Medial Longitudinal Fasciculus Lesions Research Articles

Abstract 102: Pseudo‐Internuclear Ophthalmoplegia in a Patient with an Acute Globus Pallidus Infarct: A Case Report

Introduction Internuclear ophthalmoplegia (INO) is an ocular movement disorder typically due to a lesion in the medial longitudinal fasciculus (MLF). Rarely, similar ocular movement abnormalities can be observed in the absence of an MLF lesion. This case report aims to highlight a potential association between acute globus pallidus (GP) infarct and an ocular movement abnormality resembling INO. Methods N/A Results Case Presentation: A 72‐year‐old male with a medical history significant for chronic myeloid leukemia, prostate cancer, type 2 diabetes mellitus, hypertension, prior stroke, and heart failure presented with dizziness. Examination revealed right INO, skew deviation with right hypertropia, left lower extremity weakness, left upper extremity dysmetria, right facial weakness (prior deficit), and ataxic gait. MRI of brain confirmed an acute lacunar infarct in the right globus pallidus with no apparent brainstem or cerebellar lesion. The patient was started on dual antiplatelet therapy and discharged with home rehabilitation services to improve his balance. Discussion: The patient presented with pseudo‐INO in the setting of an acute globus pallidus infarct. This case introduces the idea that ocular motor abnormalities resembling INO could occur due to a GP lesion, which was not previously reported. The basal ganglia control saccadic eye movements by means of their connection to the superior colliculus (SC). GP was shown to have a role in this connection which may provide a plausible explanation for this observation. Another possible explanation can be based on the concept of diaschisis, where a lesion in a specific area of the brain (GP in this case) can lead to deficits or impairments in various functions associated with that region (the SC and its pathway for controlling saccadic eye movement). Conclusion This case emphasizes that slow adducting saccades and associated nystagmus is not always INO.

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

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. 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. 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. 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

BackgroundVideo-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.MethodsWe prospectively compared structural MRI findings and functional VOG measures of 63 MS patients to assess their diagnostic agreement for INO.ResultsMRI 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%).ConclusionMRI 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 Characterizes Multiple Sclerosis Rather Than Neuromyelitis Optica Spectrum Disease.

Neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS) share clinical presentations including optic neuritis and brainstem syndromes. Internuclear ophthalmoplegia (INO) is characterized by slowed ipsilateral adduction saccades and results from a lesion in the medial longitudinal fasciculus (MLF). Although INO is a common clinical finding in MS, its prevalence in NMOSD is unknown. The objective of this work is to determine the comparative frequencies of INO in patients with NMOSD and MS and compare clinical features of both disease processes. This is a retrospective study of patients 18 years and older who have an established diagnosis of NMOSD or MS and were evaluated by both neuro-ophthalmology and neuro-immunology specialists between 2014 and 2020. Electronic medical records were screened for documentation of an acute INO at any time during follow-up. Incidence rates were calculated from number of cases of new-onset INO and patient years observed. Logistic regression was used to evaluate the likelihood of developing an INO at any time point for NMOSD vs MS patients. Multivariable analysis was performed by adjusting for age, race, gender, and length of follow-up. Two hundred eighty patients (80 NMOSD, 200 MS) were included. Age range was 18-79 years with a mean age of 35.14 (SD ± 12.41 years). Average length of follow-up in MS and NMOSD patients was 4.18 years vs 3.79 years, respectively (P > 0.05), and disease duration before the start of the study in MS and NMOSD was 8.76 years vs 4.65 years, respectively (P < 0.01). Mean disease duration and follow-up time of both groups was 7.58 years and 4.07 ± 2.51 years, respectively. NMOSD patients were predominantly seropositive for AQP4 antibody (61.25%, n = 49). Individuals who had MOG antibody but also met NMOSD criteria were also included (18.75%, n = 15). The frequency of INO at any time point was 1.25% (n = 1) in NMOSD compared with 16% (n = 32) in MS. The incidence rate of new-onset INO in NMOSD (excluding MOGAD) was 3.8/1,000 person years and 23.9/1,000 person years in MS. Adjusted analysis showed that NMOSD patients were 13.89 times (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.01-0.598, P = 0.015) less likely to develop an INO compared with those with MS when including MOGAD patients, 12.5 times less likely (OR 0.08, 95% CI: 0.10-0.67, P = 0.02) when excluding MOGAD patients and 9.62 times less likely (OR 0.10, 95% CI: 0.01-0.87, P = 0.036) for AQP4+ patients. Our study shows that the incidence of new INO (3.8 vs 23.9 per 1,000 person years), and the odds of having INO at any time point are significantly lower in NMOSD than MS. This suggests that INO and consequently MLF lesions are less common in NMOSD. The presence of an INO may help in the differentiation of NMOSD from MS and may aid in earlier implementation of disease appropriate therapy.

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

Background and purposeThe 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).MethodsIn 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.ResultsThis 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.ConclusionThis 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.

An Anatomic, Imaging, and Clinical Review of the Medial Longitudinal Fasciculus

The medial longitudinal fasciculus (MLF) is a paired, highly specialized, and heavily myelinated nerve bundle responsible for extraocular muscle movements, including the oculomotor reflex, saccadic eye movements an smooth pursuit, and the vestibular ocular reflex. Clinically, lesions of the MLF are classically associated with internuclear ophthalmoplegia. However, clinical manifestations of a lesion in the MLF may be more complex and variable. We provide an overview of the neuroanatomy, neurologic manifestations, and correlative examples of the imaging findings on brain MRI of MLF lesions to provide the clinician and radiologist with a more comprehensive understanding of the MLF and potential clinical manifestations for an MLF lesion.

Central Lesions With Selective Semicircular Canal Involvement Mimicking Bilateral Vestibulopathy.

Bilateral vestibulopathy (BVP), which is due to peripheral lesions, may selectively involve certain semicircular canal (SCC). Recent eye movement recordings with search coil and video head impulse test (HIT) have provided insight in central lesions that can cause bilateral and selective SCC deficit mimicking BVP. Since neurological signs or ocular motor deficits maybe subtle or absent, it is critical to recognize central lesions correctly since there is prognostic and treatment implication. Acute floccular lesions cause bilateral horizontal SCC (HC) impairment while leaving vertical SCC function unaffected. Vestibular nuclear lesions affect bilateral HC and posterior SCC (PC) function, but anterior SCC (AC) function is spared. When both eyes are recorded, medial longitudinal fasciculus lesions cause horizontal dysconjugacy in HC function and catch-up saccades, as well as selective deficiency of PC over AC function. Combined peripheral and central lesions may be difficult to distinguish from BVP. Anterior inferior cerebellar artery stroke causes two types of deficits: 1. ipsilateral pan-SCC deficits and contralateral HC deficit and 2. bilateral HC deficit with vertical SCC sparing. Metabolic disorders such as Wernicke encephalopathy characteristically involve HC but not AC or PC function. Gaucher disease causes uniform loss of all SCC function but with minimal horizontal catch-up saccades. Genetic cerebellar ataxias and cerebellar-ataxia neuropathy vestibular areflexia syndrome typically do not spare AC function. While video HIT does not replace the gold-standard, search coil HIT, clinicians are now able to rapidly and accurately identify specific pattern of SCC deficits, which can aid differentiation of central lesions from BVP.

Unilateral Internuclear Ophthalmoplegia Due to Microvascular Pontine Infarction

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 &amp; Hospital on 27/05/2017.Anwer Khan Modern Medical College Journal Vol. 9, No. 1: Jan 2018, P 71-74

Vestibulo-ocular reflex deficits with medial longitudinal fasciculus lesions

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.

Axonal conduction in multiple sclerosis: A combined magnetic resonance imaging and electrophysiological study of the medial longitudinal fasciculus

Objective: The objective of this paper is to inform the pathophysiology of medial longitudinal fasciculus (MLF) axonal dysfunction in patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (MS), and develop a composite structural-functional biomarker of axonal and myelin integrity in this tract. Methods: Eighteen patients with definite MS and clinically suspected INO underwent electrical vestibular stimulation and search-coil eye movement recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR) were analyzed to probe the latency and fidelity of MLF axonal conduction. The MLF and T2-visible brainstem lesions were defined by high-resolution MRI. White matter integrity was determined by diffusion-weighted imaging metrics. Results: eVOR onset latency was positively correlated with MLF lesion length (left: r = 0.66, p = 0.004; right: r = 0.75, p = 0.001). The mean conduction velocity (±SD) within MLF lesions was estimated at 2.72 (±0.87) m/s. eVOR onset latency correlated with normalized axial diffusivity (r = 0.66, p < 0.001) and fractional anisotropy (r = 0.44, p = 0.02) after exclusion of cases with ipsilateral vestibular root entry zone lesions. Conclusions: Axonal conduction velocity through lesions involving the MLF was reduced below levels predicted for natively myelinated and remyelinated axons. Composite in vivo biomarkers enable delineation of axonal from myelin processes and may provide a crucial role in assessing efficacy of novel reparative therapies in MS.

66.: Medial longitudinal fasciculus: A window on axonal function in multiple sclerosis

This study aims to inform the pathophysiology of axonal dysfunction in the medial longitudinal fasciculus (MLF) in patients with internuclear ophthalmoplegia (INO) in multiple sclerosis (MS), and develop a composite functional-structural biomarker that indirectly distinguishes demyelination from remyelination in this tract. Eighteen patients with definite MS and clinically suspected INO underwent electrical vestibular stimulation and search-coil eye movement recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR) were analyzed to probe the latency and fidelity of MLF axonal conduction. Using a semi-automated technique, the MLF and T2-visible brainstem lesions involving the central vestibular pathways were defined by high-resolution MRI. White matter integrity was determined by diffusion-weighted imaging metrics. INO was associated with a T2-visible lesion within the MLF in all cases. Vestibular root entry zone (VREZ) lesions were observed in five patients (three bilateral, two unilateral). eVOR onset latency was positively correlated with MLF lesion length (left: r = .66, p = .004; right: r = .75, p = .001). Mathematical modelling estimated mean conduction velocity (± standard deviation) within MLF lesions of 2.72 (± 0.87) m/s. eVOR onset latency correlated with normalized axial diffusivity (r = .66, p

Bilateral Postsynaptic Actions of Pyramidal Tract and Reticulospinal Neurons on Feline Erector Spinae Motoneurons

Trunk muscles are important for postural adjustments associated with voluntary movements but little has been done to analyze mechanisms of supraspinal control of these muscles at a cellular level. The present study therefore aimed to investigate the input from pyramidal tract (PT) neurons to motoneurons of the musculus longissimus lumborum of the erector spinae and to analyze to what extent it is relayed by reticulospinal (RS) neurons. Intracellular records from motoneurons were used to evaluate effects of electrical stimulation of medullary pyramids and of axons of RS neurons descending in the medial longitudinal fasciculus (MLF). The results revealed that similar synaptic actions were evoked from the ipsilateral and contralateral PTs, including disynaptic and trisynaptic EPSPs and trisynaptic IPSPs. Stimulation of the MLF-evoked monosynaptic and disynaptic EPSPs and disynaptic or trisynaptic IPSPs in the same motoneurons. All short-latency PSPs of PT origin were abolished by transection of the MLF, while they remained after transection of PT fibers at a spinal level. Hence, RS neurons might serve as the main relay neurons of the most direct PT actions on musculus (m.) longissimus. However, longer-latency IPSPs remaining after MLF or PT spinal lesions and after ipsilateral or contralateral hemisection of spinal cord indicate that PT actions are also mediated by ipsilaterally and/or contralaterally located spinal interneurons. The bilateral effects of PT stimulation thereby provide an explanation why trunk movements after unilateral injuries of PT neurons (e.g., stroke) are impaired to a lesser degree than movements of the extremities.

MRI characteristics of the MLF in MS patients with chronic internuclear ophthalmoparesis.

Internuclear ophthalmoparesis (INO) is one of the most common and exquisitely localizing brainstem syndromes in patients with multiple sclerosis (MS). The authors imaged the medial longitudinal fasciculus (MLF) in 58 patients with MS and chronic INO to determine which MRI technique best shows the characteristic lesion associated with this ocular motor syndrome. Using quantitative infrared oculography, the authors determined the ratios of abduction to adduction for velocity and acceleration, to confirm the presence of INO and to determine the severity of MLF dysfunction in the 58 patients with MS and INO. Conventional MRI techniques, including proton density imaging (PDI), T2-weighted imaging, and fluid-attenuated inversion recovery (FLAIR) imaging, were used to ascertain which technique best shows MLF lesions within the brainstem tegmentum. T1-weighted imaging was performed to determine the frequency of brainstem tegmentum hypointensities. All patients studied had evidence of an MLF lesion hyperintensity on PDI, whereas T2-weighted imaging and FLAIR imaging showed these lesions in 88% and 48% of patients, respectively. With PDI, dorsomedial tegmentum lesions were seen in the pons in 93% of patients and in the midbrain of 66% of patients. Lesions were observed at both locations in 59% of patients. Only one patient had an MLF lesion with a corresponding T1 hypointensity. A number of the cases of INO identified oculographically were not evident on clinical examination and many patients suspected of having unilateral INO were found to have bilateral INOs on oculography. Amongst the conventional MRI techniques available, proton density imaging best shows the MLF lesions associated with INO in patients with MS.—Nancy J. Newman

MRI characteristics of the MLF in MS patients with chronic internuclear ophthalmoparesis.

The authors imaged the medial longitudinal fasciculus (MLF) in 58 patients with MS and chronic internuclear ophthalmoparesis (INO) to determine which MRI technique best shows the characteristic lesion associated with this ocular motor syndrome. Using quantitative infrared oculography, the authors determined the ratios of abduction to adduction for velocity and acceleration, to confirm the presence of INO and to determine the severity of MLF dysfunction in 58 patients with MS and INO. Conventional MRI techniques, including proton density imaging (PDI), T2-weighted imaging, and fluid-attenuated inversion recovery (FLAIR) imaging, were used to ascertain which technique best shows MLF lesions within the brainstem tegmentum. T1-weighted imaging was performed to determine the frequency of brainstem tegmentum hypointensities. All patients studied had evidence of an MLF lesion hyperintensity on PDI, whereas T2-weighted imaging and FLAIR imaging showed these lesions in 88% and 48% of patients, respectively. With PDI, dorsomedial tegmentum lesions were seen in the pons in 93% of patients and in the midbrain of 66% of patients. Lesions were observed at both locations in 59% of patients. One patient had an MLF lesion with a corresponding T1 hypointensity. PDI best shows the MLF lesion in patients with MS and INO.

Internuclear ophthalmoplegia in 14 patients: Clinical and topographic correlation using magnetic resonance imaging

In a clinicotopographic study of 14 patients with internuclear ophthalmoplegia (INO) confirmed by electrooculography (EOG), the pattern of visual dysfunction was compared to the location and severity of lesions of the medial longitudinal fasciculus (MLF) visualized by magnetic resonance imaging (MRI). Of the 12 patients with classically-defined 'anterior' INO, nine were classed as having definite multiple sclerosis (MS), and three as probable or possible. Five of the 12 had MR-imaged MLF lesions, and five including one with MLF lesions, had cerebellum-associated lesions. Of the two patients with so-called 'posterior' INO, one presented a heredodegenerative disease and cerebellum-related lesions, and in the other, a non-visual neurological condition was not diagnosed. The finding that MR-imaged MLF lesions do not always occur simultaneously with INO may indicate that INO could be the expression of a functional disorder in the posterior fossa, preceding MLF lesion development.

The vestibulothalamic pathway: Contribution of the ascending tract of deiters

Axoplasmic transport techniques were used to determine the contribution of the ascending tract of Deiters (ATD) to the vestibulothalamic projection in cats. Large injections of HRP into the thalamus centered on the border region between the ventrobasal complex and the caudal ventrolateral nucleus resulted in bilateral retrograde labeling of cells in the vestibular nuclear complex and the nucleus prepositus hypoglossi (PH). Similar thalamic injections were also made in animals with extensive bilateral lessions of the medial longitudinal fasciculus (MLF) and the brachium conjuctivum (BC). HRP-positive neurons in these cases were localized principally to the ventral lateral vestibular nucleus and adjacent superior vestibular nucleus ipsilateral to the thalamic injection, evidence that vestibulothalamic neurons in these nuclei may project to the thalamus over the unlesioned ATD. Injections of [ 35S]methionine into the rostral vestibular nuclear complex in animals with MLF and BC lesions comfirmed these findings, demonstrating orthograde transport of radiolabel in the ATD with termination in thalamus. These experiments document a contribution of the ATD to the ipsilateral vestibulathalamic projection; other sources of the vestibulothalamic pathway ( PH, Y group) likely travel through projection systems destroyed in the lesions made in the present study.

Internuclear ophthalmoplegia. II. Pursuit, optokinetic nystagmus, and vestibulo-ocular reflex.

Smooth pursuit, optokinetic nystagmus (OKN) and the vestibulo-ocular reflex (VOR) were studied in four patients with internuclear ophthalmoplegia (two with bilateral and two with unilateral lesions). Horizontal smooth pursuit by an adducting eye on the side of a medial longitudinal fasciculus (MLF) lesion was normal in three of four patients; vertical pursuit was abnormal in all four. The horizontal VOR gain of slow components made by an adducting eye on the side of an MLF lesion was normal in all four patients. The vertical VOR gain was decreased in the two patients tested. It is concluded that either there are pathways independent of the MLF for horizontal pursuit and vestibular signals that are not available to vertical signals, or vertical pursuit and vestibular eye movements require a higher rate of oculomotor neuron firing than equal-velocity horizontal eye movements.

Internuclear Ophthalmoplegia

Saccades (horizontal and vertical) and dissociated nystagmus were quantitatively assessed in four patients with internuclear ophthalmoplegia. Two patients had bilateral medial longitudinal fasciculus (MLF) lesions associated with multiple sclerosis and two had unilateral lesions associated with brain stem vascular disease. Adducting saccades made on the side of an MLF lesion were slowed in each patient (P less than .01). At the same time, abducting saccades in the contralateral eye had normal velocity, but consistently overshot the target. After the overshoot, the eye returned to the target with an exponentially decaying course. With large angular deviations (usually more than 15 degrees), the abducting eye developed nystagmus characterized by slow components that moved toward the midposition with an initially high velocity followed by a segment of slower velocity. The adducting eye had either no nystagmus or a low-amplitude nystagmus characterized by a rounded junction between the fast and slow component. The saccade abnormalities and waveform of the dissociated nystagmus can be explained by a pulse-step mismatch at the agonist motoneurons.

Spinal cord effects of a brainstem cholinergic system

Eserine has been found to produce two patterns of lumbar monosynaptic reflex (MSR) alteration: the first pattern was MSR depression followed by return to control amplitude; the second pattern was a gradual depression of the reflex followed by partial recovery and then further depression followed by a gradual return to control amplitude. The lack of evidence of primary afferent depolarization and of sensitivity to picrotoxin indicated that the MSR depression was post-synaptic in nature. The eserine-induced alteration of the MSR was of brainstem origin. The alteration did not occur following spinal cord transection and was not sensitive to strychnine. A slight depression of the Renshaw cell firing rate indicated that the inhibition was not due to Renshaw cell activity. Medial longitudinal fasciculus lesions and cerebellectomy did not prevent or modify the eserine induced MSR alteration. Interneuronal destruction, accomplished by thoracic aorta ligation, did not prevent eserine-induced MSR depression. Spinal cord tracts mediating the eserine effect appear to travel in the lateral funiculus. Eserine produced spike activity in the nucleus reticularis pontis caudalis and a depression of neck muscle tone. Atropine sulphate reversed eserine-induced MSR alteration. It is thought that eserine (1) sensitizes a group of brainstem neurones, perhaps those in the Magoun inhibitory centre, to produce inhibitory postsynaptic potentials (IPSPs) on motoneurones, (2) triggers an episode of desynchronized sleep which produces a bombardment of IPSPs on motoneurones and (3) activates an independent system which results in MSR rebound or partial recovery from inhibition.

Bilateral internuclear ophthalmoplegia. Association with occlusive cerebrovascular disease.

In a series of 72 cases of internuclear ophthalmoplegia, 12 of 41 bilateral lesions were associated with occlusive cerebrovascular disease. Two were verified pathologically. This frequency is more in keeping with the pathologic substrate of brain stem infarction in general, and of those with medial longitudinal fasciculus (MLF) involvement in particular, than has been acknowledged previously. Convergence, abducting nystagmus, and tropias were not reliable in differentiating midbrain and pontine involvement. Bilateral vascular involvement is frequently associated with at least transient impairment of consciousness. Associated horizontal conjugate gaze paralysis occurred as often as in unilateral lesions. The one-and-a-half syndrome in a comatose patient suggests underlying bilateral MLF lesions. While multiple sclerosis remains the leading cause of bilateral internuclear ophthalmoplegia, vascular lesions are not uncommon.