Bulbar paralysis associated with Miller-Fisher syndrome and its overlaps in Chinese patients.

The study aimed to determine the incidence and the onset time of bulbar paralysis (BP) associated with Miller-Fisher syndrome (MFS) and its overlaps, to better understand the clinical characteristics among patients with MFS and its overlaps. Medical records from 48 patients with MFS and its overlaps were divided into two groups based on the presence (MFS-BP+) or absence (MFS-BP-) of BP. Their clinical features, laboratory and electrophysiological findings, neuroimaging data, and treatment plan were analyzed and compared between two groups. The incidence of BP associated with MFS and its overlaps was 48%. Eighty-two percent of the patients developed BP within 1 week after the onset of MFS and its overlaps. The cerebrospinal fluid (CSF) protein level in patients was higher in MFS-BP+ than in MFS-BP- group (67.69 ± 26.59 vs. 50.15 ± 20.44 mg/dl; P < 0.05). Frequencies of severe limb weakness, hypoglossal paralysis, disturbance of consciousness, and tracheal intubation required were also significantly higher in MFS-BP+ than in MFS-BP- group. Positive results of anti-GQ1b and anti-GT1b antibodies were all found in MFS-BP+ group. The prevalence of BP in MFS and its overlap was higher, the majority of BP occurred within 7 days after the onset of the disease, and early diagnosis of BP concurrence is helpful to decide the treatment plan.

Smoking is not a risk factor for sporadic amyotrophic lateral sclerosis in an Australian population.

BACKGROUND: Controversy persists as to whether smoking is a risk factor for sporadic amyotrophic lateral sclerosis (SALS), the most common form of sporadic motor neuron disease (SMND). We therefore undertook a large case-control study of smoking and SALS in Australia. METHODS: Cases and controls were recruited Australia-wide over a 10-year period. SALS and the other subgroups of SMND were categorised on the basis of neurologists' reports. Controls were partners or friends of SMND patients or community volunteers. Individuals filled in a questionnaire regarding smoking habits. A total of 809 patients with SMND (631 with SALS) and 779 controls were included in the study. SALS males and females were analysed separately. RESULTS: No differences between SALS patients and control groups were found with regard to (1) the odds ratios of ever-smokers, ex-smokers or current smokers compared to never-smokers, (2) the means of numbers of cigarettes per day, years of smoking, pack years or age smoking began or (3) the proportions of their parents who had ever smoked. The proportion of ever-smokers and mean pack years did not differ between the clinical subgroups of SMND or between different sites of SALS onset. Partner smoking did not increase the risk of SMND. CONCLUSION: This Australian case-control study does not support a link between cigarette smoking and any form of SMND.

Population based epidemiology of amyotrophic lateral sclerosis using capture-recapture methodology.

BACKGROUND: Variation in the incidence rate in epidemiological studies on amyotrophic lateral sclerosis (ALS) may be due to a small population size and under ascertainment of patients. The previously reported incidence decline in the elderly and a decrease in the male:female ratio in postmenopausal age groups have yet to be confirmed. METHODS: ALS epidemiology in a large population based register in The Netherlands was studied between 1 January 2006 and 31 December 2009, and applied capture-recapture methodology in separate age and gender groups to adjust for the number of unobserved patients. RESULTS: 1217 incident patients were observed, and a capture-recapture incidence of 2.77 per 100 000 person-years (95% CI 2.63 to 2.91). Prevalence on 31 December 2008 was 10.32 per 100 000 individuals (95% CI 9.78 to 10.86). The incident cohort had a higher median age at onset (63.0 vs 58.1 years) and more bulbar onset patients (30.0% vs 19.1%) compared with the prevalent cohort. Incidence and prevalence peaked in the 70-74 year age group followed by a rapid decline in older age. The male:female ratio in the premenopausal age group (1.91, 95% CI 1.32 to 2.79) was not significantly higher than that in the postmenopausal age group (1.50, 95% CI 1.34 to 1.67). CONCLUSION: The marked difference in patient characteristics between incident and prevalent cohorts underscores the importance of including incident patients when studying susceptibility or disease modifying factors in ALS. The incidence decline in the elderly may suggest that ALS is not merely the result of ageing. Absence of a significant postmenopausal drop in the male:female ratio suggests that the protective role of female sex hormones in ALS is limited.

APOE ε4 allele is associated with an increased risk of bulbar-onset amyotrophic lateral sclerosis in men.

OBJECTIVE: Several association studies have identified possible susceptibility factors for sporadic amyotrophic lateral sclerosis (SALS). Studies on the APOE gene provided conflicting results, especially about the effect on bulbar onset. We assessed the possible role of APOE gene in a large cohort of patients with ALS and matched controls. METHODS: The APOE alleles were determined in 1482 patients with SALS and 955 controls and analysed by univariate and multivariate statistics, taking into account gender, site-of-onset and age-at-onset. RESULTS: Patients with bulbar onset were more likely to be women [odds ratio (OR)=2.17; 95% CI: 1.74-2.72] and to be older (OR=3.47; 95% CI: 2.58-4.67). The ε4-carriers were more frequent in the bulbar-onset group than in the limb-onset group (OR=1.39 bulbar onset versus limb onset; 95% CI: 1.08-1.80) but this association was observed amongst men (OR=1.78; 95% CI: 1.25-2.53) and not women (OR=1.09; 95% CI: 0.75-1.59). CONCLUSION: Our study provides evidence for a contribution of the ε4 allele in the occurrence of bulbar-onset ALS amongst men. We propose that men are normally protected by androgens against bulbar onset and that the ε4 allele inhibits this protection, perhaps by interfering with the androgen pathway.

Epidemiology of ALS in Padova district, Italy, from 1992 to 2005.

BACKGROUND AND PURPOSE: Several studies have reported an increase in ALS incidence in recent years but population-based studies in Europe do not confirm this trend. To analyze ALS incidence over time we conducted a retrospective incidence study in the Padova district of Italy (1992 to 2005). We had previously conducted a survey in the same area in the years 1980-1991. METHODS: We used the archives of all the neurological wards of the Padova district to identify all subjects with a discharge diagnosis of ALS or motor neuron disease and resident in the Padova district. RESULTS: We ascertained 182 patients (85 males and 97 females; male:female ratio 0.88:1) over the 14-year study period. The annual incidence rates adjusted by sex and age increased from 1.31/100,000/year in the years 1992-1994 to 1.92/100,000/year in the years 2004-2005. CONCLUSIONS: This study confirmed an ALS incidence increase over the last 25 years in the Padova district. The increase in incidence may be partially explained by the ageing of the general population rather than by an improved diagnostic assessment.

Brown-Vialetto-Van Laere syndrome.

The Brown-Vialetto-Van Laere syndrome (BVVL) is a rare neurological disorder characterized by progressive pontobulbar palsy associated with sensorineural deafness. Fifty-eight cases have been reported in just over 100 years. The female to male ratio is approximately 3:1. The age of onset of the initial symptom varies from infancy to the third decade. The syndrome most frequently presents with sensorineural deafness, which is usually progressive and severe. Lower cranial nerve involvement and lower and upper motor neuron limb signs are common neurological features. Other features include respiratory compromise (the most frequent non-neurological finding), limb weakness, slurring of speech, facial weakness, and neck and shoulder weakness. Optic atrophy, retinitis pigmentosa, macular hyperpigmentation, autonomic dysfunction, epilepsy may occur. The etiopathogenesis of the condition remains elusive. Approximately 50% of cases are familial, of which autosomal recessive is suggested. The remaining cases are sporadic. The diagnosis is usually based on the clinical presentation. Investigations (neurophysiological studies, magnetic resonance imaging of the brain, muscle biopsy, cerebrospinal fluid examination) are done to exclude other causes or to confirm the clinical findings. The differential diagnoses include the Fazio-Londe syndrome, amyotrophic lateral sclerosis, Nathalie syndrome, Boltshauser syndrome and Madras motor neuron disease. Treatment with steroids or intravenous immunoglobulin may result in temporary stabilization of the syndrome. However, the mainstays of management are supportive and symptomatic treatment, in particular assisted ventilation and maintenance of nutrition via gastrostomy. The clinical course of BVVL is variable and includes gradual deterioration (almost half of cases), gradual deterioration with stable periods in between (a third of cases) and deterioration with abrupt periods of worsening (just under a fifth of cases). After the initial presentation, one third of patients survive for ten years or longer.

[Longitudinal analysis of age at onset and initial symptoms in patients with amyotrophic lateral sclerosis].

To investigate the longitudinal changes in age at onset and the initial symptom of patients with sporadic amyotrophic lateral sclerosis (ALS), we performed a single hospital-based retrospective study over the past 38 years. A total of 280 sporadic ALS patients (169 men and 111 women) hospitalized in our department between 1965 and 2003 were investigated in this study. The clinical features including age at onset and the initial symptom of these patients were obtained from medical records. All the patients underwent an intensive diagnostic evaluation including electrophysiological examination, laboratory examinations of blood and cerebrospinal fluid, and neuroimagings of the brain and spinal cord to exclude other conditions similar to ALS. The mean age at onset was 58.3 +/- 11.3 years and age at onset significantly increased at the rate of 0.459 years per year (r = 0.406, p< 0.001). The percentage of patients whose age at onset was > or = 70 years has increased from 3.0% (1980-1984) to 31.1% (2000-2003). To investigate the initial symptom of senile-onset ALS, patients whose age at onset was > or = 70 years were analyzed. The percentages of bulbar palsy-onset patients with onset in terms of age were 62.5% (30/48 patients; > or = 70 years) and 23.3% (54/232 patients; <70 years). The odd ratio for bulbar palsy was 5.40 (95% confidence interval, 2.79-10.44). Taken together, our study demonstrates that the ratio of senile-onset ALS has significantly increased, and that there were more bulbar palsy-onset patients among the patients.

Percutaneous endoscopic gastrostomy (PEG) in patients with ALS and bulbar dysfunction.

OBJECTIVE: To compare characteristics of ALS patients with and without percutaneous endoscopic gastrostomy (PEG). METHODS: Using the ALS Patient Care Database, data from patients with and without PEG with ALS Functional Rating Scale-bulbar subscale (ALSFRSb) scores < or = 5 were analyzed; follow-up data were also collected. RESULTS: PEG use was markedly increased with declining ALSFRSb scores. Demographics did not differ, but ALSFRS composite scores and bulbar and arm subscale scores were lower (P<0.0001). PEG patients used significantly more assistive devices, multidisciplinary care, home care nurses and aides, had more frequent physician and emergency department visits and hospital admissions (P<0.0001), and had lower health status based on the mini-SIP scale (P=0.0047). PEG use varied greatly between ALS centers. In the follow-up study, positive impact of PEG was noted in 79 % of PEG patients but in only 37.5% of patients who received PEG later, based on a small number of patients. PEG use showed no survival benefit. CONCLUSION: Patients did not receive PEG until bulbar function was severely reduced and overall ALS had markedly progressed. PEG may have been performed too late to demonstrate survival benefits. Aggressive proactive nutritional management appears essential in patients with ALS. To determine whether PEG provides benefits, it must be performed at earlier stages of the disease and prospectively studied.

Motor neurone disease in South Estonia. Diagnosis and incidence rate.

The current study evaluated the diagnostic standards of MND and epidemiological markers of MND in Estonia. A total of 108 patients were referred to the University Hospital from 1986 to 1995 with the first suggested diagnosis or final diagnosis of amyotrophic syndrome, amyotrophic lateral sclerosis (ALS), progressive bulbar paralysis (PBP) or progressive muscular atrophy (PMA). In addition neurologists of the region and the National Society of Neuromuscular disorders were contacted. Some 94 patients satisfied the diagnostic criteria. The annual incidence rate in South Estonia and in the city of Tartu ranged from 0.5 to 2.8 per 100,000. The mean annual incidence rate in Tartu is 1.98 and in South Estonia in general 1.3. The highest incidence rate was 8.3 for men in the age group 60 to 64 years and 7.49 in the age group 70-74; among female patients the highest incidence rate -4.6 was in the age group from 65 to 69.

Incidence and predictors of bulbar palsy after surgery for acoustic neuroma.

We present a retrospective review of the perioperative management and complications of 102 cases of acoustic neuroma operated on at an English teaching hospital over the last 9 years. Nine patients had a bulbar palsy postoperatively; five of those patients developed pulmonary complications. A bulbar palsy was more likely to occur in those with tumours > or = 3 cm. The occurrence of intraoperative bradycardias, present in nearly half of the bulbar palsy cases, did not help predict who would sustain this injury postoperatively. However, episodes of intraoperative hypotension served to better predict a bulbar palsy complication in conjunction with the presence of a large tumour. Post-operative airway management is an area of possible conflict of interest: the desire for early extubation to avoid the possibility of coughing and bucking on the endotracheal tube and the need to protect the airway of the patient with a lower cranial nerve deficit. Almost 10% of our patients did have such a deficit after surgery; and over half of them developed respiratory complications making this an important cause of postoperative morbidity. We recommend that the timing of extubation be judged on an individual basis for each patient. Those with tumours > or = 3 cm warrant particular concern. All patients should receive careful observation in a high dependency area for at least the first postoperative day.

Paralisia bulbar progressiva do adulto: seria uma entidade nosológica autônoma? / Progressive bulbar palsy: could it be an autonomous nosological entity

Neste artigo säo considerados aspectos nosológicos e discutida a autonomia da PBP. É mostrada a tendência entre autores modernos, a considerar a íntima relaçäo com a esclerose lateral amiotrófica (forma bulbar)

The Scottish Motor Neuron Disease Register: a prospective study of adult onset motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989.

The Scottish Motor Neuron Disease Register (SMNDR) is a prospective, collaborative, population based study of motor neuron disease (MND) in Scotland. The register started in January 1989 with the aim of studying the clinical and epidemiological features of MND by prospectively identifying incident patients. It is based on a system of registration by recruitment from multiple sources, followed by the collection of complete clinical data and follow up, mainly through general practitioners. In this report the register's methodology and the demography and incidence data for the first year of study are presented. One hundred and fourteen newly diagnosed patients were identified in 1989 giving a crude incidence for Scotland of 2.24/100,000/year. Standardised incidence ratios showed a non-significant trend towards lower rates in north eastern regions and island areas.

Clinical features and associations of 560 cases of motor neuron disease.

In 560 cases of motor neuron disease, studied retrospectively from their case notes in three teaching centres, the age at onset ranged from 13 to 87 years (mean 56 years), and the mean duration of illness until death was 2.6 years. In the subgroup of the disease presenting with progressive bulbar palsy presenting after age 59 years, there was a previously unrecognised excess of females sufficient to equalize the sex ratio of incidence of the disease in this age group. No potentially causative clinical associations emerged; no relation was noted between occupational exposure to leather products, trauma or surgical procedures and the disease. There was a trend for patients with motor neuron disease to give a history of abstention from alcohol.

Motor neuron disease in Cantabria.

Sixty-two patients with motor neuron disease (MND), encompassing amyotrophic lateral sclerosis (ALS), progressive bulbar palsy (PBP) and progressive muscular atrophy (PMA), were selected from within a defined area (Cantabria) in northern Spain, from 1974 to 1985. The annual incidence of MND was 1.01 per 100,000 inhabitants and the prevalence rate was 3.52 per 100,000. The male to female ratio was 1.78:1. Age-specific incidence rates increased with advanced age, with a maximum between 60 and 69 years for males and over 70 years for females. The median age at onset was 60.5 years. The average interval between the onset symptoms and diagnosis was 11 months. Fifty-three per cent of the patients had conventional or pseudopolyneuritic ALS, 36% had PBP and 11% had PMA. There were three familial cases. Two PMA patients had had acute poliomyelitis. The mean duration of the disease was 26.6 months and was significantly longer in males aged under 60 years. The survival rates in 50 patients with adequate follow-up were 18% after 5 years from onset and 6% after 10 years.

Descriptive epidemiology of motor neuron disease in Benghazi, Libya.

A total of 23 patients with motor neuron disease (MND), encompassing 17 cases of amyotrophic lateral sclerosis, 4 of progressive muscular atrophy and 2 of progressive bulbar palsy, was diagnosed in Benghazi, north-eastern Libya, between 1980 and 1985. The male to female ratio was 2.3:1. The average incidence of MND was 0.89/100,000 population/year (0.87 when age and sex-adjusted to the Libyan population). Eighteen patients were alive on the prevalence day, September 15, 1985, which provided a prevalence rate of 3.47/100,000 population (3.42 if adjusted). Age-specific incidence rates were highest in the 50- to 59-year-old age group, 8.14/100,000/year for men and 6.10/100,000/year for women. The median age at the time of diagnosis was 51 years, and the median duration for the 5 dead MND patients after the onset of the disease was 30 months. The median survival time for all MND cases combined was 42 months.

Motor neuron disease in Nova Scotia.

Fifty-two cases of motor neuron disease seen in two Halifax hospitals were reviewed.Thirty-three (63.5%) had amyotrophic lateral sclerosis, 14 (26.9%) had primary muscular atrophy, four (7.7%) had bulbar palsy and one (1.9%) had primary lateral sclerosis. There were no unusual features in this series when compared with a similar series from the United States. These cases were used to illustrate the features of this disorder and to comment on recent research observations.