Spasticity In Amyotrophic Lateral Sclerosis Research Articles

Botulinum toxin therapy improves masseter spasticity in Amyotrophic Lateral Sclerosis

Fifteen ALS patients, with troublesome symptoms linked to masseter spasticity, benefited from BoNT-A injections in each masseter. Based on the medical records of patients, the effect of the first injection was assessed one month later. We retrospectively collected information for 12 patients. Eight of them reported a beneficial effect after the injection for the following symptoms: trismus, tongue, lip and cheek biting, and jaw clonus. Five patients indicated that dental care was easier after injection. Our study showed that injections of BoNT-A unequivocally reduced masseter spasticity in ALS patients who subsequently enjoyed greater comfort in their daily living.

Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis

Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS. Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life. A total of 465 patients (mean age 64.7years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life. The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.

Degeneration of serotonin neurons triggers spasticity in amyotrophic lateral sclerosis.

Spasticity occurs in a wide range of neurological diseases, including neurodegenerative diseases, after trauma, and after stroke, and is characterized by increased reflexes leading to muscle hypertonia. Spasticity is a painful symptom and can severely restrict everyday life, but might also participate in maintaining a low level of motor function in severely impaired patients. Constitutive activity of the serotonin receptors 5-HT2B/C is required for the development of spasticity after spinal cord injury and during amyotrophic lateral sclerosis (ALS). We sought here to provide direct evidence for a role of brainstem serotonin neurons in spasticity. SOD1(G37R) mice expressing a conditional allele of an ALS-linked SOD1 mutation were crossed with Tph2-Cre mice expressing Cre in serotonergic neurons. Measurement of long-lasting reflex using electromyography, behavioral follow-up, and histological techniques was used to characterize spasticity and motor phenotype. Deleting mutant SOD1 expression selectively in brainstem serotonin neurons was sufficient to rescue loss of TPH2 immunoreactivity and largely preserve serotonin innervation of motor neurons in the spinal cord. Furthermore, this abrogated constitutive activity of 5-HT2B/C receptors and abolished spasticity in end-stage mice. Consistent with spasticity mitigating motor symptoms, selective deletion worsened motor function and accelerated the onset of paralysis. Degeneration of serotonin neurons is necessary to trigger spasticity through the 5-HT2B/C receptor. The wide range of drugs targeting the serotonergic system could be useful to treat spasticity in neurological diseases. Ann Neurol 2017;82:444-456.

Safety and efficacy of botulinum toxin A for the treatment of spasticity in amyotrophic lateral sclerosis: results of a pilot study.

Spasticity can be a very disabling problem in some amyotrophic lateral sclerosis (ALS) phenotypes, such as upper motor neuron-dominant ALS (UMN-D ALS) and primary lateral sclerosis (PLS). Our aim is to describe the safety and efficacy of botulinum toxin A (BoTox-A) for improving gait in those ALS phenotypes. UMN-D ALS and PLS outpatients experiencing gait disturbances, secondary to moderate-to-severe spasticity despite optimized oral medication, were offered BoTox-A treatment.Stretching exercises were indicated to complement BoTox-A effect, and ankle-foot orthotics were prescribed when appropriate. Tolerance (muscle strength, disease progression rate) and efficacy (10-m walk test) were measured at baseline and after treatment. Eight out of 122 ALS outpatients were offered BoTox-A treatment. One declined and the other seven were administered BoTox-A in the lower limbs, every 5-8months. All of them experienced improvement in the clinical outcome and all but one referred subjective improvement. Moreover, after a median follow-up of 16months and three injections, BoTox-A effect was maintained with no adverse events. This study provides class IV evidence that BoTox-A is safe , and could be beneficial in the short term and long term in a subset of ALS patients with moderate-to-severe spasticity.

Degeneration of serotonergic neurons in amyotrophic lateral sclerosis: a link to spasticity

Spasticity is a common and disabling symptom observed in patients with central nervous system diseases, including amyotrophic lateral sclerosis, a disease affecting both upper and lower motor neurons. In amyotrophic lateral sclerosis, spasticity is traditionally thought to be the result of degeneration of the upper motor neurons in the cerebral cortex, although degeneration of other neuronal types, in particular serotonergic neurons, might also represent a cause of spasticity. We performed a pathology study in seven patients with amyotrophic lateral sclerosis and six control subjects and observed that central serotonergic neurons suffer from a degenerative process with prominent neuritic degeneration, and sometimes loss of cell bodies in patients with amyotrophic lateral sclerosis. Moreover, distal serotonergic projections to spinal cord motor neurons and hippocampus systematically degenerated in patients with amyotrophic lateral sclerosis. In SOD1 (G86R) mice, a transgenic model of amyotrophic lateral sclerosis, serotonin levels were decreased in brainstem and spinal cord before onset of motor symptoms. Furthermore, there was noticeable atrophy of serotonin neuronal cell bodies along with neuritic degeneration at disease onset. We hypothesized that degeneration of serotonergic neurons could underlie spasticity in amyotrophic lateral sclerosis and investigated this hypothesis in vivo using tail muscle spastic-like contractions in response to mechanical stimulation as a measure of spasticity. In SOD1 (G86R) mice, tail muscle spastic-like contractions were observed at end-stage. Importantly, they were abolished by 5-hydroxytryptamine-2b/c receptors inverse agonists. In line with this, 5-hydroxytryptamine-2b receptor expression was strongly increased at disease onset. In all, we show that serotonergic neurons degenerate during amyotrophic lateral sclerosis, and that this might underlie spasticity in mice. Further research is needed to determine whether inverse agonists of 5-hydroxytryptamine-2b/c receptors could be of interest in treating spasticity in patients with amyotrophic lateral sclerosis.

Poster 272 Intrathecal Baclofen Therapy for Spasticity in Amyotrophic Lateral Sclerosis 4

PM&RVolume 4, Issue 10S p. S281-S282 2012 AAPM&R Annual Assembly Abstract Poster 272 Intrathecal Baclofen Therapy for Spasticity in Amyotrophic Lateral Sclerosis 4 David Rosenblum MD, David Rosenblum MD Gaylord Hospital, Wallingford, CT, United StatesSearch for more papers by this author David Rosenblum MD, David Rosenblum MD Gaylord Hospital, Wallingford, CT, United StatesSearch for more papers by this author First published: 23 October 2012 https://doi.org/10.1016/j.pmrj.2012.09.885Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume4, Issue10SOctober 2012Pages S281-S282 RelatedInformation

Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease

Spasticity commonly affects patients with motor neuron disease. It is likely to contribute to worsening muscle dysfunction, increased difficulty with activities of daily living and deteriorating quality of life. This is an update of a review first published in 2003 and previously updated in 2005 and 2008. The objective of this review is to systematically review treatments for spasticity in amyotrophic lateral sclerosis, also known as motor neuron disease. We searched the Cochrane Neuromuscular Disease Group Specialized Register (4 July 2011), CENTRAL (2011, Issue 2), MEDLINE (January 1966 to July 2011), EMBASE (January 1980 to July 2011 ), CINAHL Plus (January 1937 to July 2011), AMED (January 1985 to July 2011) and LILACS (January 1982 to July 2011 ). We reviewed the bibliographies of the randomized controlled trials identified, and contacted authors and experts in the field. We included quasi-randomized or randomized controlled trials of participants with probable or definite amyotrophic lateral sclerosis according to the El Escorial diagnostic criteria (or a revised version) or the Airlie House revision. We would have included trials of physical therapy, modalities, prescription medications, non-prescription medications, chemical neurolysis, surgical interventions, and alternative therapies. Our primary outcome measure was reduction in spasticity at three months or greater as measured by the Ashworth (or modified Ashworth) spasticity scale. Our secondary outcome measures were: validated measures based on history, physical examination, physiological measures, measures of function, measures of quality of life, all adverse events, and measures of cost. Two authors independently screened the abstracts of potential trials retrieved from the searches. Two authors extracted the data. We also contacted the author of the paper and obtained information not available in the published article. All three authors assessed the methodological quality of all included trials independently. We identified only one randomized controlled trial that met our inclusion criteria and no further trials were identified in subsequent updates. The included study was a trial of moderate intensity, endurance type exercise versus 'usual activities' in 25 patients with amyotrophic lateral sclerosis. The risk of bias was high and no adverse events were reported. At three months patients performing the 15 minute twice daily exercises had significantly less spasticity overall (mean reduction of -0.43, 95% confidence interval (CI) -1.03 to +0.17 in the treatment group versus an increase of +0.25, 95% CI -0.46 to +0.96 in control) but the mean change between groups was not significant (-0.68, 95% CI -1.62 to +0.26), as measured by the Ashworth scale (possible scores 0 to 5, where higher is worse). The single trial performed was too small to determine whether individualized moderate intensity endurance type exercises for the trunk and limbs are beneficial or harmful. No other medical, surgical or alternative treatment and therapy has been evaluated in a randomized fashion in this patient population. More research is needed.

Intrathecal baclofen for spasticity‐related pain in amyotrophic lateral sclerosis: Efficacy and factors associated with pain relief

Clinical signs and symptoms of spasticity include hypertonia, involuntary movements (spasms, clonus), decreased range of motion, contractures, and often spasm-related pain. When spasticity is refractory to medical management, patients may be referred for intrathecal baclofen (ITB) pump placement. We reviewed a cohort of amyotrophic lateral sclerosis (ALS) patients with intractable spasticity requiring ITB to further define the impact of ITB on pain relief in this patient population. From 2003 to 2005, eight patients (mean age 43.8 years; 5 men, 3 women) with ALS received ITB for pain associated with intractable spasticity at our institution. Mean disease duration preoperatively was 47.4 months, mean follow-up was 9.8 months, and pain was evaluated using a 0-10 scoring system. All patients experienced spasticity relief in response to a preoperative bolus test injection of ITB (25-50 microg) via lumbar puncture. Following ITB pump placement, the average reduction of pain was 54% (P = 0.0082). Six patients (75%) experienced pain score reduction, three of whom had complete pain relief. Postoperative pain reduction was predicted by the degree of pain reduction following preoperative ITB test injection. These results support ITB as a treatment modality for pain associated with spasticity in ALS.

Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease.

Spasticity commonly affects patients with motor neuron disease and it is likely to contribute to worsening muscle dysfunction, increased difficulty with activities of daily living and deteriorating quality of life. The objective of this review is to systematically review all types of treatments for spasticity in amyotrophic lateral sclerosis, also known as motor neuron disease. We searched the Cochrane Neuromuscular Disease Group specialised trials register (searched January 2003), MEDLINE (January 1966 to January 2003), EMBASE (January 1980 to January 2003), CINAHL (January 1982 to January 2003), AMED (January 1985 to January 2003) and LILACS (January 1982 to January 2003) for randomized controlled trials. We reviewed the bibliographies of the randomized trials identified, and contacted trial authors and known experts in the field. We included quasi-randomized or randomized controlled trials of participants with probable or definite amyotrophic lateral sclerosis according to the El Escorial diagnostic criteria (or a revised version) or the Airlie House revision. We would have included trials of physical therapy, modalities, prescription medications, non-prescription medications, chemical neurolysis, surgical interventions, alternative therapies. Our primary outcome measure was reduction in spasticity at three months or greater as measured by Ashworth (or modified Ashworth) spasticity scale. Our secondary outcome measures were: validated measures based on history, physical examination, physiological measures, measures of function, measures of quality of life, serious adverse events, and measures of cost. We identified only one randomized controlled trial that met the inclusion criteria for this review. Two authors extracted the data. We also contacted the author of the paper and obtained further information not available in the published article. The included study was a trial of moderate intensity, endurance type exercise versus 'usual activities' in 25 patients with amyotrophic lateral sclerosis. At three months patients performing the 15 minute twice daily exercises had significantly less spasticity (mean reduction of 0.43 Ashworth grades versus an increase of 0.25 in controls), as measured by the Ashworth scale. Individualized, moderate intensity, endurance type exercises for the trunk and limbs may help to reduce spasticity in motor neuron disease. No other medical, surgical or alternative treatment and therapy has been evaluated in a randomized fashion in this patient population.

Intrathecal baclofen for intractable spasticity in amyotrophic lateral sclerosis

Intrathecal baclofen for intractable spasticity in amyotrophic lateral sclerosis

Therapeutic trial of intrathecal thyrotropin-releasing hormone (TRH) and a TRH-analogue in amyotrophic lateral sclerosis (ALS).

Thyrotropin-releasing hormone (TRH) is widely distributed in the central nervous system (CNS) and possibly plays an important role as a facilitatory neuromodulator and/or ergotrophic factor independent of its endocrine action[6,7,9,18]. It has been found in high concentrations in the anterior horns of the spinal cord and in cranial nerve nuclei of the brainstem, it shows excitatory actions on lower motor neurons in laboratory animals, and it has trophic effects on ventral spinal cord cultures[15]. In cats, TRH improved neurologic recovery from experimental spinal injury [5]. Its concentrations in the anterior horn regions of ALS patients on the other hand are decreased, its levels in the cerebrospinal fluid (CSF) seem to be reduced[3,12]. Engel et al.[2] reported for the first time a transient improvement of muscle strength and spasticity in ALS under very high intravenous doses of TRH (2 - 19 mg/min). Further trials with subcutaneous applications were promising and showed some clinical benefit up to 12 days[4]. Other intravenous studies had negative results[13]. Imoto et al.[8] injected TRH intramuscularly (4 mg daily) without unequivocal effects. TRH has a plasma half-life of only 4-5 min because of rapid enzymatic degradation, and its ability to cross the blood brain barrier is only limited. These difficulties might be circumvented by intrathecal application or by the use of TRH-analogues which have a protracted biological stability, therefore enhanced bioavailability to the CNS and enhanced neuro-pharmacological potency[10,11].