Early versus late injections of Botulinumtoxin type A in post-stroke spastic movement disorder: A literature review.

Post-stroke spastic movement disorder (PS-SMD) is one of the main causes of severe disability in the chronic phase after stroke. The prevalence of SMD goes up with time after stroke to more than 28% in the chronic phase., Its secondary complications such as contracture, abnormal postures and/or movement patterns, spasticity-associated pain also increase with time after stroke when physical and medical management of PS-SMD have been delayed in the early stroke phase. It has been published by several controlled studies that the earlier physical and medical measures, such as botulinum toxin type A (BoNT-A) therapy are included in rehabilitative strategies for the SMD, the fewer secondary complications, especially soft tissue contractures and pain occurred. Several studies showed that goal-orientated management of PS-SMD including BoNT-A therapy, applied within a few weeks and three months - in the early subacute phase after stroke onset - prevented or reduced the development of severe or disabling SMD and its secondary complications, more effective than late application of BoNT-A therapy - in the chronic phase after stroke. In multiple prospective cohort studies, various predictors and predictive approaches for detection of patients on risk to development PS-SMD were found. Based on that information and the controlled studies that showed reduction in PS-SMD complications following early treatment with BoNT-A nowadays, early treatment of PS-SMD in the early subacute phase following stroke is recommended to avoid or reduce the development of post-stroke disability and to improve the outcome of rehabilitation. In this review, we discuss the optimal timing to apply BoNT-A therapy in patients with already present as well as those at high risk of severe PS-SMD.

The Management of Poststroke Thalamic Pain: Update in Clinical Practice.

Poststroke thalamic pain (PS-TP), a type of central poststroke pain, has been challenged to improve the rehabilitation outcomes and quality of life after a stroke. It has been shown in 2.7-25% of stroke survivors; however, the treatment of PS-TP remains difficult, and in majority of them it often failed to manage the pain and hypersensitivity effectively, despite the different pharmacotherapies as well as invasive interventions. Central imbalance, central disinhibition, central sensitization, other thalamic adaptative changes, and local inflammatory responses have been considered as its possible pathogenesis. Allodynia and hyperalgesia, as well as the chronic sensitization of pain, are mainly targeted in the management of PS-TP. Commonly recommended first- and second-lines of pharmacological therapies, including traditional medications, e.g., antidepressants, anticonvulsants, opioid analgesics, and lamotrigine, were more effective than others. Nonpharmacological interventions, such as transcranial magnetic or direct current brain stimulations, vestibular caloric stimulation, epidural motor cortex stimulation, and deep brain stimulation, were effective in some cases/small-sized studies and can be recommended in the management of therapy-resistant PS-TP. Interestingly, the stimulation to other areas, e.g., the motor cortex, periventricular/periaqueductal gray matter, and thalamus/internal capsule, showed more effect than the stimulation to the thalamus alone. Further studies on brain or spinal stimulation are required for evidence.

Assessment, goal setting, and botulinum neurotoxin a therapy in the management of post-stroke spastic movement disorder: updated perspectives on best practice.

INTRODUCTION: Post-stroke spastic movement disorder (PS-SMD) appears up to 20% in the first week following stroke and 40% in the chronic phase. It may create major hurdles to overcome in early stroke rehabilitation and as one relevant factor that reduces quality of life to a major degree in the chronic phase. AREAS COVERED: In this review, we discuss predictors,early identification, clinical assessments, goal setting, and management in multiprofessional team, including Botulinum neurotoxin A (BoNT-A) injection for early and chronic management of PS-SMD. EXPERT OPINION: The earlier PS-SMD is recognized and managed, the better the outcome will be. The comprehensive management in the subacute or chronic phase of PS-SMD with BoNT-A injections requires detailed assessment, patient-centered goal setting, technical-guided injection, effective dosing of BoNT-A per site, muscle, and session and timed adjunctive treatment, delivered in a multi-professional team approach in conjunction with physical treatment. Evidence-based data showed BoNT-A injections are safe and effective in managing focal, multifocal, segmental PS-SMD and its complications. If indicated, BoNT-A therapy should be accompanied with adjunctive treatment in adequate time slots. BoNT-A could be added to oral, intrathecal, and surgical treatment in severe multisegmental or generalized PS-SMD to reach patient/caregiver's goals, especially in chronic PS-SMD.

The Safety and Effect of Local Botulinumtoxin A Injections for Long-Term Management of Chronic Pain in Post-Herpetic Neuralgia: Literature Review and Cases Report Treated with Incobotulinumtoxin A.

There are few reports on the safety and effectiveness of long-term botulinumtoxin A (BoNT A) therapy in severe chronic pain of post-herpetic neuralgia (PHN). The literature was searched with the term "neuropathic pain" and "botulinum" on PubMed (up to 29 February 2020). Pain was assessed with the Visual Analogue Scale (VAS) before and after BoNT A therapy. A total of 10 clinical trials and six case reports including 251 patients with PHN were presented. They showed that BoNT A therapy had significant pain reduction (up to 30-50%) and improvement in quality of life. The effect duration seems to be correlated with BoNT A doses injected per injection site. Intervals between BoNT A injections were 10-14 weeks. No adverse events were reported in cases and clinical studies, even in the two pregnant women, whose babies were healthy. The repeated (≥6 times) intra/subcutaneous injections of incobotulinumtoxin A (Xeomin®, Merz Pharmaceuticals, Germany) over the two years of our three cases showed marked pain reduction and no adverse events. Adjunctive local BoNT A injection is a promising option for severe PHN, as a safe and effective therapy in long-term management for chronic neuropathic pain. Its effect size and -duration seem to be depended on the dose of BoNT A injected per each point.

Early brain imaging predictors of post-stroke spasticity.

BACKGROUND: Post-stroke spasticity is a major factor disturbing rehabilitation and functional recovery in stroke survivors. Clinical predictors of post-stroke spasticity have often been discussed, but brain image predictors for spasticity have been insufficiently researched. The aim of this study was to use magnetic resonance imaging data to identify early brain imaging predictors for potential development of spasticity after stroke. METHODS: Consecutive patients admitted to a stroke unit were screened prospectively over 22 months. Patients with first-ever supratentorial ischaemic stroke were included in the study. Standardized clinical assessments for post-stroke spasticity were prospectively performed within 7 days and at 3 months. Brain imaging data (3 Tesla magnetic resonance imaging (3T MRI)) were collected at the baseline and evaluated. RESULTS: Brain imaging data from 103 stroke patients were collected in the hyperacute phase (< 7 days after stroke onset). A total of 23 patients developed post-stroke spasticity. The volumes of brain lesions involving motor network areas were significantly larger in patients with post-stroke spasticity compared with those without post-stroke spasticity (p < 0.01). Supratentorial lesion of < 0.5 cm3 were not associated with risk of post-stroke spasticity, except when the internal capsule and striatum was affected. CONCLUSION: Lesions involving motor network areas are considered to be a precondition of post-stroke spasticity. There is, however, a low risk of developing post-stroke spasticity with < 0.5 cm3 volumes of supratentorial brain lesions involving motor network areas. Larger volume brain lesions involving motor network areas, e.g. > 3 cm3, were significantly more common in patients with post-stroke spasticity. Pure cortical lesions has no risk of post-stroke spasticity in stroke survivors.

Site and size of lesion predict post-stroke spasticity: A retrospective magnetic resonance imaging study.

OBJECTIVE: Clinical parameters for prediction of post-stroke spasticity are well established. This report introduces 2 brain magnetic resonance imaging (MRI) parameters (infarct volume and topographic distribution) as post-stroke spasticity predictors. METHODS: Topographic and volumetric data from brain MRI for 98 patients with ischaemic stroke with spasticity, prevalent within the first 5 days after stroke and 6 months after stroke, were retrospectively correlated using Chris Rorden's MRIcron software. RESULTS: Lesions within the supply territory of the middle cerebral artery involving the pyramidal tract were more frequently associated with spasticity than without spasticity (30.8% vs 5.1%). Middle cerebral artery lesions not affecting the pyramidal tract were found more often in patients without spasticity (49.2% vs 10.3%). Spasticity showed a significantly higher association with middle cerebral artery+pyramidal tract/internal capsule lesions than did "no spasticity" (97.5% vs 18.7%, p < 0.01), and lesion volumes were significantly larger in patients with spasticity than in those without spasticity (p < 0.01). CONCLUSION: Large stroke volumes might predict post-stroke spasticity if the lesion is > 3 cm3 in size and if the lesion is located within the middle cerebral artery territory with involvement of the pyramidal tract and/or internal capsule. Lesion size ≤ 2 cm3 outside the middle cerebral artery territory is associated with lower risk of post-stroke spasticity.

What clinicians and patients want: The past, the presence, and the future of the botulinum toxins.

Botulinum toxin (BoNT) is well established in clinical practice for more than 30 years. During this time the area of applications was broaden beyond the ophtalmologic and neurologic indications. Despite of decades of BoNT application with a huge increase of expertise and supporting methods for utilization as well, both patients and physicians claim about boundaries and limits in their daily treatment practice. Most of those limits are related to the toxin itself and its pharmacokinetic properties. The challenge in the field of movement disorders, swetting, and sialorrhea to combine all fast onset, long-lasting effect, safe application free of pain, and the possibility to vary therapy strategies in dosage and application intervals is pervasive and recurrent. In the present article we attempt to name challenges, patient's and physician's wishes. On the base of the toxins that we have and that we are going to get we imagine optimized therapy settings for the core neurological indications spastic movement disorder, dystonia, swetting, and sialorrhea.

Omental Approach to Functional Recovery After Cerebrovascular Disease.

OBJECTIVE: To review and synthesize the clinical literature regarding risks and benefits of omentum transplantation and transposition surgery in patients with ischemic stroke of other etiology (non-MMD) and Moyamoya disease (MMD), and to evaluate the evidence for biological underpinnings of the presumed physiologic effects of omentum transplantation and transposition on vascularization of brain parenchyma. METHODS: Articles were searched on scientific databases using predefined key terms. Data abstraction was based on the clinical course as reported in the articles. For further analysis, patients were divided into groups according to their diagnosis (MMD or non-MMD). Descriptive statistics were computed for better integration of the results. RESULTS: The final literature review contained 15 articles (11 case series, 4 single case studies) with data on 93 patients (29 non-MMD, 64 MMD). At post-assessment 56% of patients showed substantial gains in functional domains (24% in the non-MMD group, 71% in the MMD group) and 92% demonstrated improvements of cerebral vascularization (55% in the non-MMD group, 98% in the MMD group). Differences in improvement became apparent with regard to the initial symptomatology wherein transient ischemic attacks were related to superior recovery rates and language pathologies showed least improvement. CONCLUSIONS: Surgical revascularization using omental tissue has shown good success rates, particularly for recurrent transient ischemic attacks and prevention of further strokes and should be considered as treatment option for selected patients. Experimental data on the physiologic basis for postoperative improvement delivered convincing evidence for its arteriogenic potential and recent developments in omental stem cell research suggest a role in recovery from long-standing neurological deficits.