THEME 2 RESPIRATORY AND NUTRITIONAL MANAGEMENT

P39 INITIAL RESULTS FROM THE HIGH FAT/HIGH CALORIE VERSUS OPTIMAL NUTRITION IN ALS CLINICAL TRIAL

Wills A^1,2

Hubbard J¹

Macklin E^1,2

Mahoney K¹

Grasso D¹

Soodoo N¹

Lisi J¹

Simpson E¹

Lawson R¹

Yu H¹

Cudkowicz M^1,2

^aMassachusetts General Hospital, Boston, MA, USA

^bHarvard Medical School, Boston, MA, USA

Email address for correspondence: [email protected]

Keywords: hyperalimentation, metabolism, diet

Background: Unintentional weight loss is a significant clinical problem in amyotrophic lateral sclerosis (ALS). Mild obesity is associated with improved survival in ALS in a dose-dependent manner. Animal studies have shown that diets high in fat calories increase median survival time of SOD1^G93A mice. We hypothesized that hyperalimentation might improve survival in ALS.

Objectives: The High Fat/High Calorie Diet versus Optimal Nutrition in ALS clinical trial (NCT00983983, funded by the Muscular Dystrophy Association), is a phase II, double-blind, placebo-controlled randomized clinical trial to study the safety, tolerability and feasibility of hyperalimentation using standard and high-fat diets. Secondary outcome measures include changes in body mass, body composition, respiratory function, disease progression, and survival.

Methods: Patients with ALS receiving percutaneous enteral nutrition were randomized 1:1:1 to 100% of caloric needs using Jevity 1.0 (control diet), 125% of caloric needs using Jevity 1.5 (high calorie diet), or 125% of caloric needs using Oxepa which contains 55% fat calories (high fat/high calorie diet) (all Abbott Laboratories, Abbott Park, IL) and followed for four months. Energy needs were estimated based upon the Measured Resting Energy Expenditure or participants’ current nutrition requirements, whichever was greater. Participants and evaluating investigators were blinded to treatment assignment. Primary endpoints included adverse events (AE) and compliance rates.

Results: A total of 28 participants were screened and 24 participants were enrolled between December 2009 and October 2012. Seven participants were randomized to the control diet, nine to the high calorie diet, and eight to the high fat/high calorie arms, although four participants (1, 1, and 2, respectively) withdrew after randomization but before starting study diet. Baseline demographics were similar among the three study arms. Four participants (3, 0, and 1, respectively) discontinued the study diet due to adverse events. Overall, the tolerability rate was 43% vs. 89% vs. 63%. There were four deaths during the study, all due to respiratory failure: 3 in the control, 0 in the high calorie, and 1 in the high fat/high calorie arm. No deaths were considered related to study diet. There were 42 AE and 9 SAE in the control, 24 AE and 0 SAE in the high calorie and 49 AE and 3 SAE in the high fat/high calorie group. The most common AE were gastrointestinal (71% vs. 44% vs. 63% of participants experiencing at least one AE) and most common SAE were pulmonary (43% vs. 0% vs. 25%).

Discussion: This is the first clinical trial conducted in ALS patients who require percutaneous enteral nutrition. The early results of this study demonstrate significant barriers to enrolment and a high frequency of pulmonary and gastrointestinal AE. Results of functional and other secondary outcome measures will also be presented.

P40 EFFECT OF BCAA SUPPLEMENTATION ENRICHED OF LEUCINE IN AMYOTROPHIC LATERAL SCLEROSIS PATIENTS

Bongioanni P

Corbianco S

Dini M

Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, NeuroCare onlus, Pisa, Italy

Email address for correspondence: [email protected]

Keywords: leucine, branched chain amino acids (BCAA), body mass index(BMI)

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease with high risk of malnutrition. Malnutrition itself can produce neuromuscular weakness and adversely affect patients’ quality of life, thereby creating a vicious circle. The nutritional status of ALS patients (PALS) can be assessed with dietary review and measurements of weight (w) and height (h): a Body Mass Index (BMI = w/h²) below 18.5–20 kg/m² indicates a state of malnutrition. Arm muscle area (AMA) and bioelectrical impedance analysis can assess body composition.

Objective: The purpose of this study was to evaluate the efficacy of Branched Chain Amino Acid (BCAA) supplementation on nutritional and functional parameters of PALS.

Method: A prospective randomized double-blind study was performed with 12 PALS, divided into two groups: the treatment group received BCAA supplementation (80 mg/kg bodyweight/day with ratio leucine/isoleucine/valine of 6/1/1), whereas the control group received placebo. They underwent prospective nutritional and functional assessment for 12 months. All measurements were taken before (baseline), every 4 months (mid-points) and at the end of the trial (end-point).

Results: Patients in the treatment group showed weight gain, increased BMI, and increased AMA. In the control group, biochemical parameters did not change. The other blood biomarkers did not show any significant change throughout the trial.

Discussion and conclusion: This pilot study indicates that leucine could be proposed as a promising pharmaconutrient in the prevention and treatment of sarcopenia, and the BCAA supplementation may be useful in the nutritional therapy of PALS.

P41 PROSPECTIVE STUDY OF HYDRATION STATUS IN ALS PATIENTS

Tandan R¹

Bromberg M²

Kasarskis E³

Mitsumoto H⁴

Simmons Z⁵

Matthews D¹

^cUniversity of Vermont College of Medicine, Burlington, VT, USA

^dUniversity of Utah, Salt Lake City, USA

^eUniversity of Kentucky, Lexington, USA

^fColumbia University, New York, USA

^gPennsylvania State UNiversity, Hershey, USA

Email address for correspondence: [email protected]

Keywords: hydration, water turnover, survival

Background: Dehydration is of concern in ALS and is frequently overlooked (1). Suboptimal hydration predisposes to enhanced morbidity and possibly mortality. The Center for Medicare and Medicaid Services (CMS) has benchmarks for assessing dehydration in elderly.

Objectives: Compare water turnover and total body water (TBW) in ALS patients and healthy controls using labeled water (LW) (2,3); Identify at-risk patients for dehydration Validate water intake predicted from published CMS equations (4,5) against LW.

Methods: Five centers participated in study in definite or probable ALS. Parameters were examined at baseline and every 4 months for 12 months. Paired t-test and Pearson correlation analyzed TBW in patients and controls; t-test compared risk of abnormal water turnover from known prognostic variables in ALS. Absolute and percentage differences in water intake between LW and predictive CMS equations were compared using paired t-test. Significance at p < 0.05 was accepted.

Results: Fifty-seven patients revealed at baseline: males 60%; bulbar-onset 33.3%; mean (± SD) age 59.5 ± 12.0 years; disease duration 24.3 ± 16.2 months; BMI 27.3 ± 4.7 kg/m; ALSFRS-R 35.2 ± 5.7; and FVC 75.2 ± 16.2%. Patients showed significantly different values, as follows (normal controls vs. ALS): BMI 25.7 ± 3.8 vs. 27.5 ± 4.6; fat-free mass 49.6 ± 12.3 vs. 47.2 ± 10.9 (kg); TBW 36.3 ± 8.9 vs. 34.4 ± 7.9 L; and water turnover 3.04 ± 0.66 vs. 2.75 ± 0.85 L. Water turnover was significantly lower in females, bulbar-onset patients, and in those with lower BMI and FVC, the predicted intake of water ranged from − 12.9% to + 36.3%. Data on longitudinal changes in hydration status and effects on disease progression and survival will be presented.

Discussion and conclusion: By LW, water turnover and TBW are 10% and 6% lower in ALS patients than in matched controls. About 20% of patients show decreased water turnover. Females, bulbar-onset patients, and those with lower BMI, ALSFRS and FVC are at-risk for dehydration. Published equations in normal controls inaccurately predict water requirement in ALS patients.

Acknowledgements

Research support from NIH grant RO1 NS045087, NIH GCRC grants MO1-RR00109, RR02602, RR00645, RR10732, CO6-RR016499; the Cynthia Shaw Crispen Endowment; ALS Hope Foundation; and ALS patients and families.

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P42 PERFORMANCE OF NUTRITION TEAM SPECIALIZED IN TREATMENT OF PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS-ALS

Stanich P

Salvioni CCS

Almeida CS

Gomes M

Teixeira EZ

Bassolli L

Oliveira ASB

University Federal of Sao Paulo, São Paulo/ São Paulo, Brazil

Email address for correspondence: [email protected]

Keywords: enteral nutrition, body mass index, nutritional status

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by a loss of motor neurons in the cerebral cortex, brainstem and spinal cord, leading to skeletal muscle atrophy, paralysis and death. The clinical onset can be bulbar, affecting swallowing and phonation, or spinal, presenting as skeletal muscle atrophy. Dysphagia is a condition that leads to decreased food intake and body mass, malnutrition and dehydration. Weight and muscle loss are related to the disease progression. For this reason, some therapeutic measures are adopted in order to minimize this impact as the systematic nutritional monitoring.

Objective: To present clinical and nutritional conditions of the patients accompanied by experts in nutrition in ALS.

Methods: There were 28 patients evaluated: 23 (82%) had appendicular involvement, 10 (43.5%) women and 13 (56.5%) men; 5 (18.0%) had bulbar involvement, three (60%) women and two (40%) men. The nutrition evaluation included: anamnesis, assessing the appetite and food consistency, meal frequency, dysphagia, nutritional status, intestinal function and functionality scale (ALSFRS-R). The assessments were conducted by a dietitian team of the Neuromuscular Disease Research Department of University Federal of São Paulo.

Results: Co-morbidity was observed in 10 (36%) patients; seven (70%) had hypertension and three (30%) diabetes mellitus. The average duration of the disease was 68 months (6–264). The appendicular involvement, 14 patients (50%) with initial commitment of upper limbs, nine (32%) with lower commitment and five (18%) bulbar involvement. Dysphagia was observed in 83% of patients. As NIV, 14 (50%) of patients hadn’t indicated. As appetite, reduction was observed in 43%, increased in 14% and no changes in 43% of patients. Consistency modification diet was found in 12 (56%) patients, to pasty or liquid diet. The exclusion of oral diet was found in four (14%) patients. Only five (18%) patients had the proper diet, fractionation with 3 hours range. Constipation was present in the majority (75%). An alternative way of feeding was found in 43% of cases, with the majority (72%) with GEP. The average BMI was 22.7 Kg/m² (16–29) and the average ALSFRS score of 15 (10–42).

Discussion: The change of nutritional status in ALS is a multifactorial cause. Factors such as presence of co-morbidities, eating habits (mainly the choice of food and nutritional status) and prior to onset of disease. The form of manifestation of the disease and the intensity of the symptoms are also factors that may influence on the nutritional development.

Conclusions: Nutritional monitoring carried out by expert team can ensure the monitoring of factors that contribute negatively to nutritional status and that can accelerate the evolution of disease.

P43 GASTROSTOMY USE IN MND: FACTORS INFLUENCING DECISIONS, CHALLENGES AND BENEFITS FROM THE PERSPECTIVE OF PATIENTS AND THEIR INFORMAL CARERS

Stavroulakis T¹

Baird W²

Baxter S²

Walsh T¹

Shaw PJ¹

Mcdermott C¹

^hSheffield Institute for Translational Neuroscience (SITraN)

ⁱSchool of Health and Related Research (ScHARR); The University of Sheffield, Sheffield, UK

Email address for correspondence: [email protected]

Keywords: gastrostomy, timing, impact

Background: Gastrostomy feeding is commonly used to support MND patients with severe dysphagia. The effect of gastrostomy on quality of life for patients with MND is uncertain. Furthermore, there is a paucity of MND literature describing patient and carer experiences in relation to decision-making processes about the timing of gastrostomy insertion; as well as self-perceived benefits and challenges following gastrostomy.

Objectives: To explore the experience of patients with MND, and their informal carers, regarding gastrostomy insertion including the factors influencing gastrostomy timing and the impact of gastrostomy feeding on everyday life.

Methods: Qualitative, in-depth, semi-structured interviews with patients, and carers, were carried out to explore and elicit the perceptions of patients, and their carers in relation to gastrostomy timing and the impact of gastrostomy on their lives.

Results: Ten patients and eight informal carers took part in the study. Factors such as prolonged meals, the task of food preparation, chocking/aspiration and weight loss acted as triggers for undergoing a gastrostomy. Reluctance to give up oral feeding, not realising the potential benefits and negative perceptions of gastrostomy influenced a decision to delay the procedure. Initial gastrostomy education at hospital was limited, non-structured and opportunistic. Home-based education was more comprehensive but on occasions difficult depending on individual patient needs and the geographical area in which participants lived. In addition, clinical complications, practical issues, time restrictions imposed by strict feeding regimes and the loss of the ability to share a meal, detrimentally influenced psychosocial quality of life. However, the establishment of a safe alternative route for feeding and medication and the reduced worry over difficult meals and weight loss positively influenced quality of life.

Discussion: From a clinical perspective, offering early gastrostomy insertion to patients presents a number of potential benefits. However, this advice does not outweigh the personal perceptions and psychosocial factors for patients. It is important that clinicians are aware that a broad range of factors may act as barriers to timing-related decision-making and that due to the nature of the disease patients may require a greater amount of direction from health professionals. Once a decision to undergo gastrostomy has been made, information provision prior to insertion is important in reassuring patients and reducing their anxiety. In addition, it is essential that patients and carers are adequately trained before being sent back home regardless of the help support that follows up in the community. Continuous support is the key in the transition from oral to gastrostomy feeding.

Conclusions: Understanding the factors which influence decision-making as well as the challenges and benefits of gastrostomy for patients and their carers is important for information and care provision by health care professionals.

P44 ANALYSIS OF PREDICTIVE FACTORS FOR SURVIVAL PROGNOSIS AT THE TIME OF PERCUTANEOUS ENDOSCOPIC GASTROSTOMY IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

Bokuda K¹

Shimizu T¹

Imamura K²

Kawata A¹

Nakano I¹

^jDepartment of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan

^kDepartment of Surgery, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan

Email address for correspondence: [email protected]

Keywords: percutaneous endoscopic gastrostomy, survival prognosis, arterial carbon dioxide pressure

Background: Malnutrition is an independent prognostic factor for survival in patients with amyotrophic lateral sclerosis (ALS), and percutaneous endoscopic gastrostomy (PEG) in an early stage has been recommended. However, evidence for optimal timing of PEG has not been established.

Objective: To analyze predictive factors for survival periods after the time of PEG and to search optimal timing of PEG in patients with ALS.

Methods: In total, 105 consecutive patients with sporadic ALS who underwent PEG in our hospital were analyzed (47 men and 58 women; mean age at PEG 70 years, range: 32–90 years). We analyzed effects of clinical parameters on survival periods after PEG to endpoints for follow-up, using Kaplan–Meier survival analysis method and log-rank test. The endpoints were defined as death or ventilator use. The analyzed factors were sex; age at onset (≥ 65 or < 65 years); onset region (bulbar or spinal); forced vital capacity (% FVC); arterial carbon dioxide pressure (PCO₂); body mass index (BMI); and ALS-functional rating scale (ALSFRS) at the time of PEG. Thereafter, univariate and multivariate analyses for survival periods were performed using the Cox proportional hazard model.

Results: The log-rank test showed significant effects of PCO₂ (> 40 mmHg, p = 0.0052), %FVC (< 38%, p = 0.0018), onset region (spinal onset, p = 0.0135) on the survival periods after the time of PEG. The bulbar-onset group showed a better prognosis after the time of PEG than the spinal-onset group, although the time of PEG was earlier in the bulbar onset than the spinal onset. The analyses of correlation between clinical parameters and survival periods after PEG showed a significant correlation for PCO₂ (Spearman’s rank correlation test, p = 0.0039) and non-significant weak correlation for %FVC (p = 0.0563) and BMI (p = 0.0665). Multivariate analysis by the Cox proportional hazard model, when including the parameters of sex, onset age, onset region, BMI (≥ 18.5 or < 18.5) and PCO₂ (< 40 mmHg or ≥ 40 mmHg), showed statistically significant effects of the onset region (spinal onset) and PCO₂ (≥ 40 mmHg) on survival length after PEG.

Conclusions: PEG is recommended at an early stage of ALS at least before arterial carbon dioxide begins to accumulate. Bulbar onset may predict better survival prognosis after the time of PEG than spinal onset, which may indicate that PEG should be introduced earlier in spinal onset patients than bulbar onset ones when PCO₂ begins to be elevated from normal stable levels for individual patients. BMI itself may not predict post-PEG survival prognosis. Constant evaluation of PCO₂ is recommended as well as %FVC and BMI, particularly at stages of malnutrition and respiratory deterioration.

P45 DAILY ENERGY EXPENDITURE ASSESSED BY DOUBLY LABELED WATER METHOD IN JAPANESE PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

Shimizu T¹

Ishikawa-Takata K²

Nagaoka U¹

Ichihara N³

Ishida C⁴

Nobukuni K⁵

Nakano I¹

Nishizawa M⁶

^lTokyo Metropolitan Neurological Hospital, Tokyo, Japan

^mNational Institute of Health and Nutrition, Tokyo, Japan

ⁿNational Hospital Organization Takamatsu Medical Center, Takamatsu, Japan

^oNational Hospital Organization Iou Hospital, Kanazawa, Japan

^pNational Hospital Organization Minami-Okayama Medical Center, Okayama, Japan

^qNiigata University Brain Research Institute, Niigata, Japan

Email address for correspondence: [email protected]

Keywords:malnutrition, total energy expenditure, doubly-labeled water

Background: Malnutrition is an independent prognostic factor for survival in patients with amyotrophic lateral sclerosis (ALS), and disease-specific hypermetabolism has been thought to underlie the malnutrition. To prevent progressive weight loss, percutaneous endoscopic gastrostomy (PEG) and nutritional intervention at early stage is recommended. However, precise amount of daily energy intake has not been established particularly in Asian patients with ALS.

Objective: To clarify the amount of daily energy expenditure in Japanese patients with ALS in various stages.

Methods: Seventeen patients with sporadic ALS were enrolled in the study (four men and 13 women, mean age: 67 years, range 46–78 years). Three patients were receiving non-invasive positive pressure ventilation (NPPV). Six patients had PEG at the time of examination, and 5 of 6 were receiving only enteral feeding through PEG. No patients underwent tracheostomy. Total energy expenditure (TEE) was measured using the doubly labeled water (DLW) method. Patients were given a dose of 0.14 g of ¹⁸O and 0.06 g of ²H per kg body weight orally or through PEG catheter. Urine was collected before and after administration of DLW for 14 days (a total of eight samples). We measured isotope ratio of urine ¹⁸O and ²H, and the carbon dioxide production rate was calculated. TEE (kcal/day) was calculated using modified Weir's formula.

Results: The mean body mass index (BMI) was 19.4 kg/cm² (range: 14.0–24.3), and the mean free fat mass (FFM) was 31.1 kg (range 20.1–46.8). The mean TEE was 1532.7 kcal/day (range: 897.9–2195.1), and the mean TEE per body weight (TEE/BW) was 32.9 kcal/kg/day (range: 25.7–41.5). There was a significant correlation between BMI and TEE (Spearman's rank correlation test, p < 0.05). The activity index for the patients was 1.1–1.3. TEE/BW in the patients was higher than standard values of TEE/BW in healthy Japanese subjects when the activity index was estimated as 1.2. (Standard resting energy expenditure in Japanese healthy subjects older than 50 years was reported as 21.5 kcal/kg/day in man and 20.7 in women.) TEE/BW in the patients was not significantly correlated with ALS functional rating scale and disease duration. In addition, TEE/BW was higher than calculated TEE/BW using Harris-Benedict formula.

Conclusions: Japanese ALS patients also showed increased energy consumption regardless the stages of disease. Before tracheostomy, ALS patients show constantly high energy expenditure, which might be attributed to multiple factors: disease specific hypermetabolism, increased respiratory muscle effort, and elevated sympathetic tone. Exact daily necessary energy amount should be established in the future in each stage and in each nutritional or respiratory state.

P46 EFFECTS OF COUGH AUGMENTATION ON PULMONARY MORBIDITY, SURVIVAL AND QUALITY OF LIFE IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS IN RESPIRATORY FAILURE: A RANDOMISED CONTROLLED TRIAL

Rafiq M¹

Bradburn M²

Proctor A¹

Billings C³

Bianchi S³

Mcdermott C¹

Shaw PJ¹

^rSheffield institute of translational neuroscience

^sClinical Trials Research Unit, School of Health and Related Research (ScHARR); University of Sheffield, Sheffield, Sheffield, UK

^tDepartment of Respiratory Medicine Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

Email address for correspondence: [email protected]

Keywords:cough augmentation, mechanical in-exsufflator, breath-stacking

Background: A major problem faced by patients with amyotrophic lateral sclerosis (ALS) is inability to cough effectively and remove secretions from the airways. In the absence of robust evidence, there is no clear consensus about how best to help these patients. In this randomised trial, we evaluated two cough augmentation techniques, that is, mechanical insufflator/exsufflator (MI-E) versus manual insufflator (breath-stacking technique).

Objectives: To assess the effect of cough augmentation on pulmonary morbidity, quality of life and survival in amyotrophic lateral sclerosis.

Methods: A total of 40 eligible patients were randomised to breath-stacking technique (n = 21) or MI-E (n = 19) and followed-up at three monthly intervals for at least 12 months or until death. All patients were diagnosed with respiratory failure and offered non-invasive ventilation (NIV). The primary outcome measure was number of days with symptoms of chest infection, treated with antibiotics, in the community or in the hospital. Survival and quality of life benefit, assessed by short form 36 mental component summary (MCS) and sleep apnoea quality of life index symptoms domain (sym), are the secondary outcome measures. For survival analysis, data of 20 eligible patients (matched for prognostic variables), offered NIV from the end of recruitment to the interventional arms, were also included.

Results: There were 13 episodes of chest infection in breath-stacking group and 19 episodes in MI-E group (p = 0.87), requiring 90 and 95 days of antibiotics, respectively (p = 0.85). There were six episodes of hospitalizations in each group (p = 0.87). Median survival in breath-stacking group was 535 days, 266 days in MI-E group and 244 days in the control group (p = 0.54). MCS was maintained above 75% of baseline for a median of 329 days in breath-stacking group and 205 days in MI-E group (p = 0.41).

Discussion and conclusion: In ALS patients with respiratory failure, cough augmentation improves survival and maintains quality of life. The survival benefit is superior to the benefit offered by NIV alone. Although episodes of chest infections were fewer in breath-stacking group, duration of antibiotics use and chance of hospitalization in the event of a chest infection was less in MI-E group. The study, although limited in terms of sample size, offers insightful information and supports routine domiciliary use of breath-stacking in patients with ALS requiring respiratory support. MI-E may be useful in a hospital setting, reducing the course of antibiotics and length of stay, in the event of a chest infection.

P47 THE RELATION BETWEEN THE PEAK COUGH FLOW AND THE FUNCTIONAL ORAL INTAKE SCALE ASSOCIATED WITH THE FUNCTIONALITY IN PATIENTS DIAGNOSED WITH MOTOR NEURONE DISEASES

Oda AL

Alves PCL

Sierra HNM

Silva R

Vecina ALC

Brunoro ACV

Stanich P

Oliveira ASB

Federal University of São Paulo, São Paulo/SP, Brazil

Email address for correspondence: [email protected]

Keywords: deglutition disorders, cough, deglutition

Background: Dysphagia is a common symptom of Motor Neurone Diseases (MND). There are two important factors that add to the occurrence of difficulty in swallowing: the weakness of oropharyngeal muscle and changes in the respiratory mechanics. The cough is a very important defensive mechanism used for airway protection which can minimize respiratory problems that are secondary to the difficulty in swallowing.

Objective: To analyze the relation between the peak cough flow and the functional oral intake scale associated with its functionality in patients diagnosed with MND.

Methods: There were 37 patients evaluated, 24 (64.8%) had amyotrophic lateral sclerosis (ALS) – 15 (62.5%) women and nine (37.5%) men – and 13 (35.2%) had progressive bulbar paralysis (PBP) – five (38.4%) women and eight (61.6%) men. The swallowing evaluation included anamnesis, with further examination of feeding adjustments made by patients: oral and pharyngeal phase of swallowing; functional oral intake scale (FOIS); peak cough flow (PCF); functionality scale (ALSFRS-R). The assessments were conducted by a swallowing therapist team of the Neuromuscular Disease Research Department of University Federal of São Paulo.

Results: Changes in oral phase happened in 16 ALS patients (66.67%) and 13 PBP patients (100%); changes during pharyngeal phase in 16 ALS patients (66.67%) and 13 PBP patients (100%). Every patient that showed some change in swallowing, some in oral phase and others in pharyngeal phase had to make some adjustment in food consistency in their daily meals. Patients that used an alternative way of feeding presented numbers of PCF below 115 litres/minute (l/min), while patients that used different types of food consistencies (Level 5–7 of FOIS scale) showed PCF above 230 l/min in ALS and PBP. Patients with ALS presented PCF below 100 l/min scored 1.4; 3.4; 6.2 and 11 in matters related to bulbar signs, appendicular and respiratory and the total functionality scale, respectively; from 100 to 200 l/min, 6.82; 7.09; 8.18 and 22.09; above 200 l/min, 9.75; 12.86; 11.14 and 33.71. PPB patients that presented PCF below 100 l/min scored 3; 13.3; 7.3 and 23.67 in matters related to bulbar signs, appendicular and respiratory and the total functionality scale, respectively; from 100 to 200 l/min, 4; 16.5; 9.5 and 30; above 200 l/min, 7.2; 16.2; 10.4 and 33.8.

Discussion: Changes in the oral and pharyngeal phase of swallowing can compromise the patient's nutrition and hydration, by reducing oral intake and they can also compromise the respiratory function, because of the bronchoaspiration. Feeding adjustments combined with an efficient cough can minimize complications secondary to dysphagia.

Conclusions: There was a match between the adjustments in the food consistencies with the swallowing difficulties and with the PCF measures associated with the functionality scale (ALSFRS-R) both general and specific.

P48 THE BALLOON – BASED MANOMETRY: EVALUATION OF SWALLOWING IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

Tomik J¹

Tomik B²

Gajec S¹

Skladzien J¹

Wiatr M¹

Strek P¹

Oles K¹

^uENT Department Medical College Jagiellonian University, Krakow, Poland

^vDepartment of Neurology2 Jagiellonian University, Medical College, Krakow, Poland

Email address for correspondence: [email protected]

Keywords: swallowing, balloon-based manometry

Background: Patients with bulbar onset present firstly with speech disorders, swallowing problems and dysphonia. The swallowing problems in ALS patients are frequently estimated using manometric parameters.

Objective: The aim of the study was to analyse the disturbances of the oro-pharyngeal swallowing phase of dysphagia in ALS patients by the using balloon-based manometry.

Material and methods: Thirty-six ALS patients were diagnosed in the Department of Neurology. There were 21 male (58.3%) and 15 female (41.7%) patients, aged between 26 and 78 (mean: 59.9 ± 11.4 years). Complete manometric examinations were performed thrice: at the start point of the research, and then 6 and 12 months later.

Manometric examinations of oral and pharyngeal part of gastrointestinal tract were carried out by using the esophageal ballon-based method with four balloon transducers located 5 cm away from each other, according to the procedure described in the literature. The transducers measured the changes of the pressure on the base of the tongue, the hypopharynx and the entrance to the larynx, the upper esophageal sphincter (UES) and the esophageal body. The following manometric parameters were analysed: the maximal contractions of the base of tongue (CBT) and the UES resting preasure (RP); hypopharyngeal suction pump (HSP); oropharyngeal, pharyngeal and hypopharyngeal transit time (OTT, PTT, and HTT, respectively); and velocity for bolus. The manometric examination was carried out with the use of Polygraf ID. The results were recorded in a database installed in a computer working on Polygram 98/Polygram Net.

Results: Significant weakness of CBT (p = 0.007), decrease of HSP (p = 0.006) and decrease of velocity of bolus transit (p = 0.001) were particularly marked between the first and the third examination.

Discussion: On the basis of the manometric examinations, disturbances of contraction of the base of the tongue, hypopharyngeal suction pump and pharyngeal transit time were shown in bulbar onset ALS patients. The results obtained from manometric examinations confirm progression of swallowing disorders.

Conclusion: The balloon-based manometry examination is useful in the estimation of disturbances with swallowing in ALS patients.

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P49 COORDINATION OF SWALLOWING AND BREATHING IN PATIENT WITH AMYOTROPHIC LATERAL SCLEROSIS

Bianchi F¹

Lunetta C²

Corbo M²

Mora G¹

Ginocchio D^1,2

^wSalvatore Maugeri Foundation, IRCCS, Milan, Italy

^xNEuroMuscolar Omnicentre, Serena ONLUS Foundation, Milan, Italy

Email address for correspondence: [email protected]

Keywords: dysphagia, swallowing, breathing

Background: The coordination of swallowing and breathing is essential to the prevention of pulmonary aspiration. Among the diseases that can cause an alteration of this fine coordination mechanism there are numerous neurological diseases, including amyotrophic lateral sclerosis (ALS).

Objectives: The aim of the study is to analyze the coordination of swallowing and breathing in ALS patients.

Methods: Combined Fiberoptic Endoscopic Evaluation of Swallowing, respiratory phase and submental surface EMG recordings were analyzed in 13 patients with ALS. The following swallow tasks were considered: spontaneous swallow during a 5 minutes recording with and without endoscopic control and five voluntary dry swallows; single as well as sequential deglutition with thin liquid (5, 10, and 50 ml) and semisolid bolus (5 and 10 ml). For each swallow, offline from the digitized recordings, the following variables were measured: (1) duration of the sustained swallowing apnea; (2) numbers of swallows/bolus; (3) respiratory phases surrounding each swallow. Patients were divided into those who had a “safe” swallow and those with an “unsafe” swallow, according to the grade obtained in the Penetration Aspiration Scale (PAS) and in the Dysphagia Outcome and Severity Scale (DOSS). Respiratory parameters were collected. Mann–Whitney and Spearman nonparametric tests were used for statistical analysis.

Discussion and results: No difference was found in apnea duration and number of swallows measured with endoscopic control and those measured without it (p = 0.281). A total of 644 swallows with either thin liquid or semisolid were analyzed. In 50.1% of the patients, the deglutition was followed by the expiration phase. Percentage of inspiration-deglutition-inspiration pattern depended on viscosity and decreased with semisolid bolus. The average of swallowing apnea duration was 1.7 seconds. This time lapse depended on swallowing task, bolus viscosity and size. The average ratio of swallow/bolus was 2.06. This ratio doubled in patients with an “unsafe” swallow and depended on bolus viscosity and size. A strong correlation between SpO2 and swallowing apnea duration on Spearman test was found (r = 0.8). No correlation between swallowing apnea duration and swallows/bolus ratio was found.

Conclusions: Many parameters describing coordination of swallowing and breathing in patient with ALS are modified compared with the same data found in the literature on healthy adults. Therefore the planning of speech and language treatment should include strategies to improve the coordination between swallowing and breathing in order to reduce the risk of pulmonary aspiration.

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P50 CORRELATION AMONG FORCED VITAL CAPACITY, RESTING ENERGY EXPENDITURE AND SEGMENTAL TRUNK BIOELECTRICAL IMPEDANCE ANALYSIS IN ALS PATIENTS FOR PREDICTING CLINICAL DISEASE PROGRESSION: A PRELIMINARY STUDY

Bongioanni P^1,2

Dini M^1,2

Corbianco S¹

Ciccarese R²

^yAzienda Ospedaliero-Universitaria Pisana, Pisa, Italy

^zNeuroCare onlus, Pisa, Italy

Email address for correspondence: [email protected]

Keywords: Forced Vital Capacity (FVC), segmental trunk Bioelectric Impedance Analysis (stBIA), Resting Energy Expenditure (REE)

Background: The typical ALS disease course is characterized by progressive irreversible muscle wasting of the limbs, torso, abdomen, and oropharyngeal muscle regions, and often a decline in nutritional status that is inadequately addressed in clinical practice, even though it is a significant and independent prognostic factor for survival.

Objective: To clarify if Resting Energy Expenditure (REE), Forced Vital Capacity (FVC) and segmental trunk Bioelectrical Impedance Analysis (stBIA) are correlated with clinical disease progression in ALS patients (PALS).

Methods: In 12 patients (mean age ± SD: 52.1 ± 11.5 yrs; 7 males and 5 females) with definite ALS, neurologic deficit was quantified by manual muscular testing of all extremities and the neck, as defined by the Medical Research Council. All patients were stable in pharmacological medication (50 mg riluzole twice a day); no patient received any steroid drug treatment. FVC was measured with a pneumotachograph system (Medical Graphics, St Paul): findings were expressed in relation to a theoretical calculated index value. Indirect calorimetry was performed with a VO2000 (Medical Graphics, St Paul) that was calibrated each morning before the measurements were made (1): measurements were accepted if the results were at a stable plateau for 20 min or more. The measured REE (mREE) was compared with REE obtained from a control population volunteers and with REE calculated (cREE) by using the Harris–Benedict equations. In stBIA (50 kHz) the four source electrodes and the combination of eight detecting electrodes used in this study allowed separation of the trunk into five parts, the Z of each part could then be determined (2). All PALS were tested every 4 months: in such a preliminary work a period of 24 months has been analyzed.

Results: mREE/cREE and mREE data appeared to remain stable. FVC was not associated with mREE, but with stBIA: in fact, both FVC and stBIA significantly decreased according to the PALS clinical worsening.

Conclusion: Data analysis suggests a significant (p < 0.01) correlation (0.96) among FVC, stBIA and clinical disease progression.

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P51 RESPIRATORY IMPAIRMENT IN PATIENTS WITH MOTOR NEURON DISEASE: REFERRAL PROCESS AND FIRST ASSESSMENT AT A HOME VENTILATION SERVICE IN THE NETHERLANDS

Raaphorst J¹

Tuijp J^1,2

Verweij L²

Westermann E²

van der Kooi A¹

Gaytant M²

van den Berg LH³

de Visser M¹

Kampelmacher M²

^aaDepartment of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

^abCenter for Home Mechanical Ventilation, University Medical Center Utrecht, Utrecht, The Netherlands

^acRudolf Magnus Institute of Neuroscience, Department of Neurology, Utrecht, The Netherlands

Email address for correspondence: [email protected]

Keywords: ventilation, referral, ventilation

Background: In order to further improve the care for Dutch patients with motor neuron disease, we assessed the first evaluation at a large ventilation clinic in the Netherlands.

Objective: (i) To determine what proportion of patients with motor neuron disease would benefit from earlier referral and (ii) to examine the patient preferences regarding ventilatory support.

Methods: Observational study at a single centre with a catchment area of 7.6 million inhabitants. Data on disease status, the referral process and patients’ preferences regarding ventilatory support were collected during the first home ventilation service (HVS) assessment and analysed for correlation with the presence of daytime hypercapnia and suspected nocturnal hypoventilation. The latter conditions require immediate (within 48 h) or subacute (within 3 weeks) initiation of ventilatory support.

Results: Vital capacity (in percentage of predicted value, VC % pred) was assessed by referring physicians in 84% of the 217 referred patients; the mean VC % pred was 69% (SD 16). One-hundred and ninety-one patients attended the first HVS assessment without ventilatory support, at a median of 21 days following referral: 18% had respiratory failure (daytime hypercapnia); 19% had normocapnia but were suspected of nocturnal hypoventilation; 63% had normocapnia without symptoms. Following the HVS assessment, 25 patients (13%) declined home mechanical ventilation; this occurred more often in patients with (14/70) compared with patients without respiratory impairment (11/121; p < 0.05).

Discussion and conclusion: A meaningful proportion of patients who desire ventilatory support are referred to a ventilation clinic after already developing respiratory failure. Future studies could examine means, including more sensitive respiratory measures, to detect those patients who could benefit from earlier referral.

P52 RESPIRATORY ASSISTIVE CARE APPLIED TO HYPOVENTILATION WITHOUT SIGNIFICANT DIAPHRAGMATIC DYSFUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS

Yamauchi R^1,3

Imai T²

Tsuda E¹

Yamamoto D¹

Hozuki T³

Shimohama S¹

^adSapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan

^aeSapporo Medical University School of Health Science, Sapporo, Hokkaido, Japan

^afSapporo Shirakabadai Hospital, Sapporo, Hokkaido, Japan

Email address for correspondence: [email protected]

Keywords: respiratory impairment, phrenic nerve motor response, respiratory function tests

Background: It has been reported that diaphragm compound muscle action potential (DCMAP) could be a potential indicator of respiratory impairment in ALS. However, we have experienced some ALS patients without correlation between DCMAPs and the other biomarkers such as % forced expiratory vital capacity (%FVC) and sniff nasal- inspiratory pressure (SNIP) in accordance with the respiratory dysfunction.

Objectives: We performed a longitudinal study to elucidate correlations between respiratory impairment and respiratory biomarkers including DCMAPs at the initiation of respiratory assistive care in ALS.

Methods: We enrolled 42 ALS patients from October 2006 to December 2011, and performed the follow-up study until March 2013 except for the death. All patients were assessed at least thrice approximately every 6 months. Additional assessments were performed when the respiratory assistive care was given to the patient with respiratory insufficiency according to the guidelines. Each assessment included full neurological examinations, application of the ALSFRS-R, phrenic nerve conduction study, respiratory function tests and nocturnal pulsed oximetry. The statistical analysis was performed using the Mann–Whitney U-test, Wilcoxon matched-pairs signed-ranks test and chi-squared test.

Results: The patients were divided into three groups according to the timing of respiratory assistive care such as non- invasive ventilation (NIV) or tracheostomy. Eleven patients initiated the respiratory care while DCMAP remained above 0.2 mV in group A. Eleven patients initiated it when DCMAP decreased below 0.2 mV in group B. Twenty patients received no respiratory care in the observation periods. There was no significant change of the onset age, the disease duration, ALSFRS-R, %FVC and SNIP between group A and B. Group A had a higher incidence of bulbar signs and positive plantar responses compared with those of group B. The mean DCMAP was significantly higher in group A than in group B at the initiation of respiratory assistive care. The deterioration of respiratory parameters had a linear correlation with the decrease of DCMAPs according to the progression of hypoventilation in group B. However, group A showed no significant change of DCMAP during the observation periods despite the progression of hypoventilation.

Discussion and conclusion: The respiratory impairment with preserved DCMAPs was seen in some ALS patients, especially in the patients with bulbar involvement and/or marked pyramidal signs. We should note the respiratory failure without significant diaphragmatic dysfunction in ALS.

P53 NON-TERMINAL WEANING FROM INVASIVE VENTILATION IN ALS/MND

Ratner E^1,2

Aaron T¹

Bateman A¹

^agMinneapolis VA Medical Center, Minneapolis, MN, USA

^ahUniversity of Minnesota, Minneapolis, MN, USA

Email address for correspondence: [email protected]

Keywords: ventilation, quality of life, weaning

Background: Decisions about use of non-invasive and invasive ventilatory support are among the most challenging for patients and families facing ALS (1). The medical literature on ventilator use in ALS via tracheostomy offers descriptions of its feasibility, including in the home setting, and patterns of withdrawal (2,3). It is generally presumed that invasive ventilator support will be continuous and permanent.

Objectives: To describe successful weaning from invasive ventilation in ALS.

Methods: Chart review of cases diagnosed with ALS who had patient-requested weaning of ventilator use via tracheostomy, not associated with an end-of-life care plan, at one U.S. Veterans Administration ALS program, from April 2012 to March 2013.

Case report: Four cases were identified. Case 1: 64-year old (y.o.) presented with respiratory failure, weaned from continuous to nocturnal ventilation 190 days after tracheostomy. The patient continues to live at home, ambulatory. Case 2: 67 y.o. presented with respiratory failure. Began weaning 4 days after tracheostomy and completely withdrew ventilator over several months and returned home. The patient was later re-diagnosed with Guillain–Barre instead. Case 3: 45 y.o. presented with weakness received tracheostomy 4 years later. One year after having nocturnal ventilation in a nursing facility far from home, he was weaned completely and returned to nursing facility near family. Case 4: 67 y.o. presented with weakness, received tracheostomy 2 years later. The patient was weaned to nocturnal ventilation only 7 days later and lives in a nursing facility.

Discussion: In a variety of circumstances, patients with ALS already on invasive ventilation can be weaned from substantially or completely. This can occur in the days after tracheostomy or even many months later. Without consideration of future weaning, a patient with ALS in respiratory failure may consider death preferable to long-term ventilation. Our experience with two cases presenting with respiratory failure are contrary to prior case series suggesting dire outcomes (4). Quality of life was significantly improved with opportunities to be off mechanical ventilation.

Conclusions: Despite progression of disease in ALS, initiation of invasive mechanical ventilation via a tracheostomy may be later followed by successful weaning, to permit increased mobility, physical comfort and greater options for care settings. Decisions about initiating mechanical ventilation should include the possibility of future partial or total weaning with prolonged survival.

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P54 NON-INVASIVE VENTILATION IN MOTOR NEURONE DISEASE: ONE CENTRE'S EXPERIENCE

Proctor A¹

Walsh T¹

Billings C²

Mcdermott C¹

Shaw PJ¹

^aiSheffield Institute for Translational Neuroscience, Sheffield, UK

^ajRespiratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

Email address for correspondence: [email protected]

Keywords: NIV, bulbar, survival

Background: Respiratory muscle weakness is a major feature of Motor Neurone Disease (MND) and is a strong predictor of quality of life and survival. Studies have shown that non-invasive ventilation (NIV) may be associated with a gain in survival and improved quality of life (1). NICE guidelines (2) suggest that the ongoing management and treatment for a patient with MND (pwMND) should include provision of NIV for suitable patients. Increasing use of NIV in MND is now being reported (3).

Objectives: To report on our centre’s experience of using NIV in a group of pwMND who had developed respiratory failure, assessing the effects of different factors on survival.

Methods: Routine data collected on consecutive pwMND who underwent a trial of NIV therapy for respiratory failure between February 2009 and April 2012 were analysed using SPSS Statistics 19. Survival status was noted on 30 April 2013. The effect of mean overnight pCO2 prior to initiation of NIV, bulbar status and compliance to therapy on survival was assessed using Kaplan–Meier survival curves. Median survival and percentage survival at 1 year was calculated for a group of patients who had been followed up for at least one year.

Results: Trials of NIV were performed for 117 pwMND during this period. One hundred and eight patients successfully completed the trial and were issued with machines for home use. Patients were predominantly male (72M/36F) with a mean ± sd age of 66 ± 12 years (range: 25–95) and a mean ± sd overnight pCO2 at initiation of 6.85 ± 0.87 kPa.

Kaplan–Meier survival curves showed that survival was significantly related to therapy compliance. Bulbar status was not a significant factor (p = 0.112), but there did appear to be a trend for less survival benefit in those patients with bulbar symptoms. There was no effect shown with pCO2, age or sex. In the group of patients who had been followed up for at least one year (n = 52) median survival was 295 days and percentage survival at 1 year was 40.7%.

Conclusions: Survival of this group of patients on NIV compares well with published trials. Qualitative data from a subgroup of this cohort suggest that extended survival is not at the expense of quality of life. In contrast to previous reports, patients with bulbar symptoms at the start of trial benefited from therapy. NIV should be considered for all MND patients with respiratory failure.

References

• Bourke SC et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial Lancet Neurology 2006;5:140–7.
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P55 BRAZILIAN NON-INVASIVE VENTILATION ASSISTANCE PROGRAM FOR PATIENTS WITH MOTOR NEURONE DISEASES, IN THE CITY OF SãO PAULO

Oda Al

Stanich P

Alves Pcl

de Carvalho Ev

Holsapfel Sga

Akamine Rt

Moreira Ga

Chieia Ma

Oliveira Asb

Unifesp, SÃo Paulo, SP, Brazil

Email address for correspondence: [email protected]

Keywords: NIV, survival, dyspnea

Background: The muscle weakness in Motor Neurone Diseases (MND) may compromise upper and lower limbs, pharyngolaryngeal and respiratory muscles. The changes in respiratory function may negatively affect the quality of life and the survival of MND patients. For this reason, some therapeutic measures are taken, aiming to minimize these effects, which is the case of intermittent positive pressure ventilation.

Objective: To describe the Non-Invasive Ventilation Assistance Program for patients with MND, established by the public health system and it was conducted in São Paulo, Brazil.

Methods: This is a descriptive study that delineated the influx of clinical assessment and ventilatory assistance. A program of ventilatory assistance was created to enable the supply of the bilevel ventilation equipment nationwide to all MND patients. The National Regulation determines that every patient diagnosed with MND is entitled to the bilevel ventilation equipment, in addition to its upkeep and the patient's follow-up at home.

Results: In the Neuromuscular Disease Research Department of University Federal of São Paulo, MND is diagnosed by a neurogical assessment. Afterwards the patient is conducted to a multidisciplinary assessment. After this initial assessment, quarterly follow-up visits are scheduled so that proper guidance can be given, according to the medical condition. The established criteria for the use of non-invasive mechanical ventilation (NIMV) are symptoms of alveolar hypoventilation (tiredness, dyspnea, and morning headache); waking up with dyspnea and tachycardia; sleepiness; frequent pneumonia; inefficient airway clearance. With a value of FVC (Forced Volume Capacity) of approximately 50%, the patient is conducted to a registered public health care, where the respiratory measures will be registered before the patient can be entitled to a bilevel positive airway pressure with nasal and oral mask and an integrated heated humidifier. The pressure setting is also adequate to the patient's needs. A physical therapist visits monthly and there are follow-ups from time to time in health care, to make the reports about the use of the equipment and also pressure setting, if necessary.

Discussion: The goals of non-invasive ventilation are the pulmonary gas exchange, reducing the respiratory work and the improvement of symptoms. The latest facts about the benefits of NIMV for patients with MND diseases is solid and provides improvement to symptoms like chronic hypoventilation in a short amount of time and improves the quality of life and survival. Moreover, the use of NIMV can contribute to the endoscopic gastrostomy tube placement procedure, indicated to dysphagic patients and/or undernourished patients with more than 30% FVC.

Conclusions: The Non-Invasive Ventilation Assistance Program has shown efficacy in the city of São Paulo/Brazil, meeting the expected goals, showing that it is possible to be introduced, ensuring help and improving the quality of life for patients with MND.

P56 PREOPERATIVE TESTING IN ALS PATIENTS PREDICTS DIAPHRAGMATIC RESPONSE TO DIRECT STIMULATION

Shah A^1,2

Tsimerinov E^1,2

Muthukumaran A¹

Elsayegh A¹

Baloh RH¹

Lewis R¹

^akCedars Sinai Medical Center, Los Angeles, United States, USA

^al UCLA, Los Angeles, United States, USA

Email address for correspondence: [email protected]

Keywords: diaphgragmatic, phrenic nerve conduction, diaphgragm fluoroscopy

Background: Patients with amyotrophic lateral sclerosis (ALS) ultimately develop diaphragmatic weakness and chronic hypoventilation significantly influencing the progression of the disease, and quality of life. Diaphragmatic pacing (DP) has recently been introduced as a way of improving respiratory function. It is unclear which patients are the best candidates for DP.

Method: We performed a retrospective review of pre- operative testing with phrenic nerve conduction study (PNC), and diaphragm fluoroscopy with sniff test (DF) and compared these to intraoperative direct nerve stimulation (DNS) using the NeuRx Diaphragm Pacer System^™. PNC responses of greater than 0.2 mV, DF greater than 2 cm excursion and DNS greater than 5 mV/sec were considered to be strong responses. All patients met accepted criteria for device placement based on pulmonary function testing.

Results: A total of 57 hemi-diaphragms in 29 patients underwent PNC and DNS. In 42/57 (73.5%) the PNC and DNS responses were concordant where 17/57 (29.8%) had poor responses in both and 25/57 (43.7%) had good responses in both. In 15/57 (26.3%) the responses were discordant where 10/57 (17.5%) had poor PNC and good DNS, and 5/57 (8.7%) had good PNC but poor DNS. A total of 55 hemi-diaphragms in 28 patients underwent DF and DNS. In 32/55 (58.1%) the responses were concordant where 8/55 (14.5%) had poor responses in both and 24/55 (43.6%) had good responses in both. 23/55 (41.8%) were discordant where 12/55 (21.8%) had poor DF but strong DNS responses, and 11/55 (20%) had good DF responses but poor DNS. The discordant PNC and DF were not consistent suggesting that the two pre-operative studies were independent predictors of DNS. Of the 38 discordant responses, only 16 were discordant with both tests. Twenty-two were correctly predicted by the other pre-operative test.

Conclusion: Both PNC and DF were predictive of intraoperative response in the majority of cases, with PNC having a stronger correlation. However, both pre-operative studies had false positive and negative results and many patients with poor PNC prediction had good DF prediction and vice versa. This suggests that both studies are needed to determine the suitability of diaphragmatic pacing. We are reviewing the data to determine whether PNC and DF correlate with vital capacity and, inspiratory and expiratory pressures.

P57 NOCTURNAL PULSE OXIMETRY AS AN INDICATOR OF SURVIVAL IN AN ALS CLINICAL POPULATION

Lo Coco D

Taiello A C

Spataro R

La Bella V

ALS Clinical Research Center, University of Palermo, Palermo, Italy

Email address for correspondence: [email protected]

Keywords: nocturnal pulse oximetry, survival, respiratory function

Background: Nocturnal pulse oximetry (NPO) is a simple exam that allows detection of nocturnal respiratory dysfunction in patients with amyotrophic lateral sclerosis (ALS) and has been used to guide the initiation of noninvasive ventilation. However, only few studies specifically investigated the relationship between NPO results and survival.

Objectives: The aim of this study was to evaluate NPO as a useful test to predict survival in an ALS clinical population.

Methods: We prospectively studied 106 patients with ALS. We recorded clinical and demographic data, forced vital capacity (FVC), and survival time. All subjects were submitted to NPO.

Results: We found that patients who demonstrated evidence of SaO₂ desaturation less than 90% for at least one cumulative minute throughout the duration of the nocturnal study survived significantly less than patients with normal NPO results (median survival: 15 months vs. 22 months, respectively; p = 0.001). Similar findings were also obtained when patients were divided according to mean overnight SaO₂ < 93% (median survival: 15 months vs. 20 months, respectively; p = 0.034). Interestingly, no differences were found in clinical and demographic variables between the groups of patients, including FVC. Moreover, an altered NPO result (as defined above) was identified as a significant predictor of survival in the multivariate Cox regression model, together with FVC and disease duration.

Discussion: These results confirm the importance of NPO on survival in patients with ALS and may have several consequences for the clinical management of symptomatic care in ALS.

P58 REM SLEEP BEHAVIOR DISORDER AND PERIODIC LEG MOVEMENTS IN SLEEP IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

Lo Coco D^1,3

Mattaliano P¹

Puligheddu M²

Fantini Ml⁵

Mattaliano A³

La Bella V¹

Borghero G⁴

Congiu P²

Gioi G²

^amALS Research Center, University of Palermo, Palermo, Italy

^anSleep Disorders Center

^aoALS Research Center, University of Cagliari, Cagliari, Italy

^apSleep Disorders Clinic, O.U. Neurology, Ospedale Civico ARNAS, Palermo, Italy

^aqS.C. Neurologia, Ospedali Riuniti Mondovì e Ceva, Cuneo, Italy

Email address for correspondence: [email protected]

Keywords: rem sleep behaviour disorder, sleep, periodic limb movements

Background: In the last few years, it has been increasingly recognized that patients with amyotrophic lateral sclerosis (ALS) frequently suffer of sleep-related complaints, including insomnia, restless legs syndrome, and daytime sleepiness, although, in the past, many of the nocturnal symptoms have been mainly ascribed to chronic respiratory insufficiency and hypoventilation. In addition, excluding a few single cases reported, polysomnographic studies did not look for abnormal motor activity during sleep that could be indicative of Rapid Eye Movements (REM) sleep behaviour disorder (RBD) and REM sleep without atonia (RSWA), which are highly prevalent in other neurodegenerative disorders with brainstem involvement. Finally, data on the presence of periodic leg movements in sleep (PLMS) in patients with ALS are sparse.

Objective: We sought to assess sleep characteristics and the occurrence of abnormal muscle activity during sleep such as RSWA, RBD, and PLMS in patients with ALS.

Methods: Forty-one patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography.

Results: Twenty-two patients with ALS (53.6%) reported poor sleep quality. Polysomnographic studies showed that patients with ALS had reduced total time of sleep, increased wakefulness after sleep onset, shortened REM and slow wave sleep, and decreased sleep efficiency compared to control subjects. Polysomnographic abnormalities were not different in patients reporting good or poor sleep, and were not correlated to clinical and demographic variables. PLMS index was significantly higher in patients with ALS than in healthy subjects, and 22 patients (53.6%) showed a PLMS index greater than 15 vs 4 (15.4%) control subjects (p < 0.001). Finally, two patients with ALS (4.9%) had RBD, and two more patients presented RSWA (4.9%), whereas no control subjects showed abnormalities of REM sleep.

Conclusion: Patients with ALS frequently present abnormalities of sleep that can be documented both at the clinical interview and at the polysomnographic evaluation, including insomnia, fragmented sleep, and increased PLMS. Moreover, abnormalities of REM sleep can sometimes be found in these patients.