Respiratory Dysfunction In Multiple Sclerosis

Purpose
The aim of this study was to assess the utility of clinical assessment of Respiratory Muscle Weakness in MS.

Patients & Methods
We studied 40 MS patients who performed Pulmonary Function tests using standard procedures and measures of Respiratory Muscle Strength.

Descriptive clinical indices included a history of detailed Neurologic findings, including upper and lower extremity weakness, Cerebellar signs, and evidence of Cerebral lesions and other clinical signs including dependence in activities of daily living, Shortness of Breath, Weak Voice, Dysarthria and Dysphagia.

We devised an index comprised of four clinical signs: the patient's report of difficulty in clearing Pulmonary secretions and his report of a weakened cough, the examiner's observation of the patient's cough, and ability to count on a single exhalation.

Results
Mean values of TLC (95 percent +/- 14) VC (91 percent +/- 19), and RV (106 percent +/- 34) were normal. By contrast, MVV (68 percent +/- 20), PImax (74 percent +/- 27) and PEmax (51 percent +/- 22) were decreased.

Stepwise multiple regression indicated that the best single predictor of Expiratory Muscle Weakness was the index score; the combination of index score, upper extremity weakness, and maximal voluntary Ventilation accounted for 60 percent of the variance in PEmax.

Conclusion
We conclude that clinical assessment is a better predictor of Respiratory Muscle Weakness than Spirometry and that a systematic clinical assessment supplemented by Respiratory Muscle assessment and MVV can uncover subtle Respiratory Muscle Weakness in patients with MS.

Multiple Sclerosis (MS) can produce a variety of different Respiratory Abnormalities because of the multi-focal nature of Central Nervous System involvement in the disease.

This article reviews the different patterns of Respiratory involvement in MS and correlates them with the known NeuroAnatomy of Respiratory Control. Methods of monitoring Pulmonary Function in MS are explored, and the treatment of acute Ventilatory Failure in MS is discussed.

Patients with Multiple Sclerosis (MS) show a poor exercise tolerance. A reduction in Respiratory Muscle strength has also been reported. The purpose of this study was to evaluate whether reduction in exercise tolerance was related to Respiratory Muscle dysfunction.

Twenty four Multiple Sclerosis patients (mean +/- SD age: 48 +/- 9 yrs, duration of illness 12.2 +/- 6 yrs, severity of illness as assessed by Expanded Disability Scale Score (EDSS) 5.3 +/- 2), underwent detailed evaluation of Lung Function Tests, Arterial Blood Gas Analysis, Respiratory Muscle strength and Endurance, and exercise test on an Arm Ergometer.

Sixteen of the 24 patients were able to perform the exercise test (Group I), whilst the other eight were not (group II). Arterial blood gases and Lung function tests were normal for both groups.

Respiratory Muscle strength as assessed both by Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) was significantly reduced (MIP 18-76 cmH2O; MEP 16-82 cmH2O) compared to predicted values. Inspiratory Muscle Endurance Time was significantly reduced in Group II in comparison to Group I (247 +/- 148 vs 397 +/- 154 s, respectively).

Both MIP and MEP were significantly related to Inspiratory Muscle Endurance Time. Endurance time, MIP and MEP were inversely significantly related to duration of illness, whilst only endurance time was significantly related to Expanded Disability Scale Score. (Abstract Truncated At 250 Words)

Respiratory complications occur in advanced Multiple Sclerosis (MS) but may also complicate acute relapses earlier in the disease.

We present 19 patients with MS who developed Respiratory Complications at a mean of 5.9 (range 1-12) yrs after the onset of Neurological symptoms.

Fourteen patients developed Severe Respiratory Insufficiency presenting with a combination of reduced Forced Vital Capacity (FVC), Hypoxaemia or Hypercapnia (12 patients) and Respiratory Arrest (four patients).

Two patients presented with Apneustic breathing, one with Paroxysmal Hyperventilation, one with Obstructive Sleep Apnoea and one with Bulbar Weakness leading to Aspiration Pneumonia.

Respiratory Muscle Weakness was a major factor in 14 patients (predominantly Diaphragm involvement in six), Bulbar Weakness in seven patients, Impaired Voluntary Control in three and Impaired Automatic Control in three. Twelve patients received mechanical Respiratory support of whom seven have subsequently died.

The methods of support used were Intermittent Positive Pressure Ventilation (nine patients), iron lung (three), cuirass (two) and rocking bed (one). Six patients were maintained on Respiratory support until they died after intervals varying from 24 h to 6 yrs (mean 17.7 mths).

Five patients received temporary ventilation for between 6 d and 42 d: of these four remain alive at up to 4 yrs and one died after 16 yrs. One patient remains on domiciliary nasal Intermittent Positive Pressure Ventilation (IPPV) after 1 yr.

Objective
Although fatigue is a common debilitating complaint in Multiple Sclerosis (MS), its relationship to the CardioPulmonary exercise response has yet to be defined.

Design & Setting
A patient with MS manifested primarily by profound fatigue undergoes complete Pulmonary Function testing and a maximal incremental cycle ergometry study with gas exchange measurements and determination of ejection fractions. Outpatient, community hospital Pulmonary Function laboratory.

Results
The patient is found to have Respiratory Muscle Weakness and a severely depressed exercise performance.

The latter was associated with an early anaerobic threshold but a normal central CardioVascular response (Radionuclide Ventriculography), implying problems in peripheral O2 distribution/utilization.

The Respiratory Muscle involvement, although substantial, was nonlimiting to the exercise performance.

Conclusions
Despite its Central NeuroPathoPhysiology, MS as it relates to fatigue may be associated with an abnormal Peripheral exercise response, namely, problems in Peripheral O2 utilization.

Such a concept could prove invaluable as it would provide a physiological basis for defining the severity and therapy of "MS fatigue."

A Neurological surveillance was combined with prospective recording of Upper Respiratory and GastroIntestinal Infections and serological diagnosis of five common Viral Infections in 60 Benign Multiple Sclerosis patients, with a mean follow-up of 31 months.

During 4-week at risk (AR) periods encompassing common infections, a significant excess of MS relapses was found in the AR period, with a relative risk of 1.3. A seasonal variation of the MS relapse rate was found with a minimum in Summer.

There was a significant correlation between the number of AR relapses and the number of common infections per month explaining the periannual distribution of relapses. The non-AR relapses showed no seasonal variation.

There was a significant correlation between AdenoVirus CF titer rises associated with Upper Respiratory Infections and the occurrence of a major MS relapse in the AR period (n = 7), while Influenza Infections were not followed by a major MS relapse (n = 6).

Linear homologies have been demonstrated between AdenoVirus and Myelin Basic Protein. The Epidemiological approach is essential to our understanding of Systemic Antigen triggering Multiple Sclerosis activity.

We found significant disorders in Adherence (9.07% +/- 8.18% for patients versus 28.97% +/- 5.76% for controls); Chemotaxis (18.32 +/- 3.1 for patients versus 30.49 +/- 4.52 for controls); Phagocytosis (73.6 +/- 25.25 for patients versus 111.2 +/- 25.7 for controls); Bactericidal action (10.35% +/- 5% for patients versus 25.09% +/- 4.82% for controls).

All differences were significant (p 0.001). We confirmed the results by retesting 3 to 8 months later. The depressed PMNL functions in MS patients may explain their increased susceptibility to infections of the Respiratory, Digestive, and Urinary Tracts.

Exacerbations of Multiple Sclerosis (MS) are triggered by exogenous events, the best documented being Viral Upper Respiratory Infections (URIs), which can stimulate secretion of Cytokines such as Interferon-gamma (IFN-) by Immune Cells.

In conjunction with a recent clinical trial of systemic Interferon-beta (IFN-ß) in Relapsing/Remitting MS, we studied the occurrence of Viral Infections and their correlation with MS attacks.

Thirty patients kept daily logs, noting URI symptoms in themselves, family members, and co-workers. Patients were examined every 3 months, or whenever an attack of MS occurred, and were tested for AntiBodies to common Upper Respiratory Pathogens.

A strong correlation was found between MS attacks and URIs. There were 168 URIs in 2,792 patient-weeks, including 996 weeks at risk (the interval beginning 1 week before and ending 5 weeks after onset of URI symptoms) and 1,796 weeks not at risk.

Nearly two-thirds of attacks occurred in periods at risk. Attack rates were 2.92 per year in weeks at risk compared to 1.16 per year in weeks not at risk, a significant difference (p 0.001). High-dose Interferon reduced the frequency of MS attacks, but had no effect on the number of URIs.

Although a specific Virus could not be incriminated, we concluded that URIs of presumed Viral origin are an important trigger of MS attacks, and that treatment with IFN-ß reduces the attack rate, but not by preventing URIs.

Rather, it may modulate responses to Viral Infection that would otherwise lead to Immune activation and clinical symptoms.

Signs of Respiratory distress including coughing, choking, and gagging are not uncommon during oral feedings in patients with severe Dysphagia. Aspiration Pneumonia and Chronic Lung Disease are recognized complications.

Pulse Oximetry, Respiratory Inductance Plethysmography, and Nasal Airflow measurement by thermistors are accurate noninvasive methods of monitoring CardioPulmonary adaptation during oral feedings in patients with severe Dysphagia.

We report significant, previously unrecognized, acquired Hypoxemia during oral feedings in two patients with severe Cerebral Palsy and one with Multiple Sclerosis. The episodes of Hypoxemia occurred only while swallowing specific food textures.

Periods of Hypoxemia most probably resulted from aspiration during oral feedings. CardioPulmonary adaptation may prove to be an important consideration in decisions regarding the method and advisability of continued oral feedings in patients with severe Dysphagia.

The Gamma AminoButyric Acid (GABA)-B agonist, Baclofen, is a centrally-acting, Anti-Spasmodic agent and muscle relaxant used in Spinal Cord lesions, Multiple Sclerosis and other Neurological Disorders.

In a previous pilot study of quadriplegic patients, 75% of whom were treated with Baclofen, we found a high prevalence of sleep-disordered breathing.

Because of the depressant effects of GABA on the Central Nervous System, we hypothesized that Baclofen might aggravate sleep-disordered breathing in susceptible individuals by depressing Central Ventilatory Drive, increasing Upper Airway Obstruction and/or increasing the Arousal Threshold to Apnoea.

We therefore conducted a double-blind, placebo-controlled, cross-over study of Baclofen 25 mg, administered before sleep in 10 snorers with mild sleep-disordered breathing (Respiratory disturbance index 30 events per sleep hour).

Each subject underwent two standard PolysoMnographic assessments, one week apart. Total sleep time was significantly prolonged by Baclofen (placebo 356 +/- 9.9 SEM min; Baclofen 386 +/- 9.9 min).

Both NonRapid Eye Movement (REM) and REM sleep duration were increased (nonREM: placebo 295 +/- 6.8 min; Baclofen 311 +/- 8.9 min; REM: placebo 61 +/- 7.5 min; Baclofen 76 +/- 9.0 min). Time spent awake after sleep onset was reduced after Baclofen (placebo 71 +/- 10.3 min; Baclofen 51 +/- 9.7 min).

There was a slight reduction in mean overnight Oxygen saturation (placebo 95.2 +/- 0.5%; Baclofen 94.4 +/- 0.7%). The frequency of Apnoeas plus Hypopnoeas (Respiratory disturbance index (RDI)) did not change significantly (placebo 9 +/- 1.8 events.h-1; Baclofen 13 +/- 3.4 events.h-1)

Objectives

1. To determine the prevalence of Swallowing problems in MS patients
   • And its relation to the overall disability
2. To define the most frequent symptoms suggestive of Dysphagia
3. To describe the abnormalities on ManoFluoroScopy (MFS)

Methods
Three hundred and eight consecutive MS patients were asked whether they ever had Swallowing problems.

If so the questionnaire of the Johns Hopkins Swallowing Centre was applied to qualify the Dysphagia.

A MFS was performed in 30 patients with Dysphagia covering the entire spectrum of MS. Overall disability was assessed using the Expanded Disability Status Scale (EDSS).

Results
Seventy-three of our 309 patients had permanent Dysphagia (24%). Another 5% had a history of transitory Swallowing problems only.

Permanent Dysphagia started to be a problem in mildly impaired patients (EDSS 2-3). Prevalence increased together with rising disability to reach 65% in the most severely disabled subjects (EDSS 8-9).

Two alarming symptoms of patients with Swallowing problems, Coughing or Choking during the meal and a history of Pneumonia were present in 59%, respectively, 12% of these patients.

MFS showed deficiency of the Oral Phase in all patients, while only the patients with an EDSS higher than 7.5 showed abnormalities of the Pharyngeal Phase.

Conclusions
Permanent Dysphagia may already develop in mildly impaired MS patients but becomes a rather frequent finding in MS patients with moderate or severe disability.

MFS is a sensitive and useful ancillary examination. Important qualitative changes of the Pharyngeal Phase on MFS are seen in patients with an EDSS higher than 7.5.