New updates on transcranial magnetic stimulation in chronic pain.

PURPOSE OF REVIEW: Chronic pain is the most prevalent symptomatic disease worldwide. Nonpharmacological interventions, such as noninvasive neuromodulation (NIN), have gained scientific evidence to support their use as an add-on strategy to pharmacological pain management. The most studied NIN technique is repetitive transcranial magnetic stimulation (rTMS). This review aims to identify the current indications for rTMS in the treatment of chronic pain and its new perspectives. RECENT FINDINGS: High-frequency rTMS delivered to the primary motor cortex (M1) is currently a treatment strategy with the most literature support for decreased pain intensity and alleviation of associated symptoms in peripheral neuropathic pain, fibromyalgia and migraine. It has been shown that stimulation sessions are well tolerated and tolerable, and the effects of daily stimulation sessions can be prolonged by spaced maintenance stimulation sessions. Despite its efficacy, some individuals will not respond to rTMS targeted to M1. Lines of research are currently being developed to improve rTMS efficacy either by exploring new therapeutic targets, using novel stimulation parameters or more comprehensively profiling patients who are likely to respond to this treatment modality. SUMMARY: Noninvasive brain stimulation for chronic TMS pain is a well tolerated and reasonable add-on treatment approach for pain syndromes such as neuropathic pain, migraine and fibromyalgia. Strategies to improve its efficacy are an active field of research.

Non-invasive insular stimulation for peripheral neuropathic pain: Influence of target or symptom?

OBJECTIVES: The posterior-superior insula (PSI) has been shown to be a safe and potentially effective target for neuromodulation in peripheral neuropathic pain (PNP) in humans and animal models. However, it remains unknown whether there is a measurable responder profile to PSI stimulation. Two factors were hypothesized to influence the response of repetitive transcranial magnetic stimulation (rTMS) of the PSI: differences in rTMS target (discrete subregions of the PSI) or PNP phenotype. METHODS: This is a secondary analysis from a randomized, double-blind, sham-controlled, cross-over trial assessing PSI-rTMS in PNP (N = 31, 5 days rTMS) (10.1016/j.neucli.2021.06.003). Active PSI-rTMS true responders (>50% pain reduction from baseline after active but not after sham series of treatment) were compared with not true responders, to determine whether they differed with respect to 1) rTMS neuro-navigational target coordinates, and/or 2) specific neuropathic pain symptom inventory (NPSI) clusters (pinpointed pain, evoked pain, and deep pain) at baseline. RESULTS: Mean rTMS target coordinates did not differ between true (n = 45.1%) and not true responders (p = 0.436 for X, p = 0.120 for Y, and p = 0.116 for Z). The Euclidian distance between true and not true responders was 4.04 mm. When comparing differences in responders between NPSI clusters, no participant within the evoked pain cluster was a true responder (p = 0.024). CONCLUSION: Response to PSI-rTMS may depend on pain cluster subtype rather than on differences in targeting within the PSI.

Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise.

DICER is a key enzyme in microRNA (miRNA) biogenesis. Here we show that aerobic exercise training up-regulates DICER in adipose tissue of mice and humans. This can be mimicked by infusion of serum from exercised mice into sedentary mice and depends on AMPK-mediated signaling in both muscle and adipocytes. Adipocyte DICER is required for whole-body metabolic adaptations to aerobic exercise training, in part, by allowing controlled substrate utilization in adipose tissue, which, in turn, supports skeletal muscle function. Exercise training increases overall miRNA expression in adipose tissue, and up-regulation of miR-203-3p limits glycolysis in adipose under conditions of metabolic stress. We propose that exercise training-induced DICER-miR-203-3p up-regulation in adipocytes is a key adaptive response that coordinates signals from working muscle to promote whole-body metabolic adaptations.

Brazilian version of the European Cross-Cultural Neuropsychological Test Battery (CNTB-BR): diagnostic accuracy across schooling levels

Objective: To translate, establish the diagnostic accuracy, and standardize the Brazilian Portuguese version of the European Cross-Cultural Neuropsychological Test Battery (CNTB) considering schooling level. Methods: We first completed an English-Brazilian Portuguese translation and back-translation of the CNTB. A total of 135 subjects aged over 60 years - 65 cognitively healthy (mean 72.83, SD = 7.71; mean education 9.42, SD = 7.69; illiterate = 25.8%) and 70 with Alzheimer's disease (AD) (mean 78.87, SD = 7.09; mean education 7.62, SD = 5.13; illiterate = 10%) - completed an interview and were screened for depression. The receiver operating characteristic (ROC) analysis was used to verify the accuracy of each CNTB test to separate AD from healthy controls in participants with low levels of education (≤ 4 years of schooling) and high levels of education (≥ 8 years of schooling). The optimal cutoff score was determined for each test. Results: The Recall of Pictures Test (RPT)-delayed recall and the Enhanced Cued Recall (ECR) had the highest power to separate AD from controls. The tests with the least impact from schooling were the Rowland Universal Dementia Assessment Scale (RUDAS), supermarket fluency, RPT naming, delayed recall and recognition, and ECR. Conclusions: The Brazilian Portuguese version of the CNTB was well comprehended by the participants. The cognitive tests that best discriminated patients with AD from controls in lower and higher schooling participants were RPT delayed recall and ECR, both of which evaluate memory.

Accuracy of the semantic fluency test to separate healthy old people from patients with Alzheimers disease in a low education population / Acurácia do teste de fluência semântica para separar pessoas saudáveis de pacientes com doença de Alzheimer em uma população de baixa escolaridade

OBJECTIVE: Evaluate the accuracy of two semantic categories of the verbal fluency test (supermarket and animal categories) to separate healthy elderly individuals and lower educated Alzheimer's disease patients. METHODS: We evaluated 69 older adults with less than 5 years of schooling, consisting of 31 healthy elderly, and 38 patients diagnosed with Alzheimer's disease. Semantic verbal fluency was evaluated using the animal and supermarket categories. Mann-Whitney U and Independent t Tests were used to compare the two groups, and the diagnostic accuracy of the tests was analyzed by sensitivity, specificity, likelihood ratio's, and the Area Under the Curve (AUC). RESULTS: We found a significant difference between the healthy older and Alzheimer's disease groups, in both, animal (p = 0.014) and supermarket verbal fluency (p < 0.001). The supermarket category showed better overall diagnostic accuracy (AUC = 0.840, 95% CI = 0.746-0.933; p < 0.001) compared to the animal category (AUC = 0.671, 95% CI = 0.543-0.800; p = 0.014). CONCLUSION: The supermarket category of semantic verbal fluency provides better accuracy than the animal category for the identification of dementia in a Brazilian elderly population with low educational level.

OBJETIVO: Avaliar a acurácia de duas categorias semânticas do teste de fluência verbal (categorias de supermercado e animal) para separar idosos saudáveis e pacientes com doença de Alzheimer com baixa escolaridade. MÉTODOS: Avaliamos 69 idosos com menos de 5 anos de escolaridade, consistindo em 31 idosos saudáveis e 38 pacientes diagnosticados com a doença de Alzheimer. A fluência verbal semântica foi avaliada nas categorias animal e supermercado. O teste de Mann-Whitney U e o teste t independente foram usados para comparar os dois grupos, e a precisão diagnóstica dos testes foi analisada por sensibilidade, especificidade, razão de verossimilhança e área sob a curva (AUC). RESULTADOS: Encontramos uma diferença significativa entre os grupos de idosos saudáveis e com doença de Alzheimer, tanto na fluência verbal de animais (p = 0,014) quanto na de supermercado (p < 0,001). A categoria supermercado apresentou melhor precisão diagnóstica geral (AUC = 0,840; IC 95% = 0,746- 0,933; p < 0,001) em comparação com a categoria animal (AUC = 0,671; IC 95% = 0,543-0,800; p = 0,014). CONCLUSÃO: A categoria supermercado de fluência verbal semântica fornece melhor acurácia do que a categoria animal para a identificação de demência em uma população idosa brasileira com baixo nível educacional.

Brazilian version of the European Cross-Cultural Neuropsychological Test Battery (CNTB-BR): diagnostic accuracy across schooling levels.

OBJECTIVE: To translate, establish the diagnostic accuracy, and standardize the Brazilian Portuguese version of the European Cross-Cultural Neuropsychological Test Battery (CNTB) considering schooling level. METHODS: We first completed an English-Brazilian Portuguese translation and back-translation of the CNTB. A total of 135 subjects aged over 60 years - 65 cognitively healthy (mean 72.83, SD = 7.71; mean education 9.42, SD = 7.69; illiterate = 25.8%) and 70 with Alzheimer's disease (AD) (mean 78.87, SD = 7.09; mean education 7.62, SD = 5.13; illiterate = 10%) - completed an interview and were screened for depression. The receiver operating characteristic (ROC) analysis was used to verify the accuracy of each CNTB test to separate AD from healthy controls in participants with low levels of education (≤ 4 years of schooling) and high levels of education (≥ 8 years of schooling). The optimal cutoff score was determined for each test. RESULTS: The Recall of Pictures Test (RPT)-delayed recall and the Enhanced Cued Recall (ECR) had the highest power to separate AD from controls. The tests with the least impact from schooling were the Rowland Universal Dementia Assessment Scale (RUDAS), supermarket fluency, RPT naming, delayed recall and recognition, and ECR. CONCLUSIONS: The Brazilian Portuguese version of the CNTB was well comprehended by the participants. The cognitive tests that best discriminated patients with AD from controls in lower and higher schooling participants were RPT delayed recall and ECR, both of which evaluate memory.

Experimental knee-related pain enhances attentional interference on postural control.

PURPOSE: To quantify how postural stability is modified during experimental pain while performing different cognitively demanding tasks. METHODS: Sixteen healthy young adults participated in the experiment. Pain was induced by intramuscular injection of hypertonic saline solution (1 mL, 6%) in both vastus medialis and vastus lateralis muscles (0.9% isotonic saline was used as control). The participants stood barefoot in tandem position for 1 min on a force plate. Center of pressure (CoP) was recorded before and immediately after injections, while performing two cognitive tasks: (i) counting forwards by adding one; (ii) counting backwards by subtracting three. CoP variables-total area of displacement, velocity in anterior-posterior (AP-velocity) and medial-lateral (ML-velocity) directions, and CoP sample entropy in anterior-posterior and medial-lateral directions were displayed as the difference between the values obtained after and before each injection and compared between tasks and injections. RESULTS: CoP total area ( - 84.5 ± 145.5 vs. 28.9 ± 78.5 cm2) and ML-velocity ( - 1.71 ± 2.61 vs. 0.98 ± 1.93 cm/s) decreased after the painful injection vs. Control injection while counting forward (P < 0.05). CoP total area (12.8 ± 53.9 vs. - 84.5 ± 145.5 cm2), ML-velocity ( - 0.34 ± 1.92 vs. - 1.71 ± 2.61 cm/s) and AP-velocity (1.07 ± 2.35 vs. - 0.39 ± 1.82 cm/s) increased while counting backwards vs. forwards after the painful injection (P < 0.05). CONCLUSION: Pain interfered with postural stability according to the type of cognitive task performed, suggesting that pain may occupy cognitive resources, potentially resulting in poorer balance performance.

Diagnosing dementia in lower educated older persons: validation of a Brazilian Portuguese version of the Rowland Universal Dementia Assessment Scale (RUDAS)

Objective: To validate the Rowland Universal Dementia Assessment Scale for use in Brazil (RUDAS-BR). Methods: We first completed an English-Brazilian Portuguese translation and back-translation of the RUDAS. A total of 135 subjects over 60 years of age were included: 65 cognitively healthy and 70 with Alzheimer's disease (AD) according to the DSM-IV and Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. All participants completed an interview and were screened for depression. The receiver operating characteristic curves of the RUDAS were compared with those of the Mini Mental State Examination (MMSE) regarding the sensitivity and specificity of cutoffs, taking education into consideration. Results: The areas under the curve were similar for the RUDAS-BR (0.87 [95%CI 0.82-0.93]) and the MMSE (0.84 [95%CI 0.7-0.90]). RUDAS-BR scores < 23 indicated dementia, with sensitivity of 81.5% and specificity of 76.1%. MMSE < 24 indicated dementia, with sensitivity of 72.3% and specificity of 78.9%. The cutoff score was influenced by years of education on the MMSE, but not on the RUDAS-BR. Conclusions: The RUDAS-BR is as accurate as the MMSE in screening for dementia. RUDAS-BR scores were not influenced by education. The RUDAS-BR may improve the cognitive assessment of older persons who are illiterate or of lower educational attainment.

Diagnosing dementia in lower educated older persons: validation of a Brazilian Portuguese version of the Rowland Universal Dementia Assessment Scale (RUDAS).

OBJECTIVE: To validate the Rowland Universal Dementia Assessment Scale for use in Brazil (RUDAS-BR). METHODS: We first completed an English-Brazilian Portuguese translation and back-translation of the RUDAS. A total of 135 subjects over 60 years of age were included: 65 cognitively healthy and 70 with Alzheimer's disease (AD) according to the DSM-IV and Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. All participants completed an interview and were screened for depression. The receiver operating characteristic curves of the RUDAS were compared with those of the Mini Mental State Examination (MMSE) regarding the sensitivity and specificity of cutoffs, taking education into consideration. RESULTS: The areas under the curve were similar for the RUDAS-BR (0.87 [95%CI 0.82-0.93]) and the MMSE (0.84 [95%CI 0.7-0.90]). RUDAS-BR scores < 23 indicated dementia, with sensitivity of 81.5% and specificity of 76.1%. MMSE < 24 indicated dementia, with sensitivity of 72.3% and specificity of 78.9%. The cutoff score was influenced by years of education on the MMSE, but not on the RUDAS-BR. CONCLUSIONS: The RUDAS-BR is as accurate as the MMSE in screening for dementia. RUDAS-BR scores were not influenced by education. The RUDAS-BR may improve the cognitive assessment of older persons who are illiterate or of lower educational attainment.