Contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In patients with acute brain injury (ABI), internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures, or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared with the MAP input (2.25 ± 2.46 vs. 3.39 ± 2.28; P < 0.0001), and particularly depressed in the decompressive craniectomy (DC) group (n = 24, 0.35 ± 0.62 vs. 2.21 ± 1.96; P < 0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival.

Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohistochemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median peripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.

Motor cortex stimulation for chronic neuropathic pain: results of a double-blind randomized study.

Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active ('on') or sham ('off') stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2-68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.

Robotic and standard surgical intervention as adjunct therapies for retroperitoneal ganglioneuroma resection: a case report.

BACKGROUND: Ganglioneuroma (GN) is ranked by the International Neuroblastoma Pathology Classification as a benign tumor. It can occur anywhere along the sympathetic nerve chain and surgical excision is the treatment of choice. CASE PRESENTATION: An 18-year-old female patient sought medical assistance after 6 months of constant dorsal and back pain radiating from the thoracic region to the right abdominal flank. Magnetic resonance imaging revealed a solid nodular lesion with heterogeneous post-contrast enhancement and lobulated contours, centered on the right foramina of D12-L1, with a projection to the intracanal space, which compressed and laterally displaced the dural sac and had a right paravertebral extension between the vertebral bodies of D11 and superior aspect of L2. Ganglioneuroma was diagnosed using immunohistochemical analysis. It was decided to use a surgical approach in two stages: robot assisted for the anterior/retroperitoneal mass and a posterior hemilaminectomy/microsurgical approach to attempt total resection, avoiding the traditional anterior thoracoabdominal surgical incision and optimizing the patient's postoperative outcomes. No postoperative adverse events were noted, and the patient was discharged on postoperative day 5. CONCLUSION: This retroperitoneal GN presentation was peculiar because it originated at the D12 nerve root, which extended to the retroperitoneal space and inside the spinal canal. We hope that our case report can assist future decisions in similar circumstances.

Early Tracheostomy in Severe Traumatic Brain Injury Patients: A Meta-Analysis and Comparison With Late Tracheostomy.

OBJECTIVES: To elucidate the impact of early tracheostomy on hospitalization outcomes in patients with traumatic brain injury. DATA SOURCES: Lilacs, PubMed, and Cochrane databases were searched. The close-out date was August 8, 2018. STUDY SELECTION: Studies written in English, French, Spanish, or Portuguese with traumatic brain injury as the base trauma, clearly formulated question, patient's admission assessment, minimum follow-up during hospital stay, and minimum of two in-hospital outcomes were selected. Retrospective studies, prospective analyses, and case series were included. Studies without full reports or abstract, commentaries, editorials, and reviews were excluded. DATA EXTRACTION: The study design, year, patient's demographics, mean time between admission and tracheostomy, neurologic assessment at admission, confirmed ventilator-assisted pneumonia, median ICU stay, median hospital stay, mortality rates, and ICU and hospital costs were extracted. DATA SYNTHESIS: A total of 4,219 studies were retrieved and screened. Eight studies were selected for the systematic review; of these, seven were eligible for the meta-analysis. Comparative analyses were performed between the early tracheostomy and late tracheostomy groups. Mean time for early tracheostomy and late tracheostomy procedures was 5.59 days (SD, 0.34 d) and 11.8 days (SD, 0.81 d), respectively. Meta-analysis revealed that early tracheostomy was associated with shorter mechanical ventilation duration (-4.15 [95% CI, -6.30 to -1.99]) as well as ICU (-5.87 d [95% CI, -8.74 to -3.00 d]) and hospital (-6.68 d [95% CI, -8.03 to -5.32 d]) stay durations when compared with late tracheostomy. Early tracheostomy presented less risk difference for ventilator-associated pneumonia (risk difference, 0.78; 95% CI, 0.70-0.88). No statistical difference in mortality was found between the groups. CONCLUSIONS: The findings from this meta-analysis suggest that early tracheostomy in severe traumatic brain injury patients contributes to a lower exposure to secondary insults and nosocomial adverse events, increasing the opportunity of patient's early rehabilitation and discharge.

A systematic review on the role of infrared thermography in the Brown adipose tissue assessment.

Brown adipose tissue (BAT) is an endocrine adipose tissue with attributes to dissipate energy as heat in response to changes in temperature and diet. Infrared thermography (IRT) has been studied in recent years in the assessment of BAT thermogenesis, as an option to positron emission tomography - computed tomography (PET-CT), because of several advantages. We performed a systematic review on the use of IRT in BAT assessment. Comprehensive online search was performed in different databases. The QUADAS 2 tool was used to evaluate studies' quality. 12 studies fit the inclusion criteria, whereas only one of these was considered of low risk of bias. 10 studies were favorable to IRT appliance in BAT evaluation, observing elevation of supraclavicular skin temperature correlated with BAT activity. Studies were heterogeneous in design, and a meta-analysis was precluded. Further studies with similar methodologies are needed. Conclusion: Despite the large number of published methodologies, IRT is a promising method for detecting BAT activation. Current knowledge already allows a better understanding of thermography to improve and standardize the technique.

Altered cortical excitability in persistent idiopathic facial pain.

INTRODUCTION: Persistent idiopathic facial pain is a refractory and disabling condition of unknown mechanism and etiology. It has been suggested that persistent idiopathic facial pain patients have not only peripheral generators of pain, but also central nervous system changes that would contribute to the persistence of symptoms. We hypothesized that persistent idiopathic facial pain would have changes in brain cortical excitability as measured by transcranial magnetic stimulation compared to healthy controls. METHODS: Twenty-nine persistent idiopathic facial pain patients were compared to age- and sex-matched healthy controls and underwent cortical excitability measurements by transcranial magnetic stimulation applied to the cortical representation of the masseter muscle of both hemispheres. Single-pulse stimulation was used to measure the resting motor threshold and suprathreshold motor-evoked potentials. Paired-pulse stimulation was used to assess short intracortical inhibition and intracortical facilitation. Clinical pain and associated symptoms were assessed with validated tools. RESULTS: Spontaneous pain was found in 27 (93.1%) and provoked pain was found in two (6.9%) persistent idiopathic facial pain patients. The motor-evoked potentials at 120% and 140% were significantly lower for both hemispheres compared to controls. Persistent idiopathic facial pain patients had lower short-interval intracortical inhibition compared with controls. These changes were correlated with some aspects of quality of life, and higher mood symptoms. These neurophysiological alterations were not influenced by analgesic medication, as similar changes were observed in patients with or without central-acting drugs. CONCLUSIONS: Persistent idiopathic facial pain is associated with changes in intracortical modulation involving GABAergic mechanisms, which may be related to certain aspects of the pathophysiology of this chronic pain condition. Trial registration: NTC01746355.

Evaluating cerebellar dentatotomy for the treatment of spasticity with or without dystonia.

Spasticity represents a common and very often incapacitating neurologic condition, for which a limited number of treatment options are available. Stereotactic ablation of the dentate cerebellar nuclei (dentatotomy) was widely used in the past with variable results. In the present study, we reviewed 12 consecutive cases operated on at the Midland Centre for Neurosurgery and Neurology at Birmingham University (Smetwick, UK) in the 1980s. The following clinical aspects were analyzed: severity of spasticity, occurrence of abnormal movements (dystonia/athetosis), language fluency, gait, and overall clinical condition. Follow-up ranged from 0.5 to 94 (mean: 31.6) months. Immediate improvement was noted in 10 patients, and five of them had sustained this improvement at the time of the last assessment. A more pronounced improvement was observed for gait, relative to speech and abnormal movements. No significant morbidity related to the procedure was observed. We conclude that dentatotomy is a safe procedure that should still be considered in specific cases. Here, we review the cases reported in the literature, and present a mechanistic hypothesis about how dentatotomy influences motor tonus, in light of the current knowledge about cerebellar physiology. We believe that this issue is critical for the development of alternative surgical approaches targeting the cerebellum, such as chronic electric stimulation.

Comparing methods for determining motor-hand lateralization based on fTCD signals.

The lateralization index (LI) as determined from functional transcranial Doppler sonography (fTCD) can be used to determine the hemispheric organization of neural activation during a behavioral task. Previous studies have proposed different methods to determine this index, but to our knowledge no studies have compared the performance of these methods. In this study, we compare two established methods with a simpler method proposed here. The aim was to see whether similar results could be achieved with a simpler method and to give an indication of the analysis steps required to determine the LI. A simple unimanual motor task was performed while fTCD was acquired, and the LI determined by each of these methods was compared. In addition, LI determined by each method was related to behavioural output in the form of degree of handedness. The results suggest that although the methods differed in complexity, they yielded similar results when determining the lateralization of motor functions, and its correlation with behavior. Further investigation is needed to expand the conclusions of this preliminary study, however the new method proposed in the paper has great potential as it is much simpler than the more established methods yet yields similar results.

Somatosensory investigation of patients with orofacial pain compared with controls.

The objective of this study was to investigate the sensorial characteristics of orofacial pain in patients compared with control subjects. A total of 336 subjects (282 patients and 54 control subjects) were evaluated to identify their thermal (cold and warm), tactile, and pain thresholds. Numbness was reported by 61.7% of the patients (p<0.001). Patients with trigeminal postherpetic neuralgia and burning mouth syndrome showed loss of thermal perception; patients with postherpetic neuralgia, burning mouth syndrome, and posttraumatic painful neuropathy had a decrease in tactile perception compared with the control subjects (p<0.001). In conclusion, other sensorial modalities besides pain are affected by neuropathic orofacial pain; these findings can help in the understanding of the pathophysiological mechanisms in orofacial pain.

Does deep TMS really works for smoking cessation? A prospective, double blind, randomized, sham controlled study.

INTRODUCTION: A substantial proportion of smokers wishing to quit do not stop smoking when using current therapies to aid cessation. Magnetic pulses to specific brain areas designated as transcranial magnetic stimulation may modulate brain activity and thereby change chemical dependencies. Deep transcranial magnetic stimulation (dTMS) with the H4 coil stimulates neuronal pathways in the lateral prefrontal cortex and insula bilaterally, areas involved in tobacco addiction. OBJECTIVE: To evaluate the efficacy and safety of dTMS with T4 coil in smoking cessation. METHODS: In a double blind, controlled clinical trial, adult smokers of at least 10 cigarettes/day were randomized to active (n = 50) versus sham dTMS (n = 50). The protocol involved up to 21 sessions administered over up to 12 weeks. Tobacco use was monitored by self-report and confirmed by expired air monoximetry (at each dTMS visit) and blood cotinine (at the screening visit and at the end of sessions). Participants completed abstinence, mood and cognition scales at determined timepoints during follow-up. RESULTS: In the intention to-treat-analysis, the cessation rate of the intervention and control groups was 14.0%. The reported side effects were as expected for this procedure. Although there were no serious adverse events, three participants were withdrawn according to safety criteria. CONCLUSION: Active treatment with dTMS H4 coil was safe but not effective for smoking cessation.

Successful intra-arterial thrombolysis in a patient with an intracranial meningioma.

Alteplase (recombinant tissue plasminogen activator [rt-PA]) label approval by the Food and Drug Administration remarks the contraindication of its use with known intracranial neoplasm because of potential bleeding complications. Despite this concern, the real risk of intracerebral bleeding in patients with intracranial neoplasms treated with rt-PA is unknown, and there are few reports of thrombolysis in patients with brain tumors. We report a case of a 78-year-old man who was seen in our emergency department within 2 hours from sudden onset of aphasia, right-sided hemiplegia, hypoesthesia, and homonymous hemianopsia. The National Institutes of Health Stroke Scale (NIHSS) score at admission was 20. Intra-arterial thrombolysis was performed with administration of .3 mg/kg of alteplase combined with mechanical thrombectomy. At discharge, his NIHSS score was 1, and after 90 days, his modified Rankin score was 1. To our knowledge, this is the first report of intra-arterial thrombolysis in a patient with acute ischemic stroke with an intracranial tumor.

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.