Mary-Ann Ampong

The management of motor neurone disease

The management of motor neurone disease (MND) has evolved rapidly over the last two decades. Although still incurable, MND is not untreatable. From an attitude of nihilism, treatments and interventions that prolong survival have been developed. These treatments do not, however, arrest progression or reverse weakness. They raise difficult practical and ethical questions about quality of life, choice, and end of life decisions. Coordinated multidisciplinary care is the cornerstone of management and evidence supporting this approach, and for symptomatic treatment, is growing.1–3 Hospital based, community rehabilitation teams and palliative care teams can work effectively together, shifting emphasis and changing roles as the needs of the individuals affected by MND evolve. In the UK, MND care centres and regional networks of multidisciplinary teams are being established. Similar networks of MND centres exist in many other European countries and in North America. Here, we review current practice in relation to diagnosis, genetic counselling, the relief of common symptoms, multidisciplinary care, the place of gastrostomy and assisted ventilation, the use of riluzole, and end of life issues. View this table: Table 1 Clinical syndromes of MND (ALS—amyotrophic lateral sclerosis) and related disorders (modified from Kato et al , 2003*, with permission) The average delay from onset of symptoms to diagnosis is about 14 months, about one third of expected survival. Occasionally, survival following diagnosis may be less than six months. The patient may already suspect the diagnosis …

Natural history and clinical features of the flail arm and flail leg ALS variants

Objective: We sought to define the significance of brachial amyotrophic diplegia (flail arm syndrome [FA]) and the pseudopolyneuritic variant (flail leg syndrome [FL]) of amyotrophic lateral sclerosis (ALS; motor neuron disease). Methods: We analyzed survival in clinic cohorts in London, UK (1,188 cases), and Melbourne, Australia (432 cases). Survival from disease onset was analyzed using the Kaplan- Meier method and Cox proportional hazards model. Results: In the London cohort, the FA syndrome represented 11% and the FL syndrome 6% of the sample. Median survival was 35 months for limb onset and 27 months for bulbar onset ALS, whereas this was 61 months for FA syndrome (p < 0.001) and 69 months for FL syndrome (p < 0.001). Five-year survival in this cohort was 8.8% for bulbar onset, 20% for limb onset, 52% for FA syndrome, and 64% for FL syndrome. The ratio of men to women was 4:1 in the FA group compared to 2:1 in other limb onset cases. Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS. In the Melbourne cohort, median survival for limb onset ALS was 31 months, bulbar onset 27 months, FA syndrome 66 months (p < 0.001), and FL syndrome 71 months (p = 0.001). Conclusions: The flail arm (FA) and flail leg (FL) syndromes had significantly better survival than typical amyotrophic lateral sclerosis (ALS) or progressive muscular atrophy cases that were not classified as FA or FL. Our findings underline the clinical and prognostic importance of the FA and FL variants of ALS.

Amyotrophic lateral sclerosis in an urban setting: a population based study of inner city London.

Sirs: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting cortical and spinal motor neurons. There have been several previous population studies, reporting incidences between 0.44 and 3.2 per 100,000 person-years [1, 2]. As a preliminary step in establishing a population register for ALS in South-East England, we have identified all prevalent cases in the London Boroughs of Lambeth, Southwark and Lewisham (LSL) between 1 January 1997 and 31 July 2004. Cases were identified from multiple sources to ensure ascertainment was as complete as possible, but it is important to recognise that this register covers a relatively small population, with a high rate of migration in and out of the area. Seventy-three individuals with ALS were identified, of whom 56 were newly diagnosed (23 female, 33 male). Crude incidence was 1.20 per 100,000 person-years and prevalence 4.06 per 100,000 (Table 1). For England and Wales, the projected age-adjusted incidence rate was 1.66 per 100,000 person-years (95% CI 1.30–2.03), (females 1.34 (95% CI 0.95–1.72), males 2.04 (95% CI 1.50–2.58)). The cumulative lifetime risk of ALS in LSL was 0.15% for males and 0.08% for females by age 75, (for comparison, it ranges as high as 0.43% by age 90 in the Irish register) (Table 2). The median age of onset was 63 years (males 59.7, females 66.8). Sixty individuals described themselves as White (83%), 11 Black (15%), one Asian (1%), and one declined. For comparison, 25% of the LSL population is Black and 4% Asian according to the 2001 census[3]. A binomial test for observing 11 or fewer events out of 73 when the event probability is 0.25 has p=0.03, suggesting ALS may be less common in those with African ancestry. To standardize the clinical definition of ALS, the World Federation of Neurology (WFN) has devised and subsequently revised diagnostic criteria. To examine the effect of this on incidence and prevalence rates, we used three alternative case definitions: the original WFN criteria (El Escorial), the revised WFN criteria, and only cases classified as clinically probable or definite by the original criteria [4, 5]. Not surprisingly, we found nearly two-fold variation in the calculated rates, with the lowest when including only probable and definite cases, and the highest when the original criteria were used (Table 1). The sevenfold variation in worldwide incidence may therefore partly be explained by the inclusion methods of different studies, even though most use WFN criteria. Our incidence rates are within previously reported ranges, but are at the lower end for most large studies, as can also be seen from the lifetime cumulative risk rates. In addition, in the Italian and Irish registers, the risk continues to climb with age, whereas in our data, this is not seen for those aged 85 years or over. This reflects the size of this register and the population structure in LSL, for example having only 5% ‘‘elderly’’ residents compared with 7.6% for the national average. There are fewer cases to ascertain, underascertainment is more likely, and even with complete ascertainment, rates depend on population structure [6]. (Table 2) Comparative studies using large scale population registers are necessary to determine the true variation in the worldwide incidence of ALS, to confirm if the lifetime risk continues to increase with age as suggested by the Irish and Italian data, and to explore in a larger sample the possible lower risk for those with African ancestry that we have identified. To this end, it is timely that there is now a European LETTER TO THE EDITORS J Neurol (2006) 253: 1642–1643 DOI 10.1007/s00415-006-0195-y

Amyotrophic Lateral Sclerosis in South-East England: A Population-Based Study

Background/Aims: We aimed to estimate the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in the South East of England. The reported incidence of ALS varies between 0.44 and 3.2 per 100,000 person years. This can partly be explained by differences in design and diagnostic criteria used. There is little population data concerning England, particularly the South East. Methods: A population study of South-East England (total population: 2,890,482) was carried out and multiple sources including our tertiary centre and district general hospitals were used for complete case ascertainment. Results: Between 1 January 2002 and 30 June 2006 we identified 138 people (76 males; 62 females) with a new diagnosis of ALS, giving a crude incidence of 1.06 per 100,000 person years. The projected age- and gender-adjusted annual incidence rate for England and Wales was 1.10 (95% CI 0.80–1.40). 142 people were alive on 30 June 2006, giving a point prevalence of 4.91 per 100,000 population. Conclusion: Our incidence and prevalence rates are similar to those reported in comparable studies from other countries. This argues against the role of a specific exogenous factor in the aetiology of ALS in South-East England.

The sex ratio in amyotrophic lateral sclerosis: A population based study

Abstract Replicable risk factors for ALS include increasing age, family history and being male. The male: female ratio has been reported as being between 1 and 3. We tested the hypothesis that the sex ratio changes with age in a population register covering the south-east of England. The sex ratio before and after the age of 51 years was compared using a Z-test for proportions. Kendalls tau was used to assess the relationship between age group and sex ratio using incidence and prevalence data. Publicly available data from Italian and Irish population registers were compared with results. There was a significant difference in the proportion of females with ALS between those in the younger group (30.11%) and those in the older group (43.66%) (p = 0.013). The adjusted male: female ratio dropped from 2.5 in the younger group to 1.4 in the older group using prevalence data (Kendalls tau = −0.73, p = 0.039). Similar ratios were found in the Italian but not the Irish registry. We concluded that sex ratios in ALS may change with age. Over-representation of younger patients in clinic registers may explain the variation in sex ratios between studies. Menopause may also play a role.

Management of respiration in MND/ALS patients: An evidence based review

This systematic review comprises an objective appraisal of the evidence in regard to the management of respiration in patients with motor neuron disease (MND/ALS). Studies were identified through computerised searches of 32 databases. Internet searches of websites of drug companies and MND/ALS research web sites, ‘snow balling’ and hand searches were also employed to locate any unpublished study or other ‘grey literature’ on respiration and MND/ALS. Since management of MND/ALS involves a number of health professionals and care workers, searches were made across multiple disciplines. No time frame was imposed on the search in order to increase the probability of identifying all relevant studies, although there was a final limit of March 2005. Recommendations for patient and carer‐based guidelines for the clinical management of respiration for MND/ALS patients are suggested on the basis of qualitative analyses of the available evidence. However, these recommendations are based on current evidence of best practice, which largely comprises observational research and clinical opinion. There is a clear need for further evidence, in particular randomised and non‐randomised controlled trials on the effects of non‐invasive ventilation and additional larger scale cohort studies on the issues of initial assessment of respiratory symptoms, and management and timing of interventions.

Survival of patients with ALS following institution of enteral feeding is related to pre‐procedure oximetry: A retrospective review of 98 patients in a single centre

A retrospective review was carried out on the influence of pre‐procedure respiratory assessment on survival of patients with amyotrophic lateral sclerosis (ALS) requiring nutritional support with either a gastrostomy or a nasogastric feeding tube. Over a five‐year period 98 patients (49 male, 49 female; median age 61 years, range 26–86 years) with ALS were referred for enteral feeding with either radiological inserted gastrostomy (RIG), percutaneous endoscopic gastrostomy (PEG) or nasogastric tube (NG). Case notes review was performed to record patient age, sex, pre‐procedure respiratory assessment, method of enteral feeding and survival post‐procedure. Kaplan‐Meier survival curves were constructed for each group, with Cox regression analyses performed in order to establish the effect of each variable on outcome. Median survival (with 95% confidence intervals) following RIG, PEG and NG was 6.31 months (4.58–8.04 months), 7.13 months (4.81–9.45 months) and 0.95 months (0.00–2.77 months), respectively. The survival advantage between RIG and PEG was not statistically significant (p = 0.50), but for NG versus RIG and PEG groups combined, there was a significant difference (p = 0.03). For patients with normal overnight oximetry, median survival was 8.54 months (3.88–13.21 months), compared to 4.80 months (1.20–8.39 months) in the abnormal oximetry group (p = 0.03; relative risk 1.97). It is concluded that RIG and PEG are equivalent in terms of post‐procedure survival. Abnormal oximetry prior to the procedure is a significant indicator of post‐procedure survival.

Geographical Clustering of Amyotrophic Lateral Sclerosis in South-East England: A Population Study

Background: Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons that causes progressive paralysis and eventually results in death from respiratory failure. Environmental factors that trigger ALS might result in a pattern of geographical clustering of cases. We tested this hypothesis using the South-East England ALS population register, which covers south-east London, Kent and parts of neighbouring counties. Methods: The register’s catchment area was divided into postcode districts and sectors. The expected rates of ALS (adjusted for age and sex) were compared with the observed rates using a standardised residuals method and the SaTScan programme. Results: There were 406 cases of ALS identified in the catchment area during the study period. Four of the 126 postcode districts, all in Greater London, had residuals >2.5 SDs from the mean. Similarly, there were 15 postcode sectors (out of 420) that had residuals >1.96 SDs from the mean. Nine of these were in Greater London. SaTScan identified an area that had a 5.61-km radius in which the relative risk of ALS was 1.70 (p = 0.012). This area overlapped with the postcode districts and some of the sectors identified using the residuals method. Conclusions: These findings suggest an excess of ALS cases in some postcode districts in south-east England.

Nutritional factors associated with survival following enteral tube feeding in patients with motor neurone disease.

BACKGROUND Motor neurone disease (MND) is a progressive neurodegenerative disease leading to limb weakness, wasting and respiratory failure. Prolonged poor nutritional intake causes fatigue, weight loss and malnutrition. Consequently, disease progression requires decisions to be made regarding enteral tube feeding. The present study aimed to investigate the survival, nutritional status and complications in patients with MND treated with enteral tube feeding. METHODS A retrospective case note review was performed to identify patients diagnosed with MND who were treated with enteral tube feeding. A total of 159 consecutive cases were identified suitable for analysis. Patients were treated with percutaneous endoscopic gastrostomy (PEG), radiologically inserted gastrostomy (RIG) or nasogastric feeding tube (NGT). Nutritional status was assessed by body mass index (BMI) and % weight loss (% WL). Serious complications arising from tube insertion and prescribed daily energy intake were both recorded. RESULTS Median survival from disease onset was 842 days [interquartile range (IQR) 573-1263]. Median time from disease onset to feeding tube was PEG 521 days (IQR 443-1032), RIG 633 days (IQR 496-1039) and NGT 427 days (IQR 77-781) (P = 0.28). Median survival from tube placement was PEG 200 (IQR 106-546) days, RIG 216 (IQR 83-383) days and NGT 28 (IQR 14-107) days. Survival between gastrostomy and NGT treated patients was significant (P < or = 0.001). Analysis of serious complications by nutritional status was BMI (P = 0.347) and % WL (P = 0.489). CONCLUSIONS Nutritional factors associated with reduced survival were weight loss, malnutrition and severe dysphagia. Serious complications were not related to nutritional status but to method of tube insertion. There was no difference in survival between PEG and RIG treated patients.

The association between ALS and population density: A population based study

Abstract We aimed to assess whether rural residence is associated with amyotrophic lateral sclerosis in the south-east of England using a population based register. Previous studies in different populations have produced contradictory findings. Residence defined by London borough or non-metropolitan district at time of diagnosis was recorded for each incident case in the South-East England ALS Register between 1995 and 2005. Each of the 26 boroughs or districts of the catchment area of the register was classified according to population density. Age- and sex-adjusted incidence of ALS was calculated for each region and the relationship with population density tested by linear regression, thereby controlling for the underlying population structure. We found that population density in region of residence at diagnosis explained 25% of the variance in ALS rates (r = 0.5, p < 0.01). Thus, in this cohort in the south-east of England, people with ALS were more likely to be resident in areas of high population density at diagnosis.