Advanced Amyotrophic Lateral Sclerosis Research Articles

Frontotemporal Lobe Involvement In Advanced Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), traditionally considered as a disorder limited to the motor system, is increasingly recognized to be a disease involving associative areas in addition to the motor cortex and therefore affecting cognition. ALS patients may present with a manifest frontotemporal dementia. New clinical findings suggest a connection between ALS and Frontotemporal Dementia. It is unknown that ALS-dementia is same or different from ALS in very advanced condition. The aim is to identify characteristic of brain imaging of CT findings in relatively advanced ALS patients. We performed CT examination in 25 cases of clinically definitive advanced ALS patients(M:F 12:13, age 70.3 ± 15.2 years, disease duration 8.3 years). All patients had received trachiotomy with respirator, and lost voluntary speech and severely impaired physical ability. Three patients had showed clinically dementia. We suggest that frontotemporal lobe atrophy may occur more commonly in the long-term ALS patients regardless of the clinical dementia.

Measuring function in advanced ALS: validation of ALSFRS‐EX extension items

With the aid of assistive technology, some patients with amyotrophic lateral sclerosis (ALS) are able to live for several years past the lowest measurable level of function on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R), a widely used end-point in ALS assessment. There is a research need to monitor patient function at the end of life, particularly in the face of severe impairment or 'locked in syndrome'. We used an online community for people with ALS (PALS) (PatientsLikeMe) to construct and pilot a number of new items to add to the ALSFRS-R scale to improve its sensitivity at lower levels of physical function in patients with advanced ALS. Ten new scale items were generated by a survey of PALS with advanced disease. These were added to the existing ALSFRS-R and data were received from 326 PALS at baseline with 169 PALS (52%) completing a 1-week test-retest and 218 PALS (67%) completing a 3-month retest [corrected]. Three new items were selected which conformed to the existing factor structure of the ALFRS-R. These relate to the ability to use fingers to manipulate devices, ability to show emotional expression in the face, and ability to get around inside the home. Real-world validation is the next step to assess the utility of the ALFRS-EX.

Anaesthesia for ophthalmologic surgical procedures in a patient with advanced amyotrophic lateral sclerosis: a case report

IntroductionAnaesthesia procedures for surgical interventions in patients with amyotrophic lateral sclerosis (ALS) are not commonly found in clinical practice, and often have special considerations that must be taken into account in treatment planning. As a result, these procedures are rarely subject to publication, rendering it difficult for the anaesthesiologists to find useful and reliable information on this topic. ALS also presents a contraindication to the use of nondepolarising neuromuscular blocking drugs during general anaesthesia.Case presentationIn the case presented here, a 52-year old, White man, the progression of the disease to tetraparesis and respiratory failure, in addition to having the patient on chronic mechanical ventilation support, provided additional challenges to the handling team. The maturation of cataracts severely impaired communication with the patient, and surgical treatment of the cataract presented the only means to save communication. Such interventions are generally performed under local anaesthesia with the advice of the attending anaesthesiologist. However, in this case the patients' announcements during the operation would be unreadable to the advising anaesthesiologist. Here, the authors share experiences from a successfully applied combination of topical and general anaesthesia for two cataract operations and a vitrectomy. This was tolerated well by the patient, and without any side-effects.ConclusionThe applied treatment resulted in a substantial improvement of the vision and allowed communication to be maintained with the patient.

Brain–computer interfaces in neurological rehabilitation

Recent advances in analysis of brain signals, training patients to control these signals, and improved computing capabilities have enabled people with severe motor disabilities to use their brain signals for communication and control of objects in their environment, thereby bypassing their impaired neuromuscular system. Non-invasive, electroencephalogram (EEG)-based brain-computer interface (BCI) technologies can be used to control a computer cursor or a limb orthosis, for word processing and accessing the internet, and for other functions such as environmental control or entertainment. By re-establishing some independence, BCI technologies can substantially improve the lives of people with devastating neurological disorders such as advanced amyotrophic lateral sclerosis. BCI technology might also restore more effective motor control to people after stroke or other traumatic brain disorders by helping to guide activity-dependent brain plasticity by use of EEG brain signals to indicate to the patient the current state of brain activity and to enable the user to subsequently lower abnormal activity. Alternatively, by use of brain signals to supplement impaired muscle control, BCIs might increase the efficacy of a rehabilitation protocol and thus improve muscle control for the patient.

Effects of the PPARγ activator pioglitazone on p38 MAP kinase and IκBα in the spinal cord of a transgenic mouse model of amyotrophic lateral sclerosis

Emerging evidence suggests the involvement of programmed cell death and inflammation in amyotrophic lateral sclerosis (ALS). To assess molecular pathological effects of the anti-inflammatory peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist pioglitazone in ALS, we verified changes in the population of neurons, astrocytes, and microglia in the ventral horns of spinal cord lumbar segments from the pioglitazone-treated and non-treated groups of mice carrying a transgene for G93A mutant human superoxide dismutase-1 (SOD1) (ALS mice) and non-transgenic littermates (control mice), performed immunohistochemical and immunoblot analyses of PPARgamma, active form of phosphorylated p38 mitogen-activated protein kinase (p-p38) and inhibitor of nuclear factor-kappaB (NF-kappaB)-alpha (IkappaBalpha) in the spinal cords, and compared the results between the different groups. Image analysis revealed that optical density of NeuN-immunoreactive neurons was significantly lower in the non-treated groups of presymptomatic and advanced ALS mice than in the non-treated groups of age-matched control mice and was recovered with pioglitazone treatment, and that optical densities of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia were significantly higher in the non-treated group of advanced ALS mice than in the non-treated group of control mice and were recovered with pioglitazone treatment. Immunohistochemical analysis demonstrated that immunoreactivities for PPARgamma and p-p38 were mainly localized in neurons, and that IkappaBalpha immunoreactivity was mainly localized in astrocytes and microglia. Immunoblot analysis showed that pioglitazone treatment resulted in no significant change in nuclear PPARgamma-immunoreactive density, a significant decrease in cytosolic p-p38-immunoreactive density, and a significant increase in cytosolic IkappaBalpha-immunoreactive density. Our results suggest that pioglitazone protects motor neurons against p38-mediated neuronal death and NF-kappaB-mediated glial inflammation via a PPARgamma-independent mechanism.

Longitudinal 1H MRS in advanced amyotrophic lateral sclerosis

Longitudinal 1H MRS in advanced amyotrophic lateral sclerosis

Longitudinal 1H MRS in advanced amyotrophic lateral sclerosis

Background: Standard MRI in patients suffering from amyotrophic lateral sclerosis (ALS) provides only little information on stage of disease and its progression. Besides the description of non-specific hyperintense signal alterations of the corticospinal tracts (CST), there are variable findings of enlargements of the central sulcus. Objectives: Several approaches have been made to investigate whether or not proton magnetic resonance spectroscopy (1H MRS) may serve in detecting upper motor neuron degeneration in ALS. Even so, lowered concentrations of N-acetyl-aspartate (NAA) in cortical motor regions as well as raised concentrations of creatine (Cr) and choline (Cho) in the internal capsule have been observed in patients with ALS compared to healthy controls. According to progression of disease, longitudinal decrease of NAA-concentrations was detected. The objective of this study was to investigate the longitudinal development of the concentration of brain metabolites in defined motor regions in advanced ALS. Methods: Ten patients with definite ALS according to Revised El Escorial criteria underwent standard single-voxel spectroscopy of the left- and right-hemispheric motor cortex and of the white matter including the CST in a six month follow-up series of three measurements. 1H MRS data were coregistered with tissue-segmented MRI data to obtain concentrations of the metabolites while fully automated post-processing included spectral fitting of the peak areas of NAA, Cr, and Cho. Results: In a cross-sectional view, the NAA/(Cr + Cho)-ratio of the motor cortex was reduced as expected, as a reflection of decreased NAA. All patients showed a markable decline of NAA in the motor cortex areas with nearly stable concentrations of Cr and Cho in the longitudinal follow-up. In contrast, neither the concentration of NAA nor the NAA/(Cr + Cho)-ratio showed comparable dynamics in paraventricular white matter areas. Conclusions: The NAA/(Cr + Cho)-ratio of the motor cortex is in a continuous decline corresponding proportionally to a decrease of NAA as a neuron-specific marker. Consecutively, NAA seems to be a promising candidate as a surrogate marker for in-vivo detection of disease progression and staging.

An outcome study of riluzole in amyotrophic lateral sclerosis--a population-based study in Ireland, 1996-2000.

Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period. Using data from the Irish ALS Register, we examined the survival of patients diagnosed with ALS between 1 January 1996 and 31 December 2000 who attended a general neurology clinic (n = 264 patients, MD = 16). An intention to treat analysis is employed. 149 (61 %) patients were prescribed riluzole and the remaining 99 (39 %) were not. Riluzole therapy reduced mortality rate by 23 % and 15 % at 6 and 12 months respectively and prolonged survival by approximately four months. This beneficial effect was lost in prolonged follow-up. Suspected or possible ALS patients receiving riluzole experienced similar improvement in survival as the overall cohort. Survival benefit was more marked among patients with bulbar-onset disease. Multivariate analysis did not show riluzole to be an independent predictor of survival. We conclude that riluzole therapy improves ALS survival in everyday clinical practice by a short period of time. This beneficial effect is transient and stopping the medication in advanced ALS should be reconsidered. Bulbar-onset patients appear to particularly benefit from riluzole for unclear reasons. Our initial observations support riluzole use in early ALS.

Expanding the role of hospice care in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, ultimately fatal, motor neuron disease that poses a myriad of clinical and end-of-life problems. The needs of advanced ALS patients are well suited to the interdisciplinary, multi-modality setting of hospice, where comprehensive palliative strategies may ease suffering and allow the patient to die with dignity in the home. Unfortunately, hospice services are far underutilized in this setting. There is a great need to increase awareness of both patients and clinicians regarding the effectiveness of hospice in the care of advanced ALS patients.

Against all odds: positive life experiences of people with advanced amyotrophic lateral sclerosis.

The study discussed in this article describes the nature of positive life experiences of 13 people coping exceptionally well while living with advanced amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, and the resulting significant physical disability. The most powerful themes to emerge were the use of cognitive reappraisal, reframing, and intellectual stimulation as coping mechanisms; the development of wisdom; and the vital importance of interpersonal relationships. On the basis of our findings, we make suggestions for ways professionals can assist people with ALS and their significant others.

Communication Status and Survival with Ventilatory Support

The use of ventilatory support via an indwelling tracheostomy tube in the management of advanced amyotrophic lateral sclerosis patients demands the commitment of enormous resources. The use of noninvasive respiratory aids can facilitate and simplify home management, decrease expense and prepare patients and families for decision making regarding tracheostomy if and when this becomes necessary. The purposes of this study were to: describe the utility of noninvasive respiratory aids, determine to what extent survival might be expected to increase by the use of mechanical ventilation, and explore the consequences of patient disposition and communication status on survival. Eighty-nine patients survived a mean of 4.4 +/- 3.9 yr (range = 1 month to 26.5 yr) using respiratory support. This included 37 patients who were still alive. The up to 24 h use of noninvasive intermittent positive pressure ventilation (IPPV) methods delayed or eliminated tracheostomy for 25 patients. Survival was comparable for patients maintained at home or in chronic care facilities. The maintenance of effective communication appeared to favor patients remaining in the community. It could not be shown to affect survival, but it greatly increased quality of life. The use of noninvasive respiratory muscle aids can eliminate the need for "crisis" decision making regarding tracheostomy for many individuals with ALS.

FASCICULAR MUSCLE TWITCHINGS IN AMYOTROPHIC LATERAL SCLEROSIS

Grund1and later Shelden and Woltman2found that the intrathecal injection of procaine in an amount sufficient to produce complete motor paralysis of the legs did not abolish the muscular fibrillations in patients with amyotrophic lateral sclerosis. These experiments were interpreted as showing that the impulses causing these fibrillations did not arise from the cell bodies of the motor neurons of the ventral horn. Each of these investigations consisted of but 1 experiment; the nature of the muscular twitchings was not controlled by electrical recordings, and no further attempt was made to locate the source of the impulses causing the fibrillations. For these reasons the present study was undertaken. PROCEDURE Three patients with typical and advanced amyotrophic lateral sclerosis and 2 others with progressive muscular atrophy with muscular fibrillation3were utilized in this study. Three of the patients exhibited many and 2 relatively infrequent muscular fibrillations at