Autonomic Pupillary Dysfunction in MS

Primary DeMyelination with relative preservation of Axons is considered to be one pathological hallmark of Multiple Sclerosis (MS), a chronic inflammatory disease of the Central Nervous System.

However, Imaging and PathoMorphological studies have stimulated a recent re-emergence of interest in the Axonal, NeuroDegenerative aspect of MS Pathology. Axonal injury appears to be a key factor of disability and permanent Neurological deficit in MS patients.

In the present ElectroPhysiological study, Visual Potentials evoked by pattern reversal (VEPs) were recorded in 25 MS patients with normal Visual Acuity and unimpaired Visual functions.

Compared to a control population, VEP amplitudes for two different spatial frequencies were significantly decreased.

From this observation, we conclude that an underlying pathological process threatening Axonal integrity may not be reliably reflected by clinical parameters due to the distinct ability of the Visual System to compensate for Axonal Loss.

Pattern VEP may thus serve as an objective tool to diagnose and to monitor Axonal Pathology in MS.

To investigate Optic Neuritis as a model for Atrophy in Multiple Sclerosis (MS) lesions we performed serial Magnetic Resonance Imaging (MRI) on 10 patients with a history of Optic Neuritis using a fat saturated short-echo fast Fluid-Attenuated Inversion Recovery (sTE fFLAIR) sequence.

The first study was performed a median of 19.5 months after the onset of Optic Neuritis and the second 1 year later. Using a computer-assisted contouring technique, a blinded observer calculated the mean area of the intro-orbital Optic Nerves.

The mean area of affected Optic Nerves decreased over 1 year by 0.9 mm2 from 11.1 to 10.2 mm2 (p = 0.01). Poor Visual Acuity and decreased Visual-Evoked Potential (VEP) amplitude were associated with Atrophy.

These findings suggest that Atrophy is a feature of focal DeMyelinating lesions, it may evolve over several years, and may have functional significance.

Optic Neuritis provides a model to study the effect of inflammatory DeMyelination through the ability to accurately measure Visual function and to visualize and measure the Optic Nerves using Magnetic Resonance Imaging.

Multiple Sclerosis (MS) Fatigue is one of the most common symptoms in MS, but its PathoPhysiology is still not understood SympathoVagal imbalance was suggested as a reason for Fatigue in Chronic Fatigue Syndrome.

We examined the role of an imbalance in the Central Autonomic Nervous System (ANS) as a cause of MS Fatigue in 51 MS patients and a control group of 22 healthy volunteers.

Fatigue was assessed with the revised MS Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Depression was evaluated with the Beck Depression Inventory (BDI).

Disintegration of the Central ANS expressed by Pupillary Fatigue waves was measured with Pupillography and documented in the Pupillary Unrest Index (PUI). All subjects had less than five points on the seven-point Stanford Sleepiness Scale and were therefore not sleepy.

MS patients had significant higher mean FSS scores (p=0.001) and mean MFIS scores (p=0.003) than our control group.

Mean BDI scores were significant higher (p=0.001) in the MS group, but were in the lowest score range (0-10 points) in both groups.

Surprisingly, we found a statistically significant inverse correlation between PUI values and either FSS scores (p=0.001; r=-0.521) or MFIS scores (p=0.002; r=-0.423) in the MS group, but not in healthy participants.

We therefore conclude that Autonomic instability, as measured by Pupillary unrest is not associated with MS Fatigue severity.

CardioVascular Autonomic functions were investigated in a prospective, controlled study of 22 consecutive Relapsing/Remitting Multiple Sclerosis (MS) patients and 22 healthy subjects using 5 simple noninvasive tests and Sympathetic Skin Response Testing.

Tests included the Heart Rate response to deep breathing, Valsalva maneuver and standing, blood pressure response to standing and sustained hand grip, and were graded according to the Ewing and Clark classification as early, definite or severe impairment.

The relationship between Autonomic Dysfunction and disease-related parameters such as the Expanded Disability Status Scale (EDSS) and disease duration was studied.

Ninety percent of the patients had symptoms related with Autonomic Dysfunction, and 45.5 % had abnormal results in CardioVascular Autonomic Function testing with 4 patients also having abnormal Sympathetic Skin Responses.

Statistical analysis indicated that patients with a long disease duration rather than high EDSS carried a risk of Autonomic involvement in MS.

Both ParaSympathetic and Sympathetic functions were impaired and this could have been easily overlooked by a standard EDSS follow-up.

In this regard, Autonomic function testing seems necessary in order to detect subclinical changes in MS patients and should be considered in outcome measures.

Copyright 2002 S. Karger AG, Basel

Objectives
To assess, by magnetic resonance imaging, the volumes and Magnetization Transfer Ratio (MTR) values of Optic Nerves (ONs) from patients with Multiple Sclerosis (MS) who had incomplete or no visual recovery after Optic Neuritis.

And, to compare these quantities with those derived from ONs from patients with MS who showed a marked clinical recovery after Optic Neuritis, ONs from healthy volunteers, and ONs from patients with Leber Hereditary Optic Neuropathy (LHON).

Methods
Conventional and Magnetization Transfer Magnetic Resonance Images of the ONs were obtained from 30 patients with MS, 18 healthy volunteers, and 10 patients with LHON.

The ON from patients with MS were classified as:
1. Clinically unaffected (n = 18);
2. Clinically affected with recovery (n = 20; Visual Acuity > or =20/25 at least 6 months after Optic Neuritis); and
3. Clinically affected with incomplete or no recovery (n = 22; Visual Acuity < 20/25 at least 6 months after Optic Neuritis).
4. The ON volumes and MTR values were measured.

Results
Volumes (P =.002) and MTR values (P < .001) of the ONs from patients with MS and incomplete or no recovery were both lower than those of the ONs from patients with MS and recovery, but not different from those of the ONs from patients with LHON.

Volumes and MTR values of the affected ONs from patients with MS and recovery did not differ from those of clinically unaffected ONs, which were similar to those of healthy volunteers.

Conclusion
These findings suggest that, in patients with MS, NeuroDegeneration is associated with persistent functional deficits secondary to incomplete recovery from relapses.

Autonomic Nervous System disturbances such as Pupillary Abnormalities have rarely been evaluated in Multiple Sclerosis (MS). However, Pupillary impairment is not uncommon in MS and its origin is still unclear.

The aim of this study was to investigate Pupillary disturbances in MS and to try to correlate Pupillary defects with Spinal Cord and BrainStem Magnetic Resonance Imaging (MRI) findings. We prospectively studied 45 MS patients and 30 normal subjects.

Methods
The Pupillary contraction latency and the amplitude of contraction were recorded by Pupillometry. We also determined Afferent and Efferent Pathway defects by comparing the direct and Consensual Pupillary Reflexes.

We evaluated BrainStem and Spinal Cord DeMyelinating lesions and Spinal Cord Cross-Sectional Area on MRI. At least one Pupillometric parameters were significantly impaired in 60% of patients and in none of the controls.

We did not find any correlation between Pupillary defect and DeMyelinating lesions on MRI. The most frequent abnormality was Efferent Pathway shift and this was correlated with Spinal Cord Atrophy (P < 0.02).

These results confirm that the Autonomic Nervous System, and especially Pupillary function, is frequently impaired in MS.

The ParaSympathetic System is most commonly affected and this is most likely linked to Axonal Loss (demonstrated by Spinal Cord Atrophy) rather than to DeMyelinating lesions.

To study Pupillary Autonomic function in Multiple Sclerosis (MS), we examined 36 subjects with low disability, preserved Visual Acuity and no recent history (2 years) of Optic Neuritis or actual visual complaints.

Compared to controls, MS patients showed a greater dilatator reaction with darkness and, for the light reflex, a lower amplitude and contraction rate and a greater recovery of Pupillary diameter 5 seconds after the stimulus.

Within the MS group, no difference was found comparing patients with or without the following characteristics:

1. MRI evidence of MidBrain lesions
2. Increased Visual Evoked Potential
3. P100 latency
4. Previous history of Optic Neuritis

No correlation was found between P100 latency, duration of disease and Pupillometric parameters.

Our results indicate that in MS patients there is Autonomic Dysfunction with a reduction of ParaSympathetic tone and a relative increase in Sympathetic dilatator tone to the Pupils.

We suggest that Pupillary abnormalities could be due to non-specific impairment of the Central pathways subserving Pupil functions (Cranial Nerve III).

Relative Afferent Pupillary Defects were found in 69 of 386 patients (18%) seen by the author at the University of British Columbia Multiple Sclerosis Clinic between Feb. 1, 1985, and Apr. 30, 1987.

Pupil defects were more common in patients with Clinically Definite Multiple Sclerosis, those with recent or unilateral Optic Neuritis and those with unilateral or asymmetric Optic Atrophy.

A Relative Afferent Pupillary Defect was found in 15 patients with no history of Optic Neuritis, 5 patients with no Optic Atrophy and 2 patients with normal Visual Evoked Potentials.

The frequency of Relative Afferent Pupillary Defects after Optic Neuritis in this group of patients was much lower than that found in a previous study of patients who presented with Optic Neuritis.