A clearer view of upper motor neuron dysfunction in amyotrophic lateral sclerosis

The Arrhenius and z-value models were compared for thermal inactivation analysis of a mesophilic bacterium. The models produced a linear curve for the thermal inactivation data. Concerning the rate constant of inactivation, the D and k values predicted by the models at a constant temperature were similar. For extrapolated temperatures the z-value model predicted an insignificant decrease in the survival ratio compared to the Arrhenius model. The dynamic temperature survival curves predicted by the models were similar, and the models characterized the results. These results demonstrated that the models can be used for thermal inactivation analysis of mesophiles at various temperatures.     

Ultrastructural abnormalities with inclusions in Onuf's nucleus in motor neuron disease (amyotrophic lateral sclerosis)

This study describes an ultrastructural examination focused on motor neurons in Onuf's nucleus in the spinal cord of four control patients without neurological disease (45-70 years) and six motor neuron disease (MND) patients (38-79 years; duration 8 months-19 years) who showed no somato-vesical dysfunction. Prompted by recent studies suggesting some sphincteric motor neurons may succumb to MND, this study sought to determine whether the wider population of neurons in Onuf's nucleus display ultrastructural cytopathology which is normally undetectable in histological preparations. Spinal cords were removed 3-20 h after death, and 1 mm slices of cord rapidly fixed in modified Karnovsky medium were processed for both light- and electronmicroscopy. 'Control motor neurons' had intact neuronal and nuclear membranes. Nissl bodies chiefly comprised ordered structures of alternate lamellae of rough endoplasmic reticulum and arrays of polyribosomes. The Golgi complexes consisted of multilamellated curvilinear stacks of ER. No intraneuronal filamentous or Bunina body inclusions were observed, but occasional axonal spheroids were seen in the neuropil. In MND, histological evidence of sparing in Onuf's nucleus was associated with abnormal ultrastructure of the motor neurons. Some sphincteric neurons were atrophic, whereas in the others, Nissl bodies were reduced in number, showed loss of structural organization or comprised polyribosomal aggregates. Golgi complexes had disrupted lamellated organization or consisted solely of distended ER. Intraneuronal filamentous Lewy-body or skein-like inclusions and Bunina bodies were identified in Onuf's nucleus of three subjects (duration of MND 8 months-2 years). The results of the present study indicate that Onuf's nucleus is vulnerable in MND, and preservation of sphincter function with qualitative histological evidence of 'sparing' does not necessarily imply a corresponding lack of ultrastructural cytopathology in this nucleus.     

A loss of functional spinal alpha motor neurons in amyotrophic lateral sclerosis

We obtained motor unit number estimates (MUNEs) of the hypothenar and the extensor digitorum brevis muscles in ALS patients by our new technique. One year after symptom onset, the MUNEs had decreased to +/-30% of normal. Accordingly, we suggest that 70% of functional spinal alpha motor neurons are lost in the first post-onset year in ALS.     

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.     

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.     

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.     

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.     

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.     

Upper and lower motor neuron lesions in the upper extremity muscles of tetraplegics

The Rorschach was given to 60 school children in two designs: CA and MA orthogonal (9 and 12 years) and CA =MA (for 6, 9 and 12 years). Responses were scored for Form Accuracy, Complexity, Movement, and Friedman's Developmental Level (DL) Scoring System. There were significant MA effects independent of CA on Form Accuracy, Complexity and DL, and significant CA effects on Complexity and Movement. Form Accuracy was highly correlated with the DL score and correlated with MA at a slightly higher level than DL with MA. The Complexity score provided some additional information about development. Movement decreased with age but was higher in intelligent subjects. The results suggested that the DL system does assess MA independently of CA, but this is accounted for primarily by Form Accuracy.     

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.     

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.     

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.