Sleep-disordered breathing in amyotrophic lateral sclerosis

OBJECTIVES: Our study was designed to determined the significance of aortogenic embolism in an unselected autopsy collective. BACKGROUND: Although embolism arising from atherosclerotic plaques in the aorta has been acknowledged, the role of aortic atheromatosis among other well known sources of embolism remains to be further clarified. METHODS: We examined the proximal part of the arterial system with regard to the presence of atherosclerotic lesions as well as cardiac changes in 120 consecutive necropsy studies. Pathologic evidence of embolic events was recorded. Clinical and neuropathologic data were also surveyed in all patients. RESULTS: Among atherosclerotic lesions, fibrous plaques (p < 0.05) and calcified (p < 0.0001) and ulcerated lesions (p < 0.0001) as well as thrombi (p < 0.005) were observed significantly more frequently in the aortic arch and in the descending aorta than in the ascending aorta, whereas fatty streaks were distributed uniformly. In 40 (33%) of the 120 patients, we found pathologic evidence of arterial embolization. Multiple logistic regression analysis revealed a significant correlation between embolism and complicated atherosclerotic plaques in the aortic arch (odds ratio [OR] 5.8, 95% confidence interval [CI] 1.1 to 31.7, p < 0.05), severe ipsilateral carotid artery disease (OR 3.1, 95% CI 3.1 to 45.3, p < 0.001) and atrial fibrillation (OR 3.5, 95% CI 1.1 to 9.9, p < 0.05). CONCLUSIONS: Complicated atherosclerotic plaques in the aortic arch represent an independent risk factor for systemic embolism similar to atrial fibrillation and severe atherosclerosis of the carotid arteries.     

Cricopharyngeal myotomy in amyotrophic lateral sclerosis

Reported herein is the experience of the authors with 38 amyotrophic lateral sclerosis (ALS) patients for whom cricopharyngeal myotomy was performed. The major surgical objectives were facilitation of swallowing and amelioration of the tendency of these patients to aspirate ingestants and secretions. In the group of these patients in which the follow-up information has been adequate, 64% were improved and 36% experienced no significant benefits. The authors' surgical indications, methods of anesthesia, surgical technique, and postoperative care are described.     

Prognostic factors in amyotrophic lateral sclerosis

Survival in patients with amyotrophic lateral sclerosis is highly variable. In a prospective study of 71 patients, we analyzed the influence of several clinical factors on survival: age of onset, sex, initial involvement (bulbar, upper extremities or lower extremities) and familial history. Mean time of evolution was 2.6 years, with 25% survival 5 years after onset. Patients under 45 years old had better survival than those over 45 (5.8 and 2.2 years, respectively, p < 0.002). The prognosis for women was worse (2.07 and 3.6 years for women and men, respectively, p < 0.001), probably because age of onset was later in women (61 versus 53 years, respectively, p < 0.006). Neither first symptom or familial history of the disease affected prognosis. We conclude that age at onset is a decisive prognostic factor that is inversely related to survival. In the design of clinical trials in which survival is a variable, the treatment and control groups should be matched for age.     

Prognosis in hereditary amyotrophic lateral sclerosis

Two different forms of hereditary amyotrophic lateral sclerosis (ALS) has been separated according to duration of illness. A rapid course with short survival as seen in sporadic ALS is usual, but a comparatively benign type with a mean survival of 12 years has been reported in some families. Four patients from an ALS-afflicted family with five affected members in three generations were examined and then followed up. A conspicuous variability in progression among the patients was observed, with death occurring from 26 months to 12 years after onset; one patient is alive 13 years after onset. Wide differences were also found with respect to initial site of involvement and pyramidal tract signs. Three other families with this mixed pattern of prognosis have been reported previously. Affected individuals within involved families had either short or long duration of the disease, rather than displaying a continuum. However, in view of the existence of a type of hereditary ALS with marked intrafamilial variability, prognosis, even in the presence of previous benign cases, should be cautiously given.     

Skin involvement in amyotrophic lateral sclerosis

BACKGROUND: Patients with sporadic amyotrophic lateral sclerosis (ALS) show disorganised collagen and elastin of the dermis. We looked for inflammatory alterations to cutaneous blood vessels. PATIENTS AND FINDINGS: Seven patients with sporadic ALS were investigated; five were confined to bed, but none had bedsores. Light and electron microscopy of skin showed an oedematous dermis with collagen fibrils of irregular diameter. Small blood vessels were characterised by duplicated basement membranes and deposition of beta-amyloid protein, the main component of the neuronal and non-neuronal amyloid deposits in Alzheimer's disease. These skin changes were seen in all degrees of disability, but none was found in age-matched and sex-matched controls. INTERPRETATION: The skin in ALS is characterised by a distinctive pattern of alterations of connective tissue and blood vessels. Examination of skin in an additional and easily accessible investigation which may help elucidate the pathogenesis of ALS.     

Prognostic factors and survival in amyotrophic lateral sclerosis

This study of clinical outcome in amyotrophic lateral sclerosis (ALS) evaluated 148 patients (93 men and 55 women) diagnosed in Hordaland county, Norway, during the period 1970 to 1990. In addition to evaluation of clinical data, data were available on sex, age at diagnosis, time from appearance of symptoms to diagnosis, family history, EMG and spinal fluid. Sixty-nine cases were bulbar ALS and 79 were spinal ALS. Median survival from diagnosis was 16.5 months, 26.0 months in the spinal and 12.1 months in the bulbar form. The survival time decreased with increasing age at the start of disease. A brief interval from start of symptoms to diagnosis was also a poor prognostic factor. Cases with mainly spastic clinical appearance had longer survival than those with marked atrophy. Sex, appearance of familial cases, increased protein level in the spinal fluid, or disease confirmed or not by EMG had no influence on the prognosis. The importance of the prognostic variables was assessed simultaneously using a proportional hazards model. To test the validity of the prognostic factors, a binary survival outcome was established and a predictive rule determined by logistic regression. The data were applied on 11 ALS cases collected outside Hordaland county. Only 1 out of 7 patients with a predicted probability of living more than 1 year actually died within this time period. Two out of 4 patients in the poor prognostic group were dead within a year from the time of diagnosis.     

Oculomotor nuclear pathology in amyotrophic lateral sclerosis

We examined the oculomotor and/or trochlear nuclei of 27 amyotrophic lateral sclerosis (ALS) patients and 10 controls by histological and immunohistological methods. Their neurons were relatively well preserved. In 7 of 22 sporadic ALS patients (including 3/3 ALS with ophthalmoplegia) and in 4 of 5 ALS patients with dementia, some morphological changes similar to those in anterior horns (Bunina bodies, ubiquitin-positive skein-like inclusions, Lewy body-like inclusions, conglomerate inclusions and spheroids) were rarely, but clearly seen. These changes were not observed in controls. Our results suggest that the oculomotor and trochlear nuclei in ALS patients are slightly affected in a manner similar to that in the anterior horns, but the degree is less than that necessary for development of ophthalmoplegia in the majority of ALS patients.     

Clinical aspects of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a progressive degenerative disease of upper and lower motor neurons with a prevalence of 4.3/100.000. The clinical symptoms include peripheral weakness and central spastic paresis and bulbar paralysis (weakness of mimic muscles, atrophy of the tongue, dysarthria). The prognosis leads to death within a few years. Pathogenetic factors are free O2-radicals, a disturbance of glutamate-metabolism, abnormal accumulation of neuronal proteins and autoimmunological mechanisms.     

Clinical epidemiology of amyotrophic lateral sclerosis

The introduction of palliative therapies in amyotrophic lateral sclerosis (ALS) will alter the epidemiology of ALS as it is known now. Although incidence rates will remain unchanged in the near future, prevalence rates will likely increase dramatically. Better understanding of the age-specific presentation of motor neuron diseases worldwide will shed light on the vexing questions concerning the variable incidence rates in some countries and apparent incidence gradients in North America and Europe.     

Patient resistance and prognosis in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is usually considered a disease that will have a fatal termination in 1 to 3 years. A prospective study of 100 patients with this disorder revealed that 20 of them were living 5 years after the onset of their disorder. Review of other published series reveals that patients have been reported who lived for longer than 5 years and have then usually been reported as atypical cases, although the only way in which they are described as atypical is the duration of the disease. It is our assumption, based on these data as well as on additional clinical observations, that many patients with amyotrophic lateral sclerosis live for longer than 5 years and, rarely, they may have remissions of their illness. The possible significance of these observations is discussed.     

Long-term mechanical ventilation in amyotrophic lateral sclerosis

BACKGROUND: Acute respiratory insufficiency (ARI) with alveolar hypoventilation or incapacitating dyspnoea but without peripheral muscle involvement can be an early manifestation of respiratory involvement in amyotrophic lateral sclerosis (ALS). Some of these patients benefit from assisted ventilation. The object of this study was to analyse the results of long-term mechanical ventilation (LTMV) in ten patients with ALS. METHODS: A retrospective analysis of intensive care unit (ICU) or ambulant patients with ALS who underwent LTMV in a conventional hospital ward was performed. Erect and supine spirometry, blood gas analysis and pulse oximetry were performed before the start and during the course of ventilation. RESULTS: Ten patients on LTMV were included. Four from the ICU were ventilated via tracheostomy, and six ambulant patients had non-invasive (nasal) ventilation. In all cases, ventilation was performed in a conventional hospital ward. The ambulant patients improved symptomatically during ventilation, confirmed by measurement of gas exchange and of SaO2 by continuous pulse oximetry. Three of the ten patients survive in long-term care--two with nasal and one with tracheostomy ventilation. CONCLUSIONS: LTMV outside ICU was possible in ten patients, seven of whom returned home. Returning home is very difficult for patients dependent on a ventilator who lack family support.     

Temporal lobe pathology in amyotrophic lateral sclerosis. Do amyotrophic lateral sclerosis and Alzheimer's disease share a common etiological factor?

An autopsy study was performed on temporal lobe samples from 20 non-demented patients with amyotrophic lateral sclerosis (ALS), 17 age-matched non-demented controls and 4 Alzheimer's disease (AD) patients. Formalin fixed, paraffin embedded sections from the hippocampus with adjacent parahippocampal gyrus and from the superior temporal gyrus were stained with conventional and immunohistochemical stains. Immunohistochemical staining for the A4 protein was enhanced by pretreatment with 0.25% pepsin before 100% formic acid. The incidence and severity of AD-like pathological changes were similar in ALS patients and non-demented controls. In both groups, pathological changes increased with age. This study does not support the hypothesis that ALS and AD share an etiopathogenetic background.     

Aspects of phosphorus and carbohydrate metabolism in amyotrophic lateral sclerosis

The behaviour of glycaemia, insulinaemia, phosphoraemia, somatotropinaemia,free glycerol and triglyceridaemia was studied in six patients with A.L.S. following sugar load (1 g/Kg) in fasting. The results of glycaemia and insulinaemia were in tune with published data which have pointed to reduced sugar tolerance and reduced insulin secretion in patients with A.L.S. In the present experiments, particularly significant were the phosphoraemia responses. The failure of inorganic phosphorus values to fall after glucose loading suggests that the glycidic intolerance of these patients is related above all to a reduction in functioning muscular mass rather than to insufficient insulin secretion. The reduction in nervous tissue may also be of importance in this sense. In fact, not all biohumoral parameters investigated were similar to those of diabetes because the behaviour of somatotropinaemia, free glycerol and plasma triglycerides was normal. The changed behaviour of phosphorus would thus indicate altered glucose uptake at peripheral tissue level.     

Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis

Bulbar involvement in amyotrophic lateral sclerosis (ALS) is often related to a worse prognosis on account of the higher risk of pulmonary aspiration and undernutrition due to dysphagia. The aim of our study was to assess the effects of enteral feeding by percutaneous endoscopic gastrostomy (PEG) in a long-term follow-up of ALS patients. We report the results of PEG in 31 ALS patients with bulbar involvement. The patients were observed at 3-monthly intervals over a period of 2 years after PEG. All the data were compared with those obtained from a control group of 35 ALS patients who refused PEG. Mortality did not differ significantly between the two groups of patients during the first 6 months of observation, whereas after this period it was lower in the PEG group. In the patients who had had PEG, the body mass index showed a mild but statistically significant improvement after tube insertion while in the control group it decreased significantly. The findings of this study demonstrate that PEG can improve survival in elderly and young ALS patients with bulbar involvement; it enhances their quality of life and helps their integration in their social and family surroundings. We think that PEG should be included symptomatic treatment of all ALS patients with bulbar involvement from the onset of symptoms.