InterNuclear Ophthalmoplegia

  1. InterNuclear Ophthalmoplegia: unusual causes in 114 of 410 patients
    Arch Neurol 2005 May;62(5):714-7

  2. MRI characteristics of the MLF in MS with chronic InterNuclear Ophthalmoparesis
    Neurology 2001 Sep 11;57(5):762-8

  3. Complete bilateral horizontal gaze paralysis disclosing Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2001 Feb;70(2):252-255

  4. Bulk Listing
    Pupillary Abnormalities & INO In Multiple Sclerosis

  1. Horizontal Monocular Saccadic failure: an unusual Clinically Isolated Syndrome progressing to Multiple Sclerosis
    Mult Scler 2003 Feb;9(1):55-8

  2. Quantitative Oculographic characterisation of InterNuclear Ophthalmoparesis in Multiple Sclerosis: the Versional Dysconjugacy Index Z score
    J Neurol NeuroSurg Psychiatry 2002 Jul;73(1):51-5

  3. Abduction Paresis with rostral Pontine and/or Mesencephalic lesions: PseudoAbducens Palsy and its relation to the so-called posterior InterNuclear Ophthalmoplegia of Lutz
    BMC Neurol 2001 Dec 18;1(1):4

  4. InterNuclear Ophthalmoplegia and Cerebellar Ataxia: report of one case
    CerebroVasc Dis 2001;12(4):346-8

  5. BrainStem Infarcts presented Medial Longitudinal Fasciculus (MLF) Syndrome and Cerebellar Ataxia - report of three cases
    Rinsho Shinkeigaku 1990 May;30(5):533-9

  6. Magnetic Resonance Imaging correlates of InterNuclear Ophthalmoplegia
    Int J NeuroSci 1990 May;52(1-2):39-43

  7. Abnormalities of Horizontal Gaze. Clinical, OculoGraphic and Magnetic Resonance Imaging findings. II. Gaze Palsy and InterNuclear Ophthalmoplegia
    J Neurol NeuroSurg Psychiatry 1990 Mar;53(3):200-7

  8. Identification of InterNuclear Ophthalmoplegia signs in Multiple Sclerosis patients: Saccade test analysis
    J Neurol 2008 May 2

  9. Modeling Uhthoff's phenomenon in MS patients with InterNuclear Ophthalmoparesis
    Neurology 2008 Mar 25;70(13 Pt 2):1098-106

  10. Ocular Contrapulsion in Multiple Sclerosis: clinical features and PathoPhysiological mechanisms
    J Neurol NeuroSurg Psychiatry 2001 May;70(5):688-92

  11. Complete BiLateral Horizontal Gaze Paralysis disclosing Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2001 Feb;70(2):252-5

  12. Dissociated Nystagmus in side gaze. Major symptoms in the diagnosis of an InterNuclear Ophthalmoplegia
    HNO 2004 Jul;52(7):623-6


Horizontal Monocular Saccadic Failure: An Unusual Clinically Isolated Syndrome Progressing To Multiple Sclerosis

Frohman EM, Frohman TC
Mult Scler 2003 Feb;9(1):55-8
University of Texas Southwestern Medical Center at Dallas, Department of Neurology, Dallas, Texas 75235, USA
PMID# 12617269

This paper describes an unusual Clinically Isolated Syndrome of Inflammatory DeMyelination that was characterized by a right VI Nerve Palsy and right InterNuclear Ophthalmoparesis (INO), along with an unusual form of dissociated Nystagmus.

Magnetic Resonance Imaging (MRI) revealed an isolated lesion within the right DorsoMedioLateral Pontine Tegmentum.

Four years later, the subject developed a partial Sensory Transverse Myelitis, confirming Clinically Definite Multiple Sclerosis (MS).

This paper extends the range of Isolated Syndromes associated with MS.


Quantitative Oculographic Characterisation Of Internuclear Ophthalmoparesis In Multiple Sclerosis: The Versional Dysconjugacy Index Z Score

Frohman EM, Frohman TC, O'Suilleabhain P, Zhang H, Hawker K, Racke MK, Frawley W, Phillips JT, Kramer PD
J Neurol NeuroSurg Psychiatry 2002 Jul;73(1):51-5
University of Texas Southwestern Medical Center, Department of Neurology, Dallas, Texas 75235, USA
PMID# 12082045

There is a poor correlation between Multiple Sclerosis disease activity, as measured by Magnetic Resonance Imaging, and clinical disability.

To establish OculoGraphic criteria for the diagnosis and severity of InterNuclear Ophthalmoparesis (INO), so that future studies can link the severity of Ocular Dysconjugacy with NeuroRadiological abnormalities within the DorsoMedial BrainStem Tegmentum.

The study involved 58 patients with Multiple Sclerosis and chronic INO and 40 normal subjects.

Two dimensional infrared Oculography was used to derive the Versional Dysconjugacy Index (VDI)-the ratio of abducting to adducting eye movements for peak velocity and acceleration.

Diagnostic criteria for the diagnosis and severity of INO were derived using a Z score and Histogram analysis, which allowed comparisons of the VDI from Multiple Sclerosis patients and from a control population.

For a given Saccade, the VDI was typically higher for acceleration v velocity.

Whereas the Z scores for velocity measures were always higher than values derived from comparable acceleration VDI measures; this was related to the greater variability of acceleration measures.

Thus velocity was a more reliable measure from which to determine Z scores and thereby the criteria for INO and its level of severity. The mean (SD) value of the VDI velocity derived from 40 control subjects was 0.922 (0.072).

The highest VDI for velocity from a normal control subject was 1.09, which was 2.33 SD above the normal control mean VDI.

We therefore chose 2 SD beyond this value (that is, a Z score of 4.33) as the minimum criterion for the OculoGraphic confirmation of INO.

Of patients thought to have UniLateral INO on clinical grounds, 70% (16/23) were found to have BiLateral INO on OculoGraphic assessment.

INO can be confirmed and characterised by level of severity using Z score analysis of quantitative OculoGraphy.

Such assessments may be useful for linking the level of severity of a specific clinical disability with NeuroRadiological measures of Brain tissue pathology in Multiple Sclerosis.


Abduction Paresis With Rostral Pontine And/Or Mesencephalic Lesions: PseudoAbducens Palsy And Its Relation To The So-Called Posterior Internuclear Ophthalmoplegia Of Lutz

Thomke F, Hopf HC
BMC Neurol 2001 Dec 18;1(1):4
University of Mainz, Deparment of Neurology, Mainz, Germany
PMID# 11570979

The existence of a PreNuclear Abduction Paresis is still debated.

In a retrospective design, we identified 22 patients with isolated UniLateral (n = 20) or BiLateral (n = 2) Abduction Paresis and ElectroPhysiologic abnormalities indicating rostral Pontine and/or Mesencephalic lesions.

Another 11 patients had Unilateral Abduction Paresis with additional Ocular Motor abnormalities indicating MidBrain Dysfunction. Eight of these 11 patients also had ElectroPhysiological abnormalities supporting this location.

ElectroPhysiological examinations in all patients included Masseter and Blink Reflexes (MassR, BlinkR), BrainStem Auditory Evoked Potentials (BAEP), and direct current Elctro-OculoGraphy (EOG).

UniLateral MassR abnormalities in patients with UniLateral Abduction Paresis were seen in 17 patients and were almost always (in 16 of 17 patients) on the side of the Abduction Paresis.

Another 11 patients had BiLateral MassR abnormalities. BlinkR was always normal.

EOG disclosed slowed Abduction Saccades in the non-paretic eye in 6 patients and slowed Saccades to the side opposite to the Abduction Paresis in another 5 patients.

Re-examinations were done in 27 patients showing normalization or improvement of Masseter Reflex abnormalities in 18 of 20 patients and in all patients with EOG abnormalities. This was always associated with clinical improvement.

ElectroPhysiologically documented or clinically evident rostral Pontine and/or Mesencephalic lesions in our patients exclude an Infranuclear IntraPontine 6th Nerve lesion and indicate the existence of an Abduction Paresis of PreNuclear origin.

An increased tone of the antagonistic Medial Rectus muscle during Lateral Gaze either by abnormal Convergence or impaired Medial Rectus inhibition seems most likely.


InterNuclear Ophthalmoplegia And Cerebellar Ataxia: Report Of One Case

Krespi Y, Aykutlu E, Coban O, Tuncay R, Bahar S
CerebroVasc Dis 2001;12(4):346-8
University of Istanbul, Istanbul School of Medicine, Department of Neurology, Edip Aktin Stroke Unit, Capa, Istanbul, Turkey
PMID# 11721107

Deep Hemispheric or BrainStem small Infarcts can lead to atypical Lacunar Syndromes. Unilateral InterNuclear Ophthalmoplegia (INO) and Cerebellar Ataxia has not been reported previously.

A 57-year-old hypertensive female presented with BiLateral Appendicular and left truncal Cerebellar Ataxia and right INO.

Cranial MRI showed a right ParaMedian Infarct of lacunar size located in the Tegmentum of caudal Mesencephalon.

At this level the involvement of Medial Longitudinal Fascicle (MLF) led to right INO and the lesion of Brachium Conjunctivum caused the BiLateral Cerebellar Ataxia.

Ipsilateral involvement of both Cerebellofugal Fibers, before and after decussation, was responsible for bilateral Cerebellar Ataxia.

Copyright 2001 S. Karger AG, Basel


BrainStem Infarcts Presented Medial Longitudinal Fasciculus (MLF) Syndrome And Cerebellar Ataxia - Report Of Three Cases

Sakakibara S, Sakato S, Shima T, Ide Y, Takamori M
Rinsho Shinkeigaku 1990 May;30(5):533-9
Kanazawa University, School of Medicine, Department of Neurology
PMID# 2205435

Vascular Disorders of the BrainStem manifest characteristic Neurologic symptoms according to their localization.

The Medial Longitudinal Fasciculus (MLF) lies in the ParaMedian portion of the upper BrainStem Tegmentum, and the lesion in this fasciculus shows specific abnormality of the Eye Movement Pattern which is known as the MLF Syndrome.

Although the MLF Syndrome was reported frequently to be accompanied by varieties of other Neurologic deficits according to the lesion extending into the adjacent structures in the BrainStem.

The combination of MLF syndrome and Cerebellar Ataxia has attracted less attention of Neurologists. Recently we experienced three cases of Cerebellar Ataxia arisen simultaneously with MLF Syndrome.

Magnetic Resonance Imaging (MRI) tomography or X-ray computed tomography visualized lacunar lesion(s) in the upper BrainStem Tegmentum in all of three cases. It was obvious that the lesion included the MLF and caused the MLF Syndrome in these cases.

It was speculated that Ventro-Caudal extension of the lesion involved the Decussation of the Superior Cerebellar Peduncle, and was responsible for the association of Cerebellar Ataxia with MLF Syndrome.

According to the recent discussion about the feeding arteries in the BrainStem, we decided that the damage of the ParaMedian branches diverging from the Basilar Tip resulted in the lacunar lesion(s).

The development of diagnostic procedures especially MRI enables the diagnosis of the Vascular Disorders in the BrainStem with considerable accuracy.


Magnetic Resonance Imaging Correlates Of InterNuclear Ophthalmoplegia

Awerbuch G, Brown M, Levin JR
Int J NeuroSci 1990 May;52(1-2):39-43
Wayne State University School of Medicine, Department of Neurology, Detroit, Michigan 48201
PMID# 2265923

InterNuclear Ophthalmoplegia (INO) is a Gaze Disorder characteristic of lesions involving the Medial Longitudinal Fasciculus (MLF).

Two patients aged 62 and 74 years presented with acute Neurologic deficits characteristic of INO. Computed axial Tomography (CT) did not detect abnormalities in the region of the MLF.

Magnetic Resonance Imaging (MRI) however, demonstrated BrainStem hypersignals with long T2 characteristics in the region of the MLF which correlated with the clinical symptoms.

These cases illustrate the value of the MRI in evaluation of patients with INO and suggest that MRI is superior to CT in evaluating Gaze Disorders attributable to Brain Dysfunction.


Abnormalities Of Horizontal Gaze. Clinical, Oculographic And Magnetic Resonance Imaging Findings. II. Gaze Palsy And InterNuclear Ophthalmoplegia

Bronstein AM, Rudge P, Gresty MA, Du Boulay G, Morris J
J Neurol NeuroSurg Psychiatry 1990 Mar;53(3):200-7
Institute of Neurology, Medical Research Council Neuro-Otology Unit, National Hospital, London, United Kingdom
PMID# 2324752

The site of lesions responsible for Horizontal Gaze Palsy and various types of InterNuclear Ophthalmoplegia (INO) was established by identifying the common areas where the abnormal MRI signals from patients with a given Ocular-Motor Disorder overlapped.

Patients with UniLateral Gaze Palsy had lesions in the ParaMedian area of the Pons, including the Abducens Nucleus, the Lateral part of the Nucleus Reticularis Pontis Caudalis and the Nucleus Reticularis Pontis Oralis.

Patients with Abducens Nucleus lesions showed additional clinical signs of Lateral Rectus weakness. Lesions responsible for BiLateral Gaze Palsy involved the Pontine Tegmental Raphe.

Since this region contains the Saccadic Omnipause Neurons, this finding suggests that damage to Omnipause Cells produces slowing of Saccades rather than OpsoClonus, as previously proposed.

All INOs, regardless of the presence of impaired Abduction or Convergence, had similar MRI appearances.

Frequently the lesions in patients with INO, were not confined to the Medial Longitudinal Fasciculus (MLF) but also involved neighboring structures at the Pontine and MidBrain levels.

There was a statistically significant association between the clinical severity of the INO and the presence of abnormal Abduction or Convergence.

The findings suggest that the lesions outside the MLF, which may affect Abducens, Gaze or Convergence Pathways, are responsible for the presence of features additional to INO, depending on the magnitude of functional disruption they produce.


Identification Of InterNuclear Ophthalmoplegia Signs In Multiple Sclerosis Patients: Saccade Test Analysis

Jozefowicz-Korczynska M, Lukomski M, Pajor A
J Neurol 2008 May 2
Medical University of Lodz, Dept. of Otolaryngology, 22, Kopcinskiego str., 90-153, Lodz, Poland
PMID# 18446308

Background And Purpose
Patients with Multiple Sclerosis (MS), due to the diverse nature of the disease, have many types of eye movement disorders, particularly InterNuclear Ophthalmoplegia (INO).

The aim of the study was to evaluate the usefulness of a quantitative statistical saccade test analysis for identification of INO in MS patients.

Sixty MS patients and 50 volunteers underwent clinical bedside ocularmotor examination and Electrooculographic Evaluation in a tertiary referral university hospital.

Simultaneous Electro-Oculography recordings of each eye separately were made.

In the Saccade test, the versional dysconjugacy index (VDI) for saccades velocity and the Z score analysis were applied.

Clinical eye movements disorders were found in 32 % of patients. In the MS patients saccades velocity was significantly lower compared with the control group.

Based on the results of the control group, we established the cut off values for VDI (1.04) and corresponded Z score (4.46) as the criterion indicated the presence of INO signs in MS patients.

We confirmed clinical evidence of different degrees of INO in 15 % of patients, and found subclinical INO signs in 20 % of patients.

The EOG registration is a sensitive ElectroPhysiological method for detecting subtle deficits of Ocular motility.

Saccade test analysis with calculation of the VDI and the Z-test score is a valuable method for identifying subclinical INO signs in MS patients.


Modeling Uhthoff's Phenomenon In MS Patients With InterNuclear Ophthalmoparesis

Davis SL, Frohman TC, Crandall CG, Brown MJ, Mills DA, Kramer PD, Stüve O, Frohman EM
Neurology 2008 Mar 25;70(13 Pt 2):1098-106
University of Texas Southwestern Medical Center at Dallas, Department of Neurology, 5323 Harry Hines Boulevard, Dallas, TX 75390 Elliot
PMID# 18287569

The goal of this investigation was to demonstrate that InterNuclear Ophthalmoparesis (INO) can be utilized to model the effects of body temperature-induced changes on the fidelity of Axonal Conduction in Multiple Sclerosis (Uhthoff's phenomenon).

Ocular motor function was measured using infrared Oculography at 10-minute intervals in patients with Multiple Sclerosis (MS) with INO (MS-INO; n = 8), patients with MS without INO (MS-CON; n = 8), and matched healthy controls (CON; n = 8) at normothermic baseline.

During, whole-body heating (increase in core temperature 0.8 degrees C as measured by an ingestible temperature probe and transabdominal telemetry), and after whole-body cooling.

The Versional Disconjugacy Index (velocity-VDI), the ratio of abducting/adducting eye movements for velocity, was calculated to assess changes in interocular disconjugacy.

The First Pass Amplitude (FPA), the position of the adducting eye when the abducting eye achieves a centrifugal fixation target, was also computed.

Velocity-VDI and FPA in MS-INO patients was elevated (p < 0.001) following whole body heating with respect to baseline measures, confirming a compromise in Axonal electrical impulse transmission properties.

Velocity-VDI and FPA in MS-INO patients was then restored to baseline values following whole-body cooling, confirming the reversible and stereotyped nature of this characteristic feature of DeMyelination.

We have developed a NeuroPhysiologic model for objectively understanding temperature-related reversible changes in Axonal Conduction in Multiple Sclerosis.

Our observations corroborate the hypothesis that changes in core body temperature (heating and cooling) are associated with stereotypic decay and restoration in Axonal Conduction mechanisms.


Ocular Contrapulsion In Multiple Sclerosis: Clinical Features And PathoPhysiological Mechanisms

Frohman EM, Frohman TC, Fleckenstein J, Racke MK, Hawker K, Kramer PD
J Neurol NeuroSurg Psychiatry 2001 May;70(5):688-92
University of Texas Southwestern Medical Center, Department of Neurology, 5323 Harry Hines Boulevard, Dallas, Texas 75235, USA
PMID# 11309470

The objective was to describe in Multiple Sclerosis, a Cerebellar Eye Movement Syndrome that resulted from an acute episode of Inflammatory DeMyelination.

    Contrapulsion is an Ocular Motor Disturbance characterised by a triad of:
  1. Hypermetric Saccadic eye movements in a direction opposite from a precisely localized lesion within a specific White Matter Pathway, the Uncinate Fasciculus:
  2. Hypometric Saccades towards the side of the lesion
  3. Oblique Saccades directed away from the side of the lesion on attempted Vertical Saccades

Infrared OculoGraphy was used to demonstrate the characteristic features of Contrapulsion in two patients with Multiple Sclerosis. Brain MRI showed lesions within the region of the Uncinate Fasciculus and Superior Cerebellar Peduncle in both patients.

Eye movement recordings showed Saccadic Hypermetria away from the side of the lesion and Saccadic Hypometria towards the side of the lesion.

The Hypometria decomposed into a series of stepwise movements as the Eye approached the target. Oblique Saccades directed away from the side of the lesion were seen on attempted Vertical Saccades.

In conclusion, Ocular Contrapulsion can be seen in patients with Multiple Sclerosis and results from a lesion in the region of the SCP, involving the Uncinate Fasciculus.


Complete BiLateral Horizontal Gaze Paralysis Disclosing Multiple Sclerosis

Milea D, Napolitano M, Dechy H, Le Hoang P, Delattre JY, Pierrot-Deseilligny C
J Neurol NeuroSurg Psychiatry 2001 Feb;70(2):252-5
Hopital de la Pitie-Salpetriere, Department of Ophthalmology, Paris, France
PMID# 11160480

Two women presented with BiLateral InterNuclear Ophthalmoplegia evolving in a few days to complete BiLateral Horizontal Gaze Paralysis. Convergence and Vertical Eye Movements were normal.

Cerebral MRI showed a few Small White matter lesions in the Lateral Ventricle regions, and, at the BrainStem level, a single, small, BiLateral lesion affecting the posterior part of the Medial Pontine Tegmentum and responsible for the clinical syndrome.

The condition gradually improved in both patients, following a similar progression as at the onset.

Improvement first involved the Adduction movements in both eyes, whereas BiLateral Abduction Paresis still persisted for a few weeks, before complete recovery of eye movements.

BiLateral damage to the Medial Longitudinal Fasciculus and subsequent lateral extent of damage to the region of the two Abducens emerging Fibers may explain the clinical findings. In both cases, the cause was probably Multiple Sclerosis.


Dissociated Nystagmus In Side Gaze. Major Symptoms In The Diagnosis Of An InterNuclear Ophthalmoplegia

Neugebauer P, Neugebauer A, Fricke J, Michel O
HNO 2004 Jul;52(7):623-6
Klinik und Poliklinik fur Hals-Nasen-Ohren-Heilkunde des Klinikums der Universitat zu Koln
PMID# 15309261

A prerequisite for a qualified analysis of Nystagmus is the recognition of uncommon forms of this condition. In InterNuclear Ophthalmoplegia (INO), a Dissociated Nystagmus in Side Gaze is typical.

This is accompanied by limited medial excursion of the Adducted Eye together with a Dissociated Nystagmus, which is stronger in the Abducting Fellow Eye.

This motility disturbance stems from a lesion in the Medial Longitudinal Fasciculus running in the BrainStem between the Sixth and the Third Nerve Nuclei.

The lesion is often due to Multiple Sclerosis, but can also be Ischemic, Traumatic, Neoplastic or Inflammatory (e.g. HIV infection).

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