Respiratory Dysfunction
In Multiple Sclerosis

Objective
To evaluate the contribution of Respiratory muscle weakness (part 1) and Respiratory muscle training (part 2) to pulmonary function, cough efficacy, and functional status in patients with advanced Multiple Sclerosis (MS).

Design & Setting
Survey (part 1) and randomized controlled trial (part 2). Rehabilitation center for MS.

Patients
Twenty-eight bedridden or wheelchair-bound MS patients (part 1); 18 patients were randomly assigned to a training group (n = 9) or a control group (n = 9) (part 2).

Intervention
The training group (part 2) performed three series of 15 contractions against an Expiratory resistance (60% maximum Expiratory pressure [PEmax]) two times a day, whereas the control group performed breathing exercises to enhance maximal Inspirations.

Main Outcome Measures
Forced Vital Capacity (FVC), Inspiratory, and Expiratory muscle strength (PImax and PEmax), Neck Flexion Force (NFF), cough efficacy by means of the Pulmonary Index (PI), and functional status by means of the Extended Disability Status Scale (EDSS).

Results
Part 1 revealed a significantly reduced FVC (43% +/- 26% predicted), PEmax (18% +/- 8% predicted), and PImax (27% +/- 11% predicted), whereas NFF was only mildly reduced (93% +/- 26% predicted).

The PI (median score, 10) and EDSS (median score, 8.5) were severely reduced.

PEmax was significantly correlated to FVC, EDSS, and PI (r = .77, -.79, and -.47, respectively).

In stepwise multiple regression analysis. PEmax was the only factor contributing to the explained variance in FVC (R2 = .60), whereas body weight (R2 = .41) was the only factor for the PI.

In part 2, changes in PImax and PEmax tended to be higher in the training group (p = .06 and p = .07, respectively).

The PI was significantly improved after 3 months of training compared with the control group (p < .05). After 6 months, the PI remained significantly better in the training group.

Conclusions
Expiratory muscle strength was significantly reduced and related to FVC, cough efficacy, and functional status. Expiratory muscle training tended to enhance Inspiratory and Expiratory muscle strength.

In addition, subjectively and objectively rated cough efficacy improved significantly and lasted for 3 months after training cessation.

This study aimed to determine the relationship between Pulmonary Function, Respiratory Muscle Function and Neurological Function in Multiple Sclerosis (MS).

Sixty patients (27 males and 33 females) aged 27-75 yrs (mean +/- SD 48 +/- 12 yrs) were prospectively studied. The Kurtzke Expanded Disability Status Scale (EDSS; range 0-10) score was 6.5 +/- 1.5.

The different Functional Systems Scores (FSS; ranges 0-5 and 0-6) were:
1. Pyramidal 3.4 +/- 1.1
2. BrainStem 1.9 +/- 1.2
3. Mental 1.3 +/- 0.9
4. Cerebellar 2.2 +/- 1.0
5. Sphincter 1.8 +/- 1.5
6. Visual 1.4 +/- 1.4
7. Sensory 2.0 +/- 1.5

Results of Lung function tests were: Vital Capacity (VC) 80 +/- 23% of predicted; single-Breath Transfer Factor of the Lung for Carbon Monoxide (TL, CO, sb) 83 +/- 17% pred; maximal static Expiratory Mouth Pressure (MEP) 30 +/- 16% pred; and maximal static Inspiratory Mouth Pressure (MIP) 47 +/- 23% pred, indicating a marked Respiratory Muscle Dysfunction, with a minor restrictive defect.

In 70% of the patients, a TransCutaneous Oxygen Saturation (Stc, O2) of less than 92% at night was found.

Comparison of Lung function and Disability Scores showed that the abnormalities in both tended to be correlated to each other, and that this was significant for EDSS versus Lung volumes, for most FSS with VC, and also for some FSS with MEP and/or MIP.

Duration of disease was significantly correlated with the EDSS, but not with the different FSS scores (with the exception of mental status) and not with Lung function. Multiple Sclerosis leads to Lung Function Abnormalities attributable to Respiratory Pump Dysfunction.

Respiratory complications are common in the terminal stages of Multiple Sclerosis and contribute to mortality in these patients. When Respiratory Motor Pathways are involved, Respiratory Muscle Weakness frequently occurs.

Although it is well established that weakness of the Respiratory Muscles produces a Restrictive Ventilatory Defect, the degree of Muscle Weakness and Pulmonary Function are poorly related.

Respiratory Muscle Weakness was observed in patients with normal or near normal Pulmonary Function. Expiratory Muscle Weakness is more prominent than Inspiratory Muscle Weakness and may impair performance of coughing.

Subsequently, in addition to Bulbar Dysfunction, Respiratory Muscle Weakness may contribute to Ineffective Coughing, Pneumonia, and sometimes even acute Ventilatory Failure may ensue.

Respiratory Muscle Weakness may also occur early in the course of the disease. Recent studies suggest that the Respiratory Muscles can be trained for both strength and endurance in Multiple Sclerosis patients.

Whether Respiratory Muscle training delays the development of Respiratory Dysfunction and subsequently improves exercise capacity and cough efficacy, prevents Pulmonary complications or prolongs survival in the long-term remains to be determined.

Pulmonary Function was studied in 25 patients with clinically definite Multiple Sclerosis with a range of Motor Impairment.

Forced Vital Capacity (FVC), Maximal Voluntary Ventilation (MVV), and Maximal Expiratory Pressure (MEP) were normal in the ambulatory patients (mean greater than or equal to 80% predicted) but reduced in bedridden patients (mean, 38.5%, 31.6%, and 36.3% predicted.

FCV, MVV, and MEP, respectively) and wheelchair-bound patients with upper extremity involvement (mean, 69.4%, 50.4%, and 62.6% predicted; FVC, MVV, and MEP, respectively).

Forced vital capacity, MVV, and MEP correlated with Kurtzke Expanded Disability Status scores (tau = -0.72, -0.70, and -0.65) and Expiratory Muscle Weakness occurred most frequently.

These findings demonstrate that marked Expiratory Weakness develops in severely Paraparetic patients with Multiple Sclerosis and the weakness increases as the upper extremities become increasingly involved.

In 11 patients with moderately severe Multiple Sclerosis, lasting 11.2 +/- 7.3 years, in stable condition, and in 10 age- and sex-matched control subjects, we investigated Lung Function, Respiratory Muscle Strength, and Ventilatory Control System.

Respiratory Muscle Strength was assessed by measuring Maximal Inspiratory and Expiratory mouth pressures (Pimax and Pemax, respectively).

Respiratory central drive was evaluated in terms of NeuroMuscular (P0.1) and ventilatory (Ve) output, breathing room air and during CO2 rebreathing.

In the absence of any significant impairment of Lung function, patients showed a reduction of Pimax and Pemax amounting to about 40 percent and 60 percent of the predicted value at Functional Residual Capacity (FRC), respectively.

A significant, inverse correlation was found between both Pimax and Pemax at FRC and the severity score of the disease.

While at rest Ve was similar to that of control subjects, baseline P0.1 was significantly higher in patients (1.97 +/- 0.79 vs 0.97 +/- 0.20 cm H2O, p < 0.005).

Compared with the control group, during CO2 rebreathing P0.1/PetCO2 slope, although less steep, was not dissimilar in patients (0.34 +/- 0.13 vs 0.46 +/- 0.19 cm H2O/mm Hg, NS).

On the other hand, Ve/PetCO2 slope was much lower in the patient group (1.93 +/- 0.91 vs 3.27 +/- 1.11 L/min/mm Hg, p < 0.01) and was significantly related to the functional stage of disease and to Pimax and Pemax values at FRC.

These results indicate that in patients with clinically stable, moderately severe Multiple Sclerosis, the Respiratory Muscle Function is abnormal.

Moreover, the Inspiratory drive at rest is increased and the drive response to CO2 appears normal, while the Ventilatory Response to CO2 is significantly impaired.