THEME 4 RESPIRATORY AND NUTRITIONAL MANAGEMENT

P68 NUTRITIONAL SUPPORT IN AMYOTROPHIC LATERAL SCLEROSIS

Ivanova M¹

Blinov I³

Kovalenok K³

Brylev L²

Avdunina I¹

Lysogorskaya E¹

Chervyakov A¹

Vorobyeva A¹

Fominykh V¹

Shtabnitskiy V³

Sonkina A⁴

Fominykh M³

Byalik M³

Dikhter E³

Zakharova M¹

^aResearch Center of Neurology RAMS, Moscow, Russia

^bMoscow Clinical Hospital 12, Moscow, Russia

^cMiloserdie Medical Center, Moscow, Russia

^dRussian National Research Medical University, Moscow, Russia

Email address for correspondence: [email protected]

Keywords: dysphagia, quality of life, percutaneous endoscopic gastrostomy (PEG)

Background: Pyramidal tract neuronal death in ALS leads to impairment of voluntary movements including swallowing and respiration. Dysphagia is associated with fatal complications such as aspiration pneumonia, undernutrition and dehydration. Optimization of nutritional support in ALS patients is necessary. Studies assessing quality of life in ALS patients with dysphagia and gastrostomy risks and benefits are lacking.

Objectives: To assess benefits and challenges of nutritional support especially gastrostomy in Russian ambulatory ALS patients.

Methods: Dysphagia in ALS patients was evaluated clinically and in some cases by video-radioscopy. Mild dysphagia was managed through diet modifications. Patients with severe dysphagia underwent gastrostomy. Patients or carers were interviewed, 30 patients with gastrostomy were questioned 1 year after gastrostomy. Results: Percutaneous endoscopic gastrostomy (PEG) was performed in all patients with severe dysphagia except one (radiologic placement). Mean disease duration before gastrostomy was 849 days. Forced vital capacity (FVC) before gastrostomy was < 50% in 20 % of patients. 4 patients had short-term fever that reduced without treatment after gastrostomy. One patient had an anterior abdominal wall abscess which required replacement of the gastrostomy tube. 28 of 30 patients had a benefit from gastrostomy. Most of patients had weight stabilization; taking meals caused fewer difficulties and was less time-consuming. Gastrostomy was more favourable than nasogastral tube feeding utilized in several patients before gastrostomy since it did not cause mucosal irritation and hypersecretion.

Discussion and conclusion: PEG improves the quality of life of ALS patients with severe dysphagia, rarely causes major or long-term complications and should be used more frequently.

P69 GASTROSTOMY IN PATIENTS WITH ALS: MENTAL REPRESENTATIONS IN PATIENTS AND IN PHYSICIANS

Pietra S¹

Belingher C²

Verschueren A²

Rousseau M-C¹

Pouget J²

^eHôpital San Salvadour (AP-HP), hyeres, France

^fReference centre for neuromuscular diseases and ALS, Hôpital de la Timone, marseille, France

Email address for correspondence: [email protected]

Keywords: mental representation, quality of life, percutaneous endoscopic gastrostomy (PEG)

Background: Enteral nutrition via gastrostomy is the standard method for ALS patients needing nutritional support and has to be discussed respecting the patient’s social and cultural background and their peculiarities. If guidance exists, a big part of the deliberation is of the responsibility of the physicians according to their appreciation and judgment. From then on, the mental representations of gastrostomy in the patient and in the physician, as well as the mutual interactions can influence the decisions and the implementation of the device.

Objectives: The objectives of this qualitative research study are to establish the mental representations associated with the gastrostomy of the ALS patients and of the physicians involved in their care.

Methods: Twenty six ALS patients answered a semi-directive interview on gastrostomy. 26 physicians answered another semi-directive interview on the same theme. The interview grid consisted of 7 questions about the time when gastrostomy was discussed: the overall mental representations; the feeling when it had been discussed; the doubt or the acceptance towards the device; the arguments for the positive points and for the negative aspects of gastrostomy; and finally a summarized word of free association. Each interview was recorded and then retranscribed to allow data processing with analysis of contents and discourse analysis (Tropes software).

Results: Gastrostomy was noted in a predominantly positive way (22/26 for patients and 21/26 for physicians), with a recognition of its relevance and its interest which is upper to the constraints. For the most part patients, even if there was hesitation, stated that gastrostomy was considered as ‘must be made’, but as late as possible. Concerning the physicians, they put into words the doubt (16/26) and questioned the interest of gastrostomy and the risk-benefit assessment in advanced diseases (8/26). The notion of quality of life was present only in the discourse of the physicians. The timing of gastrostomy insertion was an important point in the concerns of the patients which is scheduled as late as possible. The feelings were strongly associated with the time and the progression of disease. Offering gastrostomy led to ambivalence for 60 % of the physicians, making nutritional assistance concomitantly a way of meaning the progression of disease.

Discussion and conclusion: The discussion about nutritional support by gastrostomy makes the recognition of technical relevance of the device coexist psychologically with the fears of confrontation with the disease progression. This is the case for patients but also for physicians. As any paradoxical contents, these probably generate a strain and influence the physician’s recommendations, as much as the reception by the patient.

P70 EXPERIENCE OF AN EARLY-IMPLANTATION PERCUTANEOUS ENDOSCOPIC GASTROSTOMY PROTOCOL ON ALS PATIENTS IN A MULTIDISCIPLINARY CLINIC

Paipa AP

Gomez PR

Povedano MP

Martinez YA

Hospital Universitari de Bellvitge, Barcelona, Spain

Email address for correspondence: [email protected]

Keywords: percutaneous endoscopic gastrostomy (PEG), early use, protocol

Background: A positive effect of percutaneous endoscopic gastrostomy (PEG) has been described in ALS patients. Its systematic use is recommended by international guidelines. Since the year 2011 we have implemented a protocolized PEG education and offer it to our ALS patients in the context of a multidisciplinary clinic. We sought to evaluate the effect of such a protocol within our population.

Methods: Retrospective analysis of ALS patient survival before and after the implementation of an early-implantation PEG protocol.

Results: We analyzed a total of 140 patients. Mean age at symptom onset was 63 years. Mean diagnostic delay was 9 months (rank 1 to 25). 71 patients had a bulbar onset(38 female, 33 male) and 68 a spinal onset (28 female, 40 male); this difference was not significant (p = 0.2).

Time from symptom onset to PEG was significantly reduced since the protocol implementation (mean 19.7 vs 25 months, p = 0.009). There was no difference on age, use of non- invasive ventilation (58% vs 54%) use of riluzole or diagnostic delay, although patients on the intervention group had a non-significant tendency to an older age (66 vs. 62 years, p 0.87).

The control group had a predominance of bulbar onset patients (56.5%) while after the protocol implementation there was a trend toward more spinal onset patients receiving PEG (58.3%, p = 0.77).

Only one patient had a surgical infection which prompted removal and later reimplantation of the PEG. There were no other adverse events.

Discussion and conclusion: The early use of PEG is a safe treatment on ALS patients. We did not find an effect on survival. PEG use must be understood as a treatment destined to improve quality of life and patient well-being.

References:

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P71 SAFETY OF PEG TUBE INSERTION IN PATIENTS WITH ALS USING PROPOFOL SEDATION IN AN OUTPATIENT SURGICAL CENTER

Kittrell P¹

Tobon A¹

Jackson C¹

Fincke C²

Motazedi T¹

^gUTHSCSA, San Antonio, TX, USA

^hMethodist Healthcare System, San Antonio, TX, USA

Email address for correspondence: [email protected]

safety, percutaneous endoscopic gastrostomy (PEG), sedation

Background: Practice guidelines published by the American Academy of Neurology for the management of patients with ALS recommend the use of percutaneous endoscopic gastrostomy (PEG) for prolonging survival. ALS patients with weak respiratory muscles (demonstrated by a Forced Vital Capacity (FVC) < 30%) have been considered at high risk for complications related with the procedure. Our goal is to demonstrate the safety profile, peri-procedural and post-interventional complications of PEG tube insertion performed in an outpatient surgical center.

Objectives: To review the authors’ experience of PEG tube placement in patients with amyotrophic lateral sclerosis with different degrees of impaired respiratory function.

Methods: Retrospective review of medical records of patients treated at the University of Texas Health Science Center of San Antonio ALS clinic that were referred for PEG tube placement using propofol sedation at an outpatient surgical center.

Results: From 2011 until 2014, 61 patients had PEG placement under propofol sedation. The average age was 64 (range 31–84) with 31 males and 30 females. Patients were assigned to three groups based on FVC (FVC < 30% 9 subjects, 30–50% 26 and > 50% 24). Total propofol dose ranged from 60 to 500mg. Procedure duration (anesthesia time/surgery time) averaged 29/11 minutes (range 19–45/4–27). Patients currently on Bipap brought their own devices and used them in the intra and post-operative period as needed. No patients required invasive ventilatory support in the immediate post op period and there were no symptomatic cardiac arrhythmias or hypotension. Four patients developed perioperative complications: (1) death of unknown cause at home 24 hours after procedure (pre-op FVC 64%); (2) cellulitis at peg site 2 weeks post insertion; (3) abscess at peg site 10 days post insertion that required drainage and replacement of feeding tube; (4) Transient desaturation during surgery that stabilized but two days later had respiratory event and died in the hospital (pre-op FVC 43%). Mortality rate at 30 days was 4.9% (3 out of 61). All three patients had FVC > 40%. All patients that developed complications also had significant comorbidities. There was no correlation between complications and FVC, BMI, disease duration or ALSFRS scale.

Conclusions: PEG tube placement with propofol sedation and Bipap support performed at a specialized outpatient surgical center can be achieved at a reasonable risk even in patients with very low FVC (less than 30%).

References:

• Miller RG et al. Neurology 2009; 73(15):1218–1226.
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P72 ENTERAL TUBE FEEDING AND SURVIVAL PATTERN OF 407 PATIENTS WITH MOTOR NEURONE DISEASE

Chhetri SK^1,2

Bradley BF²

Majeed T¹

Lea RW²

ⁱPreston MND care and Research centre, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK

^jUniversity of Central Lancashire, Preston, UK

Email address for correspondence: [email protected]

Key words: enteral feeding, nutrition, percutaneous endoscopic gastrostomy (PEG)

Background: Motor Neurone Disease (MND) patients with dysphagia and impaired nutritional status are usually offered enteral feeding (EF). The findings of prospective and retrospective studies investigating the impact of EF on survival have demonstrated little consensus (1, 2).

Objective: To assess the impact of enteral feeding on survival of patients with MND.

Methods: We conducted a retrospective review of the MND database and case notes of MND patients between 2005 and 2012. We identified cases that had undergone gastrostomy tube placement for EF. Statistical analyses of association between clinical manifestation, survival and gastrostomy tube insertion were evaluated using SPSS version 21. A forward stepwise cox regression was used to evaluate whether EF offers survival advantage. We also assessed survival in the bulbar and limb onset subgroups with and without EF using log-rank analysis.

Results: A total of 407 patients were identified. 345 cases with complete data were analysed of which 213 were limb onset, 130 bulbar onset and 2 respiratory onset. 93 patients (31 limb onset, 61 bulbar onset and 1 respiratory onset) received enteral feeding. After adjusting for effects of gender, onset age, onset site, age at diagnosis and riluzole treatment, EF was not associated with a statistically significant survival advantage (χ2 (1) = 1.96, p = 0.16). Log-Rank analysis revealed no significant difference in survival times between bulbar onset and limb onset illness, either with or without EF (Log-Rank χ2 (1) = 0.56, p = 0.45). Median (95% CI limits) survival times for limb onset MND with and without EF were 777 days (498.67-1055.13) and 715 days (620.47-809.53) respectively. Median survival times for bulbar onset with and without EF were 799 days (677.64-920.36) and 645 days (414.77-875.24) respectively.

Discussion and conclusion: There are no appropriately designed trials to inform decisions on nutritional management of MND patients and clinical practice is largely guided by expert clinical opinion and consensus. Our retrospective review did not find a survival advantage with enteral feeding. However the effect of enteral feeding on quality of life, an important objective of any management strategy, remains unknown. The retrospective nature of our study and lack of randomisation are potential limitations. A prospective study to evaluate impact of enteral feeding on survival and quality of life in this challenging clinical population would provide further evidence to inform and influence best clinical practice.

References:

• Miller RG. et al. Neurology 2009; 73:1218–26.
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P73 PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) PLACEMENT INCREASES SURVIVAL IN AMYOTROPHIC LATERAL SCLEROSIS: TWO DECADES IN REVIEW

Sterling LE¹

Plowman EK²

Simpson EP¹

Appel SH¹

^kHouston Methodist Hospital, Houston, TX, USA

^lUniversity of South Florida, Tampa, FL, USA

Email address for correspondence: [email protected]

Keywords: percutaneous endoscopic gastrostomy (PEG), survival

Background: Percutaneous Endoscopic Gastrostomy (PEG) placement is utilized to maintain nutritional status in individuals with ALS. Current practice guidelines recommend PEG placement prior to forced vital capacity (FVC) falling below 50% (1). Few studies with small numbers have examined the impact of PEG placement in ALS patients; therefore the specific impact on survival remains unclear.

Objectives: To determine the impact of PEG placement on survival in a large cohort of ALS patients.

Methods: A retrospective database analysis was performed on consecutive cases of individuals diagnosed with probable/definite ALS in accordance with the most current El-Escorial Criteria (2, 3) and seen at the MDA/ALS Clinic at Houston Methodist Hospital from 1992–2013. Demographic data extracted included: age, gender, disease-onset type, PEG status, and time to death from symptom onset. Frequency counts and descriptives were performed to determine pertinent characteristics of individuals with ALS presenting to this facility over the past 20 years. Survival curves were calculated using the Kaplan-Meier method for patients choosing to undergo PEG placement and for those whom did not choose PEG using a logrank test. A series of ANOVAs and an ANCOVA were performed to investigate impact of PEG status, gender and disease-onset type on survival time with alpha set at 0.05.

Results: 2192 ALS patients were seen over the 21-year period. 58.9% were male and 41.1% female; 74.9% demonstrated spinal-onset and 25.1% bulbar-onset; and 533 (24.3%) underwent PEG placement while 1659 (75.7%) did not undergo PEG placement. Overall mean survival time from date of first symptom onset was 39.13 months (SD: 28.52). In this cohort, males demonstrated significantly longer survival then females (means: 41.18 vs. 36.26 months), F (1) = 8.71, p < 0.001 and spinal-onset patients lived longer then bulbar-onset ALS patients (means: 41.46 vs. 32.48 months), F (1) = 23.21, p < 0.0001. The presence of a PEG increased average survival time by 4 months (42.05 vs. 37.74 months) in the entire group of ALS patients, F (1) = 5.97, p < 0.01. When stratified by disease-type, PEG placement did not significantly impact survival time in bulbar-onset patients (PEG: 32.74 vs. no PEG: 32.22), however increased average survival time by 9.5 months in spinal-onset patients (PEG: 48.50 vs. no PEG: 39.02 months).

Discussion and conclusion: In this retrospective review of a large cohort of ALS patients we report that gender, disease-onset type and PEG tube utilization significantly impact survival. Specifically, males, spinal-onset disease type and the presence of a PEG tube favourably impacted survival.

PEG placement represents an important intervention for maintaining nutritional status in individuals with ALS and extended survival by 9.5 months in this cohort of spinal-onset ALS patients.

References:

• Miller R. et al. Neurology 2009; 73:1218–1226.
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P74 EARLY PERFORMED PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) IN ALS PATIENTS

Herrera HV

Virgili CS

Turón SJ

Povedano MP

Andres MB

Lazo La Torre C

Bellvitge hospital, Barcelona, Spain

Email address for correspondence: [email protected]

Keywords: percutaneous endoscopic gastrostomy (PEG), nutrition

Background: Malnutrition or progressive weight loss in the early stages of ALS has been reported as a predictor of poor survival prognosis. Aetiology is multifactorial, with the most important factor, dysphagia, being prevalent in 60% of patients with bulbar onset.

PEG should be performed in the disease stages with preserved respiratory function (forced vital capacity > 50%, and arterial carbon dioxide pressure < 45 mmHg), to avoid early death after PEG and to maintain QOL with nutritional intervention through PEG. Although the appropriate amount of energy to be administered is yet to be established, high calorie diet is expected to be effective for potential improvement of survival. PEG is also necessary as a safe administration route of opioids for palliative and end-of-life care.

Objectives: To analyse the optimal timing of gastrostomy and correlate with other prognostic factors such as ponderal evolution and complications associated with gastrostomy.

Methods: A retrospective analysis was carried out in patients with ALS disease who attended the ALS Multidisciplinary Unit of a tertiary center in Barcelona, during the period from January 2012 to November 2013. Patients were selected who needed gastrostomy, and were compared with other variables such as age of onset, type of onset, time from needed nutritional support to support being provided or rejected, weight loss, and complications associated with gastrostomy.

Results: PEG was performed in 41 patients, 59% were men. 26% had spinal, 15% bulbar and 2% respiratory onset. The mean age in years was 64yrs (+ 11yrs). 71% required respiratory support by no invasive ventilation. Nutritional support in 93% and respiratory involvement in 7% were the principal indications.

Timing from diagnosis to require a gastrostomy was 11 months (IC 95%: 6–25). Timing from its indication to gastrostomy being performed was 3.1 months (IC 95% 1.5 – 12). The weight loss during this period, by percentage of lost weight, was 8% and the mean was 4.9kg (IC 95% −7.37kg to −2.5kg) (p < 0.05).

Weight stabilization was observed in all patients after a month using nutritional support by gastrostomy. The mean weight increasing was 0.46kg (IC 95%: −1.09 to 2.01).

34% of complications associated with PEG were observed, 86% being minor and 14% major complications, 50% were associated with infection and 14% to an involuntary extraction.

Mean survival in days were 335 (IC 95%: 396-274) from time of PEG performing. Survival was not influenced by PEG complications.

Discussion and conclusion: Percentage of weight lost before PEG performing is quite high. Tendency to stabilisation after using the nutritional support was observed. This stability gives almost one year in survival in most patients. A long delay in PEG placement is associated with greater weight loss, and consequently with decreased survival.

P75 CAUSES OF WEIGHT LOSS AFTER PEG PLACEMENT IN ALS PATIENTS

Schröder D¹

Wijnen C²

^mhet Roessingh, Enschede, The Netherlands

ⁿSpierziekten Nederland, Baarn, The Netherlands

Email address for correspondence: [email protected]

Keywords: weight loss, dietician, percutaneous endoscopic gastrostomy (PEG)

Background: After PEG placement weight loss continues although to a smaller extent than before PEG placement.

Objectives: Our objective was to investigate possible causes of ongoing weight loss despite dietetical interventions.

Methods: We retrospectively studied the records of patients discharged from rehabilitation or deceased between January 2010 and July 2013 in 7 ALS rehabilitation centres in the Netherlands. 59 patients were studied but 48 patients (22 men; mean age at diagnosis 63 years) were included because of incomplete data. 33 patients had a bulbar and 15 a spinal onset. All patients were followed for at least 6 months after PEG placement. Data up to 24 months after PEG placement were collected but only data up to 12 months could be analysed. Weight, estimated energy requirements and dietetical interventions were measured.

Results: The mean energy requirement when walking was 2007 kcal/24 h (N = 37); the energy requirement was lower (1890 kcal/24 h) when sitting in a wheelchair (N = 18) and was lowest for people (N = 10) sitting in an electric wheelchair (1837 kcal/24 h). Mean weight loss 3 months after PEG placement was −1.5 kg (N = 48) but varied between −8 kg or weight gain of + 3 kg. Mean weight loss between 3–6 months was −0.8 kg (N = 35), 6–9 months −1.0 kg (N = 21), 9–12 months −0.7 kg (N = 13). Average weight loss per person after four 3-month intervals (12 months after PEG placement) was not significantly different (p = 0.357) between bulbar (−1.1 ± 2.1 kg) and spinal patients (−1.7 ± 2.4 kg). The mean number of dietetical interventions each 3 months was 3, in the first 3 months after PEG placement 3.6 which declined to 2.5 after 12 months. The most prevalent reported causes of dietetical interventions between 0–3 months were loss of muscle mass and illness (eg, pneumonia), 3–6 months loss of muscle mass, illness and intolerance of additional (enteral) nutrition, 6–9 months intolerance of additional nutrition and loss of muscle mass. Non-invasive ventilation (NIV) (N = 27) did not influence changes in weight in comparison with patients without NIV.

Discussion and conclusion: We did not notice hypermetabolism in our cohort of patients. We expected stabilization of weight in patients with NIV but this did not occur. We also expected further weight loss after PEG placement, with a difference between spinal and bulbar patients. Nevertheless, large individual variations in weight changes, also in time, were seen. The dietician adjusted weight loss each consult by adding calories. It remains to be elucidated why patients could no longer tolerate additional (enteral) nutrition. Weight loss after PEG placement can be limited due to dietetical evaluations and interventions, at least once a month.

P76 THE IMMEDIATE LOW PROFILE BUTTON GASTROSTOMY: PATIENTS PREFER IT AND WE SHOULD PROVIDE IT

Onders R^1,2

Elmo M¹

Kaplan C¹

Katirji B^1,2

^oUniversity Hospitals Case Medical Center, Cleveland, Ohio, USA

^pCase Western Reserve University School of Medicine, Cleveland, Ohio, USA

Email address for correspondence: [email protected]

Keywords: percutaneous endoscopic gastrostomy (PEG), buttons, diaphragm pacing

Background: Thirty percent of ALS/MND patients present with bulbar onset and dysphagia is present in over 81% of advanced ALS/MND patients. Practice guidelines from the ANN recommend gastrostomy placement before the FVC falls below 50%. Only 43% of patients who were recommended a gastrostomy chose the therapy (1). Patients declined gastrostomy placement for the following reasons: belief their swallow was adequate, general disdain and lack of knowledge. The standard gastrostomy offered is the long external tube, the percutaneous endoscopic gastrostomy (PEG). The low profile gastrostomy tube (button) has been around for over 30 years. Safety of primary button gastrostomy insertion in adults has been demonstrated for over a decade.

Objectives: To determine ALS/MND patient preference of feeding tube style.

Methods: Subgroup analysis of all ALS/MND patients who were being evaluated for diaphragm pacing and were offered gastrostomy at a single institution. Patients were informed and offered a choice between standard PEG and button.

Results: Between 2011 and 2014, 112 patients were evaluated for diaphragm pacing and 88 did not have feeding tubes. 24 patients presented with PEG already in place. During evaluation, 47 patients had bulbar symptoms with 34 of them presenting without PEG. 32 of the patients without PEG also had FVC below 49% (22–49). 61 out of 63(97%) patients choosing gastrotomies chose the button and were safely and successfully placed. Two patients received standard PEG. One patient had a button replacement in first week from balloon rupture. After two months, two patients required conversion to standard PEG due to body habitus. Patients that chose the button ranged in age from 28 to 81 years with an average age of 57years. The average FVC was 57% (17%-110%). 19 patients choosing the button had a FVC above 60% and no bulbar symptoms. There is a 100% 6-month survival. The survival range to date is 6 months to 28 months with an average of 14.3 months.

Discussion and conclusion: When given a choice, patients overwhelmingly selected the immediate button-97%. All patients preferred the aesthetics of it. This sample showed direct button placement is safe and has a very low complication rate in ALS/MND patients. Button changes are easily performed. Also, they can be easily converted to a standard PEG if needed. A limiting factor in offering a button gastrostomy is abdominal size. Utilization requires the abdomen to be exposed and greater finger/hand dexterity to access compared to a standard PEG. One of our patients chose the standard PEG so he could perform his own feeds. Offering direct button placement could affect ALS/MND patients’ acceptance of a feeding tube allowing for placement at a safer stage of their disease.

Reference:

• Miller R. et al. Ann Neurol. 2009; 65: 24–28.
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P77 REDUCED LIP FORCE IN MND PATIENTS WITH WEIGHT LOSS WITHOUT DYSPHAGIA – A PILOT STUDY

Backman P

University Hospital, Uppsala, Sweden

Email address for correspondence: [email protected]

Keywords: lip force, weight loss, dysphagia

Background: Patients with motor neuron diseases (MND) often experience weight loss and malnutrition. The underlying causes of the weight loss are not fully understood. It can occur with or without clinical findings of dysphagia and is associated with shorter survival (1). Previous research indicates a correlation between reduced lip force and dysphagia in stroke patients, both with and without facial palsy (2). Since some of the similar muscles can be affected in MND patients and stroke patients there is a possibility that lip force is reduced in MND patients as well.

Objectives: The aim of this pilot study was to explore if MND patients with weight loss without clinical findings of dysphagia have a reduced lip force compared to healthy controls.

Methods: Seven patients with MND and 10 healthy controls matched for age participated in the pilot study. The patients with MND had an involuntary weight loss during the last year and showed no clinical signs of dysphagia or dysarthria. All patients completed sequential water swallowing of 100 ml of water within 10 seconds. Lip force was tested with an oral screen attached to a force dynamometer (Lutron, FG-5005). The oral screen was placed in the mouth between the lips and the teeth and the participants were instructed to hold the oral screen in their mouths for as long as possible by tightening the lips. When the participants no longer could hold the oral screen it came out of the mouth. The force dynamometer showed a peek value in Newton (N). Each participant made five attempts and the highest value of the peak values was registered.

Results: The results showed a reduced lip force in the patients with MND compared to the healthy controls. The MND patients mean lip force was 22.8 N (median 20.8; SD 6.1) and the mean lip force in the healthy control group was 42.5 N (median 45.2; SD 8.9).

Discussion and conclusion: The results indicate that patients with MND may have a subclinical weakness in their lips even when there are no apparent signs of dysphagia or dysarthria. Given the poor prognosis associated with weight loss it may be valuable to discover difficulties as early as possible for appropriate disease management. Further research is needed to explore lip force and how it affects MND patients.

References:

• Desport J. et al. Neurology 1999; 53:1059–1063.
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P78 ANTHROPOMETRY OF ARM: NUTRITIONAL RISK INDICATOR IN AMYOTROPHIC LATERAL SCLEROSIS (ALS)

Salvioni C

Stanich P

Pauli M

Chieia M

Quadros A

Oliveira A

Federal University of Sao Paulo, Sao Paulo, Brazil

Email address for correspondence: [email protected]

Keywords: nutritional assessment, nutrition, anthropometry

Background: Nutritional parameters of ALS patients worsen during disease. For nutritional evaluation the body mass index (BMI) instrument alone does not reflect changes across regions of the body.

Objectives: To correlate clinical, nutritional and respiratory data with functional parameters.

Methods: 111 ALS patients between 2009 and 2010 took part in the study. Clinical data collection consisted of: site of onset; time referred to disease (TRD); and date of diagnosis. Assessment times were divided into 3 groups: T1 (symptoms until diagnostic confirmation); T2 (symptoms and nutritional evaluation); T3 (diagnosis and nutritional evaluation). The anthropometric assessment included: triceps skinfold thickness (TSF); midarm circumference (MAC); arm muscle area (AMA); midarm muscle circumference (MAMC); and arm fat area (AFA). For classification of nutritional status, BMI and anthropometry were examined individually and later in association with protein-caloric malnutrition score (PCMS). ALSFRS scale was applied and analyzed individually and grouped in main domains. Each item in the scale was correlated with the second site of onset, spinal group (GA) or bulbar group (GB).

Results: In patients from the bulbar group (GB) the T1 and T3 was earlier with respect to those patients in the spinal onset group (GA). A statistically significant difference was observed for T2 (p < 0.012). On correlation between anthropometric parameters and times, to GA we observe that T2 showed significant positive correlation with %TSF and negative for MAMC, %MAMC, AMA and %AMA. For T3, positive significant association was found with TSF, %TSF, whilst a negative association was found with MAMC. The analysis between FVC and anthropometric measurements showed that there was a significant association for GA and GB. In GA there was also a positive correlation with MAC, MAMC, % MAMC, AMB and PCMS, while for GB only a correlation could be found with body weight. On correlation of nutritional parameters and ALSFRS for GA patients we observed that MAC and % MAC presented positive association with both issues of D1 and D2. For GB, total score: in addition to a positive correlation with anthropometric parameters related to lean body mass (MAMC, AMA and %AMA) there was also a negative association associated with body fat.

Discussion and conclusion: A positive association was found between T2 and TSF, negative with all measures of muscle mass estimate suggests that delay in nutritional intervention can have a negative effect on loss of muscle. With respect to FVC and anthropometric measures we can infer that respiratory loss can be a sign of nutritional decline, with the reverse also being true. On correlation between anthropometry and ALSFRS, the results suggest that evaluation of measures, in particular measures to estimate muscle mass, may be related to motor impairment in evolution disease.

Anthropometry of arm was important for analysis justifying the importance of nutritional evaluation. The ALSFRS, in particular the D2, indicated nutritional impairment. The application of scale could serve as screening instrument, in order to anticipate the referral to dietician working with better prognosis in ALS.

P79 DOES BULBAR DYSFUNCTION RENDER RESPIRATORY ASSESSMENT BY STANDARD PULMONARY FUNCTION TESTS MEANINGLESS? QUANTIFYING THE IMPACT OF BULBAR DYSFUNCTION ON MEASURES OF RESPIRATORY INSUFFICIENCY IN 100 PATIENTS WITH ALS

Jenkins L¹

Sakamuri S^1,2

Miller RG¹

Forshew D¹

Guion L¹

Moore D¹

Katz J¹

^qForbes Norris ALS/MDA clinic, California Pacific Medical Center, San Francisco, California, USA

^rStanford Hospital & Clinics, Stanford, California, USA

Email address for correspondence: [email protected]

Keywords: respiratory, phrenic, bulbar

Background: Diaphragmatic weakness is the primary cause of hypoventilation in ALS. Phrenic nerve conduction studies assess diaphragmatic innervation and correlate with respiratory failure (1). In contrast, standard pulmonary function tests (PFTs), when used in ALS, are affected by other factors including accessory muscle weakness and bulbar dysfunction (2).

Objectives: To examine how bulbar dysfunction affects PFTs in ALS.

Methods: We prospectively recorded phrenic nerve conduction studies, upright and supine FVC, maximum inspiratory pressure (MIP), sniff nasal inspiratory pressure (SNIP), ALSFRS-R and bulbar subscore (FRSb) in 100 patients with ALS.

Results: Of the 100 subjects: 41 were female, 69 had spinal onset, and the average symptom duration was 24.2 months. The correlation co-efficients between diaphragmatic CMAP amplitude (Pamp) and standard PFTs were: supine FVC 0.48 (p < 0.001); upright FVC 0.45 (p < 0.001); MIP 0.37 (p < 0.001) and SNIP 0.28 (p < 0.001)). To quantify the independent effect of bulbar dysfunction on these measures, we used logistic regression analysis to eliminate the joint effect of Pamp on the PFT results. We found a marked decline in the performance of all standard respiratory measures as a result of bulbar dysfunction alone, independent of diaphragmatic innervation (p < 0.001). The effect on MIP was substantial: a drop on the FRSb from just 12 to 11 resulted in a fall in the MIP from 65cmH₂0 to 54cmH₂0, and to 44cmH₂0 at a score of 10. The SNIP was similarly affected. The bulbar related drop in FVC was less, falling from 88% predicted at an FRSb of 12, to 82% at 11, and to 75% at 10. More moderate bulbar involvement caused PFT results to decline even further into ‘abnormal’ ranges. For example, an FRSb score of 6 resulted in a MIP of 32cmH₂0, a SNIP of 20 cmH₂0 and an FVC of 60%, independent of diaphragmatic dysfunction as measured by phrenic nerve conduction studies.

Discussion and conclusion: Standard PFTs are of limited utility in the assessment of diaphragm dysfunction. The presence of modest bulbar disease leads to results so abnormal that the clinician is essentially blind to the true state of the diaphragm, while a drop of just one point on the FRSb resulted in predicted MIP values below the threshold for initiating NIV, presumably because of bulbar factors alone. FVC and MIP are still the main instruments used in respiratory assessment and clinical trials. We show that phrenic nerve conduction studies, or other direct assessments of the diaphragm, may be needed to provide key data on diaphragm dysfunction in bulbar patients.

Acknowledgements: We are grateful to our patients for contributing their time to this research.

References:

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P80 ASSESSING DIAPHRAGM FUNCTION IN ALS: COULD A STANDARD INSPIRATION CHEST X-RAY WITH AN ADDITIONAL RELAXATION VIEW PROVIDE THE ANSWER?

Onders R^1,2

Elmo M¹

Kaplan C¹

Katirji B^1,2

Schilz R^1,2

^sUniversity Hospitals Case Medical Center, Cleveland, Ohio, USA

^tCase Western Reserve University, Cleveland, Ohio, USA

Email address for correspondence: [email protected]

Keywords: diaphragm pacing, chest x-ray, hypoventilation

Background: The diaphragm is the primary muscle of respiration and failure of function leads to hypoventilation and respiratory failure. Assessing diaphragm function in patients with ALS/MND involves functional pulmonary function tests but these tests may underestimate unilateral diaphragm dysfunction. Standard chest x-ray can have patients air stacking which can falsely suppress abnormal unilateral diaphragm. Fluoroscopic sniff tests assess bilateral diaphragm function but can be difficult to perform in all centres. Also the use of accessory respiratory muscles can give the false appearance of diaphragm movement.

Objective: This report analyses a new simplified radiographic technique of assessing ALS patients’ upper motor neuron (UMN) control of their diaphragm.

Methods: Consecutive patients with ALS/MND at a single site under an IRB approved protocol to assess for suitability of diaphragm pacing were evaluated. All patients had a standard assessment which included: pulmonary function tests; arterial blood gasses; fluoroscopic sniff diaphragm analysis using a grid measuring system; phrenic nerve conduction studies (PNCS); and subsequent intra-operative diaphragm strength grading under direct stimulation, which identifies the intact lower motor neurons (LMN) with their associated diaphragm motor units. In addition each patient had a standard chest x-ray with the addition of a relaxation image after they take a breath. The inspiration compared to relaxation should correlate to the continuous fluoroscopic evaluation of the diaphragm.

Results: 26 consecutive ALS subjects had this battery of tests with the addition of inspiration/relaxation chest x-rays. 19 patients (73%) had diaphragm movement correlation between inspiration/relaxation diaphragm movement and fluoroscopy. In analysing each hemidiaphragm separately there was a 77% correlation (40 of 52). In a multivariate analysis of all factors the following relationships had a p-value < 0.05: forced vital capacity (FVC) is correlated to maximal inspiratory pressure (MIP) and radiographic diaphragm movement; MIP is correlated to radiographic diaphragm movement; and arterial CO₂ is correlated to radiographic diaphragm movement- in which hypercarbia is related to decreased movement of diaphragm. The operative assessment of diaphragm movement under direct stimulation did not correlate to pre-operative testing.

Discussion and conclusion: The simplified inspiration/relaxation chest x-ray correlates with fluoroscopy and can easily be performed radiologic departments. The inspiration/relaxation chest x-ray is 50% less expensive in charges in the US (461 versus 993 US dollars). These tests analyze UMN control of the diaphragm but diaphragm pacing is based on the intact LMNs. Patients with poor diaphragm movement on these radiologic tests can be good diaphragm pacing candidates if they have intact LMNs to stimulate as identified by PNCS or intraoperative assessment. PNCS primarily assess anterior diaphragm while posterior diaphragm is the most important diaphragm for ventilation. Laparoscopic diaphragm evaluation focuses on posterior diaphragm and the ability to stimulate the LMN motor units that have lost UMN control is how diaphragm pacing improves ventilation.

P81 LONG TERM SURVIVAL OF ALS/MND PATIENTS WITH DIAPHRAGM PACING IMPLANTATION WITH LOW FORCED VITAL CAPACITY BELOW 45% PREDICTED

Ondes R^1,2

Elmo M¹

Kaplan C¹

Katirji B^1,2

Schilz R^1,2

^uUniversity Hospitals Case Medical Center, Cleveland, Ohio, USA

^vCase Western Reserve University School of Medicine, Cleveland, Ohio, USA

Email address for correspondence: [email protected]

Keywords: diaphragm pacing, respiratory failure, forced vital capacity (FVC)

Background: Forced vital Capacity (FVC) is widely used as an indicator of prognosis in ALS, need for non-invasive ventilation (NIV) or diaphragm pacing (DP). Therapy with DP may be excluded because of no previous data or experience if the FVC is less than 45% predicted. Previously it has been described that there can be adequate stimulatable intact motor units with associated lower motor neurons in ALS patients with FVC below 45% predicted. (1). This reports the long term survival of patients implanted with diaphragm pacing with a FVC below 45% predicted.

Objective: To analyze surgical morbidity, mortality and long term survival patients with FVC < 45% implanted with DP.

Methods: Retrospective analysis of all patients implanted with DP and a FVC below 45% predicted from a prospective database at a single site under an IRB protocol for ALS patients from November 2011 until April 2013.

Results: 24 ALS subjects were implanted with FVC below 45%. The average FVC at implant was 35.6 +/+7.9 (range 17–45); average MIP was 26.4 +/+9.7; and PCO₂ was 45.0 +/+7.3. There was no peri-operative mortality with only one early tracheostomy although DP was continued. Within the first 6 months, two other early deaths involved uncontrollable secretions and an additional one involved a mucous plug. Only one patient stopped DP within two months of surgery and has been lost to long term follow-up. The median survival using Kaplan Meier analysis is 11.8 +/+2.9 months. 9 out of the 24(37.5%) patients are still alive an average of 19.33 months post implant with the longest at 29 months.

Discussion and conclusion: DP surgery can be safely implanted in patients with FVC below 45%. In this late stage group of patients there is still a stimulatable diaphragm motor units were DP can delay respiratory failure and subsequent death with a significant patients surviving over 19.3 months post-surgery. Patients should be adequately informed about options to maintain diaphragm function with DP even when late in the disease course.

Reference:

• Onders R. et al. ALS 2013; 14s:62.
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P82 EFFECT OF TIRASEMTIV ON SUBMAXIMAL RODENT DIAPHRAGM STRENGTH AND RESPIRATORY FUNCTION

Hwee DT

Kennedy A

Malik FI

Jasper JR

Cytokinetics, Inc., South San Francisco, CA, USA

Email address for correspondence: [email protected]

Keywords: diaphragm, respiratory function, calcium sensitivity

Background: Diaphragm weakness, which is characterized by significant losses in function, is a primary component of the pathophysiological changes that lead to respiratory failure. Tirasemtiv is a fast skeletal troponin activator, previously shown to increase submaximal force in rat and human lower leg muscles.

Objective: The objective of this study was to characterize the effect of Tirasemtiv on calcium sensitivity and force production ex vivo in rat and mice diaphragm muscle.

Methods: For in vitro skinned (permeabilized) fiber studies, Sprague Dawley rat diaphragm muscles were rapidly dissected, rinsed in physiological saline, and then incubated in skinning and storage solution. Single muscle fibers were dissected from larger segments of tissue in rigor buffer. The fibers were then suspended between a force transducer and a fixed post. The muscle force-calcium (pCa) relationship in diaphragm muscle was investigated in single rat diaphragm fibers treated with either 1% DMSO (vehicle treatment), or Tirasemtiv (0.1μM, 1μM, or 10μM) over –log (10) calcium concentrations (pCa) ranging from 8 to 4.

For intact diaphragm muscle, contractile force was measured by electrical field stimulation in an organ bath system. The diaphragm and the last floating rib from B6SJL mice were excised, rinsed in physiological saline, placed in a temperature controlled water-jacketed chamber containing Krebs-Henseleit buffer. Braided silk sutures were tied at the central tendon and floating rib and attached to a force transducer between two platinum electrodes. The force-frequency profile of the muscle was obtained by stimulating the muscle at frequencies between 5–150 Hz. Tirasemtiv (1 μM in DMSO) was directly added into the bath.

Results: Tirasemtiv increased the calcium sensitivity of rat diaphragm muscle, shifting the force-pCa relationship of skinned fibers in a dose-dependent manner. Compared to DMSO-treated skinned diaphragm muscle fibers, 10μM Tirasemtiv increased the pCa at 50% maximum tension (pCa₅₀) 10-fold (vehicle: 5.43 ± 0.05, 10μM Tirasemtiv: 6.74 ± 0.02, n = 5/group). In intact muscle, at submaximal stimulation frequencies less than 20Hz, Tirasemtiv (1μM) increased mouse diaphragm tension ex vivo compared to vehicle-treated diaphragm strips (vehicle n = 11,Tirasemtiv n = 5, p < 0.05 at 5, 10, and 20 Hz).

Discussion and conclusion: Pathological conditions that lead to diaphragm weakness can have severe consequences, ranging from dyspnea and reduced quality of life to respiratory failure and death. The fast skeletal troponin activator, Tirasemtiv, increased calcium sensitivity in a dose-dependent manner and increased submaximal force production ex vivo. These results suggest that Tirasemtiv and other fast skeletal muscle troponin activators may be viable therapeutics for improving respiratory muscle function.

Acknowledgements: All authors are currently employees of Cytokinetics, Inc. and were compensated financially for their work.

P83 LONG-TERM IMPACT OF EXPIRATORY MUSCLE STRENGTH TRAINING ON RESPIRATORY FUNCTION AND DISEASE PROGRESSION IN TWO PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS: A CASE SERIES

Rosado KM

Tabor L

Turner K

Gaziano J

Richter J

Vu T

Gooch C

Plowman EK

University of South Florida, Tampa, Florida, USA

Email address for correspondence: [email protected]

Keywords: Expiratory Muscle Strength Training (EMST), ALSFRS-R, exercise

Background: The role of exercise in individuals with ALS is controversial. We have recently reported that expiratory muscle strength training (EMST) is feasible, safe and leads to improvements in expiratory force generating pressures immediately following a five-week treatment program in a pilot study of 25 ALS patients. The long-term impact of EMST on respiratory function and disease progression in this patient population has not yet been studied.

Objective: To determine the long-term impact of expiratory muscle strength training on expiratory force generating pressures (maximum expiratory pressure) and global disease progression (ALSFRS-R) in two individuals with ALS.

Methods: Two individuals with a diagnosis of ALS (Revised El-Escorial Criteria) participated in an eight-week EMST program. Training consisted of 5 weekly sessions of 25 repetitions at 50% of individualized MEP. Outcome measures included MEPs and ALSFRS-R scores, evaluated at baseline, immediately post-EMST, and every three-month post-EMST.

Results: Patient 1 was a spinal-onset 58-year-old male, 11 months post-symptom onset and a Baseline ALSFRS-R score of 45. Following eight-weeks of EMST, he demonstrated a 43% improvement in MEPS (179.66 vs. 257.00cmH₂0) and his ALSFRS-R score remained unchanged. At this time point, Patient 1 continued the EMST program. At the three- and six-month follow-up evaluations, Patient 1 demonstrated a 26.71% and 14.47% improvement of MEPs respectively compared to his baseline MEP (227.66cmH₂0 and 205.66 cmH₂0). His ALSFRS-R did not decline across the three- and six- month time points.

Patient 2 was a 67-year-old bulbar-onset male, 14 months post-symptom onset and a Baseline ALSFRS-R score of 37. Following eight-weeks of EMST, MEPS increased by 41% (104.00 vs. 146.67cmH₂0) and his ALSFRS-R score did not change. Patient 2 ceased EMST at this time point. At the three- and six-month follow up evaluations, he demonstrated a 36.22% and 58.01% decline in MEPs from baseline levels (66.33 and 43.66 cmH₂0 respectively). His ALSFRS-R score dropped to 36 (-2.70%) and 28 (-28%) at the 3- month and 6-month follow up time points respectively. Follow up data out to 12 months will be presented.

Discussion and conclusion: In these two cases we document an immediate effect of EMST on expiratory force generating pressures and global disease status. Specifically, MEPs increased by 41–43% in these patients and ALSFRS-R scores remained unchanged pre vs. post-EMST. Improvements in MEPs did not carry-over beyond three months in the patient who discontinued EMST, however were maintained with continued exercise (Patient 1) out to 8 months.

Strength training of bulbar musculature may be beneficial for improving and maintaining expiratory generating pressures and may impact measures of global disease progression. Further work is warranted to validate these preliminary data in a larger cohort of individuals with ALS.

P84 NON-INVASIVE VENTILATION INFLUENCES RESTING ENERGY EXPENDITURE IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

Marinou K¹

Bovio G²

Cena H³

Mariani P⁴

Mora G¹

^wDepartment of Neurological Rehabilitation

^xMetabolic-Nutritional Unit and Palliative Care Unit

^yClinical Nutrition Department Salvatore Maugeri Foundation, Pavia, Italy

^zDepartment of Public Health, Section of Human Nutrition and Dietetics, University of Pavia, Pavia, Italy

Email address for correspondence: [email protected]

Keywords: non-invasive ventilation(NIV), energy expenditure, indirect calorimetry

Background: Non-invasive ventilation (NIV) has been demonstrated to be the treatment of choice for respiratory failure in patients with amyotrophic lateral sclerosis (ALS) because it reduces respiratory muscles activity and improves gas exchanges.

Two studies investigated the resting energy expenditure (REE) in ALS patients undergoing invasive ventilation. Both studies found a decreased REE, attributed to the reduced respiratory work load supported by the invasive ventilation. To our knowledge no study compared REE in ALS patients with and without NIV.

Objectives: The primary aim of our study was to determine whether respiratory failure and NIV have an influence on the REE in ALS patients. The secondary aim was to determine whether the Harris-Benedict formula (pREE) correctly predicts the REE in these patients.

Methods: We studied 9 ALS patients (4 M, 5 F, 4 bulbar and 5 spinal onset), mean age 66.1 ± 7.7 years. All patients have been using NIV during sleep for at least 4 months. All patients underwent neurological, respiratory and nutritional evaluation. Nutritional assessment included weight, height, body mass index and bio-impedance analysis and, on alternate days, indirect calorimetry during spontaneous breathing and during NIV, to measure the REE (mREE) in these two conditions.

The mREE was also compared to pREE. Patients were considered hypermetabolic if mREE/pREE was higher than 10%, hypometabolic if the ratio was lower than 10% and normometabolic if the ratio ranged between + 10 % and +10 %.

Results: The mean BMI was 24.54 ± 2.7 kg/m² (range 19.2–28.8). The mean mREE obtained without NIV was 1123 ± 181 kcal/day, while mREE obtained during NIV was 1019 ± 180 (p = 0.036). The mREE obtained without NIV showed normometabolism in 5 patients and hypometabolism in 4 patients. The mREE during NIV showed hypometabolism in 8 patients, while one patient was normometabolic.

In patients without NIV, pREE overestimated the basal metabolic rate of 14.7 ± 12 %; in patients with NIV, pREE overestimated the basal metabolic rate of 23 ± 8.4 %.

Discussion and conclusion: 1) Respiratory failure produces an increase in mREE probably due to respiratory muscles hyperactivity; 2) mREE is significantly reduced during NIV; 3) pREE overestimates REE in patients both in spontaneous breathing and during NIV; 4) Indirect calorimetry is recommended for nutritional assessment in ALS patients.

P85 EFFECTS OF EARLY NON INVASIVE VENTILATION ON PULMONARY FUNCTION IN ALS PATIENTS: PRELIMINARY RESULTS OF A RANDOMIZED CONTROL TRIAL

Gonzalez N¹

Prats E¹

Rodriguez-Gonzalez MJ²

Marti S³

Lujan M⁴

Povedano MP¹

Turon SJ¹

Antón A⁵

Calle M⁶

Farrero E¹

^aaHospital Universitari de Bellvitge, L’Hospitalet, Barcelona, Spain

^abHospital Gregorio Marañon, Madrid, Spain

^acHospital Vall Hebron, Barcelona, Spain

^adHospital Parc Tauli, Sabadell, Barcelona, Spain

^aeHospital Sant Pau, Barcelona, Spain

^afHospital Clinico San Carlos, Madrid, Spain

Email address for correspondence: [email protected]

Keywords: non-invasive ventilation(NIV), early initiation, survival

Background: Non-invasive ventilation has demonstrated an improvement of survival and quality of life in ALS patients. Recent studies (1, 2) suggest that early initiation, in early stages of respiratory muscle weakness, would give a greater increase in survival

Objective: To assess the effects from early use of non-invasive ventilation (NIV) in progression of respiratory muscle weakness, measured by rate of decline in Forced Vital Capacity (FVC).

Methods: A multicentre, randomized, open-label, controlled clinical trial including patients with FVC < 75% who are randomized to: 1; early NIV (treatment initiation after randomization) and 2; standard NIV (treatment initiation when FVC < 50% predicted, presence of orthopnea, and/or PaCO2 > 45 mmHg). Patients were assessed every three months. Variables collected included: anthropometric variables and data of ALS disease, functional respiratory variables (spirometry, arterial blood gases and nocturnal pulseoxymetry).

Non parametric test were used to compare groups at baseline. Differences in the FVC decline between groups, over consecutive visits were compared using U Mann-Whitney and Wilcoxon test was used to analyze differences within each of the two groups.

Results: 41 patients have been included in the trial overall; for the purpose of this study we analysed 25 patients (10 patients in early NIV group and 15 patients in the standard group; 52 % men, mean age 59 (12) years; 92 % of cases the onset of the disease was limb). There were no differences between both groups in anthropometric variables, data of ALS disease, arterial blood gases or nocturnal pulseoxymetry values. During the follow-up we only observed a slight significant decrease in FVC at 6 months in the early NIV group (FVC baseline 69%, FVC 3 months 69%, FVC 6 months 62% p = 0.01) while there was a highly significant and progressive decrease in the standard group (FVC baseline 68%, FVC 3 months 53% p = 0.0001, FVC 6 months 45% p = 0.009). Differences between groups were significant at 3 and 6 months.

Conclusion: Preliminary results in our study show a highly significant beneficial effect of early NIV in ALS patients, slowing-down the progressive decline of Functional Vital Capacity.

Acknowledgements: SOCAP, ISCIII PI11/01209, Esteve-Teijin.

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P86 SAFETY AND TOLERABILITY OF SYSTEMIC BETA-2-ADRENERGIC AGONIST (ALBUTEROL) AS PHARMACOLOGICAL THERAPY IN NON-INVASIVE VENTILATION (NIV)-SUPPORTED AMYOTROPHIC LATERAL SCLEROSIS (ALS) PATIENTS WITH CHRONIC RESPIRATORY FAILURE

Brooks BR^1,4

Kandinov B¹

Langford VL¹

Lindblom SS^1,4

Sanjak MS¹

Wright KA¹

Ward AL^1,6

Holsten SE¹

Fischer MP¹

Lucas NM¹

Smith NP¹

Nichols MS¹

Belcher SL¹

Lary C¹

Nemeth J¹

Russo PC¹

Bockenek WL^3,4

Bravver EK^1,4

Desai UG^1,4

Story SJ^1,4

^agCarolinas Neuromuscular/ALS-MDA Center

^ahDepartment of Internal Medicine - Carolinas Medical Center, Charlotte NC, USA

^aiDepartment of Physical Medicine and Rehabilitation - Carolinas Rehabilitation, Charlotte NC, USA

^ajUniversity of North Carolina School of Medicine – Charlotte Campus, Charlotte NC, USA

^akDepartment of Kinesiology, University of North Carolina - Charlotte, Charlotte NC, USA

^alCabbarus College of Health Sciences - Occupational Therapy, Concord NC, USA

Email address for correspondence: [email protected]

Keywords: beta-adrenergic agonist, albuterol, non-invasive ventilation (NIV)

Background: NIV decreases the rate of respiratory function decline in ALS patients (1, 2). Few clinical trials have addressed improving respiratory function or extending time before NIV daytime-dependency in these patients (3). Beta-2-adrenergic agonists (albuterol/clenbuterol) have increased vital capacity and neck strength short-term in ALS and spinal muscular atrophy patients (4, 5, 6).

Objective: Clinical audit of use of systemic albuterol in NIV-supported ALS patients at an ALS Multidisciplinary Clinic.

Methods: In this study we carried out a retrospective audit of albuterol utilization in NIV-supported ALS patients from 2010–2013. Vital signs (pulse rate, respiratory rate, blood pressure, vital capacity (% predicted-Knudsen (adult), ALSFRS-R individual or combined bulbar-and respiratory-subscores) were reviewed in 108 NIV-supported ALS patients (55M; 52F) at the start of NIV or at the start of albuterol on NIV and then at 3 and 6 months subsequently. In NIV-supported ALS patients with difficulty maintaining breathing capacity associated with bulbar and respiratory dysfunction, Albuterol was started at a median systemic dose (tablet/liquid) of 6 + 3(SD) mg/day.

Results: Albuterol was tolerated for 6 months in 49/52 (31M; 18F) NIV-supported ALS patients but not in 3 patients (1M, 2F; 94.2% tolerability) with no further VC reduction for 3 months. More male patients (p = 0.0262) with VC below 70% predicted (VC = 61.0% predicted (95%CI = 53.9–68.2)) were given albuterol compared with NIV-supported ALS patients (23M; 32F) not receiving albuterol (VC = 77.3% (95%CI = 70.7–83.9)). ALSFRS-R respiratory, but not bulbar-sub-score was significantly (p = 0.0006) decreased in albuterol treated patients (6.4(95%CI = 5.4–7.3)) compared with patients not receiving albuterol (9.2(95%CI = 8.0–10.6)). Pulse rate increased 10% from baseline but the population variability of this change within the normal pulse rate range was not significant. VC remained unchanged at 3 months (VC = 57.7% (95%CI = 49.8–65.5)) but declined at 6 months on albuterol (VC = 50.0% (95% CI = 35.8–58.5)).

Discussion and conclusion: Systemic albuterol is 94.2% tolerable when used in NIV-supported ALS patients. Male NIV-supported ALS patients more commonly required albuterol. VC was maintained at 3 months without change but not at 6 months in albuterol-treated NIV-supported ALS patients. Further studies are required on pharmacologically enhancing the treatment of NIV-supported ALS patients.

Acknowledgements: Carolinas ALS Research Fund/ Pinstripes Fund/Carolinas Garden of Hope/Carolinas Healthcare Foundation/Muscular Dystrophy Association Patient Services Grant.

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P87 TIMING OF THE INTRODUCTION OF NONINVASIVE VENTILATION AND MECHANICALLY ASSISTED COUGHING IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

Kano O

Takazawa T

Hirayama T

Yanagihashi M

Ishikawa Y

Miura K

Hanashiro S

Sawada M

Kawabe K

Ikeda K

Iwasaki Y

Toho University School of Medicine, Tokyo, Japan

Email address for correspondence: [email protected]

Keywords: mechanically assisted coughing (MAC), forced vital capacity (FVC), peak cough expiratory flow (PCEF)

Background: Since most patients with ALS die from respiratory failure, diagnosis and management of respiratory insufficiency is critical. Forced vital capacity (% FVC) and peak cough expiratory flow (PCEF) are the most common respiratory measurement techniques used for the introduction of non-invasive ventilation (NIV) and mechanically assisted coughing (MAC), respectively, in patients with ALS.

Objectives: To study the timing of introduction of NIV and MAC using %FVC and PCEF, respectively, and compare bulbar onset (BO) to spinal onset (SO).

Methods: A total of 40 patients met the revised El Escorial criteria. We selected patients with a %FVC of < 50% or a PECF of < 270 L/min. The mean age (SD) of the patients was 59.4 ± 15.0 years in the BO (n = 10) group and 66.1 ± 8.8 years in the SO (n = 13) group. We evaluated the PCEF approximately every 3 months. The PCEF was determined thrice per measurement, and the maximum value was taken as the PCEF. In addition, the body mass index (BMI) and the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score were also studied.

Results: A total of 23 patients were enrolled in this study. A decline in the PECF (< 270 L/min) prior to a decline in %FVC (< 50%) was observed in 7 and 10 patients in the BO and SO groups, respectively. However, with regard to the speech item on the ALSFRS-R, BO patients showed more speech impairment than SO patients (2.1 ± 0.9 vs. 3.3 ± 0.7; P = 0.04). No significant difference was observed in the BMI between the 2 groups.

Discussion and conclusion: According to the Report of Quality Standards Subcommittee of the American Academy of Neurology, one of the parameters for considering NIV is a %FVC of < 50% and the parameter for MAC is a PCEF of < 270 L/min. NIV and MAC are important for improving respiratory function and clearing upper airway secretions. Patients in the BO group as well as most patients in the SO group showed a decline in the PCEF (< 270 L/min) prior to a decline in the %FVC (< 50%), although bulbar symptoms on the ALSFRS-R was different between the 2 groups.

The results of this study suggest that MAC may be introduced earlier than NIV in patients with both BO and SO.

References:

• Miller RG. et al. Neurology 2009; 73(15): 1218–26.
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P88 EVALUATION OF THE COUGHASSIST E70 COMPARED TO COUGHASSIST 3000 IN ADULTS WITH AMYOTROPHIC LATERAL SCLEROSIS

Jackson C¹

Lotz G²

Jasko J²

Boyce C²

Schroth M³

Jackson L¹

Kittrell P¹

^amUniversity of Texas Health Science Center San Antonio, San Antonio, TX, USA

^anPhillips Respironics, Monroeville, PA, USA

^aoChildren’s Hospital, University of Wisconsin Hospital and Clinics, Madison, WI, USA

Email address for correspondence: [email protected]

Keywords: mechanical insufflation/exsufflation, airway clearance, Cough Assist

Background: Pulmonary complications are a major cause of morbidity and mortality in patients with compromised airway clearance mechanisms. Coughing is a protective reflex that helps to remove secretions from the airways. The CoughAssist clears secretions by applying a positive pressure to the airway, then rapidly shifting to a negative pressure. This rapid shift in pressure produces a high expiratory flow rate from the airways, simulating a cough. The E70 further assists by loosening secretions through high frequency oscillatory vibrations during inspiration, expiration, or both.

Objectives: The primary objective of this study was to demonstrate E70 improved usability and comfort compared with subjects’ current device over 14 days. Secondary outcomes were to evaluate subjects’ global impressions of benefit and to gather information about the use of oscillation.

Methods: Subjects prescribed daily Cough Assist use were recruited and used the E70 for 14 days. Subjects/caregivers completed questionnaires capturing E70 usability and impressions of benefit. Usability questions were based on a 1–5 Likert scale: 1 = strongly disagree and 5 = strongly agree. Global impressions were based on a 1–10 Likert scale: 1 is much better, 5 is no change, and 10 is much worse.

Results: Six adult subjects diagnosed with amyotrophic lateral sclerosis (ALS) and one adult diagnosed with spinal muscle atrophy (SMA) ages 23 to 72 years old were recruited. Based on the usability questionnaire data, subjects or caregivers rated the E70 performance equivalent or better than the Cough Assist 3000 for ease of use at home (p = 0.047), ease of use outside the home (p = 0.184), durability (p = 0.017), and overall satisfaction (p = 0.002). The E70 proved superior in sputum production (p = 0.002), and ease of breathing (p < 0.001). Participants preferred the added oscillation and battery features of the E70 that were lacking in the previous device.

The Global Impression Questionnaire showed non-significant trends that tended to favour the E70 with respect to activity limitations (p = 0.134), symptoms (p = 0.121), emotions (p = 0.253) and overall quality of life (p = 0.341).

Discussion and conclusion: The Cough Assist E70, with the oscillation feature, was preferred by subjects and/or caregivers over their previous device for secretion management. The E70 performed equivalent to or better than the Cough Assist 3000 with respect to subject usability and comfort over 14 days.

References:

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P89 SLEEP QUALITY AND PATIENT-VENTILATOR ASYNCHRONY DURING NONINVASIVE VENTILATION IN AMYOTROPHIC LATERAL SCLEROSIS

Vrijsen B¹

Buyse B¹

Belge C¹

Van Damme P²

Testelmans D¹

^apUniversity Hospitals Leuven, Department of Pulmonology, LUCS, Leuven, Belgium

^aqUniversity Hospitals Leuven, Department of Neurology, Leuven, Belgium

Email address for correspondence: [email protected]

Keywords: non-invasive ventilation (NIV), sleep quality, patient-ventilator asynchrony

Background: In amyotrophic lateral sclerosis (ALS) patients treated with noninvasive ventilation (NIV), sleep quality or sleep architecture has not been shown to be improved (1) and a high patient-ventilator asynchrony (PVA) index was present (2). Prospective studies examining sleep quality by polysomnography (PSG) before and after initiation of NIV in ALS are lacking.

Objectives: To analyse sleep quality and PVA at the start of NIV and one month later.

Methods: Full-video PSG, with incorporation of transcutaneous carbon dioxide (P_tcCO₂) and Trilogy 100 ventilator software, was used to analyze sleep epoch-by-epoch, respiratory events and PVA breath-by-breath in 19 ALS patients (61 ± 9 years, 10 non-bulbar). After diagnostic PSG, NIV was titrated during 3 consecutive nights. Sleep quality was evaluated at discharge and after 1 month. Data are presented as median and interquartile range.

Results: In non-bulbar patients sleep efficiency (SE), arousal-awakening index (AAI) and amount of rapid-eye-movement (REM) sleep were improved at discharge (SE: 70.9% (62.6–81.1),p < 0.01; AAI: 18.9/h sleep (14.3–23.9), p < 0.01; REM: 21.7% (18.5–27.9), p < 0.01) in comparison to the diagnostic PSG (SE: 60.8% (18.6–73.3); AAI: 43.0/h sleep (33.6–70.1); REM: 3.8% (0.0–10.1)) and remained improved after one month (SE: 74.1% (43.4–85.0), p < 0.01; AAI: 19.1/h sleep (10.5–30.4), p < 0.01; REM: 20.2% (13.0–23.4), p < 0.01). Median time of nocturnal P_tcCO₂ > 55 mmHg decreased from 42.4% (0.1–96.1) at diagnostic night to 0% (0.0–12.6, p < 0.05) at discharge and 0% (0.0–14.2, p = 0.12) after one month. Bulbar patients only showed improvement in the amount of slow-wave-sleep (discharge: 25.5% (13.3–38.6) vs 12.3 (1.5–21.7), p < 0.01; one month: 21.5% (4.0–28.8), p < 0.05) without any improvement in P_tcCO2. Non-bulbar patients showed a PVA index of 31.8 (2.5–167.8)/h sleep at discharge and 17.5 (2.2–55.2)/h sleep at one month. PVA caused an arousal/awakening of 1.9 (0.4–5.9)/h sleep at discharge and 1.1 (0.1–2.3)/h sleep at 1 month. Bulbar patients had a PVA index of 4.3 (2.7–31.3)/h sleep at discharge and 15.4 (3.9–30.7)/h sleep at one month. PVA followed by an arousal/awakening were 0.3 (0.0–1.1)/h sleep at discharge and 0.4 (0.0–1.8) at one month. No differences were found on the amount of PVA during or outside leak occurrence.

Discussion and conclusion: Non-bulbar patients showed improvements in sleep quality, sleep architecture and P_tcCO₂, while bulbar patients only showed improvement in SWS. PVA are present in bulbar and non-bulbar patients but have no or minor impact on sleep quality/architecture.

Acknowledgements: The authors received financial support from ABMM - Téléthon.

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P90 TRACHEOSTOMY AND INVASIVE VENTILATION IN JAPANESE ALS PATIENTS: DECISION-MAKING AND SURVIVAL ANALYSIS

Kimura F

Tagami M

Ota S

Tukahara A

Osaka Medical college, Takatsuk-city, Osaka, Japan

Email address for correspondence: [email protected]

Keywords: NIPPV, long-term care, tracheostomy invasive ventilation (TIV)

Objectives: To evaluate the factors related to the choice of a tracheostomy and invasive ventilation in amyotrophic lateral sclerosis patients and to determine survival time after a tracheostomy at a single institute in Japan between 1990 and 2010.

Methods: Data for survival time until death or tracheostomy were obtained from 160 patients. Fifty-two patients (33%) underwent tracheostomy/ mechanical ventilation.

Results: Tracheostomy and invasive ventilation prolonged median survival time (74 months), as did non-invasive ventilation (48 months) when compared to a non-ventilation-supported control group (32 months; p < 0.001 each). The ratio of tracheostomy/mechanical ventilation in patients > 65 years old significantly increased after 1999 (27%) compared to earlier years (10%, p = 0.002). Cox proportional modelling confirmed an age of 65 years as advantageous for long-term survival after a tracheostomy. In univariate logistic regression analysis, factors related to the decision to perform a tracheostomy included: an age of 65 years; greater use of non-invasive ventilation; the presence of a spouse; interval and speed from disease onset to diagnosis/tracheostomy; and preservation of motor function. In multivariate logistic regression analysis, age, shorter duration from disease onset until tracheostomy and the presence of a spouse were independently associated with the decision to perform a tracheostomy. Kaplan-Meier plots revealed longer survival times in patients who resided at home after a tracheostomy compared to patients who stayed at a hospital (p = 0.007).

Discussion and conclusion: Several reasons may explain the high frequency and increased rate of TIV over past 20 years. First, frequency of TIV appears higher not only in Japan, but also in Asian countries (12.7–21%). Recent reports have described TIV being performed in around 30% of the overall ALS population from Italy Japanese government covers all costs for home non-invasive/invasive mechanical ventilation at any age for both inpatients and outpatients. Regular follow-up in the same institute may influence the rate of TIV and peer counselling by the Japanese ALS Association (JALSA) has contributed to increased adoption of TIV. The implementation of the LTCI as a new and fundamentally reformed social insurance system in 2000 may have facilitated multidisciplinary team care and an associated increase in use of TIV.

Tracheostomy and invasive ventilation are frequently used in Japan. Various factors impact patients’ decisions to have these procedures. This study identified factors related to the decision-making process and post-tracheostomy survival.

Acknowledgements: This work was supported by grants from The Osaka Medical Research Foundation for Incurable Diseases.

References:

• Fujimura-Kiyono C et al. J Neurol Neurosurg Psychiatry 2011; 82: 1244–9.
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P91 AN UPDATE ON OPINIONS AND BEHAVIORS OF JAPANESE AND AMERICAN ALS CAREGIVERS REGARDING TRACHEOSTOMY WITH INVASIVE VENTILATION (TIV)

Christodoulou G¹

Ogino M²

Goetz R³

Mitsumoto H¹

Rabkin J³

The American and Japanese Tiv Study Group^1,2

^arEleanor and Lou Gehrig MDA/ALS Research Center, Columbia University Medical Center, New York, New York, USA

^asDepartment of Neurology, Kitasato University School of Medicine, Kanagawa, Japan

^atNew York State Psychiatric Institute & Department of Psychiatry, Columbia University, New York, New York, USA

Email address for correspondence: [email protected]

Keywords: caregivers, tracheostomy invasive ventilation (TIV), Japan

Background: Caregivers play an integral role in the lives and care of patients with amyotrophic lateral sclerosis (ALS). Their opinions can be highly influential throughout the disease course. Past studies have shown highly dissimilar rates of TIV among different countries with Japan exceeding the United States substantially. A multi-site survey assessing Japanese and American patients to determine preferences found that contrary to past reports, Japanese patients were more likely to oppose TIV, demonstrating the influence of other factors in the ultimate decision-making (1).

Objectives: To assess caregiver preferences and their determinants concerning TIV in America and Japan.

Methods: 154 American caregivers from five, geographically distributed ALS Clinics and 66 Japanese caregivers from six sites in several cities completed questionnaires regarding TIV.

Results: Caregivers were similar demographically: mean age was around 57, 70–76% were female, 70–72% were spouses/partners, and 41–47% were working full-time. American caregivers were more likely to report excellent health (59%) compared to Japanese caregivers (16%). More American caregivers reported to share the role of head of household and associated decision-making with their spouses (60%) compared to Japanese caregivers (2%). American caregivers reported more emotional support and someone to confide in than Japanese caregivers (93% vs. 71%) but fell short of Japanese caregivers in obtaining assistance in caregiving from others (35% vs. 52%). More Japanese caregivers knew someone utilizing TIV (32%) than American caregivers (6%). When asked whether they were in favour of TIV, 33% of American caregivers were in favour compared to 53% of Japanese caregivers; 44% of American and 37% of Japanese caregivers were undecided; and 22% of American and 10% of Japanese caregivers were opposed to TIV. The most common reason for being in favour of TIV in the American sample was that the patient could maintain quality of life (79%), while Japanese caregivers believed the patient reaching a milestone to be a main contributing factor (51%). All comparisons listed above were significant (p < 0.05). Reasons for opposing TIV did not significantly differ between the two samples.

Discussion and conclusion: As predicted, higher rates of TIV in Japan can be attributed to caregiver and neurologist preferences. These findings solidify the importance of caregivers’ roles in patient care. This study looked at intentions specifically; therefore, further studies investigating outcome rates must be considered.

Acknowledgements: MDA Wings Over Wall Street; M. Ogino received a Health and Labor Sciences Research Grant on Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan; Koko Muraoka, Toho University; and the patients who participated in this study.

Reference:

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P92 COMPARISON OF COMMUNICATION ABILITY STAGE WITH ADVERSE CLINICAL SIGNS IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS (ALS) ON TRACHEOSTOMY INVASIVE VENTILATION (TIV)

Nakayama Y¹

Matsuda C¹

Shimizu T²

Mochizuki Y^3,4

Hayashi K²

Nagao M²

Kawata A²

Oyanagi K⁵

Nakano I²

^auLaboratory of Nursing Research for Intractable Disease, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

^avDepartments of Neurology

^awDepartments of Pathology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan

^axDepartment of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Centre for the Disabled, Tokyo, Japan

^ayDepartment of Brain Disease Research, Shinshu University School of Medicine, Nagano, Japan

Email address for correspondence: [email protected]

Keywords: tracheostomy invasive ventilation (TIV), impaired communication, adverse clinical signs

Background: Patients with amyotrophic lateral sclerosis (ALS) on tracheostomy invasive ventilation (TIV) have adverse clinical signs and develop communication impairment with disease progression (1). We proposed a classification of advanced ALS focusing on the patient's communication ability (2) and the classification scheme's utility for nursing and for studies. The classification includes four stages: Stage I = communicates in sentences; Stage II = communicates with one word responses; Stage III = communicates with nonverbal yes/no responses; Stage IV = cannot communicate, except for unreliable yes/no; Stage V = cannot communicate by any means (2).

Objective: To clarify the relationship between the stages of communication ability and adverse clinical signs in ALS patients on TIV.

Methods: We enrolled 46 patients with ALS on TIV at home from 2005 to 2013. We classified them by stage of communication ability at the end point. Data was collected on sex, age of onset, duration of disease, duration of TIV, and time from onset to start of TIV. Retrospectively, we assessed the presence or absence of 16 adverse clinical signs as follows: fatigability of eye movement; dry eye; drooling or dry mouth; megaloglossia; unstable blood pressure; disturbance of thermoregulation; dysuria; nausea; unstable blood glucose; otitis media, pneumonia; urinary tract infections; cholelithiasis; tracheal granuloma; urinary stones; decubitus. Data analysis was performed using SPSS, version 21. The Kruskal-Wallis test was used to compare three groups (stages I, II-IV, and V), and p-values < 0.05 were considered significant.

Results: The patients were divided into three groups: stages I (n = 21); II-IV (n = 19); V (n = 6). Statistical significance between-group differences were noted for the time from onset to start of TIV (I: 59.0 months; II-IV: 27.0 months; V: 24.0 months, p = 0.039) and the number of adverse signs per person (I: 4.0; II-IV: 7.0; V: 9.5, p = 0.0001). No significance between-group difference was noted for either the disease duration or the TIV duration.

Discussion and conclusion: This is the first report evaluating the multiple adverse signs in ALS patients on TIV. We found that the patients with ALS in advanced stages showed an early requirement for TIV and had more adverse signs. Clinicians should give careful attention to the adverse signs of ALS patients on TIV to prevent communication impairment.

Acknowledgements: JSPS KAKENHI (Grant-in-Aid for Scientific Research [B]) Grant Number 25293449 and by the Joint Program for ALS Research at the Tokyo Metropolitan Institute of Medical Science.

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