Dysarthria and dysphagia in patients with mitochondrial diseases.

BACKGROUND: Information about dysarthria and dysphagia in mitochondrial diseases (MD) is scarce. However, this knowledge is needed to identify speech and swallowing problems early, to monitor the disease course, and to develop and offer optimal treatment and support. This study therefore aims to examine the prevalence and severity of dysarthria and dysphagia in patients with MD and its relation to clinical phenotype and disease severity. Secondary aim is to determine clinically relevant outcome measures for natural history studies and clinical trials. METHODS: This retrospective cross-sectional medical record study includes adults (age ≥ 18 years) diagnosed with genetically confirmed MD who participated in a multidisciplinary admission within the Radboud center for mitochondrial medicine between January 2015 and April 2023. Dysarthria and dysphagia were examined by administering the Radboud dysarthria assessment, swallowing speed, dysphagia limit, test of mastication and swallowing solids (TOMASS), and 6-min mastication test (6MMT). The disease severity was assessed using the Newcastle mitochondrial disease scale for adults (NMDAS). RESULTS: The study included 224 patients with MD with a median age of 42 years of whom 37.5% were male. The pooled prevalence of dysarthria was 33.8% and of dysphagia 35%. Patients with MD showed a negative deviation from the norm on swallowing speed, TOMASS (total time) and the 6MMT. Furthermore, a significant moderate relation was found between the presence of dysarthria and the clinical phenotypes. There was a statistically significant difference in total time on the TOMASS between the clinical phenotypes. Finally, disease severity showed a significant moderate relation with the severity of dysarthria and a significant weak relation with the severity of dysphagia. CONCLUSION: Dysarthria and dysphagia occur in about one-third of patients with MD. It is important for treating physicians to pay attention to this subject because of the influence of both disorders on social participation and wellbeing. Referral to a speech and language therapist should therefore be considered, especially in patients with a more severe clinical phenotype. The swallowing speed, TOMASS and 6MMT are the most clinically relevant tests to administer.

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.

[Subjective oral health, malocclusions and oral health related quality of life in patients with Duchenne muscular dystrophy]. / De subjectieve mondgezondheid, malocclusies en orale kwaliteit van leven van patiënten met Duchenne-spierdystrofie.

Duchenne muscular dystrophy is a hereditary progressive neuromuscular disorder. Deterioration and weakening of the muscles is also present in orofacial muscles. Both weakness of the muscles and the fact that patients become more dependent of care, can make oral care more difficult. At this moment, it is unknown how patients with Duchenne muscular dystrophy experience their oral health and which problems regarding oral health and oral care may impact their oral health related quality of life. In this cross-sectional study, we found that, despite a high percentage of gingivitis, a high percentage of patients who experience halitosis and a high percentage of malocclusions, patients score their oral health related quality of life as good.

Swallowing dysfunction in patients with nephropathic cystinosis.

INTRODUCTION: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is mentioned in patients with cystinosis, but in clinical practice swallowing investigations are only performed when the patient has complaints. The aim of this study was to explore the swallowing function in patients with cystinosis by use of the Test of Mastication and Swallowing Solids (TOMASS), and to compare their performance with patients with myotonic dystrophy type 1 - a neuromuscular disease in which dysphagia for solid food is a known problem. METHODS: Twenty adult patients with cystinosis (11 men and 9 women, range 19-51 years) and 10 patients with myotonic dystrophy type 1 (5 men and 5 women, range 20-60 years) were included. All cystinosis patients were treated with cysteamine. Data of the two groups were compared with normative data using independent-samples t-tests. In case the variables were not normally distributed, the non-parametric Mann-Whitney U test was used. RESULTS: There was a significant difference in the number of bites, masticatory cycles, swallows and total time between the normal values and cystinosis patients. The results of the cystinosis patients were comparable to those of the patients with myotonic dystrophy. DISCUSSION AND CONCLUSION: Adult patients with cystinosis have significant dysphagia for solid food. Clinicians treating these patients should be aware of this fact. The TOMASS can be performed easily in clinical practice to investigate whether patients with cystinosis have swallowing dysfunction. The swallowing dysfunction can now be diagnosed by use of a non-invasive, very simple, non-harmful test. It can be discussed whether this should be added to the regular care scheme of cystinosis patients in order to regularly follow-up swallowing function.

The 6-min mastication test: a unique test to assess endurance of continuous chewing, normal values, reliability, reproducibility and usability in patients with mitochondrial disease.

In patients with mitochondrial disease, fatigue and muscle problems are the most common complaints. They also experience these complaints during mastication. To measure endurance of continuous mastication in patients with mitochondrial diseases, the 6-min mastication test (6MMT) was developed. This study included the collection of normal data for the 6MMT in a healthy population (children and adults). During 6 min of continuous mastication on a chew tube chewing cycles per minute, total amount of chewing cycles and the difference between minute 1 (M1 ) and minute 6 (M2 ) were collected in 271 healthy participants (5-80 years old). These results were compared with those of nine paediatric and 25 adult patients with a mitochondrial disease. Visual analogue scale (VAS) scores were collected directly after the test and after 5 min. A qualitative rating was made on masticatory movements. The reproducibility of the 6MMT in the healthy population with an interval of approximately 2 weeks was good. The inter-rater reliability for the observations was excellent. The patient group demonstrated lower total amount of chewing cycles or had greater differences between M1 and M6 . The 6MMT is a reliable and objective test to assess endurance of continuous chewing. It demonstrates the ability of healthy children and adults to chew during 6 min with a highly stable frequency of mastication movements. The test may give an explanation for the masticatory problems in patient groups, who are complaining of pain and fatigue during mastication.

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.

Characterizing the face in facioscapulohumeral muscular dystrophy.

OBJECTIVE: To evaluate facial weakness in patients with FSHD to better define clinical signs, and pilot a facial weakness severity score. METHODS: 87 FSHD patients and 55 controls were video recorded while performing seven facial tasks. The videos were assessed by three independent examiners to compile an overview of signs of facial weakness. Next, videos were semi-quantitatively assessed using a newly developed 4-point facial weakness score (FWS). This score was evaluated and correlated to other FSHD disease characteristics. RESULTS: Patients had lower scores on the total FWS than controls (mean score 43 ± 28, range 4-118, vs 14 ± 9, range 0-35, p < 0.001) and on all seven individual facial tasks (all p < 0.001). 54% of patients had FWS scores outside the range of controls. Patients had more asymmetry between the left and right side of the face than controls. About 10% of the patients had very mild facial weakness. These were mostly males (89%) with longer D4Z4 repeat sizes of 7-9 units. More severe facial weakness correlated to more severe overall disease severity and shorter D4Z4 repeat size, but not to disease duration. Interobserver agreement for the FWS between three raters was low with a Fleiss Kappa of 0.437. CONCLUSION: This study provides an overview of the clinical spectrum of facial weakness and its relation to other disease characteristics. The 4-point scale we introduced to grade the severity of facial weakness enables correlation of facial weakness to disease characteristics, but is not suited as clinical outcome measure for longitudinal studies.

[Neurological defects and developmental disorders following neonatal extracorporeal membrane oxygenation: results of a follow-up study after 5 years]. / Neurologische afwijkingen en ontwikkelingsstoornissen na extracorporele membraanoxygenatie van pasgeborenen: resultaten van een follow-uponderzoek na 5 jaar.

OBJECTIVE: Descriptive study of the development of children 5 years after neonatal extracorporeal membrane oxygenation (ECMO). DESIGN: Descriptive. METHOD: 98 treated children were subjected to a paediatric, neurological, psychological, physiotherapeutic and logopaedic examination. The children came from 2 Dutch ECMO-centres (the Erasmus MC-Sophia Children's Hospital in Rotterdam and the University Medical Centre St Radboud in Nijmegen, The Netherlands). RESULTS: Neurological disorders were found in 17 of the 98 investigated children, and in 6 cases these were serious. Among the remaining 92 children, 24 had motor disorders and 11 had delayed cognitive development. The average IQ (100.5) was within the normal range. CONCLUSION: A significant proportion ofthe children that had been treated with ECMO had long-term morbidity in the form of neurological defects and developmental disorders.

Dysphagia, malnutrition and gastrointestinal problems in patients with mitochondrial disease caused by the m3243A>G mutation.

BACKGROUND: Previous research has shown that dysphagia and gastrointestinal problems occur frequently in carriers of the m.3243A>G mutation; however, the exact frequency and severity have not been determined. We hypothesise that adult carriers have an increased risk for malnutrition. METHODS: In this observational study we evaluated the presence of gastrointestinal problems and dysphagia in 92 carriers of the m.3243A>G mutation. The severity of the general disease involvement was classified using the Newcastle Mitochondrial Disease Adult Scale (NMDAS). Gastrointestinal involvement, dysphagia and the risk for malnutrition were scored using the Gastrointestinal Symptoms Questionnaire and the Malnutrition Universal Screening Tool. Gastrointestinal symptoms and anthropometrics were compared with healthy controls. RESULTS: Our results show that the height, weight and body mass index (BMI) of these carriers were lower than the national average (p < 0.05). Seventy-nine carriers (86%) suffered from at least one gastrointestinal symptom, mainly flatulence or hard stools. Both frequency and severity of symptoms were significantly increased compared with reference data of healthy Dutch adults. Of the carriers, 45% reported (mostly mild) dysphagia. Solid foods cause more problems than liquids. A negative correlation between BMI and heteroplasmy levels in urinary epithelial cells (UEC) was present (Spearman correlation coefficient = - 0.319, p = 0.003). CONCLUSION: Dysphagia and gastrointestinal problems, especially constipation, are common symptoms in the total m.3243A>G carriers cohort and are not related to heteroplasmy levels in UEC or disease severity. The severity of gastrointestinal problems as well as overall disease severity is associated with an increased risk for malnutrition.

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.

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.

Validation of a Dutch language screening instrument for 5-year-old preterm infants.

AIM: The validation of the Dutch Taal Screenings Test (TST), a language-screening test, which is included in a follow-up instrument developed to enable paediatricians to assess 5-y-old preterm infants for their motor, cognitive and speech and language development. METHODS: The speech and language development of 145 5-y-old infants born before 32 wk of gestation and/or with a birth weight of less than 1500 g was assessed by a paediatrician using the TST and by a speech therapist using standardized language tests. RESULTS: All correlations between the instruments were significant. Using the original cut-off point of the TST for abnormal speech and language development (18 points), the paediatrician will only identify 62% of the children who need speech therapy. For this group of children, a cut-off point of 17 is more effective. The positive predictive value of the TST improved from 77% to 82% by using a parent and school questionnaire to evaluate in a more subjective way the speech and language development. CONCLUSION: Using the TST, paediatricians will be able to identify speech or language problems in 5-y-old preterm infants.

Development and evaluation of a follow up assessment of preterm infants at 5 years of age.

BACKGROUND: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. AIMS: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life. METHODS: A total of 431 very premature infants, mean gestational age 30.2 weeks, mean birth weight 1276 g, were studied at age 5 years. Children with severe handicaps were excluded. The percentage of children with a correctly identified developmental disturbance in the domains cognition, speech and language development, neuromotor development, and behaviour were determined. RESULTS: The follow up instrument classified 67% as optimal and 33% as at risk or abnormal. Of the children classified as at risk or abnormal, 60% had not been identified at earlier follow up assessments. The combined set of standardised tests identified a further 30% with mild motor, cognitive, or behavioural disturbances. The paediatrician's assessment had a specificity of 88% (95% CI 83-93%), a sensitivity of 48% (95% CI 42-58%), a positive predictive value of 85% (95% CI 78-91%), and a negative predictive value of 55% (95% CI 49-61%). CONCLUSIONS: Even after standardised and thorough assessment, paediatricians may overlook impairments for cognitive, motor, and behavioural development. Long term follow up studies that do not include detailed standardised tests for multiple domains, especially fine motor domain, may underestimate developmental problems.