized medicine to detect hypoplasia or atrophy of small pathways and/or brainstem nuclei in other neurological disorders.

A portosystemic shunt is an abnormal communication between the portal vascular system and the systemic circulation. A significant number of clinical signs associated with portosystemic shunting result from hepatic encephalopathy (HE); a syndrome encompassing neurological signs such as including changes in behaviour, ataxia, unresponsiveness, pacing, circling, blindness, seizures, coma and death. We present two West Highland White Terrier dogs diagnosed with HE based on clinical signs, bile acid stimulation test and imaging of the abnormal vessel communicating the portal and the systemic circulation. Magnetic resonance sequences of the brain revealed a poorly marginated and diffuse, bilateral and symmetric hyperintense lesions on T2-weighted, fluid attenuation inversion recovery and diffusion-weighted sequences relative to the brain parenchyma including the medial longitudinal fasciculus and reticular formation in the brainstem. No abnormalities were detected on T1-weighted sequences.

Background: Eight-and-a-half syndrome (EHS) is one-and-a-half syndrome [(conjugated horizontal gaze palsy and internuclear ophthalmoplegia (INO)] plus ipsilateral fascicular seventh cranial nerve palsy. Involvement of lower pontine tegmentum including the abducens nucleus, the ipsilateral medial longitudinal fasciculus (MLF), and the adjacent facial colliculus contribute to the clinical findings of EHS. Recently, nine syndrome with addition of hemiparesis or hemianesthesia to EHS (due to involvement of adjacent corticospinal tract or medial lemniscus) is suggested. Methods: Consecutive patients with presentation of EHS or nine syndrome were reviewed from referral neuro-ophthalmology and strabismus clinics. Results: Three cases of EHS were identified with different etiologies of intracerebral hemorrhage (ICH), demyelination, and neuromyelitis optica spectrum disorder. Moreover, one case of "nine syndrome" due to ICH was described. Brain magnetic resonance imaging (MRI) in all of them revealed lesion in lower tegmentum of pons. Conclusion: Apart from different etiologies, recognition of EHS or nine syndrome allows precise localization of the lesion to lower pontine tegmentum ipsilaterally.

Background Internuclear ophthalmoplegia (INO) is an eye movement disorder caused by a lesion in the medial longitudinal fasciculus (MLF) located in the midbrain. Adduction paralysis of both eyes and bilateral abduction nystagmus are the main features of INO[1]. Case presentation A 29-year-old Hispanic woman was admitted to the emergency department complaining of an intense holocranial headache lasting 9 days, associated with nausea and vomiting. She was discharged home with resolution of the headache but persistence of symptoms. However, she subsequently developed horizontal diplopia and gait abnormalities. She was readmitted to hospital because of anomalous eye movements and conjugate gaze palsy, manifested as bilateral INO. Magnetic resonance angiography (MRA) findings were consistent with dissection of the left V4 vertebral artery with multiple brain infarcts in the superior cerebellar artery territory, comprising both MLF tracts. Conclusions In young adults, bilateral INO is normally caused by demyelinating disease. In other patients, common causes include trauma, infections and autoimmune diseases with neurological symptoms. Vascular disease is implicated in over a third of cases. Learning points A vascular aetiology should be suspected when internuclear ophthalmoplegia (INO) presents with an intense headache.Almost a third of patients with bilateral INO have an identified vascular cause.Magnetic resonance imaging is the gold standard for investigating INO.

Rationale: The dorsal tegmentum of the caudal pons, including the medial longitudinal fasciculus (MLF), the paramedian pontine reticular formation (PPRF), abducens nucleus, and the adjacent facial nerve is the anatomical basis of the the fifteen and a half syndrome (15½) syndrome. No patients of 15½ Syndrome presenting with bilateral peripheral facial paralysis and one-and-a-half simultaneously at the onset have been reported up to now. Patient concerns: A 54-year-old woman complained of diplopia, slurred speech, and slightly distal numbness of the left upper limb for 4 days in our hospital. Diagnoses: The diffusion weighted image (DWI) and apparent dispersion coefficient (ADC) of MRI revealed the causative lesion in pons including bilateral pontine tegmentum and a narrow lesion along the midline in the right of the pons. Her clinical manifestations with results of MRI resulted in the diagnosis of the fifteen-and-a-half-syndrome. Interventions: The patient received antiplatelet aggregation, plaque stabilization, free radicals elimination, circulation improvement, nerves nourishment, and other symptomatic treatments. Outcomes: Two months later, her ocular movement recovered, and the bilateral facial paresis showed some improvement. Lessons: First, our patient with 15½ syndrome maybe one of mutants whose bilateral pontine tegmentum is supplied by unilateral pontine paramedian perforator artery. Second, DWI combined with ADC may be applied in the diagnosis of fifteen-and-half syndrome when the lesions of infarction are too small to be revealed by MRI scan.