Levodopa Improves Procedural Motor Learning in Chronic Stroke Patients

Rösser, Nina; Heuschmann, Peter U.; Wersching, Heike; Breitenstein, Caterina; Knecht, Stefan; Flöel, Agnes

doi:10.1016/j.apmr.2008.02.030

Cited by 87 publications

(89 citation statements)

References 64 publications

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“…However, the basic pathomorphological changes and injury mechanisms of the nigrostriatal pathway, which plays a vital role in movement adjustment,4 following ICH have been poorly investigated to date. Furthermore, prospective, randomized, and double‐blind studies have revealed that the dopamine precursor levodopa, which is administered as an alternative dopaminergic therapeutic strategy, enhances motor recovery in patients with hemiplegia and procedural motor learning disorders after stroke 5, 6, 7. This evidence suggests that protection of the nigrostriatal pathway may confer important benefits in motor recovery after stroke.…”

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confidence: 99%

Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule Stabilization After Intracerebral Hemorrhage

Yang

Zhang

et al. 2018

JAHA

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BackgroundMany previous clinical studies have demonstrated that the nigrostriatal pathway, which plays a vital role in movement adjustment, is significantly impaired after stroke, according to medical imaging and autopsies. However, the basic pathomorphological changes have been poorly investigated to date. This study was designed to explore the pathomorphological changes, mechanism, and therapeutic method of nigrostriatal impairment after intracerebral hemorrhage (ICH).Methods and ResultsIntrastriatal injection of autologous blood or microtubule depolymerization reagent nocodazole was performed to mimic the pathology of ICH in C57/BL6 mice. Immunofluorescence, Western blotting, electron microscopy, functional behavioral tests, and anterograde and retrograde neural circuit tracking techniques were used in these mice. The data showed that the number of dopamine neurons and the dopamine concentration were severely decreased and that fine motor function was impaired after ICH. Microtubule depolymerization was the main contributor to the loss of dopamine neurons and to motor function deficits after ICH, as was also proven by intrastriatal injection of nocodazole. Moreover, administration of the microtubule stabilizer epothilone B (1.5 mg/kg) improved the integrity of the nigrostriatal pathway neural circuit, increased the number of dopamine neurons (4598±896 versus 3125±355; P=0.034) and the dopamine concentration (4.28±0.99 versus 3.08±0.75 ng/mg; P=0.041), and enhanced fine motor functional recovery associated with increased acetylated α‐tubulin expression to maintain microtubule stabilization after ICH.ConclusionsOur results clarified the pathomorphological changes of the nigrostriatal pathway after ICH and found that epothilone B helped alleviate nigrostriatal pathway injury after ICH, associated with promoting α‐tubulin acetylation to maintain microtubule stabilization, thus facilitating motor recovery.

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confidence: 99%

Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule Stabilization After Intracerebral Hemorrhage

Yang

Zhang

et al. 2018

JAHA

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“…Indeed, some clinical studies showed a beneficial effect with different agents [3,4,5,6,7,8,9] while others did not [10,11,12,13,14,15]. Thus, the clinical evidence of benefit of this treatment approach is weak, as most of the aforementioned studies are limited by small sample sizes and narrow inclusion criteria.…”

Section: Introductionmentioning

confidence: 93%

“…The following rules were established to determine agents for PA for individual patients. If the emphasis of PA of rehabilitation was placed on paresis with or without cortical signs, L -dopa was chosen [3,4,11]. If aphasia with or without memory deficits was focused on, acetylcholinesterase inhibitors [6] were preferred.…”

Section: Methodsmentioning

confidence: 99%

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Safety of Pharmacological Augmentation of Stroke Rehabilitation

Engelter

Frank²,

Lyrer³

et al. 2010

Eur Neurol

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Background: Based on experimental studies, pharmacological augmentation (PA) of stroke rehabilitation might be reasonable. Whether PA is beneficial in clinical practice is unclear. Methods: We performed an observational study on the use of PA in addition to regular rehabilitative therapies in a stroke rehabilitation unit. Over 20 months, we systematically observed (1) the utilization rate of PA, (2) possible adverse events, and (3) the functional outcome of patients with versus without PA (non-PA). The primary outcome variable was the increase in abilities in activities of daily living during in-hospital rehabilitation as quantified by the delta ‘functional independence measure’ (FIM). Results: Ninety-seven of 249 (39%) patients had PA. L-Dopa was used in 63 (65%), acetylcholinesterase inhibitors in 33 (34%), and selective serotonin reuptake inhibitors in 31 (32%) PA patients. In 11 (11%) patients, PA was associated with delirium (n = 4), gastrointestinal symptoms (n = 4), electrolyte disorders (n = 2), or incontinence (n = 1). All adverse events were temporary. PA patients did not differ from non-PA patients in age (74 vs. 73 years; p = 0.62), gender ratio, and stroke type (ischemia 85 vs. 82%; p = 0.49). However, compared with non-PA patients, PA patients were more severely affected (median NIH Stroke Scale Score 7 vs. 4; p < 0.001; median FIM 58 vs. 85; p = 0.01). At discharge, the PA group had a higher median ΔFIM compared with non-PA patients (16 vs. 9; p = 0.01). None of the PA patients but 5 (3.3%) of the non-PA patients had died. Conclusion: PA of stroke rehabilitation was used frequently. The absence of safety concerns suggests that there is scope for benefit from PA in stroke rehabilitation. A large randomized controlled trial seems feasible and ethically justified.

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“…Indeed, randomized controlled clinical trials have shown benefit of PESR for several agents [3,4,5,6,7,8,9,10]. Nevertheless, the clinical evidence regarding benefits of this treatment approach is still considered weak [11] and future research is recommended [12,13] for the following reasons: (1) the beneficial findings of some studies [4,5,6,7,8,9,10] were not confirmed by others [14,15,16,17,18,19], (2) several studies were limited by small patient populations and narrow inclusion criteria, and (3) there were some concerns regarding safety of some agents (i.e. piracetam [13] and amphetamines [20,21]).…”

Section: Introductionmentioning

confidence: 99%

Frequency and Determinants of Using Pharmacological Enhancement in the Clinical Practice of In-Hospital Stroke Rehabilitation

et al. 2012

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Background: Pharmacological enhancement in stroke rehabilitation (PESR) is promising. Data about its use in clinical practice are missing. Methods: In a prospective, explorative study of four rehabilitation centers, we systematically observed the frequency and determinants of using PESR in consecutive patients. PESR was defined as using agents potentially enhancing post-stroke recovery exclusively to aid rehabilitation without an established indication. Results: 257 (55.4%) of 464 patients had agents potentially enhancing recovery. Selective serotonin reuptake inhibitors (SSRI) (n = 125, 26.9%), levodopa (n = 114, 24.6%), serotonin-noradrenaline reuptake inhibitors (SNRI) (n = 52, 11.2%), and acetylcholinesterase inhibitors (n = 48, 10.3%) were used most often. SSRI in 102/125 patients and SNRI in 46/52 patients were mostly used for accompanying depressive symptoms. 159 (34.3%) patients had PESR (without an otherwise established indication). In PESR patients, levodopa (n = 102, 64.1%) was used most commonly. PESR was primarily used for aphasia (36.5%) and paresis (25.2%). PESR patients did not differ from non-PESR patients in age, gender and stroke type. However, the utilization rates of PESR differed significantly across centers (2, 4, 38 and 55%). Conclusion: SSRI and SNRI were predominately used for accompanying depression, while levodopa was nearly exclusively used to aid stroke rehabilitation in the absence of an otherwise established indication. The differences in utilization rates for PESR between centers suggest therapeutic uncertainty and indicate the need for additional studies.

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Levodopa Improves Procedural Motor Learning in Chronic Stroke Patients

Cited by 87 publications

References 64 publications

Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule Stabilization After Intracerebral Hemorrhage

Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule Stabilization After Intracerebral Hemorrhage

Safety of Pharmacological Augmentation of Stroke Rehabilitation

Frequency and Determinants of Using Pharmacological Enhancement in the Clinical Practice of In-Hospital Stroke Rehabilitation

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