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.     

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.     

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.     

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.     

Eye movement in amyotrophic lateral sclerosis: a longitudinal study

Conservative therapy in cases of severe dysthyroid ophthalmopathy (DO) has not given satisfactory results. Since 1986, 51 patients (99 orbits) with marked DO have been treated by surgical decompression of the orbits. The procedure begins within the upper eyelid. The excision of the excessive skin and subcutaneous tissue is performed and eyelid fat is removed. In order to obtain the correction of the upper eyelid retraction, the levator aponeurosis is divided by 2-3 transverse incisions in its central part and Muller's muscle is sectioned at the level of its tarsal insertion. Through an incision in the lower eyelid, the posterior part of the orbital floor, the lateral orbit wall, as well as the periorbital and intraorbital fat are removed. Through an incision made over the medial margin of the orbit, the ethmoidal part of the medial orbital wall and the retrobulbar fat are removed. The periorbital periosteum should be incised at several sites. After operation all patients showed a significant reduction of exophthalmos (5-11 mm, 7.16 mm on average), significant reduction of intraocular pressure, marked improvement in ocular muscle function, as well as considerable reduction or disappearance of subjective symptoms. There was an improvement in vision in 68% patients who had impaired vision before the operation. There were no cases of subsequent impairment of vision or ocular motility. Mild relapse was recorded in three cases only and only one patient required unilateral reoperation. Strabismus surgery had to be performed in five patients due to unsatisfactory correction of double vision. It can be concluded that this method of orbital decompression gives very good functional and aesthetical long-term results.     

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.     

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.     

MRI and clinical features in amyotrophic lateral sclerosis

MRI of the brain and spinal cord was performed in 21 patients with amyotrophic lateral sclerosis (ALS), 8 normal volunteers and 16 neurological disease controls. High signal was seen in the intracranial corticospinal tract in 16 of the 21 patients on T2-weighted and in 10 on proton density (PD)-weighted images. In one patient, the high signal on T2-weighted images became less marked with progression of the disease. Low signal intensity was seen in the motor cortex in 12 of the 21 patients. High signal in the anterolateral column of the spinal cord on T1 weighted images was seen in 14, and high signal in the lateral corticospinal tract on T2 weighted images was seen in 7 of the 21 patients. The relationship between the abnormal images and upper motor neurone signs remained unclear. High signal intensity was seen in the corticospinal tract in the brain on T2-weighted images in two normal volunteers and four disease controls, and on PD weighted images in three disease controls. Low signal intensity in the motor cortex on T2 weighted images was seen in three normal volunteers and four disease controls. However, high signal intensity was seen in the intracranial corticospinal tract on T1 weighted images in five patients with ALS who showed pronounced upper motor neurone signs including spastic paraparesis, but not in controls. Thus, abnormalities on MRI in the brain and spinal cord should be considered in the diagnosis of ALS, and high signal intensity of the intracranial corticospinal tract on T1-weighted images may reflect the severe pathological changes of the upper motor neurones in ALS.     

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.     

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.     

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.     

Deficits in emotional and social cognition in amyotrophic lateral sclerosis.

Objective: These studies investigated whether non-demented ALS patients display impairments on tests of emotional decision making and social and emotional cognition, sensitive to frontal variant Frontotemporal Dementia (fvFTD). Previous studies have shown predominant executive dysfunction and dorsolateral prefrontal involvement in ALS, but evidence of other prefrontal dysfunction implicated in fvFTD is sparse. Method: In Study A, 19 ALS patients and 20 healthy controls undertook a test of affective decision making, modified Iowa Gambling Task (IGT). Behavioral measures included the Frontal Systems Behavior Scale. In Study B, 14 ALS patients and 20 controls undertook tests of social and emotional cognition (Judgment of Preference based on eye gaze, the Mind in the Eyes, recognition of Facial Expressions of Emotion). Results: In Study A, ALS patients demonstrated a significantly different performance profile from healthy controls on the IGT and did not learn to avoid the disadvantageous stimuli (Block 3, d = 0.60, Block 4 days = 0.68). Behavior ratings showed increased apathy from premorbid levels. In Study B, ALS patients were impaired on attentionally demanding (d = 3.12) and undemanding (d = 7.52) conditions of the Judgment of Preference task, despite many showing intact executive functions. A smaller subset showed impaired emotion recognition. Behavior change was also evident. Conclusions: The findings reveal a Theory of Mind deficit on a simple test that was dissociated from the presence of executive dysfunction and suggests a profile of cognitive and behavioral dysfunction indicative of a subclinical fvFTD syndrome. The relative contribution of prefrontal pathways to the cognitive profile in ALS is considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.