Katja Kollewe

EFNS guidelines on the clinical management of Amyotrophic Lateral Sclerosis (MALS) - revised report of an EFNS task force

Background:  The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak.

EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives

Despite being one of the most devastating diseases known, there is little evidence for diagnosing and managing patients with amyotrophic lateral sclerosis (ALS). Although specific therapy is lacking, correct early diagnosis and introduction of symptomatic and specific therapy can have a profound influence on the care and quality of life of the patient and may increase survival time. This document addresses the optimal clinical approach to ALS. The final literature search was performed in the spring of 2005. Consensus recommendations are given graded according to the EFNS guidance regulations. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. People affected with possible ALS should be examined as soon as possible by an experienced neurologist. Early diagnosis should be pursued and a number of investigations should be performed with high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with vital capacity <50%. Non‐invasive positive pressure ventilation improves survival and quality of life but is underused. Maintaining the patients ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be fully discussed early with the patient and relatives respecting the patients social and cultural background.

Changes of resting state brain networks in amyotrophic lateral sclerosis.

The defining feature of amyotrophic lateral sclerosis is degeneration of upper and lower motor neurons but extramotor involvement, evidenced for example by executive dysfunction, has also been demonstrated. Here we employed a novel functional imaging approach, the analysis of resting state activity, followed by the definition of functionally connected brain networks by independent component analysis (ICA) to assess differences between ALS patients (n=20) and healthy controls (n=20). ICA analysis revealed 5 typical brain networks among which the so-called default mode network and the sensori-motor network showed distinct differences between patients and controls. The default mode network showed less activation in patients in several regions including the ventral anterior cingulate cortex, posterior cingulate cortex and the left and right inferior parietal cortex, regions that have been linked previously to executive functions. The sensori-motor network showed group differences in the premotor cortex. We propose that resting state analysis affords a new and simple means to assess disease-related neurofunctional alterations in widespread brain networks. A decisive advantage is that no task is demanded from the subjects and, thus, the problem of differential task difficulty and effort between groups is circumvented.

Good practice in the management of amyotrophic lateral sclerosis : clinical guidelines. An evidence-based review with good practice points. EALSC Working Group.

The evidence base for diagnosis and management of ALS is still weak, and curative therapy is lacking. Nonetheless, early diagnosis and symptomatic therapy can profoundly influence care and quality of life of the patient and relatives, and may increase survival time. This review addresses the current optimal clinical approach to ALS. The literature search is complete to December 2006. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. We conclude that a diagnosis of ALS can be achieved by early examination by an experienced neurologist. The patient should be informed of the diagnosis by the consultant. Following diagnosis, a multi‐diciplinary care team should support the patient and relatives. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with VC <50%: RIG may be a better alternative. Non‐invasive positive pressure ventilation improves survival and quality of life but is underused in Europe. Maintaining the patients ability to communicate is essential. During the course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be discussed early with the patient and relatives if they so wish.

ALSFRS-R score and its ratio: a useful predictor for ALS-progression.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. To determine predictors of survival, we studied different parameters in our ALS Database including 479 patients. The effects of individual prognostic factors of survival were studied using Kaplan-Meier life table. The prognostic value of each factor of interest was expressed in terms of a hazard ratio. Survival from symptom-onset ranged from 4 months up to 11.9 years. Gender had no effect on survival in our cohort. However, age, site of onset, forced vital capacity, symptom duration and ALSFRS-R score at the first visit were independent prognostic factors in our population (log-rank p<0.01). The ratio of ALSFRS-R score between first symptom and first examination, during whole disease or within 100 days, correlates with survival time. We conclude that the ratio of ALSFRS-R score within 100 days is a useful parameter for clinical trials and daily clinical work in a tertiary ALS-clinic.

Facing depression with botulinum toxin: A randomized controlled trial

Positive effects on mood have been observed in subjects who underwent treatment of glabellar frown lines with botulinum toxin and, in an open case series, depression remitted or improved after such treatment. Using a randomized double-blind placebo-controlled trial design we assessed botulinum toxin injection to the glabellar region as an adjunctive treatment of major depression. Thirty patients were randomly assigned to a verum (onabotulinumtoxinA, n = 15) or placebo (saline, n = 15) group. The primary end point was change in the 17-item version of the Hamilton Depression Rating Scale six weeks after treatment compared to baseline. The verum and the placebo groups did not differ significantly in any of the collected baseline characteristics. Throughout the sixteen-week follow-up period there was a significant improvement in depressive symptoms in the verum group compared to the placebo group as measured by the Hamilton Depression Rating Scale (F((6,168)) = 5.76, p < 0.001, η(2) = 0.17). Six weeks after a single treatment scores of onabotulinumtoxinA recipients were reduced on average by 47.1% and by 9.2% in placebo-treated participants (F((1,28)) = 12.30, p = 0.002, η(2) = 0.31, d = 1.28). The effect size was even larger at the end of the study (d = 1.80). Treatment-dependent clinical improvement was also reflected in the Beck Depression Inventory, and in the Clinical Global Impressions Scale. This study shows that a single treatment of the glabellar region with botulinum toxin may shortly accomplish a strong and sustained alleviation of depression in patients, who did not improve sufficiently on previous medication. It supports the concept, that the facial musculature not only expresses, but also regulates mood states.

Functional neuroimaging at different disease stages reveals distinct phases of neuroplastic changes in amyotrophic lateral sclerosis.

Some previous functional magnetic resonance imaging (fMRI) studies have revealed increased activation in amyotrophic lateral sclerosis (ALS) patients but longitudinal data on such activation changes are lacking. To assess the time course of changes in fMRI patterns and their potential contribution to the understanding of ALS pathophysiology, we, therefore, investigated a total of 22 patients with ALS and matched control participants while they performed a blocked motor task. Patients were assigned to three groups according to whether they had no (MRC grade 5), mild (MRC 4), or marked (MRC 3) weakness of the examined right hand. Significant activations were seen in primary motor and premotor cortex, somatosensory cortex, supplementary motor area and subcortical areas in all groups. The size of the activated area in the contralateral sensorimotor cortex was increased to a similar degree in all three ALS groups compared to control participants irrespective of weakness on clinical examination. Whereas movement related signal change and beta weights extracted from the activated cluster were unchanged relative to controls in ALS patients with no weakness, a marked decrease of these parameters was seen in patients with weakness. Two distinct stages of neuroplastic changes could be identified in ALS (first: increase of the activated area in contralateral sensorimotor cortex; second: reduction of signal change and beta weights with increasing weakness). We interpret the increase of the activated area as a result of decreased intracortical inhibition and the reduction of movement related signal change and beta weights as a consequence of loss of upper motor neurons. Hum Brain Mapp, 2011.

A long-term follow-up of botulinum toxin A in cervical dystonia

Abstract Objective: Cervical dystonia (CD) is the most common form of adult-onset focal dystonia, and botulinum toxin A (BoNT-A) has become the first-line treatment for this condition. Methods: In this work, we present data of 207 CD patients treated with BoNT-A for 6.7 ± 3.5 years. One hundred and sixty-three patients were treated with Dysport (mean dose, 389 ± 144 U) and 44 with Botox (mean dose, 145 ± 44 U). Results: The mean clinical benefit, based on a 0–3 scale (0=no effect, 1=slight, 2=moderate and 3=marked improvement) was similar for Dysport (2.5 ± 0.3) and Botox (2.2 ± 0.4). Adverse events were mild and similar for both products. Fewer than 2% of the patients developed neutralizing antibodies. Discussion: These data confirm the efficacy and safety of BoNT-A treatment in CD over an extended period of up to 14 years.

Onset and spreading patterns of upper and lower motor neuron symptoms in amyotrophic lateral sclerosis.

The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. There is ongoing discussion as to whether ALS is primarily a disease of UMNs or LMNs.

The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen: A cross-sectional comparison of established screening tools in a German-Swiss population

Abstract The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) has recently been developed as a fast and easy cognitive screening tool specifically designed for patients with motor impairments in routine clinical use. The German/Swiss-German version of the ECAS was validated in a German-Swiss consortium. One hundred and thirty-six non-demented ALS patients and 160 healthy controls were included in the study. In addition, the Frontal Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA) and Consortium to Establish a Registry for Alzheimers Disease plus Scale (CERAD plus) were administered to subgroups of patients. Results showed that administration of ECAS was fast (mean 24 min). Similar to the population in the UK version, ALS patients performed significantly worse in the ALS-specific functions (p < 0.001), specifically in the domain of language (p < 0.001), verbal fluency (p = 0.005) and executive functions (p = 0.02), but not for the non-ALS-specific functions. Carers reported behavioural abnormalities in about 30% and psychotic symptoms in 6% of the patients. Compared to ECAS, FAB, MoCA and CERAD were more generic and performance was not adjusted to motor speed. We conclude that the German/Swiss-German version of the ECAS is a fast and easy to administer cognitive screening instrument sensitive for ALS-specific dysfunctions and behaviour change.