The Use of the Voice Trainer App for Vocal Control in People with a Degenerative Ataxia: A Pilot Intervention Study.

Dysarthria is disabling in persons with degenerative ataxia. There is limited evidence for speech therapy interventions. In this pilot study, we used the Voice trainer app, which was originally developed for patients with Parkinson's disease, as a feedback tool for vocal control. We hypothesized that patients with ataxic dysarthria would benefit from the Voice trainer app to better control their loudness and pitch, resulting in a lower speaking rate and better intelligibility. This intervention study consisted of five therapy sessions of 30 min within 3 weeks using the principles of the Pitch Limiting Voice Treatment. Patients received real-time visual feedback on loudness and pitch during the exercises. Besides, they were encouraged to practice at home or to use the Voice trainer in daily life. We used observer-rated and patient-rated outcome measures. The primary outcome measure was intelligibility, as measured by the Dutch sentence intelligibility test. Twenty-one out of 25 included patients with degenerative ataxia completed the therapy. We found no statistically significant improvements in intelligibility (p = .56). However, after the intervention, patients were speaking slower (p = .03) and the pause durations were longer (p < .001). The patients were satisfied about using the app. At the group level, we found no evidence for an effect of the Voice trainer app on intelligibility in degenerative ataxia. Because of the heterogeneity of ataxic dysarthria, a more tailor-made rather than generic intervention seems warranted.

Botulinum toxin-A injections vs radiotherapy for drooling in ALS.

OBJECTIVES: Botulinum neurotoxin (BoNT) injections in the salivary glands and radiotherapy (RT) on these glands are commonly used to alleviate severe drooling in patients with amyotrophic lateral sclerosis (ALS). This study compares BoNT type A with RT based on patient-rated evaluations. MATERIALS & METHODS: A prospective randomized controlled pilot study to compare RT (n = 10; on the parotid and the posterior part of the submandibular glands) with BoNT-A treatment (n = 10; in the parotid glands only, because of the risk of increasing oropharyngeal weakness) in patients with ALS. The primary outcome was the drooling status (burden of drooling), and our secondary interests were the degree of salivation, global change of drooling after treatment, and level of satisfaction with the treatment and negative experiences. RESULTS: There were no statistically significant between-treatment differences for the drooling status after treatment. Only at twelve weeks more saliva reduction was achieved by RT (P = 0.02). Patients treated with RT also described more transient negative experiences (like pain in mandible) directly after treatment. Subgroup analysis showed that patients with very severe dysphagia (no oral intake) were less satisfied and experienced a lower global change of drooling after treatment. CONCLUSIONS: This pilot study showed no significant difference in the burden of drooling between the treatments. However, with RT more saliva reduction was achieved, including negative experiences directly after treatment, but without the risk of decreasing oropharyngeal function. In addition, patients with very severe dysphagia do not seem to benefit from either treatment.

Prognostic value of decreased tongue strength on survival time in patients with amyotrophic lateral sclerosis.

Decreased tongue strength (TS) might herald bulbar involvement in patients with amyotrophic lateral sclerosis (ALS) well before dysarthria or dysphagia occur, and as such might be prognostic of short survival. The purpose of this study was to investigate the prognostic value of a decreased TS, in addition to other prognostic factors, such as site of onset, bulbar symptoms, bulbar signs, age, sex, maximum phonation time, time from symptoms to diagnosis, and gastrostomy, for survival time in patients with ALS. TS was measured in four directions in 111 patients who attended the diagnostic outpatient motor neuron clinic of our university hospital. Of these patients, 54 were diagnosed with ALS. TS was considered abnormal if the strength in minimally one direction was at least two standard deviations below the reference values obtained from comparable age category and sex-groups of healthy controls (n = 119). Twenty of the patients with ALS had a decreased TS. Multivariable analysis showed that, in addition to age, TS was an independent prognostic factor for survival time in patients with ALS.

Prevalence of oropharyngeal dysphagia in Parkinson's disease: a meta-analysis.

Dysphagia is a potentially harmful feature, also in Parkinson's disease (PD). As published prevalence rates vary widely, we aimed to estimate the prevalence of oropharyngeal dysphagia in PD in a meta-analysis. We conducted a systematic literature search in February 2011 and two independent reviewers selected the papers. We computed the estimates of the pooled prevalence weighted by sample size. Twelve studies were suitable for calculating prevalence rates. Ten studies provided an estimate based on subjective outcomes, which proved statistically heterogeneous (p < 0.001), with a pooled prevalence estimate with random effect analysis of 35% (95% CI 28-41). Four studies provided an estimate based on objective measurements, which were statistically homogeneous (p = 0.23), with a pooled prevalence estimate of 82% (95% CI 77-87). In controls the pooled subjective prevalence was 9% (95% CI 2-17), while the pooled objective prevalence was 23% (95% CI 13-32). The pooled relative risk was 3.2 for both subjective outcomes (95% CI 2.32-4.41) and objective outcomes (95% CI 2.08-4.98). Clinical heterogeneity between studies was chiefly explained by differences in disease severity. Subjective dysphagia occurs in one third of community-dwelling PD patients. Objectively measured dysphagia rates were much higher, with 4 out of 5 patients being affected. This suggests that dysphagia is common in PD, but patients do not always report swallowing difficulties unless asked. This underreporting calls for a proactive clinical approach to dysphagia, particularly in light of the serious clinical consequences.

Speech pathology interventions in patients with neuromuscular diseases: a systematic review.

PURPOSE: A systematic review was conducted to summarize and evaluate the literature on the effectiveness of speech pathology interventions in adults with neuromuscular diseases. METHOD: Databases searched included the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, PsycINFO and PubMed. A total of 1,772 articles were independently screened on title and abstract by 2 reviewers. RESULTS: No randomized controlled trials or clinical controlled trials were found. Four other designs were included. Only one study on oculopharyngeal muscle dystrophy (OPMD) appeared to have sufficient methodological quality. There is evidence indicating that correction of head position in patients with OPMD improves swallowing efficiency (level III evidence). CONCLUSION: Despite 1,772 studies, there is only evidence of level III regarding the effectiveness of speech pathology interventions in patients with OPMD. Recommendations for future research are given.

Dysphagia in spinal muscular atrophy type II: more than a bulbar problem?

OBJECTIVE: In patients with spinal muscular atrophy (SMA) type II, feeding problems and dysphagia are common, but the underlying mechanisms of these problems are not well defined. This case control study was designed to determine the underlying mechanisms of dysphagia in SMA type II. METHODS: Six children with SMA type II and 6 healthy matched controls between 6.4 and 13.4 years of age were investigated during swallowing liquid and solid food in 2 different postures using surface EMG (sEMG) of the submental muscle group (SMG) and a video fluoroscopic swallow study (VFSS). RESULTS: The VFSS showed postswallow residue of solid food in the vallecula and above the upper esophageal sphincter (UES), which can be responsible for indirect aspiration. Better results in swallowing were achieved in a more forward head position. These findings were supported by the sEMG measurements of the SMG during swallowing. CONCLUSIONS: Dysphagia in spinal muscular atrophy type II is due to a neurologic dysfunction (lower motor neuron problems from the cranial nerves in the brainstem) influencing the muscle force and efficiency of movement of the tongue and the submental muscle group in combination with a biomechanical component (compensatory head posture). The results suggest an integrated treatment with an adapted posture during meals and the advice of drinking water after meals to prevent aspiration pneumonias.

Prevalence and definition of drooling in Parkinson's disease: a systematic review.

Drooling (saliva loss) is a frequently reported symptom in patients with Parkinson's disease (PD), but an accurate estimate of the prevalence of drooling is lacking. The aim of this study was to systematically review the prevalence of drooling in published research papers. A systematic PubMed and CINAHL search was done, including studies published until January 2009. Eight studies were found, presenting prevalence rates of drooling based on responses of PD patients to questionnaires. The statistical heterogeneity was highly significant (P < 0.0001), with prevalence rates ranging from 32 to 74%. The pooled prevalence estimate with random effect analysis was of 56% (95% CI 44-67) for PD patients and 14% (95% CI 3-25) for healthy controls; the pooled relative risk (RR) with random effect analysis was 5.5 (95% CI 2.1-14.4). All studies reported data of community dwelling idiopathic PD patients, with a mean age around 65 years and mild PD in 50-60% of the cases. Heterogeneity was mainly caused by differences in definition or frequency of drooling. The highest prevalence rates included nocturnal drooling where others noted only diurnal drooling. Analysis of the data of two studies showed that drooling is reported frequently by 22-26% of the patients. Prevalence rates were lower in milder PD patients. The summarized findings demonstrate that drooling can be present in half of all PD patients. In about a quarter of PD patients, drooling appears to be a frequently occurring problem. We recommend to report drooling in future studies with more detailed consideration of severity, frequency and nocturnal versus diurnal complaints.

Dysphagia is present but mild in myotonic dystrophy type 2.

The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant feature in DM1, has not yet been examined in DM2. In a recent nationwide questionnaire survey of gastrointestinal symptoms in DM2, 12 out of 29 DM2 patients reported to have difficulty in swallowing for solid food. The aim of the study was to investigate the presence of dysphagia in patients with genetically proven DM2 who reported difficulty in swallowing for solid food at the questionnaire survey. Swallowing function and fiberoptic endoscopic evaluation of swallowing (FEES) were examined by a speech therapist and otorhinolaryngologist, respectively. In DM2 patients who reported difficulty in swallowing the presence of dysphagia could be confirmed (clinically in 100%, by FEES in 88%). A correlation exists between Dysphagia Outcome and Severity Score (DOSS) and age (p=0.05). None of the patients was underweight, and none of the patients had suffered aspiration pneumonia in the past. Dysphagia is present among DM2 patients and is more severe in older patients. However, dysphagia is generally mild, and do not lead to weight loss, or aspiration pneumonia.

Warming up improves speech production in patients with adult onset myotonic dystrophy.

UNLABELLED: This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls were examined, using a protocol that requires subjects, to speak continuously for at least 10 min. In MD patients, warming up led to an increase in speech rate and a decrease in speech variability without causing signs of fatigue or exhaustion as a result of prolonged and intensive use of the speech musculature. No significant changes were found in the controls. After warming up, MD patients achieved a habitual speech rate in reading and reciting similar to that of healthy controls. LEARNING OUTCOMES: As a result of this activity the reader will learn that 1. In contrast to most neuromuscular disorders, speech production in patients with adult onset myotonic dystrophy improves by activity. 2. Myotonia in speech musculature in patients with adult onset myotonic dystrophy can be reduced by instructing them to warm up their muscles by repetitive movements. 3. Warming up is a valuable intervention because it improves the velocity and fluency of speech production without aggravating the signs of flaccid dysarthria.

Dysphagia in facioscapulohumeral muscular dystrophy.

Dysphagia is not considered a symptom of facioscapulohumeral muscular dystrophy (FSHD). In this study, the authors found that dysphagia does occur in patients with advanced FSHD showing mild involvement of the jaw and lingual muscles. Dysphagia is seldom life threatening in these patients. The authors conclude that dysphagia should not be considered an exclusion criterion for FSHD.

Ptosis aggravates dysphagia in oculopharyngeal muscular dystrophy.

BACKGROUND: Ptosis and dysphagia are important features in oculopharyngeal muscular dystrophy (OPMD). OBJECTIVE: Retroflexion of the head is a well known compensatory mechanism for ptosis, but generally retroflexion has a negative effect on swallowing. We hypothesised that severity of ptosis is related to degree of retroflexion and that this compensation is responsible for deteriorating dysphagia. METHODS: Nine OPMD patients were examined in the conditions "head position adapted to ptosis" and "head position slightly flexed". Ptosis was quantified by photogrammetry and retroflexion of the head by digital photographs. The severity of dysphagia was measured using visual analogue scales (VAS) and by calculating swallowing volumes and oropharyngeal swallow efficiency (OPSE) based on videofluoroscopy. RESULTS: Statistical analyses show a significant relationship between ptosis and degree of retroflexion. The degree of retroflexion of the head correlated significantly with VAS scores and with the maximum swallowing volume. The slightly flexed head position significantly improved VAS scores as well as swallowing volumes and OPSE. CONCLUSION: In OPMD patients, ptosis significantly correlates with retroflexion of the head, which has a negative effect on swallowing. Subjective and objective reduction of swallowing problems was found when patients were instructed to eat and drink with a slightly flexed head position.

Detecting antibodies with similar reactivity patterns in the HLDA8 blind panel of flow cytometry data.

The blind panel collected for the 8th Human Leucocyte Differentiation Antigens Workshop (HLDA8; ) included 49 antibodies of known CD specificities and 76 antibodies of unknown specificity. We have identified groups of antibodies showing similar patterns of reactivity that need to be investigated by biochemical methods to evaluate whether the antibodies within these groups are reacting with the same molecule. Our approach to data analysis was based on the work of Salganik et al. (in press) [Salganik, M.P., Milford E.L., Hardie D.L., Shaw, S., Wand, M.P., in press. Classifying antibodies using flow cytometry data: class prediction and class discovery. Biometrical Journal].

Myotonia and flaccid dysarthria in patients with adult onset myotonic dystrophy.

BACKGROUND: Myotonia and weakness are the most important components of dysarthric speech in myotonic dystrophy. OBJECTIVE: To specify and quantify possible defects in speech execution in patients with adult onset myotonic dystrophy. METHODS: Studies on speech production were done on 30 mildly affected patients with myotonic dystrophy. Special attention was paid to myotonia. Because muscle activity can result in a decrease of myotonia, speech characteristics were measured before and after warm up. The possibility that warming up causes increased weakness was also assessed. RESULTS: As with other motor skills, a warm up effect was found in speech production, resulting in an increase in repetition rate and a decrease in variability of repetition rate. Signs of fatigue did not occur. CONCLUSIONS: Warming up is valuable for patients with myotonic dystrophy in reducing the influence of myotonia on speech production.

Cost-effectiveness of an interdisciplinary intervention in geriatric inpatients to prevent malnutrition.

BACKGROUND: In order to reduce protein-energy malnutrition in older people during hospitalisation an early interdisciplinary intervention is needed. We developed a protocol which includes screening for malnutrition, dysphagia and dehydration on admission, followed by immediate interventions. OBJECTIVE: To assess effectiveness of the protocol on nutritional status, hospital-acquired infections and pressure sores, and to evaluate the protocol s economical feasibility. DESIGN: Prospective, controlled study. SETTING: The inpatient geriatric service of a university hospital (UMC Nijmegen) and a geriatric ward of a non-academic teaching hospital (Rijnstate Hospital, Arnhem). SUBJECTS: 298 older patients (>60 years). METHODS: One of the geriatric wards applied the protocol (N=140) while the other provided standard care (N=158). All non-terminally ill patients admitted for more than two days were included. Body mass was measured on admittance and discharge and hospital-acquired infections and pressure sores were scored and costs related to nutrition, infections and length of hospital stay were assessed. RESULTS: There was a 0.8 kg loss (SEM 0.3 kg) in average weight in the standard care group and a 0.9 kg gain (SEM 0.2 kg) in the intervention group (p<0.001). The number of hospital acquired infections was significantly lower in the intervention group (33/140 versus 58/158, p=0.01) but no significant difference in number of patients with pressure sores (23/140 versus 33/158) was found. Costs were not significantly different: 7516 versus 7908 Euro/patient for intervention versus controls, respectively. CONCLUSION: An early interdisciplinary intervention approach can be effective in reducing protein-energy malnutrition and related hospital-acquired infections and appears to be economically feasible.

Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim.

This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34(+) yield 0.5-1.9 x 10(6)/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20 microg/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20 microg/kg/day plus filgrastim 5-10 microg/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of >or=3 x 10(6) CD34(+) cells/kg. In both groups, CD34(+) yield (x 10(6)/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 10(6)/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 10(6)/kg BW in the prior mobilization as in those with 0.76-1.99 x 10(6)/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34(+) cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.

A novel epitope of CD59 expressed by primitive human hematopoietic progenitors.

OBJECTIVE: The aim of this study was to determine the identity of the cell surface molecule on primitive hematopoietic cells recognized by monoclonal antibody HCC-1. MATERIALS AND METHODS: Screening of a cDNA expression library prepared from human bone marrow stromal cells with HCC-1 yielded a single cDNA, which when expressed in FDCP-1 cells, resulted in the specific acquisition of HCC-1 binding. The cDNA demonstrated complete identity with CD59, a phosphoinositol glycan-linked membrane protein that protects cells against autologous complement attack. The ubiquitous expression of CD59 is in marked contrast to the restricted reactivity of HCC-1. Studies were performed to examine the basis for the novel specificity of HCC-1 for CD59. The epitope on CD59 identified by HCC-1 was mapped using a series of rat/human CD59 chimeric proteins. Immunoprecipitation analyses were performed to determine whether CD59 associates with other membrane proteins. RESULTS: Mutagenesis of Asn18 did not alter the binding of HCC-1 to CD59, suggesting that N-linked carbohydrates are not responsible for the binding specificity of HCC-1. The epitope for HCC-1 was shown to differ from that identified by previously described CD59 antibodies, encompassing residues A31, L33, R55, and L59. An 80 kDa protein co-immunoprecipitated with CD59 in the HCC-1(-) cell line HL-60 but not in HCC-1(+) K562 cells. CONCLUSION: Collectively, these data support the hypothesis that the unique specificity of HCC-1 for CD59 is due in part to recognition of a novel epitope, which is masked as a result of association with an as yet unidentified 80 kDa protein.

Monoclonal antibody BB9 raised against bone marrow stromal cells identifies a cell-surface glycoprotein expressed by primitive human hemopoietic progenitors.

OBJECTIVE: The identification of cell-surface antigens whose expression is limited to primitive hematopoietic progenitor cells (HPC) is of major value in the identification, isolation, and characterization of candidate stem cells in human hemopoietic tissues. Based on the observation that bone marrow stromal cells and primitive HPC share several cell-surface antigens, we sought to generate monoclonal antibodies to HPC by immunization with cultured human stromal cells. METHODS: BALB/c mouse were immunized with human bone marrow (BM)-derived stromal cells. Splenocytes isolated from immunized mice were fused with the NS-1 murine myeloma cell line and resulting hybridomas selected in HAT medium, then screened for reactivity against stromal cells, peripheral blood (PB), and BM cells. RESULTS: A monoclonal antibody (MAb), BB9, was identified based on its binding to stromal cells, a minor subpopulation of mononuclear cells in adult human BM, and corresponding lack of reactivity with leukocytes in PB. BB9 bound to a minor subpopulation of BM CD34(+) cells characterized by high-level CD34 antigen and Thy-1 expression, low-absent expression of CD38, low retention of Rhodamine 123, and quiescent cycle status as evidenced by lack of labeling with Ki67. CD34(+)BB9(+) cells, in contrast to CD34(+)BB9(-) cells, demonstrated a capacity to sustain hematopoiesis in pre-CFU culture stimulated by the combination of IL-3, IL-6, G-CSF, and SCF. BB9 also demonstrated binding to CD34(+) cells from mobilized PB. CONCLUSION: Collectively, these data therefore demonstrate that MAb BB9 identifies an antigen, which is selectively expressed by hierarchically primitive human HPC and also by stromal cells.

Prolonged release and c-kit expression of haemopoietic precursor cells mobilized by stem cell factor and granulocyte colony stimulating factor.

Mobilization of haemopoietic precursor cells into the circulation by the combination of cytokines, stem cell factor (SCF) and G-CSF in previously untreated patients with carcinoma of the breast resulted in increased yield of collected peripheral blood precursor cells (PBPC). This mobilization of PBPC by SCF with G-CSF lasted several days after ceasing the cytokines in comparison to the rapid fall of PBPC after ceasing G-CSF. Possible mechanisms for this increased and prolonged mobilization were investigated. Immunological phenotyping with CD38, Thy-1 and MDR-1 of the CD34-positive mobilized PBPC detected no difference in maturity compared to PBPC mobilized by G-CSF alone. However, the down-regulation of c-kit, which is associated with the mechanism of mobilization, was much greater in the PBPC mobilized by SCF and G-CSF. The potential clinical implication of increased and prolonged mobilization is increased yield, allowing transplantation of heavily pre-treated patients, transplantation with PBPC from a single apheresis, or PBSC support for multiple courses of high-dose therapy from one mobilization procedure.