Publications by authors named "Manoel Jacobsen Teixeira"

439 Publications

Estimation of intracranial pressure by ultrasound of the optic nerve sheath in an animal model of intracranial hypertension.

J Clin Neurosci 2021 Apr 8;86:174-179. Epub 2021 Feb 8.

Division of Neurosurgery, University of São Paulo Medical School, São Paulo, Brazil; Hospital Samaritano, Americas Serviços Médicos, São Paulo, Brazil.

Background: Ultrasound of the optic nerve sheath diameter (ONSD) has been used as a non-invasive and cost-effective bedside alternative to invasive intracranial pressure (ICP) monitoring. However, ONSD time-lapse behavior in intracranial hypertension (ICH) and its relief by means of either saline infusion or surgery are still unknown. The objective of this study was to correlate intracranial pressure (ICP) and ultrasonography of the optic nerve sheath (ONS) in an experimental animal model of ICH and determine the interval needed for ONSD to return to baseline levels.

Methods: An experimental study was conducted on 30 pigs. ONSD was evaluated by ultrasound at different ICPs generated by intracranial balloon inflation, saline infusion, and balloon deflation, and measured using an intraventricular catheter.

Results: All variables obtained by ONS ultrasonography such as left, right, and average ONSD (AON) were statistically significant to estimate the ICP value. ONSD changed immediately after balloon inflation and returned to baseline after an average delay of 30 min after balloon deflation (p = 0.016). No statistical significance was observed in the ICP and ONSD values with hypertonic saline infusion. In this swine model, ICP and ONSD showed linear correlation and ICP could be estimated using the formula: -80.5 + 238.2 × AON.

Conclusion: In the present study, ultrasound to measure ONSD showed a linear correlation with ICP, although a short delay in returning to baseline levels was observed in the case of sudden ICH relief.
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http://dx.doi.org/10.1016/j.jocn.2021.01.021DOI Listing
April 2021

Abnormal sensory thresholds of dystonic patients are not affected by deep brain stimulation.

Eur J Pain 2021 Mar 19. Epub 2021 Mar 19.

Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.

Background: Unlike motor symptoms, the effects of deep brain stimulation (DBS) on non-motor symptoms associated with dystonia remain unknown.

Methods: The objective of this study was to assess the effects of DBS on evoked experimental pain and cutaneous sensory thresholds in a crossover, double-blind on/off study and compare these results with those of healthy volunteers (HV).

Results: Sixteen patients with idiopathic dystonia (39.9 ± 13 years old, n = 14 generalized) with DBS of the globus pallidus internus underwent a battery of quantitative sensory testing and assessment using a pain top-down modulation system (conditioned pain modulation, CPM). Results for the more and less dystonic body regions were compared in on and off stimulation. The patients' results were compared to age- and sex-matched HV. Descending pain modulation CPM responses in dystonic patients (on-DBS, 11.8 ± 40.7; off-DBS, 1.8 ± 22.1) was abnormally low (defective) compared to HV (-15.6 ± 23.5, respectively p = .006 and p = .042). Cold pain threshold and cold hyperalgesia were 54.8% and 95.7% higher in dystonic patients compared to HV. On-DBS CPM correlated with higher Burke-Fahn-Marsden disability score (r = 0.598; p = .014). While sensory and pain thresholds were not affected by DBS on/off condition, pain modulation was abnormal in dystonic patients and tended to be aggravated by DBS.

Conclusion: The analgesic effects after DBS do not seem to depend on short-duration changes in cutaneous sensory thresholds in dystonic patients and may be related to changes in the central processing of nociceptive inputs.
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http://dx.doi.org/10.1002/ejp.1757DOI Listing
March 2021

Two decades of research towards a potential first anti-epileptic drug.

Seizure 2021 Mar 3. Epub 2021 Mar 3.

Physiology Department, Universidade Federal de São Paulo, São Paulo, SP, Brazil; Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, RJ, Brazil. Electronic address:

The basic mechanisms by which brain insults, such as trauma, stroke or status epilepticus produce epilepsy are not completely understood, and effective preventive measures and treatment are still not available in the clinical setting. Over the last 2 decades we have conducted several studies with animal models of epilepsy (rodents and non-human primates) and demonstrated that drugs that modify neuronal plastic processes, such as anticholinergic agents (e.g., antimuscarinic compounds), if administered soon after brain injury and over a period of 10-20 days, have the potential to modify the natural course of post-traumatic epilepsy. To that end treatment with scopolamine showed promising results as a candidate agent in both the pilocarpine and kainate models. We then showed that biperiden, yet another cholinergic antagonist acting in the muscarinic receptor, that is widely used to treat Parkinson's disease, also decreased the incidence and intensity of spontaneous epileptic seizures, delaying their appearance in the pilocarpine model of epilepsy. In other words, biperiden showed to be a potential candidate to be further investigated as an antiepileptogenic agent. Accordingly, we tested the safety of biperiden in a small group of patients (as a small phase II safety assessment) and confirmed its safety in the context of traumatic brain injury (TBI). Now, we provide information on our ongoing project to evaluate the efficacy of biperiden in preventing the development of epilepsy in patients that suffered TBI, in a double blind, randomized, placebo-controlled trial.
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http://dx.doi.org/10.1016/j.seizure.2021.02.031DOI Listing
March 2021

Prevalence and characteristics of new-onset pain in COVID-19 survivours, a controlled study.

Eur J Pain 2021 Feb 23. Epub 2021 Feb 23.

Pain Center, Department of Neurology, University of São Paulo, São Paulo, Brazil.

Background: We assessed whether COVID-19 is associated with de novo pain and de novo chronic pain (CP).

Methods: This controlled cross-sectional study was based on phone interviews of patients discharged from hospital after COVID-19 compared to the control group composed of individuals hospitalized during the same period due to non-COVID-19 causes. Patients were classified as having previous CP based on the ICD-11/IASP criteria, de novo pain (i.e. any new type of pain, irrespective of the pain status before hospital stay), and de novo CP (i.e. persistent or recurring de novo pain, lasting more than 3 months) after COVID-19. We assessed pain prevalence and its characteristics, including headache profile, pain location, intensity, interference, and its relationship with fatigue, and persistent anosmia. Forty-six COVID-19 and 73 control patients were included. Both groups had similar sociodemographic characteristics and past medical history.

Results: Length of in-hospital-stay and ICU admission rates were significantly higher amongst COVID-19 survivours, while mechanical ventilation requirement was similar between groups. Pre-hospitalisation pain was lower in COVID-19 compared to control group (10.9% vs. 42.5%; p = 0.001). However, the COVID-19 group had a significantly higher prevalence of de novo pain (65.2% vs. 11.0%, p = 0.001), as well as more de novo headache (39.1%) compared to controls (2.7%, p = 0.001). New-onset CP was 19.6% in COVID-19 patients and 1.4% (p = 0.002) in controls. These differences remained significant (p = 0.001) even after analysing exclusively (COVID: n = 40; controls: n = 34) patients who did not report previous pain before the hospital stay. No statistically significant differences were found for mean new-onset pain intensity and interference with daily activities between both groups. COVID-19 pain was more frequently located in the head/neck and lower limbs (p < 0.05). New-onset fatigue was more common in COVID-19 survivours necessitating inpatient hospital care (66.8%) compared to controls (2.5%, p = 0.001). COVID-19 patients who reported anosmia had more new-onset pain (83.3%) compared to those who did not (48.0%, p = 0.024).

Conclusion: COVID-19 was associated with a significantly higher prevalence of de novo CP, chronic daily headache, and new-onset pain in general, which was associated with persistent anosmia.

Significance: There exists de novo pain in a substantial number of COVID-19 survivours, and some develop chronic pain. New-onset pain after the infection was more common in patients who reported anosmia after hospital discharge.
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http://dx.doi.org/10.1002/ejp.1755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013219PMC
February 2021

Cortical spreading depolarization and ketamine: a short systematic review.

Neurophysiol Clin 2021 Mar 18;51(2):145-151. Epub 2021 Feb 18.

Division of Neurosurgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), Brazil. Electronic address:

Introduction: Cortical spreading depolarization (SD) describes pathological waves characterized by an almost complete sustained depolarization of neurons and astrocytes that spreads throughout the cortex. In this study, we carried out a qualitative review of all available evidence, clinical and preclinical, on the use of ketamine in SD.

Methods: We performed a systematic review of Medline, with no restrictions regarding publishing date or language, in search of articles reporting the use of ketamine in SD. The search string was composed of "ketamine," "spreading," "depolarization," and "depression" in both (AND) and (OR) combinations.

Results: Twenty studies were included in the final synthesis. Many studies showed that ketamine effectively blocks SD in rats, swine, and humans. The first prospective randomized trial was published in 2018. Ten patients with severe traumatic brain injury or subarachnoid hemorrhage were enrolled, and ketamine showed a significant, dose-dependent effect on the reduction of SD.

Conclusion: The available evidence from preclinical studies is helping to translate the role of ketamine in blocking spreading depolarizations to clinical practice, in the settings of migraine with aura, traumatic brain injury, subarachnoid hemorrhage, and hemorrhagic and ischemic stroke. More randomized controlled trials are needed to determine whether interrupting the ketamine-blockable SDs effectively leads to an improvement in outcome and to assess the real occurrence of adverse effects.
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http://dx.doi.org/10.1016/j.neucli.2021.01.004DOI Listing
March 2021

Letter to the Editor Regarding "Predictors of Nonroutine Discharge Disposition Among Parasagittal/Parafalcine Meningioma Patients".

World Neurosurg 2021 Feb;146:428

Division of Neurosurgery, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Department of Neurology, Hospital Samaritano, Americas Serviços Medicos, Sao Paulo, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2020.08.061DOI Listing
February 2021

Reoperation for recurrent glioblastomas: What to expect?

Surg Neurol Int 2021 3;12:42. Epub 2021 Feb 3.

Department of Neurosurgery, Eberhard Karls University, Tübingen, Germany.

Background: The current standard treatment for glioblastoma (GBM) is maximal safe surgical resection followed by radiation and chemotherapy. Unfortunately, the disease will invariably recur even with the best treatment. Although the literature suggests some advantages in reoperating patients harboring GBM, controversy remains. Here, we asked whether reoperation is an efficacious treatment strategy for GBM, and under which circumstances, it confers a better prognosis.

Methods: We retrospectively reviewed 286 consecutive cases of newly diagnosed GBM in a single university hospital from 2008 to 2015. We evaluated clinical and epidemiological parameters possibly influencing overall survival (OS) by multivariate Cox regression analysis. OS was calculated using the Kaplan-Meier method in patients submitted to one or two surgical procedures. Finally, the survival curves were fitted with the Weibull model, and survival rates at 6, 12, and 24 months were estimated.

Results: The reoperated group survived significantly longer ( = 63, OS = 20.0 ± 2.3 vs. 11.4 ± 1.0 months, < 0.0001). Second, the multivariate analysis revealed an association between survival and number of surgeries, initial Karnofsky Performance Status, and age (all < 0.001). Survival estimates according to the Weibull regression model revealed higher survival probabilities for reoperation compared with one operation at 6 months (83.74 ± 3.42 vs. 63.56 ± 3.59, respectively), 12 months (64.00 ± 4.85 vs. 37.53 ± 3.52), and 24 months (32.53 ± 4.78 vs. 12.02 ± 2.36).

Conclusion: Our data support the indication of reoperation for GBM, especially for younger patients with good functional status. Under these circumstances, survival can be doubled at 12 and 24 months.
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http://dx.doi.org/10.25259/SNI_538_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881499PMC
February 2021

Evaluation of Changes in Preoperative Cortical Excitability by Navigated Transcranial Magnetic Stimulation in Patients With Brain Tumor.

Front Neurol 2020 22;11:582262. Epub 2021 Jan 22.

LIM-62/Division of Neurosurgery, Department of Neurology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

This prospective study aimed to evaluate the cortical excitability (CE) of patients with brain tumors surrounding or directly involving the (CST) using navigated transcranial magnetic stimulation (nTMS). We recruited 40 patients with a single brain tumor surrounding or directly involving the CST as well as 82 age- and sex-matched healthy controls. The patients underwent standard nTMS and CE evaluations. Single and paired pulses were applied to the primary motor area (M1) of both affected and unaffected cerebral hemispheres 1 week before surgery. The CE parameters included resting motor threshold (RMT), motor evoked potential (MEP) ratio for 140 and 120% stimulus (MEP 140/120 ratio), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Motor outcome was evaluated on hospital discharge and on 30-day and 90-day postoperative follow-up. In the affected hemispheres of patients, SICI and ICF were significantly higher than in the unaffected hemispheres (=0.002 and =0.009, respectively). The 140/120 MEP ratio of patients' unaffected hemispheres was lower than that in controls (=0.001). Patients with glioblastomas (GBM) had a higher interhemispheric RMT ratio than patients with grade II and III gliomas ( = 0.018). A weak correlation was observed among the RMT ratio and the preoperative motor score ( = 0.118, = 0.017) and the 90-day follow-up ( = 0.227, = 0.016). Using preoperative nTMS, we found that brain hemispheres affected by tumors had abnormal CE and that patients with GBM had a distinct pattern of CE. These findings suggest that tumor biological behavior might play a role in CE changes.
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http://dx.doi.org/10.3389/fneur.2020.582262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863982PMC
January 2021

The nerve to the levator scapulae muscle as donor in brachial plexus surgery: an anatomical study and case series.

J Neurosurg 2021 Jan 29:1-8. Epub 2021 Jan 29.

Objective: Nerve transfers are commonly used in treating complete injuries of the brachial plexus, but donor nerves are limited and preferentially directed toward the recovery of elbow flexion and shoulder abduction. The aims of this study were to characterize the anatomical parameters for identifying the nerve to the levator scapulae muscle (LSN) in brachial plexus surgery, to evaluate the feasibility of transferring this branch to the suprascapular nerve (SSN) or lateral pectoral nerve (LPN), and to present the results from a surgical series.

Methods: Supra- and infraclavicular exposure of the brachial plexus was performed on 20 fresh human cadavers in order to measure different anatomical parameters for identification of the LSN. Next, an anatomical and histomorphometric evaluation of the feasibility of transferring this branch to the SSN and LPN was made. Lastly, the effectiveness of the LSN-LPN transfer was evaluated among 10 patients by quantifying their arm adduction strength.

Results: The LSN was identified in 95% of the cadaveric specimens. A direct coaptation of the LSN and SSN was possible in 45% of the specimens (n = 9) but not between the LSN and LPN in any of the specimens. Comparison of axonal counts among the three nerves did not show any significant difference. Good results from reinnervation of the major pectoral muscle (Medical Research Council grade ≥ 3) were observed in 70% (n = 7) of the patients who had undergone LSN to LPN transfer.

Conclusions: The LSN is consistently identified through a supraclavicular approach to the brachial plexus, and its transfer to supply the functions of the SSN and LPN is anatomically viable. Good results from an LSN-LPN transfer are observed in most patients, even if long nerve grafts need to be used.
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http://dx.doi.org/10.3171/2020.8.JNS201216DOI Listing
January 2021

Dural-based lesions: is it a meningioma?

Neuroradiology 2021 Jan 18. Epub 2021 Jan 18.

Division of Neurological Surgery, Universidade de Sao Paulo, Rua Dr Eneas de Carvalho Aguiar, 255, São Paulo, Brazil.

Purpose: Meningiomas are the most common extra-axial intracranial neoplasms with typical radiological findings. In approximately 2% of cases, histopathological reports reveal different neoplasms or non-neoplastic lesions that can closely mimic meningiomas. We describe radiological features of meningioma mimics highlighting imaging red flags to consider a differential diagnosis.

Methods: A total of 348 lesions with radiological diagnosis of meningiomas which underwent to surgical treatment or biopsy between December of 2000 and September of 2014 were analyzed. We determined imaging features that are not a typical finding of meningiomas, suggesting other lesions. The following imaging characteristics were evaluated on CT and MRI: (a) bone erosion; (b) hyperintensity on T2WI; (c) hypointensity on T2WI; (d) bone destruction; (e) dural tail; (f) leptomeningeal involvement; (g) pattern of contrast enhancement; (h) dural displacement sign.

Results: We have a relatively high prevalence of meningioma mimics (7.2%). Dural-based lesions with homogeneous contrast enhancement (52%) are easily misdiagnosed as meningiomas. Most lesions mimic convexity (37.5%) or parafalcine (21.9%) meningiomas. We have determined five imaging red flags that can alert radiologists to consider meningioma mimics: (1) bone erosion (22.2%); (2) dural displacement sign (36%); (3) marked T2 hypointensity (32%); (4) marked T2 hyperintensity (12%); (5) absence of dural tail (48%). The most common mimic lesion in our series was hemangiopericytomas, followed by lymphomas and schwannomas.

Conclusion: The prevalence of meningioma mimics is not negligible. It is important to have awareness on main radiological findings suggestive of differential diagnosis due to a wide range of differentials which lead to different prognosis and treatment strategies.
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http://dx.doi.org/10.1007/s00234-021-02632-yDOI Listing
January 2021

Routine postoperative computed tomography scan after craniotomy: systematic review and evidence-based recommendations.

Neurosurg Rev 2021 Jan 15. Epub 2021 Jan 15.

Division of Neurosurgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Av. Dr. Eneas de Carvalho Aguiar, 255, Sao Paulo, Brazil.

Over the last few years, the role of early postoperative computed tomography (EPOCT) after cranial surgery has been repeatedly questioned, but there is yet no consensus on the practice. We conducted a systematic review to address the usefulness of EPOCT in association with neurological examination after elective craniotomies compared to the neurological examination alone. Studies were eligible if they provided information about the number of patients scanned, how many were asymptomatic or presented neurological deterioration before the scan and how many of each of those groups had their management changed due to imaging findings. CTs had to be performed in the first 48 h following surgery to be considered early. Eight studies were included. The retrospective studies enrolled a total of 3639 patients, with 3737 imaging examinations. Out of the 3696 CT scans performed in asymptomatic patients, less than 0.8% prompted an intervention, while 100% of patients with neurological deterioration were submitted to emergency surgery. Positive predictive values of altered scans were 0.584 for symptomatic patients and 0.125 for the asymptomatic. The number of altered scans necessary to predict (NNP) one change in management for the asymptomatic patients was 8, while for the clinically evident cases, it was 1.71. The number of scans needed to diagnose one clinically silent alteration is 134.75, and postoperative imaging of neurologically intact patients is 132 times less likely to issue an emergency intervention than an altered neurological examination alone. EPOCT following elective craniotomy in neurologically preserved patients is not supported by current evidence, and CT scanning should be performed only in particular conditions. The authors have developed an algorithm to help the judgment of each patient by the surgeon in a resource-limited context.
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http://dx.doi.org/10.1007/s10143-021-01473-wDOI Listing
January 2021

Increased Anxiety-Like Behavior in the Acute Phase of a Preclinical Model of Periodontal Disease.

Front Neurol 2020 22;11:598851. Epub 2020 Dec 22.

Dental Team, and Dental Research Group on Pain and Mental Health of Institute of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil.

Periodontal disease (PD) is an infectious-inflammatory oral disease that is highly prevalent among adolescence and adulthood and can lead to chronic orofacial pain and be associated with anxiety, stress and depression. This study aimed to identify anxiety-like behaviors in the ligature-induced murine preclinical model of PD in different phases of the disease (i.e., acute vs. chronic). Also, we investigated orofacial mechanical allodynia thresholds and superficial cortical plasticity along the orofacial motor cortex in both disease phases. To this aim, 25 male Wistar rats were randomly allocated in acute (14 days) or chronic (28 days) ligature-induced-PD groups and further divided into active-PD or sham-PD. Anxiety-like behavior was evaluated using the elevated plus maze, mechanical allodynia assessed using the von Frey filaments test and superficial motor cortex mapping was performed with electrical transdural stimulation. We observed increased anxiety-like behavior in active-PD animals in the acute phase, characterized by decreased number of entries into the open arm extremities [ = 2.42, = 0.04], and reduced time spent in the open arms [ = 3.56, = 0.01] and in the open arm extremities [ = 2.75, = 0.03]. There was also a reduction in the mechanical allodynia threshold in all active-PD animals [Acute: = 8.81, < 0.001; Chronic: = 60.0, < 0.001], that was positively correlated with anxiety-like behaviors in the acute group. No differences were observed in motor cortex mapping. Thus, our findings show the presence of anxiety-like behaviors in the acute phase of PD making this a suitable model to study the impact of anxiety in treatment response and treatment efficacy.
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http://dx.doi.org/10.3389/fneur.2020.598851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782965PMC
December 2020

Clinical outcome assessments of motor status in patients undergoing brain tumor surgery.

Clin Neurol Neurosurg 2021 Feb 13;201:106420. Epub 2020 Dec 13.

Division of Neurosurgery, LIM-62, Department of Neurology, University of Sao Paulo Medical School, Sao Paulo, 01246-903, Brazil; Hospital Samaritano Paulista, Sao Paulo, 01333-030, Brazil.

Introduction: Clinical outcome assessment (COA) is an important instrument for testing the effectiveness of treatments and for supporting healthcare professionals on decision-making. This review aims to assess the use of COAs, and the evaluation time points of motor status in patients with brain tumor (BT) undergoing surgery.

Methods: We performed a scoping review through MEDLINE, EMBASE, and LILACS databases, looking for original studies in primary or secondary BT, having motor function status as the primary outcome.

Exclusion Criteria: mixed sample, BT recurrence, and an unspecific description of motor deficits evaluation.

Results: Nine studies met the eligibility criteria. There were 449 patients assessed. A total of 18 scales evaluated these BT patients, 12 performance outcomes measures (PerfO) tested motor function. Four scales were the clinician-reported outcome measures (ClinRO) found in this review, two assessed performance status, and two rated ambulation. Two patient-reported outcome measures (PRO) appraised functionality.

Conclusions: A variety of instruments were used to assess BT patients. Rehabilitation studies are more likely to associate the use of PerfO and PRO concerning motor and functional status. The use of specific validated scales to the BT population was rare. The lack of a standardized approach hampers the quality of BT patient's assessment.
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http://dx.doi.org/10.1016/j.clineuro.2020.106420DOI Listing
February 2021

Association between craniofacial pain complaints, somatoform symptoms and chronic diseases.

Arch Oral Biol 2021 Feb 29;122:104892. Epub 2020 Aug 29.

Chairman of Neurosurgery, Neurology Department, Medical School, University of São Paulo, Brazil.

Objective: This case-control study aimed to investigate associations between craniofacial pain complaints, somatoform symptoms and chronic diseases.

Design: 306 subjects were included in this study (174 patients and 132 healthy subjects). The evaluation consisted of demographic data, number of functional and nonfunctional chronic diseases, medications, somatoform symptoms (xerostomia, dry mucosa, numbness, gastrointestinal complaints), and pain complaints with associated characteristics (number of pain areas, sensation of tired face, bruxism, sleep disturbances, masticatory musculoskeletal evaluation). Statistical analysis included descriptive data, tested with chi-square, Fisher's exact, nonparametric Kolmogorov-Smirnoff, Student's t-test, Pearson's coefficient, two-steps cluster classification, multivariate linear and LASSO regressions.

Results: Functional disorders were prevalent in 111 (63.8 %) patients with facial pain. They were taking more medication (p < 0.001) and had more sleep disturbances (p < 0.001), higher xerostomia scores (p < 0.001) and more gastrointestinal complaints (p < 0.001) than controls. There was a positive correlation between the functional score and the number of cranial areas with headache (R = 0.266, <0.001). The regression models for facial pain (R = 0.632), craniofacial pain (R = 0.623) and headache (R = 0.252) showed significant dependency of functional disorders (p < 0.001).

Conclusion: craniofacial pain was associated with functional diseases and somatoform symptoms. This association needs further investigation to understand the role of those disorders in craniofacial pain, considering that pain complaints are common somatoform and functional symptoms.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104892DOI Listing
February 2021

The Effects of Repetitive Transcranial Magnetic Stimulation on Anxiety in Patients With Moderate to Severe Traumatic Brain Injury: A Analysis of a Randomized Clinical Trial.

Front Neurol 2020 4;11:564940. Epub 2020 Dec 4.

Department of Neurology, University of São Paulo, São Paulo, Brazil.

Traumatic brain injury (TBI) is one of the leading causes of neuropsychiatric disorders in young adults. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to improve psychiatric symptoms in other neurologic disorders, such as focal epilepsy, Parkinson's disease, and fibromyalgia. However, the efficacy of rTMS as a treatment for anxiety in persons with TBI has never been investigated. This exploratory analyzes the effects of rTMS on anxiety, depression and executive function in participants with moderate to severe chronic TBI. Thirty-six participants with moderate to severe TBI and anxiety symptoms were randomly assigned to an active or sham rTMS condition in a 1:1 ratio. A 10-session protocol was used with 10-Hz rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) for 20 min each session, a total of 2,000 pulses were applied at each daily session (40 stimuli/train, 50 trains). Anxiety symptoms; depression and executive function were analyzed at baseline, after the last rTMS session, and 90 days post intervention. Twenty-seven participants completed the entire protocol and were included in the - analysis. Statistical analysis showed no interaction of group and time ( > 0.05) on anxiety scores. Both groups improved depressive and executive functions over time, without time and group interaction ( < 0.05). No adverse effects were reported in either intervention group. rTMS did not improve anxiety symptoms following high frequency rTMS in persons with moderate to severe TBI. www.ClinicalTrials.gov, identifier: NCT02167971.
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http://dx.doi.org/10.3389/fneur.2020.564940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746857PMC
December 2020

Pharmacological treatment of central neuropathic pain: consensus of the Brazilian Academy of Neurology.

Arq Neuropsiquiatr 2020 14;78(11):741-752. Epub 2020 Dec 14.

Universidade de São Paulo, Faculdade de Medicina, Centro de Dor, Departamento de Neurologia, São Paulo SP, Brazil.

Background: Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions.

Objective: To develop recommendations for the treatment of CNP in Brazil.

Methods: Systematic review, meta-analysis, and specialists opinions considering efficacy, adverse events profile, cost, and drug availability in public health.

Results: Forty-four studies on CNP treatment were found, 20 were included in the qualitative analysis, and 15 in the quantitative analysis. Medications were classified as first-, second-, and third-line treatment based on systematic review, meta-analysis, and expert opinion. As first-line treatment, gabapentin, duloxetine, and tricyclic antidepressants were included. As second-line, venlafaxine, pregabalin for CND secondary to spinal cord injury, lamotrigine for CNP after stroke, and, in association with first-line drugs, weak opioids, in particular tramadol. For refractory patients, strong opioids (methadone and oxycodone), cannabidiol/delta-9-tetrahydrocannabinol, were classified as third-line of treatment, in combination with first or second-line drugs and, for central nervous system (CNS) in multiple sclerosis, dronabinol.

Conclusions: Studies that address the treatment of CNS are scarce and heterogeneous, and a significant part of the recommendations is based on experts opinions. The CNP approach must be individualized, taking into account the availability of medication, the profile of adverse effects, including addiction risk, and patients' comorbidities.
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http://dx.doi.org/10.1590/0004-282X20200166DOI Listing
December 2020

Dentate nucleus stimulation for essential tremor.

Parkinsonism Relat Disord 2021 Jan 3;82:121-122. Epub 2020 Dec 3.

Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.parkreldis.2020.12.001DOI Listing
January 2021

Little Brain, Big Expectations.

Brain Sci 2020 12 7;10(12). Epub 2020 Dec 7.

Functional Neurosurgery Division, Department of Neurology, School of Medicine, University of São Paulo, 01000-000 São Paulo, Brazil.

The cerebellum has been implicated in the mechanisms of several movement disorders. With the recent reports of successful modulation of its functioning, this highly connected structure has emerged as a promising way to provide symptomatic relief not yet obtained by usual treatments. Here we review the most relevant papers published to date, the limitations and gaps in literature, discuss why several papers have failed in showing efficacy, and present a new way of stimulating the cerebellum. References for this critique review were identified by searches on PubMed for the terms "Parkinson's disease", "ataxia", "dystonia", "tremor", and "dyskinesias" in combination with the type of stimulation and the stimulation site. Studies conducted thus far have shed light on the potential of cerebellar neuromodulation for attenuating symptoms in patients with some forms of isolated and combined dystonia, dyskinesia in Parkinson's disease, and neurodegenerative ataxia. However, there is still a high heterogeneity of results and uncertainty about the possibility of maintaining long-term benefits. Because of the complicated architecture of the cerebellum, the modulation techniques employed may have to focus on targeting the activity of the cerebellar nuclei rather than the cerebellar cortex. Measures of cerebellar activity may reduce the variability in outcomes.
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http://dx.doi.org/10.3390/brainsci10120944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762222PMC
December 2020

Surgical treatment of spontaneous intracranial hemorrhage in patients with cancer: Analysis of prognostic factors.

J Clin Neurosci 2021 Jan 3;83:140-145. Epub 2020 Dec 3.

Division of Neurosurgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil. Electronic address:

Background: Intracranial hemorrhage (ICH) is the most common cerebrovascular event in patients with cancer. We sought to evaluate the outcomes of surgical treatment for ICH and to determine possible pre-operative outcome predictors.

Methods: We retrospectively reviewed surgical procedures for the treatment of ICH in patients with cancer. Analysis included clinical and radiological findings of the patients. Primary endpoints were survival and mortality in index hospitalization.

Results: Ninety-four emergency neurosurgeries were performed for ICH in 88 different patients with cancer over ten years. 51 patients had chronic subdural hematomas (CSDH: 54.3%), 35 with intraparenchymal hemorrhage (37.2%), 6 with acute subdural hematoma (ASDH: 6.4%), and only 2 with epidural hemorrhages (2.1%). Median patient follow-up was 63 days (IQR = 482.2). 71 patients (75.5%) died at follow-up, with a median survival of 33 days. Overall 30-day mortality was 38.3%; 27.5% for patients with CSDH. Lower survival was associated to higher absolute leucocyte count (HR 1.06; 95%CI 1.04-1.09), higher aPTT ratio (HR 3.02; 95% CI 1.01-9.08), higher serum CRP (HR 1.01; 95%CI 1.01-1.01), and unresponsive pupils (each unresponsive pupil - HR 2.65; 95%CI 1.50-4.68).

Conclusion: Outcomes following surgical treatment of ICH in patients with cancer impose significant morbidity and mortality. Type of hematoma, altered pupillary reflexes, coagulopathies, and increased inflammatory response were predictors of mortality for any type of ICH.
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http://dx.doi.org/10.1016/j.jocn.2020.11.002DOI Listing
January 2021

C-Reactive Protein Levels Are Higher in Patients With Fusiform Intracranial Aneurysms: A Case-Control Study.

World Neurosurg 2021 Feb 3;146:e896-e901. Epub 2020 Dec 3.

Division of Neurosurgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Electronic address:

Background: Comprehending the risk factors that contribute to the formation of fusiform aneurysms (FAs) might provide some insight into treatment and prevention strategies. This case-control study aimed to compare the levels of serum C-reactive protein (CRP), as a biomarker, between patients with fusiform and saccular intracranial aneurysms.

Methods: We retrospectively analyzed medical records from 2010 to 2019. Thirty-five patients were identified as having FAs: 13 (37.1%) were ruptured, and 22 were unruptured. An age-matched sample of 70 controls (2:1) with saccular aneurysms was obtained from the same records: 36 (51.4%) ruptured and 34 unruptured.

Results: Patients with FAs had median CRP values of 0.61 mg/dL (IQR: 1.5), compared with 0.29 mg/dL (IQR: 0.42) in controls (P < 0.01). Within both the ruptured and the unruptured group, median CRP was higher in patients with FAs compared with controls (P < 0.01). Diabetes, smoking status, hypertension, and sex did not significantly influence CRP levels. Age-adjusted analyses showed that fusiform morphology was independently associated with higher CRP levels for unruptured aneurysms (OR 1.2, 95% CI 1.05-1.43), but not for ruptured aneurysms (OR 1.02, 95%CI 0.99-1.05).

Conclusions: CRP was higher in patients with FAs than controls, and it constituted an independent predictor of fusiform morphology for patients with unruptured aneurysms. Inflammation might be an especially important factor in FA formation and growth, and further studies could use this finding to design new treatment strategies.
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http://dx.doi.org/10.1016/j.wneu.2020.11.042DOI Listing
February 2021

Transcutaneous magnetic spinal cord stimulation for freezing of gait in Parkinson's disease.

J Clin Neurosci 2020 Nov 20;81:306-309. Epub 2020 Oct 20.

Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address:

Dopaminergic drugs partially alleviate gait problems in Parkinson's disease, but the effects are not sustained in the long-term. Particularly, the freezing of gait directly impacts patients' quality of life. Experimental epidural spinal cord stimulation (SCS) studies have suggested positive effects on locomotion among PD patients, but the effects of non-invasive stimulation have never been explored. Here, we investigated in a prospective, open-label, pilot study the efficacy and safety of non-invasive magnetic stimulation of the spinal cord in five patients with PD who experienced gait problems, including freezing of gait. A trial of transcutaneous magnetic SCS was performed at the level of the fifth thoracic vertebra. The primary outcome was the change in freezing of gait 7 days after stimulation. Secondary outcome measures included changes in gait speed and UPDRS part III. After non-invasive spinal cord stimulation, patients experienced a 22% improvement in freezing of gait (p = 0.040) and 17.4% improvement in the UPDRS part III (p = 0.042). Timed up and go times improved by 48.2%, although this did not reach statistical significance (p = 0.06). Patients' global impression of change was 'much improved' for four patients. Improvement in gait after stimulation was reversible, since it returned to baseline scores 4 weeks after stimulation. No severe side effects were recorded. This pilot study suggests that transcutaneous magnetic spinal cord stimulation is feasible and can potentially improve gait problems in PD, without severe adverse effects. Large scale phase II trials are needed to test this hypothesis.
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http://dx.doi.org/10.1016/j.jocn.2020.10.001DOI Listing
November 2020

Comparison of surgical and endovascular treatments for fusiform intracranial aneurysms: systematic review and individual patient data meta-analysis.

Neurosurg Rev 2020 Nov 17. Epub 2020 Nov 17.

Department of Neurology, Division of Neurosurgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Fusiform intracranial aneurysms (FIA) are associated with significant morbidity and mortality. We carried out a systematic review and meta-analysis of individual participant data with propensity score adjustment to compare the functional and angiographic outcomes between surgical and endovascular approaches to FIA. We conducted a systematic review for articles on the treatment of FIA with individual patient-level detailing. Data from patients treated for FIA in our institution from 2010 to 2018 were also collected. The primary studied outcome was morbidity, and secondary outcomes were angiographic results and retreatment. Propensity score-adjusted mixed-effects logistic regression models evaluated treatment options, stratified by anatomical location. Compiling original and published data, there were 312 cases, of which 79 (25.3%) had open surgery, and 233 (74.5%) were treated with endovascular procedures. There were no differences between treatment groups, for neither cavernous ICA (OR 1.04, 95% CI 0.05-23.6) nor supraclinoid aneurysms (OR 7.82, 95% CI 0.65-94.4). Both size (OR 1.11, 95% CI 1.03-1.19) and initial mRS (OR 2.0, 95% CI 1.2-3.3) were risk factors for morbidity, independent of location. Neither age nor rupture status influenced the odds of posterior morbidity. Unfavorable angiographic outcomes were more common in the endovascular group for supraclinoid and vertebrobasilar aneurysms (χ, P < 0.01). There were no differences between morbidity of surgical and endovascular treatments for FIA, regardless of aneurysm location. Size and initial mRS were correlated with functional outcomes, whereas age and rupture status were not. Microsurgery seems to yield better long-term angiographic results compared to endovascular procedures.
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http://dx.doi.org/10.1007/s10143-020-01440-xDOI Listing
November 2020

Laser interstitial thermal therapy as an adjunct therapy in brain tumors: A meta-analysis and comparison with stereotactic radiotherapy.

Surg Neurol Int 2020 29;11:360. Epub 2020 Oct 29.

Institute of Neurology, University of São Paulo, São Paulo, Brazil.

Background: Minimally invasive procedures are gaining widespread acceptance in difficult-to-access brain tumor treatment. Stereotactic radiosurgery (SRS) is the preferred choice, however, laser interstitial thermal therapy (LITT) has emerged as a tumor cytoreduction technique. The present meta-analysis compared current SRS therapy with LITT in brain tumors.

Methods: A search was performed in Lilacs, PubMed, and Cochrane database. Patient's demographics, tumor location, therapy used, Karnofsky performance status score before treatment, and patient's outcome (median overall survival, progression-free survival, and adverse events) data were extracted from studies. The risk of bias was assessed by Cochrane collaboration tool.

Results: Twenty-five studies were included in this meta-analysis. LITT and SRS MOS in brain metastasis patients were 12.8 months' versus 9.8 months (ranges 9.3-16.3 and 8.3-9.8; = 0.02), respectively. In a combined comparison of adverse effects among LITT versus SRS in brain metastasis, we found 15% reduction in absolute risk difference (-0.16; 95% confidence interval < 0.0001).

Conclusion: We could not state that LITT treatment is an optimal alternative therapy for difficult-to-access brain tumors due to the lack of systematic data that were reported in our pooled studies. However, our results identified a positive effect in lowering the absolute risk of adverse events compared with SRS therapy. Therefore, randomized trials are encouraged to ascertain LITT role, as upfront or postoperative/post-SRS therapy for brain tumor treatment.
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http://dx.doi.org/10.25259/SNI_152_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656052PMC
October 2020

Cavernous carotid aneurysms do not influence the occurrence of upstream ipsilateral aneurysm.

Br J Neurosurg 2020 Nov 10:1-3. Epub 2020 Nov 10.

Division of Neurological Surgery, Hospital das Clinicas, University of São Paulo Medical School, Sao Paulo, Brazil.

Objective: Cavernous carotid aneurysms (CCA) comprehend around 5% of all intracranial aneurysms. The main risk factors for an intracranial aneurysm seem not to influence the incidence of CCAs. The aim of this study was to investigate the association of CCAs and the presence of upstream aneurysms.

Methods: 1403 patients, admitted in Hospital das Clinicas de São Paulo, Brazil, from September 2009 to August 2018, enrolled this study. Diagnosis was performed with Digital Subtraction Angiography (DSA). Upstream aneurysm was defined as an intracranial aneurysm on anterior cerebral circulation, ipsilateral to the CCA (if present) or crossing the midline (e.g. anterior communicating artery).

Results: 177 individuals were diagnosed with CCA (12.6% of the population), totalizing 225 aneurysms (10% of the total number of aneurysms, 2253). No association was found between CCA and UA ( .090, OR: 1.323, 95% CI: 0.957-1.828). Studying only patients with CCA, multivariable analysis showed smoking as the only factor associated with UA ( .010, OR: 0.436, 95% CI: 0.232-0.821).

Conclusions: Cavernous carotid aneurysms were present in 12% of our population, mostly in female. They seem to be independent of the modifiable risk factors already associated with intracranial aneurysms. A higher frequency of mirror aneurysms was seen in this location. CCA did not influence the presence of ipsilateral and anterior circulation aneurysms.
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http://dx.doi.org/10.1080/02688697.2020.1820950DOI Listing
November 2020

Multiple and mirror intracranial aneurysms: study of prevalence and associated risk factors.

Br J Neurosurg 2020 Nov 9:1-5. Epub 2020 Nov 9.

Division of Neurological Surgery, Hospital das Clinicas, University of São Paulo Medical School, Sao Paulo, Brazil.

Objective: Multiple intracranial aneurysms (MIA) account for 30% of all intracranial aneurysms, while mirror aneurysms, a subgroup of MIA, are present in 5% of all patients with cerebral aneurysms. We investigated the risk factors associated with the presence of multiple and mirror intracranial aneurysms.

Methods: 1404 patients, 314 males (22.4%) and 1090 female (77.6%) were enrolled for this study. Diagnosis was performed with a digital subtraction angiography (DSA). Multiplicity was defined as the presence of two or more aneurysms and mirror aneurysms as one pair of aneurysms involving bilateral corresponding arteries. Patients were followed-up from September 2009 till August 2018. Individuals' characteristics such as sex, age, smoking, hypertension and use of contraceptives were evaluated.

Results: Five hundred and twelve patients (36.4%) were diagnosed with MIA, approximately 4%/year. We observed 203 pairs of mirror aneurysms, accounting for 406 aneurysms (13% of the population). There was an increased frequency of females with multiple () and mirror aneurysms (636). Smoking was associated with multiplicity (), as well as advanced age (), but there was no significant relation with presence of mirror aneurysms. We observed higher frequency of baby aneurysms (<3mm) in the group of patients with MIA, while giant aneurysms (>25 mm) were most found in patients with only one aneurysm (). No differences between patients who used contraceptives against patients who did not use were found ().

Conclusions: Gender and smoking, known risk factors to the development of a single intracranial aneurysm, are proportionally increased in patients with MIA. Hypertension and oral contraceptives were not associated with multiplicity.
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http://dx.doi.org/10.1080/02688697.2020.1817849DOI Listing
November 2020

Anatomic, qualitative, and quantitative evaluation of the variants of the infratentorial supracerebellar approach to the posteroinferior thalamus.

Neurosurg Rev 2020 Oct 24. Epub 2020 Oct 24.

Division of Neurosurgery, University of São Paulo Medical School, Dr. Enéas de Carvalho Aguiar Ave., R. 5083, Number 255, São Paulo, 05403-000, Brazil.

The posteroinferior region of the thalamus is formed by the pulvinar, and it is surgically accessed through the infratentorial supracerebellar approach, between the midline and the retromastoid region. This study aimed to compare the paramedian, lateral, extreme lateral, and contralateral paramedian corridors with the posteroinferior thalamus through a suboccipital craniotomy and an infratentorial supracerebellar access. Ten cadavers were studied, and the microsurgical dissections were accompanied by the measurement of the variables using a neuronavigation system. Statistical analysis was performed using analysis of variance (ANOVA). The distance between the access midpoint at the cranial surface and pulvinar varied between 53.3 and 53.9 mm, the contralateral access being an exception (59.9 mm). The vertical angle ranged from 20.6° in the contralateral access to 23.5° in the lateral access. There was a gradual increase in the horizontal angle between the paramedian (17.4°), lateral (31.3°), and extreme lateral (43.7°) accesses. But, this angle in the contralateral access was 14.6°, similar to that of the paramedian access. The exposed area of the thalamus was 125.1 mm in the paramedian access, 141.8 mm in the lateral access, and 165.9 mm in the extreme lateral access, which was similar to that of the contralateral access (164.9 mm). The horizontal view angle increased with lateralization of the access, which facilitated microscopic visualization. With regard to the exposure of the microsurgical anatomy, the extreme lateral and contralateral accesses circumvent the neural and vascular obstacles at the midline, allowing a larger area of anatomical exposure.
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http://dx.doi.org/10.1007/s10143-020-01405-0DOI Listing
October 2020

Biomarkers for traumatic brain injury: a short review.

Neurosurg Rev 2020 Oct 19. Epub 2020 Oct 19.

Division of Neurosurgery, University of São Paulo, São Paulo, Brazil.

Cellular response to TBI is a mixture of excitotoxicity, neuroinflammation, and cell death. Biomarkers that can track these lesions and inflammatory processes are being explored for their potential to provide objective measures in the evaluation of TBI, from prehospital care to rehabilitation. By understanding the pathways involved, we could be able to improve diagnostic accuracy, guide management, and prevent long-term disability. We listed some of the recent advances in this translational, intriguing, fast-growing field. Although the knowledge gaps are still significant, some markers are showing promising results and could be helping patients in the near future.
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http://dx.doi.org/10.1007/s10143-020-01421-0DOI Listing
October 2020

Deep brain stimulation treatment in dystonia: a bibliometric analysis.

Arq Neuropsiquiatr 2020 09;78(9):586-592

Universidade de São Paulo, Departamento de Neurologia, Centro de Distúrbios do Movimento, São Paulo SP, Brazil.

Background: Dystonia is a heterogeneous disorder that, when refractory to medical treatment, may have a favorable response to deep brain stimulation (DBS). A practical way to have an overview of a research domain is through a bibliometric analysis, as it makes it more accessible for researchers and others outside the field to have an idea of its directions and needs.

Objective: To analyze the 100 most cited articles in the use of DBS for dystonia treatment in the last 30 years.

Methods: The research protocol was performed in June 2019 in Elsevier's Scopus database, by retrieving the most cited articles regarding DBS in dystonia. We analyzed authors, year of publication, country, affiliation, and targets of DBS.

Results: Articles are mainly published in Movement Disorders (19%), Journal of Neurosurgery (9%), and Neurology (9%). European countries offer significant contributions (57% of our sample). France (192.5 citations/paper) and Germany (144.1 citations/paper) have the highest citation rates of all countries. The United States contributes with 31% of the articles, with 129.8 citations/paper. The publications are focused on General outcomes (46%), followed by Long-term outcomes (12.5%), and Complications (11%), and the leading type of dystonia researched is idiopathic or inherited, isolated, segmental or generalized dystonia, with 27% of articles and 204.3 citations/paper.

Conclusions: DBS in dystonia research is mainly published in a handful of scientific journals and focused on the outcomes of the surgery in idiopathic or inherited, isolated, segmental or generalized dystonia, and with globus pallidus internus as the main DBS target.
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http://dx.doi.org/10.1590/0004-282X20200016DOI Listing
September 2020

Assessment of hemorrhagic onset on meningiomas: Systematic review.

Clin Neurol Neurosurg 2020 Dec 22;199:106175. Epub 2020 Sep 22.

Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo, SP, Brazil.

Objective: To review the data published on the subject to create a more comprehensive natural history of the haemorrhagic onset of meningiomas (IVMs).

Patients And Methods: A Medline search up to June 2020, using the search term "bleeding meningioma," returned 136 papers. As a first selection step, we adopted the following inclusion criteria: series and case reports about bleeding meningioma. Papers written in other languages but with abstracts written in English were also evaluated.

Results: A total of 190 tumours were evaluated, specifically 109 tumours from female patients and 81 tumours from male patients with a ratio of 1.34 female to 1.0 male (mean age of 54.86 ± 16.1years old). The majority were located in the convexity (129-67.9 %). Among the 190 tumours evaluated, 171 patients (90 %) presented with GI tumours, with a predominance of the meningothelial subtype (32.6 %). Nine patients (4.7 %) presented with grade GII tumours, and 10 (5.3 %) presented with GIII tumours. The most prevalent type was intracerebral haemorrhage (ICH) at 50 %, followed by subdural at 27.36 %; the mortality rate was 13.1 % (25 deaths), the distribution of both location (prevalence of convexity: 18-72 %) and histopathology (grade 1: 22-88 %).

Conclusion: These tumours follow the histopathological distribution of meningiomas, in general. The age distribution shows prevalence among the adult population but with a greater proportion in the elderly. The fact that the overwhelming majority of cases involve meningiomas with a benign histological subtype is noteworthy. Another relevant factor observed is that most reports are from Asian origin.
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http://dx.doi.org/10.1016/j.clineuro.2020.106175DOI Listing
December 2020