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2022| April-June | Volume 1 | Issue 2
June 29, 2022
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Motor cortex inhibition as a fibromyalgia biomarker: a meta-analysis of transcranial magnetic stimulation studies
Kevin Pacheco-Barrios, Daniel Lima, Danielle Pimenta, Eric Slawka, Alba Navarro-Flores, Joao Parente, Ingrid Rebello-Sanchez, Alejandra Cardenas-Rojas, Paola Gonzalez-Mego, Luis Castelo-Branco, Felipe Fregni
April-June 2022, 1(2):88-101
Fibromyalgia (FM) is a common and refractory chronic pain condition with multiple clinical phenotypes. The current diagnosis is based on a syndrome identification which can be subjective and lead to under or over-diagnosis. Therefore, there is a need for objective biomarkers for diagnosis, phenotyping, and prognosis (treatment response and follow-up) in fibromyalgia. Potential biomarkers are measures of cortical excitability indexed by transcranial magnetic stimulation (TMS). However, no systematic analysis of current evidence has been performed to assess the role of TMS metrics as a fibromyalgia biomarker. Therefore, this study aims to evaluate evidence on corticospinal and intracortical motor excitability in fibromyalgia subjects and to assess the prognostic role of TMS metrics as response biomarkers in FM. We conducted systematic searches on PubMed/Medline, Embase, and Cochrane Central databases for observational studies and randomized controlled trials on fibromyalgia subjects that used TMS as an assessment. Three reviewers independently selected and extracted the data. Then, a random-effects model meta-analysis was performed to compare fibromyalgia and healthy controls in observational studies. Also, to compare active versus sham treatments, in randomized controlled trials. Correlations between changes in TMS metrics and clinical improvement were explored. The quality and evidence certainty were assessed following standardized approaches. We included 15 studies (474 FM subjects and 222 controls). The main findings were: (1) fibromyalgia subjects present less intracortical inhibition (mean difference [MD, including] = –0.40, 95% confidence interval [CI] –0.69 to –0.11) and higher resting motor thresholds (MD = 6.90 μV, 95% CI 4.16 to 9.63 μV) when compared to controls; (2) interventions such as exercise, pregabalin, and non-invasive brain stimulation increased intracortical inhibition (MD = 0.19, 95% CI 0.10 to 0.29) and cortical silent period (MD = 14.92 ms, 95% CI 4.86 to 24.98 ms), when compared to placebo or sham stimulation; (3) changes on intracortical excitability are correlated with clinical improvements – higher inhibition moderately correlates with less pain, depression, and pain catastrophizing; lower facilitation moderately correlates with less fatigue. Measures of intracortical inhibition and facilitation indexed by TMS are potential diagnostic and treatment response biomarkers for fibromyalgia subjects. The disruption in the intracortical inhibitory system in fibromyalgia also provides additional evidence that fibromyalgia has some neurophysiological characteristics of neuropathic pain. Treatments inducing an engagement of sensorimotor systems (e.g., exercise, motor imagery, and non-invasive brain stimulation) could restore the cortical inhibitory tonus in FM and induce clinical improvement.
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A scoping review of treatments for the vegetative and minimally conscious states
Brittan Morris, John Wong
April-June 2022, 1(2):57-79
Disorders of consciousness (DoC) including the vegetative state, now known as unresponsive wakefulness syndrome, and the minimally conscious state lead to profound disability among affected individuals while placing a major burden on health care facilities, the economy, and society. Efficacious treatment strategies are necessary to alleviate these strains, but standardized, evidence-based protocols for the treatment of DoC are lacking. Progress towards this end remains difficult when considering the current dearth of comprehensive scoping review articles to organize and present the existing literature. The present scoping review seeks to fill this gap while presenting an up-to-date comprehensive compilation of current treatment strategies and their efficacy for vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. To accomplish this, an examination of the existing literature between 2011 and 2021 was conducted using the PubMed database to compile and present current treatment strategies and their efficacy amongst patients in vegetative state/unresponsive wakefulness syndrome and minimally conscious state. Of the 112 articles collected, 32 reported successful treatment, 69 reported some incremental benefits of treatment, and 11 identified no benefit of treatment. Overall, sensory stimulation, transcranial direct current stimulation, transcranial magnetic stimulation, spinal cord stimulation, vagus nerve stimulation, rehabilitation programs, cranioplasty, and pharmacological treatments with zolpidem, amantadine, baclofen, midazolam, and clonazepam dose reduction coupled with neurorehabilitation were associated with successful treatment of DoC. Given the personal, societal, and economic burden associated with DoC, further research is warranted to determine and protocolize evidence-based strategies for effective treatment of those with DoC.
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A review on electroencephalography (EEG)-controlled upper limb exoskeletons towards stroke rehabilitation
Xin Gao, Robert Clarke, Dingguo Zhang
April-June 2022, 1(2):80-87
Stroke is a significant cause of disability in both developing and developed countries. This can cause a severe financial burden on families and society. With the development of robotics and brain-computer interfaces (BCIs), robotic exoskeletons and BCIs have received increasing clinical attention on stroke rehabilitation. Electroencephalography (EEG) is a method of recording brain signals non-invasively, which can be used as a BCI to control exoskeletons. This review focuses on rehabilitation systems of EEG-controlled upper limb exoskeletons, including the newest research progress and clinical evaluation in recent years. From the review, we find EEG-controlled exoskeletons can positively contribute to stroke rehabilitation. However, there are some issues that should be well investigated. More efforts are needed on EEG signal decoding algorithms such as deep learning methods in the clinical context. Practical applications must also bridge the gap between offline experiment and online control. In addition, this review also discusses the impact and significance of shared control, virtual reality/augmented reality, and other ways of human-computer interaction to improve EEG-controlled exoskeletons.
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Dose-response characteristics of exercise training in individuals with Parkinson's disease: an exploratory study
Xia Shen, Jia Hu, Margaret K Y. Mak
April-June 2022, 1(2):102-109
Exercise training is often prescribed as an adjunct to medication to improve postural instability in individuals with Parkinson’s disease. As the association between exercise dose and the corresponding effects on postural stability has not been established in this population, we aimed to explore this topic in the present study. This is an exploratory study conducted in the Gait and Balance Laboratory at the Hong Kong Polytechnic University in a period from June 2011 to June 2013. Eligible participants with Parkinson’s disease (
= 51) were randomly assigned to either a balance and gait training group or a strength training group. The 12-week training period included two 4-week phases of physiotherapist-supervised laboratory-based training separated by a 4-week phase of self-supervised home-based training. Blinded testers examined postural stability using the limit of stability test, single-leg-stance test, walking test, and the activities-specific balance confidence scale, at baseline and after each training phase. Baseline evaluations revealed no significant difference between the balance and gait training and strength training groups. In the balance and gait training group, the first 4-week training phase led to significant improvement in most measures of balance and gait performance (
< 0.025), and the 12-week training phase yielded further improvements in gait velocity and activities-specific balance confidence scale score. In the strength training group, the first 4-week training phase led to significant improvement in the endpoint excursion in the limit of stability test and gait velocity, and the 12-week training phase resulted in an improvement in the single-leg-stance time and stride length in the walking test. All improvements occurred during the laboratory-based training sessions. Therefore, in individuals with Parkinson’s disease, a 4-week period of balance and gait training could improve postural stability, whereas longer durations of strength training are required to gain comparable improvements.
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Trigeminal nerve stimulation for disorders of consciousness: evidence from 21 cases
Xiao-Yang Dong, Yun-Liang Tang, Long-Jun Fang, Zhen Feng
April-June 2022, 1(2):110-114
According to previous case reports, trigeminal nerve stimulation (TNS) can be successfully used to wake a non-responsive unconscious patient. However, no studies have comprehensively investigated the effect of TNS on patients with disorders of consciousness (DOC). Therefore, the present study aimed to assess the safety and efficacy of TNS in DOC patients recruited at the First Affiliated Hospital of Nanchang University. We used Coma Recovery Scale-Revised (CRS-R) scores to assess patients at baseline and after 1–4 weeks of TNS. The patients were further followed up for 4 weeks after the last stimulation to evaluate the safety of the procedure. The participant group comprised 21 DOC patients with an acquired brain injury who were more than 3 months post-injury. The participants were 44.29 ± 12.55 years old and 5.52 ± 1.83 months post-DOC onset, and included 12 patients who were in a vegetative state or had unresponsive wakefulness syndrome and 9 patients who were in a minimally conscious state. Compared with CRS-R scores at baseline, those at weeks 4 and 8 showed no significant improvements in any of the DOC patients. Nonetheless, CRS-R scores improved throughout the study period in 8 out of the 21 DOC patients. Among those with improved scores, two patients in a minimally conscious state had improved CRS-R scores at week 4, while five had improved scores at 4 weeks later. Only one patient with vegetative state/unresponsive wakefulness syndrome had recovered to a minimally conscious state at week 4. Importantly, no obvious treatment-related adverse events were considered to be related to TNS. Taken together, these data provide early evidence that TNS may be an effective and safe approach for promoting the recovery of consciousness in patients with neurological disorders.
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Sensitive sensory stimulation for the arousal treatment of a persistent vegetative state following traumatic brain injury: a care-compliant case report
Hui-Wen Mao, Yan Li
April-June 2022, 1(2):115-121
Effective treatments for patients in a persistent vegetative state due to traumatic brain injury (TBI) are currently unavailable. The purpose of this study was to investigate the therapeutic use of sensitive sensory stimulation for patients in persistent vegetative state following TBI. This case report discussed a 36-year-old male patient who experienced TBI 75 days prior to admission. Upon hospital admission, the patient was unconscious, could automatically open his eyes, but could not avoid light, trace motions, or execute commands. He was placed on a nasal feeding diet, exhibited urinary and fecal incontinence and developed postoperative urinary retention and a pulmonary infection. He showed no mobility of the upper and lower extremities with hypomyotonia. Medications for nerve repair, regaining consciousness, preventing seizure, resolving phlegm, and protecting the stomach were administered. The activity of the extremities was improved by exercise therapies and low or medium-frequency electric stimulation, bladder and bowel function was improved by acupuncture and abdominal massage, and consciousness recovery was promoted by acupuncture and hyperbaric oxygen therapy. Five months following admission, the patient regained consciousness with improved bladder and bowel function. Electroencephalogram indicated that brain function had significantly improved. Auditory evoked potentials and somatosensory evoked potentials suggested that sensation conduction pathways had improved significantly. Sensitive sensory stimulation in combination with routine rehabilitation treatment can effectively cause the regain of consciousness in patients with persistent vegetative state following TBI and improve activities of daily living and the function of the sensation conduction pathways..
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