MND Patients Research Articles

Voice banking and voice reconstruction for MND Patients

Voice banking and voice reconstruction for MND Patients

P158 A hospice motor neurone disease clinic: challenges and benefits of a new service

Background/contextThe Hospice in North Hampshire had offered support and care to MND patients but in an unstructured way. Close working between the Palliative Medicine and Neurology Consultants led to a...

Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown–Vialetto–Van Laere syndrome

IntroductionMadras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. There is a considerable overlap in the phenotype of MMND with Brown–Vialetto–Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie syndrome and Fazio–Londe syndrome. Recently a number of BVVL cases and families have been described with mutations in two riboflavin transporter genes SLC52A2 and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3 respectively). Methods and resultsWe describe six families and four sporadic MMND cases that have been clinically characterized in detail with history, examination, imaging and electrophysiological investigations. We sequenced the SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from the MMND series as well as the C9ORF72 expansion. No genetic defects were identified and the C9ORF72 repeats were all less than 10. ConclusionsThese data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. The clinico-genetic features of MMND in comparison with the BVVL group of childhood motor neuron diseases suggest that these diseases are likely to share a common defective biological pathway that may be a combination of genetic and environmental factors.

Patients’ experiences of health and social care in long-term neurological conditions in England: A cross-sectional survey

To investigate patients' experiences of health and social care services in long-term neurological conditions in England. Cross-sectional survey of 5209 patient members of the Motor Neurone Disease Association (MND, n = 890), Multiple Sclerosis Society (MS, n = 2345) or Parkinson's UK (PD, n = 1974). A questionnaire on patient experiences of health and social care was completed by 2563 (49%) (505 MND, 1157 MS and 901 PD). A mixed picture of experiences of health and social care in MND, MS or PD was found with few problems reported for some aspects of services such as obtaining information about medication (n = 117, 6.1%). In contrast, problems with planning and integration of care were reported frequently, with 78.0% of patients not having a care plan and 61.9% reporting that services do not collaborate well in planning care. Other problems included delays with diagnosis, information about medication side effects, and management of conditions whilst in hospital. Significant differences between the three conditions were found for most aspects of care, with MND patients generally reporting fewer problems. The findings highlight which areas of health and social care need to be improved and monitored. While a larger sample size was obtained than in other studies, possible limitations include the sampling frame and the 49% response rate. Planning and integration of care are key areas that require improvement.

1118 Are MND patients pre-morbidly fitter? Indirect evidence from hospital record-linkage

BackgroundCase-control studies to identify risk factors for MND suffer from the intractable problem of recall bias, and have provided conflicting results. There is a persistent anecdotal observation that MND patients...

Amyotrophic lateral sclerosis and frontotemporal dementia: A behavioural and cognitive continuum

Our objective was to compare the cognitive and behavioural profile of patients with amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD), and to explore the continuum between these disorders according to neuropsychological and behavioural performance using novel methods of testing and analysis. Twenty patients with ALS, 20 bvFTD patients and 20 healthy controls completed a neuropsychiatric and neuropsychological assessment including cognitive screening, working memory, inhibitory control, decision making and emotion recognition. The resulting neuropsychological and behavioural data were analysed by Rasch analysis. ALS patients showed a similar profile to bvFTD patients on tests of working memory, inhibitory control and behavioural measures. Nine ALS patients (45%) had cognitive impairment and five (25%) met criteria for bvFTD. Even in a subset of MND patients with no impairment on the ACE-R, subtle impairment of inhibitory control together with moderate to severe apathy, were found. The Rasch analysis confirmed that all patients could be ranked on the same continuum, based on their neuropsychological performance and behaviour. Thus, the cognitive and behavioural profiles of ALS mirror those seen in bvFTD. Impaired inhibitory control and behavioural changes suggest subtle orbitofrontal dysfunction in ALS. The Rasch analysis revealed a clear overlap between bvFTD and ALS.

PATU6 Protein interactors of EAAT2 and their role in motor neurone disease/amyotrophic lateral sclerosis

Glutamate excitotoxicity has been implicated in numerous neurodegenerative diseases, including motor neurone disease, MND/ALS. The glutamate transporter EAAT2 is the primary regulator of extracellular glutamate concentration and specific reductions in...

PATH44 Corpus callosum diffusion tensor imaging as a biomarker for motor neurone disease

BackgroundFocality of onset and spread of pathology in MND are poorly understood. Biomarkers are needed to improve diagnosis and therapeutic monitoring, but must accurately reflect the inherent clinical and prognostic...

POD12 Development of a hands-free, eye-tracking version of the Trail Making Test

BackgroundThe Trail Making Test (TMT) is a two-part written tool for detecting executive dysfunction. Part A consists of joining a “trail” of ascending numbers, which serves as a control for...

Identifying poor adaptation to a new diagnosis of motor neuron disease: A pilot study into the value of an early patient-led interview

This pilot study explored whether clinicians can identify patients who may not be coping with a diagnosis of MND early in the disease course by using patient-led interviews rather than psychological testing. Consecutive, newly diagnosed MND patients underwent a semi-structured interview six and 18 weeks after diagnosis, and completed SEIQoL-DW, ALSFRS-R, MND Coping Scale, MND Social Withdrawal Scale, SF 36 v2 and HAD. Three physicians independently used a list of factors from the literature associated with coping with a diagnosis of MND, and overall impression to assign patients from interview transcripts to groups of copers and non-copers. Ten of 13 recruited patients were categorized unanimously using the first interview alone. Four patients were categorized as non-copers. These showed significantly higher scores for depression, anxiety and social withdrawal and significantly lower scores for coping and mental composite scores on the SF 36 v2. Our pilot study suggests it is possible for experienced clinicians to identify patients who may struggle to cope with a diagnosis of MND early by patient-led interview alone. This provides some evidence for the therapeutic potential of the early follow-up appointment interview with a senior doctor soon after diagnosis, advocated by current British guidelines.

Emotional Lability in MND: Relationship to cognition and psychopathology and impact on caregivers

Emotional Lability (EL) is a well recognized symptom of cortico-bulbar pathway dysfunction in Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS), and is reported to occur in 19-49% of patients. The Emotional Lability Questionnaire (ELQ), is specifically designed to detect EL as reported by MND patients and as observed by their carers. The aims of this study were to 1) validate the Italian version of the ELQ; 2) investigate the relationship between EL and presence of cognitive dysfunction; 3) investigate the relationship between EL and presence of psychopathology. Forty one MND patients, 39 caregivers and respective control groups composed of 39 subjects and 39 partners/friends were tested. The Italian version of the ELQ was found to have good psychometric properties. Seventy-one per cent of patients reported suffering from EL. Correlations were found between bulbar involvement and EL, and between bulbar involvement and low performance on tests of fluid intelligence and working memory. However, the cognitive profile did not correlate with any aspect of EL. The findings suggests that damage to different neurological pathways underlie cognitive change and EL, which supports the concept of MND/ALS as a multisystem disorder. Moreover the outcomes suggest that EL affects patients' everyday life with the increased anxiety and emotional frailty. The findings suggest that those involved in the care of MND patients should be more aware of the effects of EL in the management of the disease.

Novel technique for diagnosing carpal tunnel syndrome

icantly reduced in SOD-1 FMND patients ( 1.2 ± 0.6%) and sporadic MND patients ( 0.7 ± 0.3%) compared to asymptomatic SOD-1 mutation carriers (8.3 ± 1.8%) and controls (8.5 ± 1.0%, p < 0.00001). SICI reduction was accompanied by increases in intracortical facilitation, motor evoked potential amplitude and magnetic stimulus-response curve gradient. In two pre-symptomatic SOD-1 mutation carriers, SICI was absent, while in 1 subject there was a 32% reduction in SICI prior to symptom-onset. Conclusions: Cortical hyperexcitability develops before the onset of clinical features of MND, thereby suggesting that cortical hyperexcitability underlies neurodegeneration in FMND.

Classification Accuracy of the Portland Digit Recognition Test in Traumatic Brain Injury: Results of a Known-Groups Analysis

The present study used a known-groups design to examine the accuracy of the Portland Digit Recognition Test (PDRT) in the detection of malingering in traumatic brain injury (TBI). Data were derived from 262 TBI patients who were classified as not malingering, possibly malingering, and malingering based on the Slick, Sherman, and Iverson (1999) criteria. The original PDRT cutoffs detected between 20 and 50% of malingering TBI patients with a false positive error rate of 5% or less. When the false positive error rate was held at 5%, across all item sets, sensitivity was as high as 70%. The results show that the original PDRT cutoffs are conservative and that higher scores detect more MND patients without causing the false positive error rate to become unacceptably high. Clinical application and future research needs are discussed.

Classification Accuracy of the Test of Memory Malingering in Traumatic Brain Injury: Results of a Known-Groups Analysis

This study used a known-groups design to determine the classification accuracy of the Test of Memory Malingering (Tombaugh, 1996, 1997) in detecting cognitive malingering in traumatic brain injury (TBI). Forty-one of 161 TBI patients met Slick, Sherman, and Iverson (1999) criteria for Malingered Neurocognitive Dysfunction. Twenty-two no-incentive memory disorder patients were also included. The original cutoffs (<45) for Trial 2 and Retention demonstrated excellent specificity (less than a 5% false positive error rate) and impressive sensitivity (greater than 45%). However, these cutoffs are actually conservative in the context of mild TBI. Over 90% of the non-MND mild TBI sample scored 48 or higher on the Retention Trial and none scored less than 46 while 60% of the MND patients claiming mild TBI were detected at those levels. Trial 1 also demonstrated excellent classification accuracy. Application of these data to clinical practice is discussed.

Detection and diagnosis of malingering in electrical injury

This paper sought to demonstrate that diagnosable malingering does occur in Electrical Injury (EI) and examine the relationship of malingering to potential indicators of the presence and severity of neurological injury. Eleven consecutive EI patients seen for neuropsychological evaluation were presented. Over half the patients met the Slick et al. (1999) criteria for at least Probable MND. Most of the MND patients lacked evidence of a biologically meaningful exposure to electrical current. These findings highlight the importance of considering biological markers of neurological injury and of non-neurological factors, including effort/malingering, in the study of the neurocognitive consequences of EI.

How Good at Neurology are you? – Answers

1. Motor neuron disease inclusion dementia (MNDID) On MRI, hyperintense signals are sometimes seen in the subcortical part of the precentral gyrus in MND patients, although their clinical significance is...

The amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-40): tests of data quality, score reliability and response rate in a survey of patients

Objectives: To evaluate response rate, data quality, and score reliability of the 40 item Amyotrophic Lateral Sclerosis Assessment Questionnaire in a survey of MND patients. Design: A survey of members of the MND Association of the UK, of which half were randomly allocated to receive a survey instrument from the MND Association and the other half allocated to receive the MND Association survey instrument and also the ALSAQ-40 questionnaire. Sample: Five hundred patients were randomly selected from the membership lists of the MND Association, of whom 250 received the MND Association Survey and the ALSAQ-40. Results: Response rate to the survey was 59.2%. Over half of the respondents received the ALSAQ-40. Data for individual items were analysed and found to be distributed across all response categories. All items were found to be highly associated with the scales to which they contribute. Internal consistency reliability of all the five scales of the ALSAQ-40 was also found to be high. Conclusion: Inclusion of the ALSAQ-40 into the survey did not have an adverse effect upon response rates. Furthermore, the ALSAQ-40 was shown to have highly desirable psychometric properties. This paper provides further evidence of the reliability and validity of the measure.

Quantitative proton magnetic resonance spectroscopy of the subcortical white matter in motor neuron disease

Using proton magnetic resonance spectroscopy, the authors have previously demonstrated a reduction in the N-acetyl aspartate/(creatine and phosphocreatine) (NAA/(Cr + PCr)) ratio in the motor region in bulbar-onset MND patients, attributed to neuronal loss or dysfunction leading to a reduction in NAA. We have expanded this analysis to evaluate absolute concentrations of NAA, (Cr + PCr) and choline-containing compounds (Cho) in the subcortical white matter in the motor region in 16 MND patients (8 with bulbar onset and 8 with limb onset) and 8 healthy, age-matched controls. Single voxel 1H-MRS was performed using a PRESS localization sequence. Metabolite concentrations were determined using the water signal as an internal standard. We found no differences in the concentrations of NAA ([NAA]), (Cr + PCr) ([Cr + PCr]) or Cho ([Cho]) in the motor region on comparing the total MND group and controls (P > 0.3). No difference was found in [NAA] in the bulbar-onset group compared with the limb-onset group (P = 0.70), but [Cr + PCr] was significantly higher in the bulbar-onset group (P = 0.04). Our results suggest that [Cr + PCr] may be affected by the pathological process in MND, and this should be considered in the interpretation of metabolite peak area ratios. The elevated (Cr + PCr) may represent gliosis in the subcortical white matter in the motor cortex region.

Quality of life assessment in MND: development of a social withdrawal scale.

A scale to measure 'social withdrawal,' was developed specifically for use with MND patients. Scale design was based upon patient-focused interviews which were used to explore patients' concerns. The impact the condition had upon their social interactions with others was salient for all patients and affected their overall quality of life. Using issues raised by patients, a 23-item scale was generated to specifically and quantitatively measure social withdrawal and this scale was psychometrically evaluated. The scale was administered to a sample of 23 patients at varied stages of progression of MND, and to a control group of patients with arthritis with similar levels of physical disability. For MND patients withdrawal from the community was found to be closely related to severity of physical symptoms and depression. Specific patients were identified who are particularly susceptible to withdrawal and depression. Comparison of the pattern of withdrawal in the MND and arthritis patient groups suggested that there may be differences between the factors governing social withdrawal in different patient populations.

Identification of brain metabolites by magnetic resonance spectroscopy in MND/ALS

Magnetic resonance spectroscopy (MRS) has provided a novel means of studying the brain biochemistry of motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) patients in vivo in situ. Previous studies have demonstrated changes in the ratios of areas under specific spectral peaks in MND/ALS patients (Jones et al., 1995). However, the significance of such findings cannot be fully elucidated without first ascertaining the biochemical identity of each peak. Each peak in a MRS spectrum corresponds to the resonance of specific protons in a particular chemical environment. Many biochemicals contain similar protons in similar environments so it is possible that a single spectral peak could represent protons from more than one biochemical. In this study of major brain MRS peaks we have demonstrated that peaks are potentially composed of a number of protons from different chemicals. For example, the peak at chemical shift 2.01 ppm, conventionally recognised as the neurotransmitter N-acetyl aspartate, may actually be a result of the protons of the N-acetyl moiety (Frahm et al., 1991). We have consequently shown that other N-acetylated compounds such as N-acetyl glutamate are also capable of producing a peak here, whereas their non-acetylated derivatives are not. We have also shown GABA is capable of producing a peak at chemical shift 3.00 ppm, a peak which is generally assigned to creatine/phosphocreatine. These findings have important implications in the identification of spectral peaks in MRS studies and in the interpretation of spectral differences between MND patients and controls.