Site matters: Central neuropathic pain characteristics and somatosensory findings after brain and spinal cord lesions.

BACKGROUND: It is unknown if different etiologies or lesion topographies influence central neuropathic pain (CNP) clinical manifestation. METHODS: We explored the symptom-somatosensory profile relationships in CNP patients with different types of lesions to the central nervous system to gain insight into CNP mechanisms. We compared the CNP profile through pain descriptors, standardized bedside examination, and quantitative sensory test in two different etiologies with segregated lesion locations: the brain, central poststroke pain (CPSP, n = 39), and the spinal cord central pain due to spinal cord injury (CPSCI, n = 40) in neuromyelitis optica. RESULTS: Results are expressed as median (25th to 75th percentiles). CPSP presented higher evoked and paroxysmal pain scores compared to CPSCI (p < 0.001), and lower cold thermal limen (5.6°C [0.0-12.9]) compared to CPSCI (20.0°C [4.2-22.9]; p = 0.004). CPSCI also had higher mechanical pain thresholds (784.5 mN [255.0-1078.0]) compared to CPSP (235.2 mN [81.4-1078.0], p = 0.006) and higher mechanical detection threshold compared to control areas (2.7 [1.5-6.2] vs. 1.0 [1.0-3.3], p = 0.007). Evoked pain scores negatively correlated with mechanical pain thresholds (r = -0.38, p < 0.001) and wind-up ratio (r = -0.57, p < 0.001). CONCLUSIONS: CNP of different etiologies may present different pain descriptors and somatosensory profiles, which is likely due to injury site differences within the neuroaxis. This information may help better design phenotype mechanism correlations and impact trial designs for the main etiologies of CNP, namely stroke and spinal cord lesions. This study provides evidence that topography may influence pain symptoms and sensory profile. The findings suggest that CNP mechanisms might vary according to pain etiology or lesion topography, impacting future mechanism-based treatment choices.

Motor corticospinal excitability abnormalities differ between distinct chronic low back pain syndromes.

OBJECTIVES: It is not known whether cortical plastic changes reported in low-back pain (LBP) are present in all etiologies of LBP. Here we report on the assessment of patients with three LBP conditions: non-specific-LBP (ns-LBP), failed back surgery syndrome (FBSS), and sciatica (Sc). METHODS: Patients underwent a standardized assessment of clinical pain, conditioned pain modulation (CPM), and measures of motor evoked potential (MEPs)-based motor corticospinal excitability (CE) by transcranial magnetic stimulation, including short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Comparisons were also made with normative data from sex- and age-matched healthy volunteers. RESULTS: 60 patients (42 women, 55.1±9.1 years old) with LBP were included (20 in each group). Pain intensity was higher in patients with neuropathic pain [FBSS (6.8±1.3), and Sc (6.4±1.4)] than in those with ns-LBP (4.7±1.0, P<0.001). The same was shown for pain interference (5.9±2.0, 5.9±1.8, 3.2±1.9, P<0.001), disability (16.4±3.3, 16.3±4.3, 10.4±4.3, P<0.001), and catastrophism (31.1±12.3, 33.0±10.4, 17.4±10.7, P<0.001) scores for FBSS, Sc, and ns-LBP groups, respectively. Patients with neuropathic pain (FBSS, Sc) had lower CPM (-14.8±1.9, -14.1±16.7, respectively) compared to ns-LBP (-25.4±16.6; P<0.02). 80.0% of the FBSS group had defective ICF compared to the other two groups (52.5% for ns-LBP, P=0.025 and 52.5% for Sc, P=0.046). MEPs (140%-rest motor threshold) were low in 50.0% of patients in the FBSS group compared to 20.0% of ns-LBP (P=0.018) and 15.0% of Sc (P=0.001) groups. Higher MEPs were correlated with mood scores (r=0.489), and with lower neuropathic pain symptom scores(r=-0.415) in FBSS. CONCLUSIONS: Different types of LBP were associated with different clinical, CPM and CE profiles, which were not uniquely related to the presence of neuropathic pain. These results highlight the need to further characterize patients with LBP in psychophysics and cortical neurophysiology studies.

Dissecting neuropathic from poststroke pain: the white matter within.

ABSTRACT: Poststroke pain (PSP) is a heterogeneous term encompassing both central neuropathic (ie, central poststroke pain [CPSP]) and nonneuropathic poststroke pain (CNNP) syndromes. Central poststroke pain is classically related to damage in the lateral brainstem, posterior thalamus, and parietoinsular areas, whereas the role of white matter connecting these structures is frequently ignored. In addition, the relationship between stroke topography and CNNP is not completely understood. In this study, we address these issues comparing stroke location in a CPSP group of 35 patients with 2 control groups: 27 patients with CNNP and 27 patients with stroke without pain. Brain MRI images were analyzed by 2 complementary approaches: an exploratory analysis using voxel-wise lesion symptom mapping, to detect significant voxels damaged in CPSP across the whole brain, and a hypothesis-driven, region of interest-based analysis, to replicate previously reported sites involved in CPSP. Odds ratio maps were also calculated to demonstrate the risk for CPSP in each damaged voxel. Our exploratory analysis showed that, besides known thalamic and parietoinsular areas, significant voxels carrying a high risk for CPSP were located in the white matter encompassing thalamoinsular connections (one-tailed threshold Z > 3.96, corrected P value <0.05, odds ratio = 39.7). These results show that the interruption of thalamocortical white matter connections is an important component of CPSP, which is in contrast with findings from nonneuropathic PSP and from strokes without pain. These data can aid in the selection of patients at risk to develop CPSP who could be candidates to pre-emptive or therapeutic interventions.

MISIAN (Minimally Invasive Surgery for Treatment of Unruptured Intracranial Aneurysms): A Prospective Randomized Single-Center Clinical Trial With Long-Term Follow-Up Comparing Different Minimally Invasive Surgery Techniques with Standard Open Surgery.

BACKGROUND: Unruptured intracranial aneurysms (UIAs) are increasingly diagnosed but treatment is still controversial. Although the descriptions and use of minimally invasive surgery (MIS) have increased, comparative studies with standard approaches are rare. OBJECTIVE: MISIAN (Minimally Invasive Surgery for Treatment of Unruptured Intracranial Aneurysms) is a prospective randomized single-center clinical trial with long-term follow-up comparing different MIS techniques with standard open surgery for treatment of UIAs. METHODS: We randomly allocated a standard pterional approach (PtA) or MIS (1:2) to 111 patients with UIAs of the anterior circulation (mean dome diameter, 6.4 mm; range, 3-20 mm). Patients selected for MIS underwent a second randomization between a transeyelid approach (TelA) or nanopterional approach (NPtA) (1:1). RESULTS: Forty-one patients were randomized to and treated with the PtA, 36 with the TelA, and 34 with the NPtA. Only patients treated with PtA had permanent facial nerve palsy (n = 4 [10%]; P = 0.032). MIS cosmetic results were considered better than those of PtA by independent observers (P < 0.001), and less temporal atrophy in the MIS group was also observed (P = 0.0034). The proportion of excellent results was higher in the TelA group than in the NPtA group (86% vs. 67.6%; P = 0.039). Patients undergoing MIS also reported consistently higher satisfaction and quality-of-life scores (P < 0.001). CONCLUSIONS: MIS is superior to standard PtA for microsurgical clipping of small UIAs of the anterior circulation in terms of cosmetic, satisfaction, and quality-of-life outcomes. The TelA or NPtA for UIAs did not show significant outcome differences at 12-18 months.

Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain - A pilot double-blind, randomized cross-over study.

OBJECTIVES: Peripheral neuropathic pain (pNeP) is prevalent, and current treatments, including drugs and motor cortex repetitive transcranial magnetic stimulation (rTMS) leave a substantial proportion of patients with suboptimal pain relief. METHODS: We explored the intensity and short-term duration of the analgesic effects produced in pNeP patients by 5 days of neuronavigated deep rTMS targeting the posterior superior insula (PSI) with a double-cone coil in a sham-controlled randomized cross-over trial. RESULTS: Thirty-one pNeP patients received induction series of five active or sham consecutive sessions of daily deep-rTMS to the PSI in a randomized sequence, with a washout period of at least 21 days between series. The primary outcome [number of responders (>50% pain intensity reduction from baseline in a numerical rating scale ranging from 0 to 10)] was significantly higher after real (58.1%) compared to sham (19.4%) stimulation (p = 0.002). The number needed to treat was 2.6, and the effect size was 0.97 [95% CI (0.6; 1.3)]. One week after the 5th stimulation day, pain scores were no longer different between groups, and no difference in neuropathic pain characteristics and interference with daily living were present. No major side effects occurred, and milder adverse events (i.e., short-lived headaches after stimulation) were reported in both groups. Blinding was effective, and analgesic effects were not affected by sequence of the stimulation series (active-first or sham-first), age, sex or pain duration of participants. DISCUSSION: PSI deep-rTMS was safe in refractory pNeP and was able to provide significant pain intensity reduction after a five-day induction series of treatments. Post-hoc assessment of neuronavigation targeting confirmed deep-rTMS was delivered within the boundaries of the PSI in all participants. CONCLUSION: PSI deep-rTMS provided significant pain relief during 5-day induction sessions compared to sham stimulation.

Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain.

OBJECTIVE: To compare the analgesic effects of stimulation of the anterior cingulate cortex (ACC) or the posterior superior insula (PSI) against sham deep (d) repetitive (r) transcranial magnetic stimulation (TMS) in patients with central neuropathic pain (CNP) after stroke or spinal cord injury in a randomized, double-blinded, sham-controlled, 3-arm parallel study. METHODS: Participants were randomly allocated into the active PSI-rTMS, ACC-rTMS, sham-PSI-rTMS, or sham-ACC-rTMS arms. Stimulations were performed for 12 weeks, and a comprehensive clinical and pain assessment, psychophysics, and cortical excitability measurements were performed at baseline and during treatment. The main outcome of the study was pain intensity (numeric rating scale [NRS]) after the last stimulation session. RESULTS: Ninety-eight patients (age 55.02 ± 12.13 years) completed the study. NRS score was not significantly different between groups at the end of the study. Active rTMS treatments had no significant effects on pain interference with daily activities, pain dimensions, neuropathic pain symptoms, mood, medication use, cortical excitability measurements, or quality of life. Heat pain threshold was significantly increased after treatment in the PSI-dTMS group from baseline (1.58, 95% confidence interval [CI] 0.09-3.06]) compared to sham-dTMS (-1.02, 95% CI -2.10 to 0.04, p = 0.014), and ACC-dTMS caused a significant decrease in anxiety scores (-2.96, 95% CI -4.1 to -1.7]) compared to sham-dTMS (-0.78, 95% CI -1.9 to 0.3; p = 0.018). CONCLUSIONS: ACC- and PSI-dTMS were not different from sham-dTMS for pain relief in CNP despite a significant antinociceptive effect after insular stimulation and anxiolytic effects of ACC-dTMS. These results showed that the different dimensions of pain can be modulated in humans noninvasively by directly stimulating deeper SNC cortical structures without necessarily affecting clinical pain per se. CLINICALTRIALSGOV IDENTIFIER: NCT01932905.

Hyperhomocysteinemia as a Risk Factor for Intracranial Aneurysms: A Case-Control Study.

OBJECTIVE: Homocysteine, an amino acid derived from methionine metabolism, has gained great importance as an important risk factor for cardiovascular diseases as the result of its thrombogenic properties and endothelial injury association. However, its role in the etiology and screening of intracranial aneurysms (IAs) has not been well studied. We aimed to test the hypothesis of a positive association between hyperhomocysteinemia (HHcy) and IAs. METHODS: A case-control study was performed at a vascular neurosurgery unit in Brazil between 2016 and 2017. In total, 180 patients were included: 142 patients with previous IAs (case group) and 38 patients with a previous diagnosis of arteriovenous malformation and no aneurysms on imaging evaluation (control group). HHcy was defined as homocysteine levels greater than 15 µmol/L. Multivariate models were designed to adjust for potential confounders: age, sex, hypertension, dyslipidemia, and smoker status. RESULTS: The case group was older (56.3 ± 12.6 years vs. 40.9 ± 14.0 years, P < 0.001) and had a greater prevalence of women (76.1% vs. 55.3%, P = 0.012), as well as hypertension (45.1% vs. 2.6%, P < 0.001), dyslipidemia (60.6% vs. 10.5%, P = 0.001), and smokers (41.5% vs. 0.0%, P < 0.001). Median homocysteine in the cases was similar to the controls (10.5 µmol/L [8.3-14.0] vs. 10.7 µmol/L [8.2-13.3], respectively, P = 0.450). There was a trend toward greater HHcy prevalence in the case group (20.4% vs. 7.9%, P = 0.073). HHcy was associated with greater age, male sex, hypertension, and smoking status. After multivariate adjustment, HHcy had no association with IAs (odds ratio 1.34, 95% confidence interval 0.30-5.97, P = 0.703). CONCLUSIONS: No association was found between HHcy and IAs.

[Cerebellar infarction: analysis of 151 patients]. / Infarto cerebelar: análise de 151 pacientes.

This report presents the treatment of 151 patients with cerebellar infarction, 98 men (65%) and 53 women (35%), mean age 62.4 years old. Occlusive hydrocephalus was diagnosed in 7.9% of the patients associated with an extensive cerebellar infarction and in all 11 surgical patients (7.2%). Four patients underwent an external ventricular drainage with 3 deaths (75%) and 7 underwent a decompressive suboccipital craniectomy with 2 deaths (28.5%). Mortality of the clinical group was 15 patients (10.7%). Vertigo, vomiting, Romberg sign and dysmetria were the signs and symptoms of cerebellar involvement that were most frequently observed. Cerebellar infarction from embolism after cardiovascular surgery occurred in 57 patients (37.7%). Cerebellar infarction, as an isolated fact, occurred in 59 patients (39%) and cerebellar plus infarction in other regions occurred in 92 patients (61%). Magnetic resonance image was the best diagnostic form for cerebellar lesions, however computerized tomography could show cerebellar infarction in 68 patients (78%).