Posts Tagged chronic

[Abstract] Myoelectric Computer Interface Training for Reducing Co-Activation and Enhancing Arm Movement in Chronic Stroke Survivors: A Randomized Trial

Background. Abnormal muscle co-activation contributes to impairment after stroke. We developed a myoelectric computer interface (MyoCI) training paradigm to reduce abnormal co-activation. MyoCI provides intuitive feedback about muscle activation patterns, enabling decoupling of these muscles.

Objective. To investigate tolerability and effects of MyoCI training of 3 muscle pairs on arm motor recovery after stroke, including effects of training dose and isometric versus movement-based training.

Methods. We randomized chronic stroke survivors with moderate-to-severe arm impairment to 3 groups. Two groups tested different doses of isometric MyoCI (60 vs 90 minutes), and one group tested MyoCI without arm restraint (90 minutes), over 6 weeks. Primary outcome was arm impairment (Fugl-Meyer Assessment). Secondary outcomes included function, spasticity, and elbow range-of-motion at weeks 6 and 10.

Results. Over all 32 subjects, MyoCI training of 3 muscle pairs significantly reduced impairment (Fugl-Meyer Assessment) by 3.3 ± 0.6 and 3.1 ± 0.7 (P < 10−4) at weeks 6 and 10, respectively. Each group improved significantly from baseline; no significant differences were seen between groups. Participants’ lab-based and home-based function also improved at weeks 6 and 10 (P ≤ .01). Spasticity also decreased over all subjects, and elbow range-of-motion improved. Both moderately and severely impaired patients showed significant improvement. No participants had training-related adverse events. MyoCI reduced abnormal co-activation, which appeared to transfer to reaching in the movement group.

Conclusions. MyoCI is a well-tolerated, novel rehabilitation tool that enables stroke survivors to reduce abnormal co-activation. It may reduce impairment and spasticity and improve arm function, even in severely impaired patients.

 

via Myoelectric Computer Interface Training for Reducing Co-Activation and Enhancing Arm Movement in Chronic Stroke Survivors: A Randomized Trial – Emily M. Mugler, Goran Tomic, Aparna Singh, Saad Hameed, Eric W. Lindberg, Jon Gaide, Murad Alqadi, Elizabeth Robinson, Katherine Dalzotto, Camila Limoli, Tyler Jacobson, Jungwha Lee, Marc W. Slutzky, 2019

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[WEB PAGE] Treatment of Traumatic Brain Injury With Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy (HBOT) is defined as the use of oxygen at higher than atmospheric pressure for the treatment of underlying disease processes and the diseases they produce. Modern HBOT in which 100% O2 is breathed in a pressurized chamber dates back to the 1930s, when it was first used for treatment of decompression illness in divers. There are currently 13 FDA-approved uses for HBOT, including decompression illness, gas gangrene, air embolism, osteomyelitis, radiation necrosis, and the most recent addition—diabetic ulcers.

Just as practicing physicians routinely identify off-label uses for medications, over the years HBOT physicians have identified many other conditions that respond to HBOT. A number of chronic neurological conditions including traumatic brain injury (TBI) have been shown to respond particularly well. There is published literature supporting HBOT’s efficacy for TBI, including human trials and animal research, but due to the impossibility of arranging sham pressure there are no rigorous double-blind placebo-controlled trials.1 As a result, HBOT is not FDA-approved for TBI, and insurance will generally not pay for it.

HBOT can dramatically and permanently improve symptoms of chronic TBI months or even many years after the original head injury. This assertion is generally met with skepticism within the medical establishment because we have been taught for generations that any post-concussion symptoms persisting more than 6 months or so after a head injury are due to permanent brain damage that cannot be repaired. Therefore, treatment has been limited to symptom management and rehabilitative services, and any claim suggesting that fundamental healing is possible is suspect. The combination of entrenched skepticism and lack of insurance coverage has made it very difficult for patients to access treatment.

Another source of skepticism has been the large number of disparate conditions that are claimed to be helped by HBOT. A brief review of the mechanisms through which HBOT triggers healing responses, with particular reference to the modern understanding of the pathophysiology of TBI, provides a theoretical framework to explain these claims.

Physiological effects of HBOT

About 97% of the total oxygen in blood is tightly bound to hemoglobin when breathing room air (21% O2) at sea level (1 atmosphere, or 1 ATM; 3% of the oxygen is dissolved in blood serum. This amounts to about 0.3 mL of oxygen dissolved in 100 mL of serum. By the time oxygen diffuses out of the circulatory system and ultimately reaches the mitochondria, there is just a trace amount present. HBOT’s primary mechanism is to temporarily hyper-oxygenate body tissues. HBOT delivered at 1.3 ATM increases dissolved oxygen in serum by a factor of 7. HBOT delivered in hard chambers at 2.5 to 3.0 ATM increases dissolved oxygen by a factor of 15 or more. Oxygen levels in body tissues outside the circulatory system will be increased commensurately.

If a hyper-oxygenated state is maintained for long periods it will cause significant oxidative damage, but when it is “pulsed” for an hour it triggers a variety of healing processes without overwhelming the body’s anti-oxidant system. The currently known mechanisms include a powerful anti-inflammatory effect, reduction of edema, increased blood perfusion, angiogenesis, stimulation of the immune system, stimulation of endogenous antioxidant systems, mobilization of stem cells from bone marrow, axonal regrowth, and modulation of the expression of thousands of genes involved in the inflammatory response and various healing responses.2,3

[…]

Continue —>  Treatment of Traumatic Brain Injury With Hyperbaric Oxygen Therapy | Psychiatric Times

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[ARTICLE] Pharmacological management of long-term aggression secondary to traumatic brain injuries – Full Text

Abstract

Aggression is common after traumatic brain injuries (TBI) in acute and chronic settings. However, there is limited guidance regarding its assessment and effective management. Whilst a number of pharmacological options are available for long term treatment, the evidence base is not of an adequate strength to support a unified practice. This article will explore the currently available guidelines and recommendations for treating chronic aggression after TBIs and evaluate the evidence for its pharmacological management.


Introduction

Aggression is a long term neurobehavioural sequelae of TBIs with incidences quoted from 11.5-33.7%.1 In TBI patients, aggressive behaviour tends to be impulsive rather than premeditated and can manifest as episodic dyscontrol syndrome, disinhibition or exacerbated premorbid antisocial traits.2 The underlying mechanisms of aggression are complex allowing numerous and diverse interventions targeting various pathways.

In acute settings, Lombard and Zafonte (2005) describe non-pharmacological measures to manage aggression including environmental alterations and ensuring minimal or non-contact restraints. Screening for systemic causes, optimising pain control and patients’ sleep-wake cycle are also advocated. In the event of failed non-pharmacological treatment, Lombard and Zafonte (2005) recommend that medication choice should be tailored to individuals; with side effect profiles taken into consideration.3

For chronic aggression, psychological therapies are used as a first line with pharmacological interventions trialled in later stages.4 Psychological therapy options include cognitive behavioural therapy (CBT), behavioural management utilising operant learning theory and contingency management. However, a review by Alderman (2013) concluded that further evidence using scientific methods is needed to analyse these approaches.5  Comparatively, there is a diverse body of literature addressing long term pharmacological treatment although quality among studies are varied. This article will focus on the aetiology for chronic post TBI aggression, current management guidelines and the evidence for long term pharmacological interventions.[…]

via Pharmacological management of long-term aggression secondary to traumatic brain injuries | ACNR | Online Neurology Journal

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[Abstract] Comparison between Transcranial Direct Current Stimulation and Acupuncture on Upper Extremity Rehabilitation in Stroke: A Single-Blind Randomized Controlled Trial

Abstract

Objective: To compare the effects of transcranial direct current stimulation (TDCS) with traditional Chinese acupuncture on upper-extremity (UE) function among patients with stroke.

Materials and Methods: Participants with subacute to chronic stroke who had moderate to severe UE functional impairment were randomly allocated to the TDCS or electro-acupuncture group, then underwent three weeks of physical therapy and occupational therapy, with 20 minutes of a-TDCS (2 mA) or electro-acupuncture applied during training once weekly. Primary outcome was determined using the Fugl-Meyer Assessment of motor recovery at 1-month follow-up.

Results: The 18 participants were allocated into two groups. Fugl-Meyer Assessment increased in both the TDCS and electroacupuncture groups (5.00±3.08, p=0.001 and 7.4±4.9, p=0.002, respectively). However, no difference was found between groups, and no significant difference was observed in grip strength and task specific performance in both groups.

Conclusion: The application of TDCS might provide benefits in recovering hand motor function among patients with subacute to chronic stroke but does not go beyond those of electro-acupuncture.

via Comparison between Transcranial Direct Current Stimulation and Acupuncture on Upper Extremity Rehabilitation in Stroke: A Single-Blind Randomized Controlled Trial | Hathaiareerug | JOURNAL OF THE MEDICAL ASSOCIATION OF THAILAND

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[Abstract] Unilateral vs. Bilateral Hybrid Approaches for Upper Limb Rehabilitation in Chronic Stroke: A Randomized Controlled Trial

Abstract

Objective

To investigate the effects of unilateral hybrid therapy (UHT) and bilateral hybrid therapy (BHT) compared with robot-assisted therapy (RT) alone in patients with chronic stroke.

Design

A single-blind, randomized controlled trial

Setting

Four hospitals

Participants

Forty-four outpatients with chronic stroke and mild to moderate motor impairment.

Intervention

UHT combined unilateral RT (URT) and modified constraint-induced therapy. BHT combined bilateral RT (BRT) and bilateral arm training. The RT group received URT and the BRT. The intervention frequency for the 3 groups was 90 min/day, 3 days/week, for 6 weeks.

Outcome measures

Fugl-Meyer Assessment (FMA, divided into the proximal and distal subscale) and Stroke Impact Scale (SIS) version 3.0 scores before, immediately after, and 3 months after treatment, and Wolf Motor Function Test (WMFT) and Nottingham Extended Activities of Daily Living (NEADL) scale scores before and immediately after treatment.

Results

The results favored BHT over UHT on the FMA total score and distal score at the posttest (p = .03 and .04) and follow-up (p = .01 and .047) assessment, and BHT over RT on the follow-up FMA distal scores (p = .03). At the posttest assessment, the WMFT and SIS scores of the 3 groups improved significantly without between-group differences, and the RT group showed significantly greater improvement in the mobility domain of NEADL, as compared to the BHT group (p<.01).

Conclusions

BHT was more effective for improving upper extremity motor function, particularly distal motor function at follow-up, and individuals in the RT group demonstrated improved functional ambulation post intervention.

via Unilateral vs. Bilateral Hybrid Approaches for Upper Limb Rehabilitation in Chronic Stroke: A Randomized Controlled Trial – Archives of Physical Medicine and Rehabilitation

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[ARTICLE] Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke – Full Text

Background and Purpose: The potential for adaptive plasticity in the post-stroke brain is difficult to estimate, as is the demonstration of central nervous system (CNS) target engagement of drugs that show promise in facilitating stroke recovery. We set out to determine if paired associative stimulation (PAS) can be used (a) as an assay of CNS plasticity in patients with chronic stroke, and (b) to demonstrate CNS engagement by memantine, a drug which has potential plasticity-modulating effects for use in motor recovery following stroke.

Methods: We examined the effect of PAS in fourteen participants with chronic hemiparetic stroke at five time-points in a within-subjects repeated measures design study: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg, comprising a total of seventy sessions. Each week, MEP amplitude pre and post-PAS was assessed in the contralesional hemisphere as a marker of enhanced or diminished plasticity. Strength and dexterity were recorded each week to monitor motor-specific clinical status across the study period.

Results: We found that MEP amplitude was significantly larger after PAS in baseline sessions off-drug, and responsiveness to PAS in these sessions was associated with increased clinical severity. There was no observed increase in MEP amplitude after PAS with memantine at any dose. Motor threshold (MT), strength, and dexterity remained unchanged during the study.

Conclusion: Paired associative stimulation successfully induced corticospinal excitability enhancement in chronic stroke subjects at the group level. However, this response did not occur in all participants, and was associated with increased clinical severity. This could be an important way to stratify patients for future PAS-drug studies. PAS was suppressed by memantine at all doses, regardless of responsiveness to PAS off-drug, indicating CNS engagement.

Introduction

The capacity of the brain to make structural, physiological, and genetic adaptations following stroke, otherwise known as plasticity, is likely to be critical for improving sensorimotor impairments and functional activities. Promotion of adaptive plasticity in the central nervous system (CNS) leading to sustained functional improvement is of paramount importance, given the personal suffering and cost associated with post-stroke disability (Ma et al., 2014). In addition to rehabilitation therapies to retrain degraded motor skills, animal and human studies have tried to augment recovery with neuropharmacologic interventions. Unfortunately, few if any have had a notable effect in patients or have come into routine use (Martinsson et al., 2007Chollet et al., 2011Cramer, 2015Simpson et al., 2015). Methods to screen drugs based on their presumed mechanism of action on plasticity in human motor systems could speed translation to patients. However, there is currently no accepted method in stroke patients for evaluating the potential effectiveness or individual responsiveness to putative “plasticity enhancing” drugs in an efficient, low-cost, cross-sectional manner, in order to establish target engagement in humans and to avoid the extensive time and cost of protracted clinical trials.

Paired associative stimulation (PAS) is a safe, painless, and non-invasive technique known to result in short-term modulation of corticospinal excitability in the adult human motor system, lasting ∼90 min (Stefan et al., 2000Wolters et al., 2003). Post-PAS excitability enhancement has been considered an LTP-like response thought to relate to transient changes in synaptic efficacy in the glutamatergic system at the N-methyl-D-aspartate (NMDA) receptor, since both human NMDA receptor deficiency (Volz et al., 2016) and pharmacological manipulation with dextromethorphan (Stefan et al., 2002) can block the effect. While PAS has been explored as a potential therapeutic intervention in patients with residual motor deficits after stroke (Jayaram and Stinear, 2008Castel-Lacanal et al., 2009), it has not previously been investigated for its potential use as an assay of motor system plasticity in this context. Prior studies have suggested that motor practice and PAS share the same neuronal substrates, modulating LTP and LTD-like plasticity in the human motor system (Ziemann et al., 2004Jung and Ziemann, 2009); therefore, as an established non-invasive human neuromodulation method (Suppa et al., 2017), we reasoned that PAS would be a suitable assay in the present study to examine the effect of a drug on motor system plasticity.

Here, we examine the effect of memantine, a drug used for treatment of Alzheimer’s disease, on the PAS response in patients with chronic stroke. Memantine is described pharmacologically as a low affinity, voltage dependent, non-competitive, NMDA antagonist (Rogawski and Wenk, 2003). At high concentrations, like other NMDA-R antagonists, it can inhibit synaptic plasticity. At lower, clinically relevant concentrations, memantine can, under some circumstances, promote synaptic plasticity by selectively inhibiting extra-synaptic glutamate receptor activity while sparing normal synaptic transmission, and hence may have clinical utility for rehabilitation (Xia et al., 2010). Interest in specifically using the drug for its interaction with stroke pathophysiology stems from animal models of both prevention (Trotman et al., 2015), in which pre-conditioning reduced infarct size, as well as for functional recovery, in which chronic oral administration starting >2 h post-stroke resulted in improved function through a non-neuroprotective mechanism (López-Valdés et al., 2014). In humans, memantine taken over multiple days has been used to demonstrate that the NMDA receptor is implicated in specific transcranial magnetic paired-pulse measures (Schwenkreis et al., 1999), and short-term training-induced motor map reorganization (Schwenkreis et al., 2005). In studies of neuromodulation, memantine blocked the facilitatory effect of intermittent theta-burst stimulation (iTBS) (Huang et al., 2007). Similarly, LTP-like plasticity induced by associative pairing of painful laser stimuli and TMS over primary motor cortex (M1) can also be blocked by memantine (Suppa et al., 2013). The effects of memantine on the PAS response have not yet been demonstrated, including examination of potential dose-response effects, which would be important for the potential clinical application of memantine for stroke recovery.

In our study, we set out to determine whether PAS might be a useful tool to probe the potential for plasticity after stroke in persons with chronic hemiparesis and apply PAS as an assay to look at drug effects on motor system plasticity using memantine. We hypothesized that (a) PAS would enhance corticospinal excitability in the contralesional hemisphere of stroke patients, and that (b) since PAS-induced plasticity is thought to involve a short-term change in glutamatergic synaptic efficacy, memantine would have a dose-dependent effect on PAS response. We predicted that at low doses, memantine would enhance PAS-induced plasticity through selective blockade of extrasynaptic NMDA receptors, whereas higher doses would inhibit PAS-induced plasticity.[…]

 

Continue —> Frontiers | Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke | Neuroscience

Figure 1. Axial MR/CT images for individual patients illustrating the stroke lesion. Images are displayed in radiological convention. Images are labeled by participant number.

 

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[Abstract] Forced, Not Voluntary, Aerobic Exercise Enhances Motor Recovery in Persons With Chronic Stroke

Background. The recovery of motor function following stroke is largely dependent on motor learning–related neuroplasticity. It has been hypothesized that intensive aerobic exercise (AE) training as an antecedent to motor task practice may prime the central nervous system to optimize motor recovery poststroke.

Objective. The objective of this study was to determine the differential effects of forced or voluntary AE combined with upper-extremity repetitive task practice (RTP) on the recovery of motor function in adults with stroke.

Methods. A combined analysis of 2 preliminary randomized clinical trials was conducted in which participants (n = 40) were randomized into 1 of 3 groups: (1) forced exercise and RTP (FE+RTP), (2) voluntary exercise and RTP (VE+RTP), or (3) time-matched stroke-related education and RTP (Edu+RTP). Participants completed 24 training sessions over 8 weeks.

Results. A significant interaction effect was found indicating that improvements in the Fugl-Meyer Assessment (FMA) were greatest for the FE+RTP group (P = .001). All 3 groups improved significantly on the FMA by a mean of 11, 6, and 9 points for the FE+RTP, VE+RTP, and Edu+RTP groups, respectively. No evidence of a treatment-by-time interaction was observed for Wolf Motor Function Test outcomes; however, those in the FE+RTP group did exhibit significant improvement on the total, gross motor, and fine-motor performance times (P ≤ .01 for all observations).

Conclusions. Results indicate that FE administered prior to RTP enhanced motor skill acquisition greater than VE or stroke-related education. AE, FE in particular, should be considered as an effective antecedent to enhance motor recovery poststroke.

via Forced, Not Voluntary, Aerobic Exercise Enhances Motor Recovery in Persons With Chronic Stroke – Susan M. Linder, Anson B. Rosenfeldt, Sara Davidson, Nicole Zimmerman, Amanda Penko, John Lee, Cynthia Clark, Jay L. Alberts,

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[ARTICLE] Pharmacological management of long-term aggression secondary to traumatic brain injuries

Abstract
Aggression is common after traumatic brain injuries (TBI) in acute and chronic settings. However, there is limited guidance regarding its assessment and effective management. Whilst a number of pharmacological options are available for long term treatment, the evidence base is not of an adequate strength to support a unified practice. This article will explore the currently available guidelines and recommendations for treating chronic aggression after TBIs and evaluate the evidence for its pharmacological management.


Introduction

Aggression is a long term neurobehavioural sequelae of TBIs with incidences quoted from 11.5-33.7%.1 In TBI patients, aggressive behaviour tends to be impulsive rather than premeditated and can manifest as episodic dyscontrol syndrome, disinhibition or exacerbated premorbid antisocial traits.2 The underlying mechanisms of aggression are complex allowing numerous and diverse interventions targeting various pathways.

In acute settings, Lombard and Zafonte (2005) describe non-pharmacological measures to manage aggression including environmental alterations and ensuring minimal or non-contact restraints. Screening for systemic causes, optimising pain control and patients’ sleep-wake cycle are also advocated. In the event of failed non-pharmacological treatment, Lombard and Zafonte (2005) recommend that medication choice should be tailored to individuals; with side effect profiles taken into consideration.3

For chronic aggression, psychological therapies are used as a first line with pharmacological interventions trialled in later stages.4 Psychological therapy options include cognitive behavioural therapy (CBT), behavioural management utilising operant learning theory and contingency management. However, a review by Alderman (2013) concluded that further evidence using scientific methods is needed to analyse these approaches.5  Comparatively, there is a diverse body of literature addressing long term pharmacological treatment although quality among studies are varied. This article will focus on the aetiology for chronic post TBI aggression, current management guidelines and the evidence for long term pharmacological interventions.

Aetiology

Post TBI aggression has been associated with lesions affecting the prefrontal cortex – particularly the orbitofrontal and ventromedial areas – causing a loss of behavioural regulation. Disruption to inhibitory pathways between the prefrontal cortex and limbic system also results in limbic kindling and inappropriate emotional responses to negative stimuli thus facilitating aggressive behaviour.2 Associated neurotransmitter abnormalities include low cortical serotonin and impaired gamma amino-butyric acid (GABA)/ glutamate levels.6 Altered catecholamine and cholinergic levels are associated with cognitive impairment2 thus distorting information processing and predisposing patients to aggression.6 In TBI patients, underlying anxiety, affective disorders, seizures and frontal lobe dysfunction also increase susceptibility.10

Differentials for aggression

When identifying a cause for chronic aggressive behaviour, a patient’s previous experiences, comorbid psychiatric conditions and alcohol and/or substance abuse must be established with a collateral history.2,7  McAllister (2008) highlights the importance of determining pre-injury behaviour in order to exclude the possibility of symptoms being an exaggeration of pre-injury personality traits.8 Additionally, psychosocial factors must be deduced to identify possible triggers.2,7

Clinicians must be aware that aggression can be a presenting feature of other psychiatric disorders. Depression has a prevalence of 18.5% to 61% in post-TBI patients  and is linked with aggression due to their shared association with frontal lobe lesions and serotonin level imbalance.9 Other differentials include manic disorders (which can involve a more marked aggressive component if secondary to TBIs), anxiety disorders and alcohol and/or substance abuse. Personality and behavioural disorders such as affective lability, behavioural disinhibition and acquired antisocial behaviour should also be considered.8

Management guidelines

The National Institute for Health and Care Excellence (NICE) refers to the Scottish Intercollegiate Guidelines Network (SIGN) for rehabilitating patients with acquired brain injuries (ABIs). Psychological treatments advocated by SIGN include CBT, contingency management procedures, music therapy and comprehensive neurobehavioural rehabilitation (CNR).10 Family involvement appears to be associated with better outcomes2 and is also recommended.10

Of the studies quoted by SIGN, CNR was found to cause a positive effect in ABI patients in one systematic review although inconsistent results were obtained for the other three methods. Regarding pharmacological treatment, SIGN advises propranolol and pindolol as first line options.10

Pharmacological treatment

The aberrant neurotransmitter changes in the cortex and limbic areas as a result of TBIs2 provide targets for pharmacological therapy (as summarised in Table 1). Theoretically, cortical behavioural regulation can be enhanced by serotonergic agents and antagonists of dopaminergic and noradrenergic neurotransmission. Limbic hyperactivity can be dampened by the use of gamma aminobutyric acid (GABA) agonists, glutamatergic antagonists and anticholinergics.6

Impaired behavioural regulation

Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) are indicated for their increase in dopamine and serotonin availability and the treatment of depression contributing to aggressive behaviour. In a trial conducted by Kant et al (1998), sertraline reduced aggression within one week of treatment although TBI severities were variable within the population.11 These results are mirrored in other trials presenting sertraline as a viable treatment option.12 Citalopram used in conjunction with carbamazepine successfully treated behavioural symptoms in a clinical trial of 22 patients conducted by Perino et al (2001)13 although the separate effects of both drugs are impossible to differentiate. A case study by Sloan et al (1992) found that fluoxetine improved emotional lability in one patient within a week.13

Tricyclic antidepressants have been shown to be useful for managing both post-traumatic and chronic aggression. Amitriptyline has reduced aggression with good tolerability despite its strong anticholinergic side effects in several studies and is suggested as the best option for treating behavioural disorders secondary to frontal lobe injuries without impairing cognition.13

Antipsychotics

There is a wide body of literature advocating antipsychotics for managing aggression due to their sedative effects.13 Nevertheless, the cognitive and extrapyramidal side effects of typical antipsychotics limit their value for chronic use. Comparatively, atypical antipsychotics have a milder side effect profile and are preferred although their cognitive impact in TBI patients is unclear.2 Furthermore, unlike older generations, atypical antipsychotics antagonise 5HT2 receptors and are therefore implicated in reduced aggression.9

Of the typical antipsychotics, chlorpromazine reduced explosiveness in one case study conducted by Sandel et al (1993). Various case studies also report haloperidol improving chronic agitation in TBI patients although significant side effects were encountered.13 Of the atypical antipsychotics the level of evidence is low. Quetiapine reduced aggression and irritability in seven patients in a trial conducted by Kim and Bijlani (2006).11 Olanzapine significantly reduced aggression within six months in a case study conducted by Umansky and Geller (2000). Clozapine was associated with varying levels of improvement in six case studies conducted by Michals et al (1993) however seizures were experienced in two patients.13

Overall, there is no reliable evidence advocating antipsychotic use for managing chronic post-TBI aggression. If antipsychotics are commenced for this purpose, it is suggested that their use is restricted to patients with psychosis.13

Beta blockers

Beta blockers are useful for cases where aggression is caused by underlying anxiety13 due to its inhibition of noradrenergic levels.9 A Cochrane review of four RCTs found that pindolol and propranolol reduced aggression within two to six weeks of starting treatment in ABI patients however no recommendations were made due to heterogeneity between samples, a small number of trials and small sample sizes.  The authors acknowledge that the trials involved high doses and so recommend caution when prescribing beta blockers for aggression.4

Methylphenidate

Methylphenidate is a psychostimulant indicated for its enhancement of dopamine and noradrenaline in the frontal lobe improving arousal and alertness.13 Mooney (1993) found in a single RCT that methylphenidate significantly improved anger scores in TBI patients.4 However other studies have yielded mixed results12,13 and no firm conclusion can be made.

Amantadine

Amantadine increases dopamine availability and acts on glutamatergic pathways. An advantage of its use is its non-sedating qualities however there is contradicting evidence for its efficacy.13 An RCT conducted by Schneider (1999) found no significant improvement4 however the trial was limited by a small sample size and large heterogeneity. Interestingly, studies of a lower level of evidence demonstrate favourable results.13 Due to this variability, its efficacy is still in question.

Buspirone

Buspirone – a serotonergic agonist licensed for treating anxiety13 – has also reduced aggression in several case studies2,12,14 warranting further research. Its side effects are amenable for use in TBIs although one disadvantage is its delayed onset.13

Hyperactive limbic drive

Anticonvulsants

The mood stabilising effects of anticonvulsants are mediated through their enhancement of GABA transmission.2 Carbamazepine has been demonstrated in studies to be effective for managing acute and chronic post- TBI aggression.12,13 Its side effects include impaired balance, sedation13 and cognitive impairment particularly in brain injured patients2 due to their heightened sensitivity. In a trial conducted by Mattes (2005), Oxcarbazepine reduced impulsive aggression however the number of TBI participants in the sample was unclear. Nine of the 48 participants also dropped out due to adverse effects11 suggesting more research is needed into its tolerability in TBI patients. Valproate has also been demonstrated to effectively manage behavioural and affective disorders13 with a milder cognitive impact compared to carbamazepine.2 Regarding other anticonvulsants, the evidence is of a lower standard. Pachet et al (2003) found that lamotrigine reduced aggression with good tolerability in one case study.11 Topiramate has been demonstrated to effectively treat manic symptoms but due to its side effects of psychosis and cognitive impairment,2 may be inappropriate for TBI patients. Case reports reference lithium to reduce post – TBI agitation however it may be unsuitable as a first line option due to its neurotoxicity.13

Benzodiazepines

Benzodiazepines are indicated for their anticonvulsive, anti-anxiety and sedative qualities facilitated by stimulation of the GABA receptor.13 There is limited literature on their chronic use in TBI patients due to their side effects of agitation, cognitive impairment and tolerance2 thus they are recommended to be more appropriate for cases of acute agitation or anxiety.11

Conclusion

There are many challenges in assessing and managing chronic aggression due to its complex aetiology. Previous literature presents a selection of pharmacological options however, their effect on TBI patients has not been confirmed resulting in limited guidance. The heterogeneity between samples also renders it impossible to predict treatment outcomes in the TBI population warranting the need for low doses, slow titration and frequent monitoring.13 A six-week trial period is advised by Fleminger et al (2006) to ascertain effects of treatment before trialling a new medication.4 Patient and family education regarding realistic treatment outcomes and side effects of treatments is also necessary to ensure treatment compliance.2 In future, a clarification of the underlying neurochemical changes is needed to identify further treatment targets. Additional larger scale RCTs are also needed to guide decision making and predict treatment outcomes. Table 2 offers a practical guide on medication choice in relation to aggressive behaviour in ABI.

References

  1. Tateno A, Jorge RE, Robinson RG. Clinical correlates of aggressive behaviour after traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2003;15(2):155-60.
  2. Kim E. Agitation, aggression and disinhibition syndromes after traumatic brain injury. NeuroRehabilitation 2002;17:297-310.
  3. Lombard LA, Zafonte RD. Agitation after traumatic brain injury: considerations and treatment options. Am J Phys Med Rehabil. 2005;84(10):797-812.
  4. Fleminger S, Greenwood RJ, Oliver DL. Pharmacological management for agitation and aggression in people with acquired brain injury. Cochrane Database Syst Rev. 2006;18(4):CD003299.
  5. Alderman N, Knight C, Brooks J. Rehabilitation Approaches to the Management of Aggressive Behaviour Disorders after Acquired Brain Injury. Brain Impairment. 2013;14(1):5-20.
  6. Siever LJ. Neurobiology of Aggression and Violence. Am J Psychiatry. 2008;165(4):429-42.
  7. McAllister TW. Neurobehavioral sequelae of traumatic brain injury: evaluation and management. World Psychiatry. 2008;7(1):3-10.
  8. Schwarzbold M, Diaz A, Martins ET, Rufino A, Amante LN, Thais ME et al. Psychiatric disorders and traumatic brain injury. Neuropsychiatr Dis Treat. 2008;4(4):797-816.
  9. Coccaro EF, Siever LJ. Pathophysiology and treatment of aggression. In: Davis KL, Charney D, Coyle JT, Nemeroff C, editors. Neuropsychopharmacology: The Fifth Generation of Progress. 5th ed. Pennsylvania: Lipincott, Williams & Wilkins; 2002:1709-23.
  10. Scottish Intercollegiate Guidelines Network. Brain injury rehabilitation in adults. Edinburgh: SIGN; 2013. 68 p. Report no.:130.
  11. Luauté J, Plantier D, Wiart L, Tell L, the SOFMER group. Care management of the agitation or aggressiveness crisis in patients with TBI. Systematic review of the literature and practice recommendations. Ann Phys Rehabil Med 2016;59(1):58-67.
  12. Warden DL, Gordon B, McAllister TW, Silver JM, Barth JT, Bruns J, et al. Guidelines for the Pharmacological Treatment of Neurobehavioral Sequelae of Traumatic Brain Injury. J Neurotrauma 2006;23(10):1468-501.
  13. Levy M, Berson A, Cook T, Bollegala N, Seto E, Tursanski S, et al. Treatment of agitation following traumatic brain injury: A review of the literature. NeuroRehabilitation 2005;20(4):279-306.
  14. Chew E, Zafonte RD. Pharmacological management of neurobehavioral disorders following traumatic brain injury – a state-of-the-art review. J Rehabil Res Dev 2009;46(6):851-79.

Anum Bhatti is currently in her final year of training for her MBchB at Keele University. She is interested in pursuing psychiatry as a career choice.

 

Dr George El-Nimr, MBChB, MSc (Neuropsych), MRCPsych, MSc (Psych), MMedEd, is a Consultant Neuropsychiatrist and Academic Secretary of the Faculty of Neuropsychiatry at the Royal College of Psychiatrists.

 

Correspondence to: Dr El-Nimr, Consultant Neuropsychiatrist, Neuropsychiatry Services, Bennett Centre, Richmond Terrace, Shelton, Stoke-on-Trent ST1 4ND. Tel: 01782 441614
Conflict of interest statement: None declared
Provenance and peer review: Submitted and externally reviewed
Date first submitted: 18/4/18
Date submitted after peer review: 21/9/18
Acceptance date: 15/5/19
To cite: Bhatti A, El-Nimr G. 
ACNR 2019;18(4);15-17
Published online: 1/8/19

via Pharmacological management of long-term aggression secondary to traumatic brain injuries | ACNR | Online Neurology Journal

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[Abstract] Nuanced effects of music interventions on rehabilitation outcomes after stroke: a systematic review

Background: Music is affordable and easily integrated in rehabilitation exercises, and has demonstrated different effects on the brain. We hypothesized that music interventions could improve rehabilitation outcomes after stroke.

Objective: the aim of our review is to determine the effectiveness of different types of music interventions according to the rehabilitation objectives after stroke.

Method: A systematic review of randomized controlled trials, clinical controlled trials and cross-over design performed on PubMed and PEDro in May 2018. All of these studies focus on acute, sub-acute or chronic stroke rehabilitation with music or rhythmic auditory stimulation intervention in adults during clinical outcomes. Two independent reviewers extracted the data and assessed the risk of bias before bringing it together.

Results: Twenty-seven studies were included and analyzed. Our review found positive effects on physical status (upper-limb activity; gait parameters, balance), on cognition (neglect, attention, communication) and mood. The analysis of the quality of the evidence showed that a majority of the studies had a high risk of bias.

Conclusion: Focusing on high to moderate level evidence, our review highlighted that rhythmic auditory stimulation has a positive effect on gait and balance; that receptive music therapy improves mood as well as some cognitive functions; that there is not enough evidence to determine the effectiveness of active music therapy and melodic intonation therapy. High-quality trials with large samples would be necessary to further assess and/or recommend these interventions.

via Nuanced effects of music interventions on rehabilitation outcomes after stroke: a systematic review: Topics in Stroke Rehabilitation: Vol 26, No 6

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[WEB PAGE] An expert opinion: upper limb rehabilitation after stroke

Key take home messages

  1. Clinically meaningful improvements are possible in chronic stroke patients
  2. The dose of rehabilitation treatment needs to be larger than currently delivered
  3. Rehabilitation is a complex intervention that cannot be reduced to a single element

Somewhere between 50-80% of stroke survivors have upper limb symptoms after acute stroke1 and persistent difficulty in using the upper limb is a major contributor to ongoing physical disability.2 A commonly held view is that most recovery from stroke occurs over the first three to six months after which little improvement is possible, especially at the level of impairment.3-6 We argue that this may be a self-fulfilling prophecy resulting in lack of provision of potentially helpful rehabilitation.

What is the best way to promote upper limb recovery after stroke? Most studies of behavioural interventions have investigated forms of constraint induced movement therapy (CIMT),7,8 repetitive task training (RTT)9 or robotics,10 each of which focuses on increasing the activity of the affected limb. Kwakkel et al8suggested that motor function, arm-hand activities and self-reported arm-hand functioning in daily life, improved immediately after CIMT and at long-term follow-up, but the comparison was often with usual care. It is worth noting that CIMT approaches were said to be more likely to be successful in promoting long term benefits if the protocol included shaping, massed practice and a behavioural transfer package, whereas simple forced use therapy was ineffective.8 RTT also has some evidence to support benefits over what is described as usual care, but the evidence for benefits over ‘matched therapy’ is less strong.9 The use of robotics can increase the number of movement repetitions, but has failed to produce clinically meaningful effects.10 Indeed, the recent RATULS study showed that compared with usual care, approximately 23 hours of robot-assisted training and matched dose ‘upper limb therapy’ did not improve upper limb function.11Overall, it would appear that asking patients to make simple repetitions of movement, however meaningful the task, is relatively ineffective without some way of actively translating any improvements into activities of daily living. Simply increasing the number of repetitions does not appear to be effective,12 and this in itself should give us pause for thought.

A few studies have tested more complex therapies incorporating a number of different elements. The ICARE study13 of upper limb treatment after stroke went beyond simple repetitions, using a structured, task-oriented motor training programme that was impairment focused, task specific, intense, engaging, collaborative, self-directed, and patient centred, starting about six weeks post-stroke. Outcomes were not improved by this approach, but on reflection it is likely that, as with many of the studies, the dose of 30 hours over ten weeks was too low (the usual care group received 11.2 hours over ten weeks). Despite scepticism that stroke patients would be able to ‘tolerate’ much higher doses,12 one study managed to deliver 300 hours of upper limb therapy to chronic stroke patients over twelve weeks and reported changes in measures of both impairment and activity that were far greater than those in lower dose studies,14 and in fact the findings of this study have recently been replicated by the same group.15 We recently reported the findings of the Queen Square Upper Limb (QSUL) Neurorehabilitation programme,16 a single centre clinical service that provides 90 hours of treatment focusing on the post-stroke upper limb. Most patients entering the programme were in the chronic stage (> 6 months post-stroke), but were able to complete the 90 hours of the programme, even though they exhibited a wide range of impairments and fatigue levels. Despite the time since stroke (median = 18 months) we observed (i) large clinically meaningful improvements in upper limb impairment and activity (of a magnitude similar to those reported by McCabe et al.), and importantly (ii) that these changes were maintained, or even improved upon, six months after treatment.

The first lesson to take from these studies is that post-stroke rehabilitation programmes and clinical trials are almost certainly under dosing patients. In future, clinical trials must investigate the effects of much higher doses than are currently being used. The second question to be raised is what are the key ‘active ingredients’ of an upper limb rehabilitation treatment? Whilst it is not clear what the optimal behavioural approach for promoting upper limb recovery should be, it is clear that simple protocol driven approaches have not led to large or sustained effects,17 both of which are necessary to produce a step change in stroke recovery. Successful post-stroke neurorehabilitation is likely to require a combination of complimentary approaches. If we accept this premise, then we are unlikely to determine the optimal combination of active ingredients simply by studying each approach in isolation, because the interactions between these elements will also have to be considered.

So how do we work out what the ‘active ingredients’ of upper limb rehabilitation are? A more sensible way forward is to look at interventions that have already demonstrated a high level of efficacy and then begin to work out their key components. Here, it is important to say that we need to start with treatments that have a high chance of achieving minimum clinically important differences (MCID) rather than small changes that might be statistically significant. Both McCabe et al14 and Daly et al,15 as well as the QSUL programme,16 produced large improvements on both impairment and activity limitation and both involved more complex treatment approaches, not restricted to one element. It is worth considering these in more detail.

  • Analysis of movement and performance in activities of daily living. The initial assessment is crucial. The question, ‘why does this person’s hand and arm not work’ should never be answered with ‘because they have had a stroke’. There needs to be an appreciation of the range of potential contributory impairments (patterns of weakness, spasticity, loss of joint range, shoulder restriction and pain, sensory loss, apraxia, cognitive deficits, depression, apathy, fatigue etc.) because each of these becomes a therapeutic target. Our view is that without informed clinical reasoning based on the presence or absence of specific impairments, the correct treatment approach is unlikely to be selected.
  • Identify and treat barriers. Avoid complications that will prevent participation in an active rehabilitation programme. We commonly see loss of passive joint range preventing people accessing finger or thumb movement, due to either spasticity or non-neural shortening. This can happen at most joints, but particularly in the hand. As well as increased finger flexion, be alert to loss of flexion at MCP joints which makes it difficult to shape the hand properly. Treatment involves splinting and optimal spasticity management. We also see pain and restriction of range in the shoulder. Restriction of external rotation in particular should raise the possibility of adhesive capsulitis. Despite the lack of a clear evidence base for treating post-stroke adhesive capsulitis, anecdotally we have had success with capsular hydrodilatation followed by physiotherapy.
  • Preparation. Manual techniques are used to optimise and improve baseline at an impairment level, for example mobilising joints to improve range, lengthening and strengthening muscles to ensure they are at a biomechanical advantage to generate force, training sensory discrimination and improving postural control and balance.
  • Reduction of impairment and re-education of quality and control of movement within activities of daily living. Individualised meaningful tasks are practiced repeatedly in order to facilitate task mastery with a focus on quality of movement. This is achieved through (i) adaptation of the task, e.g. decomposing tasks into individual components to be practiced; (ii) adaptation of the environment, e.g. fabrication of functional splints and adaptation of tools such as cutlery or screwdrivers, to enable integration of the affected hand in meaningful activities; (iii) assistance, e.g. de-weighting the arm to allow strengthening and training of movement quality and control through increased range.
  • Coaching (involving instruction, supervision, reinforcement) was considered a key component of the QSUL programme, used throughout to embed new skills and knowledge into individual daily routines. Consequently, individuals increase participation and confidence in their desired goals, enhancing self-efficacy and motivation to sustain behavioural change beyond the end of the active treatment period.
  • Sustaining change. Our view is that the approach described, delivered at a high dose is most likely to achieve clinically meaningful improvement together with improved self-efficacy and behaviour change that results in retention of gains or further improvement (something not routinely seen with many upper limb interventions that have been investigated).

Rehabilitation is often criticised for not following standardised approaches that lend themselves to investigation through clinical trials. However, when single elements are then studied in isolation the results are often not clinically meaningful and are not sustained.18,19 Looking at the difference between these approaches and those taken by McCabe et al14, Daly et al15 and QSUL16 should be informative, with a view to formally describing the key elements of a successful treatment. Whilst approaches at the activity and participation level will vary as they are tailored to an individual’s specific meaningful goals, the overall therapeutic approach taken towards specific impairments should be the same across all patients. Ideally, it should be possible to describe the principles of an optimal intervention using a format such as the TIDIER guidelines.18,19

There is a way to go before we can really say we understand both the treatment itself and the effects of the treatment on individuals. This will require careful assessment of both the ‘input’ (the nature of the behavioural intervention) and of the ‘output’ (the resulting behavioural change) at a level of fine-grained detail that is not currently achieved on a regular basis, for example using kinematic20 or neurophysiological21 assessment. In addition, this input-output relationship will be modulated by a number of patient characteristics, which could relate to behavioural characteristics (e.g. severity, presence of multiple impairments) or to biological characteristics (e.g. the nature and extent of brain damage, time since stroke, age, medication).

Overall, our experience suggests that much higher doses and intensity of upper limb neurorehabilitation can be delivered with beneficial effects. We have highlighted the need to consider the dose and the nature of the intervention as well as appropriate patient stratification in informing future clinical trial design.

Figure 1. Outcome scores for all patients on the Queen Square Upper Limb Rehabilitation programme. Each data point represents a single patient. Top row shows individual scores at admission, discharge, six weeks and six months after discharge. Bottom row shows the individual difference scores for admission to discharge, admission to six weeks post-discharge, and admission to six months post-discharge. Scores are shown for modified Fugl-Meyer (upper limb), Action Research Arm Test and Chedoke Arm and Hand Activity Inventory (CAHAI). Median (solid line) and upper and lower quartiles (dotted lines) are shown. (Reproduced with permission from Ward et al, J Neurol Neurosurg Psychiatry. 2019 May;90(5):498-506).


References

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  2. Broeks JG, Lankhorst GJ, Rumping K, Prevo AJ. The long-term outcome of arm function after stroke: results of a follow-up study. Disabil Rehabil. 1999;21:357–364.
  3. Kwakkel G, Kollen BJ, van der Grond J, Prevo AJH. Probability of regaining dexterity in the flaccid upper limb: impact of severity of paresis and time since onset in acute stroke. Stroke. 2003;34:2181–2186.
  4. Nakayama H, Jørgensen HS, Raaschou HO, Olsen TS. Recovery of upper extremity function in stroke patients: the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1994;75:394–398.
  5. Sunderland A et al. Enhanced physical therapy for arm function after stroke: a one year follow up study. J. Neurol. Neurosurg. Psychiatr. 1994;57:856–858.
  6. Wade DT, Langton-Hewer R, Wood VA, Skilbeck CE, Ismail HM. The hemiplegic arm after stroke: measurement and recovery. J. Neurol. Neurosurg. Psychiatr. 1983;46:521–524 .
  7. Corbetta D, Sirtori V, Castellini G, Moja L, Gatti R. Constraint-induced movement therapy for upper extremities in people with stroke. Cochrane Database Syst Rev CD004433 (2015). doi:10.1002/14651858.CD004433.pub3
  8. Kwakkel G, Veerbeek J, van Wegen EEH, Wolf SL. Constraint-induced movement therapy after stroke. Lancet Neurol. 2015;14:224–234.
  9. French B et al. Repetitive task training for improving functional ability after stroke. Cochrane Database Syst Rev. 2016;11:CD006073.
  10. Veerbeek JM, Langbroek-Amersfoort AC, van Wegen, EEH, Meskers CGM, Kwakkel G. Effects of Robot-Assisted Therapy for the Upper Limb After Stroke. Neurorehabil Neural Repair. 2017;31: 107–121.
  11. Rodgers H et al. Robot assisted training for the upper limb after stroke (RATULS): a multicentre randomised controlled trial. Lancet (2019). doi:10.1016/S0140-6736(19)31055-4.
  12. Lang CE et al. Dose response of task-specific upper limb training in people at least 6 months poststroke: A phase II, single-blind, randomized, controlled trial. Ann. Neurol. 2016;80:342–354.
  13. Winstein CJ et al. Effect of a Task-Oriented Rehabilitation Program on Upper Extremity Recovery Following Motor Stroke: The ICARE Randomized Clinical Trial. JAMA. 2016;315:571–581.
  14. McCabe J, Monkiewicz M, Holcomb J, Pundik S, Daly JJ. Comparison of robotics, functional electrical stimulation, and motor learning methods for treatment of persistent upper extremity dysfunction after stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2015; 96:981–990.
  15. Daly JJ et al. Long-Dose Intensive Therapy Is Necessary for Strong, Clinically Significant, Upper Limb Functional Gains and Retained Gains in Severe/Moderate Chronic Stroke. Neurorehabil Neural Repair. 1545968319846120 (2019). doi:10.1177/1545968319846120.
  16. Ward NS, Brander F, Kelly K. Intensive upper limb neurorehabilitation in chronic stroke: outcomes from the Queen Square programme. J Neurol Neurosurg Psychiatry jnnp-2018-319954 (2019). doi:10.1136/jnnp-2018-319954
  17. Pollock A et al. Interventions for improving upper limb function after stroke. Cochrane Database Syst Rev. CD010820 (2014). doi:10.1002/14651858.CD010820.pub2
  18. Hoffmann TC et al. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ. 2014;348;g1687.
  19. Walker MF et al. Improving the Development, Monitoring and Reporting of Stroke Rehabilitation Research: Consensus-Based Core Recommendations from the Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 2017;31:877–884.
  20. Balasubramanian S, Colombo R, Sterpi I, Sanguineti V, Burdet E. Robotic assessment of upper limb motor function after stroke. Am J Phys Med Rehabil. 2012;91:S255-269.
  21. Cheung VCK et al. Muscle synergy patterns as physiological markers of motor cortical damage. Proc. Natl. Acad. Sci. U.S.A. 2012;109:14652–14656.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Correspondence to: Nick Ward, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG.
Conflict of interest statement: None declared.
Provenance and peer review: Submitted and externally reviewed.
Date first submitted: 15/4/19
Date resubmitted after peer review: 10/6/19
Acceptance date: 11/6/19
To cite: Ward NS, Kelly K, Brander F. ACNR 2019;18(4):20-22
Published online: 1/8/19

via An expert opinion: upper limb rehabilitation after stroke | ACNR | Online Neurology Journal

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