Focused Ultrasound Thalamotomy Sensory Side Effects Follow the Thalamic Structural Homonculus

2020 ◽  
pp. 10.1212/CPJ.0000000000001013
Author(s):  
Michelle Paff ◽  
Alexandre Boutet ◽  
Jürgen Germann ◽  
Gavin J. B. Elias ◽  
Clement T. Chow ◽  
...  
Keyword(s):  
Side Effects ◽  
Functional Connectivity ◽  
Adverse Effects ◽  
Focused Ultrasound ◽  
Univariate Analysis ◽  
Spatial Relationship ◽  
Significant Risk ◽  
Region Of Interest ◽  
Medial Lemniscus ◽  
Sensory Nucleus

AbstractIntroduction:Focused ultrasound thalamotomy is an effective treatment for tremor, however, side effects may occur. The purpose of the present study was to investigate the spatial relationship between thalamotomies and specific sensory side effects as well as their functional connectivity with somatosensory cortex and relationship to the medial lemniscus (ML).Methods:Sensory adverse effects were categorized into four groups based on the location of the disturbance: face/mouth/tongue numbness/paresthesia, hand-only paresthesia, hemi-body/limb paresthesia, and dysgeusia. Then, areas of significant risk (ASR) for each category were defined using voxel-wise mass univariate analysis and overlaid on corresponding odds ratio maps. The ASR area associated with the maximum risk was used as a region-of-interest in a normative functional connectome to determine side-effect specific functional connectivity. Finally, each ASR was overlaid on the medial lemniscus derived from normative template.Results:Of 103 patients, 17 developed sensory side effects after thalamotomy persisting 3 months after the procedures. Lesions producing sensory side effects extended posteriorly into the principle sensory nucleus of the thalamus or below the thalamus in the ML. The topography of sensory adverse effects followed the know somatotopy of the ML and the sensory nucleus. Functional connectivity patterns between each sensory-specific thalamic seed and the primary somatosensory areas supported the role of the middle insula in processing of gustatory information and in multisensory integration.Discussion:Distinct regions in the sensory thalamus and its afferent connections rise to specific sensory disturbances. These findings demonstrate the relationship between the sensory thalamus, ML, and bilateral sensory cortical areas.

Multimodal MRI for MRgFUS in essential tremor: post-treatment radiological markers of clinical outcome

2020 ◽  
Vol 91 (9) ◽  
pp. 921-927
Author(s):  
Anish N Kapadia ◽  
Gavin J B Elias ◽  
Alexandre Boutet ◽  
Jürgen Germann ◽  
Aditiya Pancholi ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Clinical Outcome ◽  
Essential Tremor ◽  
Focused Ultrasound ◽  
Lesion Size ◽  
Post Treatment ◽  
Medial Lemniscus ◽  
Invasive Treatment ◽  
Tremor Suppression ◽  
Registration Number

BackgroundMRI-guided focused ultrasound (MRgFUS) thalamotomy is a promising non-invasive treatment option for medication-resistant essential tremor. However, it has been associated with variable efficacy and a relatively high incidence of adverse effects.ObjectivesTo assess the evolution of radiological findings after MRgFUS thalamotomy and to evaluate their significance for clinical outcomes.MethodsNinety-four patients who underwent MRgFUS between 2012 and 2017 were retrospectively evaluated. Lesion characteristics were assessed on routine MRI sequences, as well as with tractography. Relationships between imaging appearance, extent of white matter tract lesioning (59/94, on a 4-point scale) and clinical outcome were investigated. Recurrence was defined as >33% loss of tremor suppression at 3 months relative to day 7.ResultsAcute lesions demonstrated blood products, surrounding oedema and peripheral diffusion restriction. The extent of dentatorubrothalamic tract (DRTT) lesioning was significantly associated with clinical improvement at 1 year (t=4.32, p=0.001). Lesion size decreased over time (180.8±91.5 mm3 at day 1 vs 19.5±19.3 mm3 at 1-year post-treatment). Higher post-treatment oedema (t=3.59, p<0.001) was associated with larger lesions at 3 months. Patients with larger lesions at day 1 demonstrated reduced rates of tremor recurrence (t=2.67, p=0.019); however, lesions over 170 mm3 trended towards greater incidence of adverse effects (sensitivity=0.60, specificity=0.63). Lesion encroachment on the medial lemniscus (Sn=1.00, Sp=0.32) and pyramidal tract (Sn=1.00, Sp=0.12) were also associated with increased adverse effects incidence.ConclusionLesion size at day 1 predicts symptom recurrence, with fewer recurrences seen with larger lesions. Greater DRTT lesioning is associated with treatment efficacy. These findings may have implications for lesion targeting and extent.Trial registration numberNCT02252380.

scholarly journals Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor

Brain ◽  
2018 ◽  
Vol 141 (12) ◽  
pp. 3405-3414 ◽  
Author(s):  
Alexandre Boutet ◽  
Manish Ranjan ◽  
Jidan Zhong ◽  
Jurgen Germann ◽  
David Xu ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Essential Tremor ◽  
Diffusion Weighted Imaging ◽  
Focused Ultrasound ◽  
Medial Lemniscus ◽  
Intermediate Nucleus ◽  
Diffusion Weighted ◽  
Increased Risk ◽  
Clinical Benefits ◽  
Ventral Intermediate Nucleus

Abstract Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

Tractography-based targeting of the ventral intermediate nucleus: accuracy and clinical utility in MRgFUS thalamotomy

2020 ◽  
Vol 133 (4) ◽  
pp. 1002-1009 ◽  
Author(s):  
Manish Ranjan ◽  
Gavin J. B. Elias ◽  
Alexandre Boutet ◽  
Jidan Zhong ◽  
Powell Chu ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Clinical Utility ◽  
Focused Ultrasound ◽  
Patient Specific ◽  
Medial Lemniscus ◽  
Intermediate Nucleus ◽  
Increased Risk ◽  
Indirect Treatment ◽  
Ventral Intermediate Nucleus ◽  
Selection Of

OBJECTIVETractography-based targeting of the thalamic ventral intermediate nucleus (T-VIM) is a novel method conferring patient-specific selection of VIM coordinates for tremor surgery; however, its accuracy and clinical utility in magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy compared to conventional indirect targeting has not been specifically addressed. This retrospective study sought to compare the treatment locations and potential adverse effect profiles of T-VIM with indirect targeting in a large cohort of MRgFUS thalamotomy patients.METHODST-VIM was performed using diffusion tractography outlining the pyramidal and medial lemniscus tracts in 43 MRgFUS thalamotomy patients. T-VIM coordinates were compared with the indirect treatment coordinates used in the procedure. Thalamotomy lesions were delineated on postoperative T1-weighted images and displaced (“translated”) by the anteroposterior and mediolateral difference between T-VIM and treatment coordinates. Both translated and actual lesions were normalized to standard space and subsequently overlaid with areas previously reported to be associated with an increased risk of motor and sensory adverse effects when lesioned during MRgFUS thalamotomy.RESULTST-VIM coordinates were 2.18 mm anterior and 1.82 mm medial to the “final” indirect treatment coordinates. Translated lesions lay more squarely within the boundaries of the VIM compared to nontranslated lesions and showed significantly less overlap with areas associated with sensory adverse effects. Translated lesions overlapped less with areas associated with motor adverse effects; however, this difference was not significant.CONCLUSIONST-VIM leads to the selection of more anterior and medial coordinates than the conventional indirect methods. Lesions moved toward these anteromedial coordinates avoid areas associated with an increased risk of motor and sensory adverse effects, suggesting that T-VIM may improve clinical outcomes.

The Use of Methotrexate in Rheumatoid Arthritis

1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Folic Acid ◽  
Side Effects ◽  
Adverse Effects ◽  
Systemic Administration ◽  
Refractory Disease ◽  
Controlled Clinical Trials ◽  
Folic Acid Antagonist ◽  
Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

scholarly journals Knowledge, attitude, and practice of pharmacy and medical students regarding self-medication, a study in Zabol University of Medical Sciences; Sistan and Baluchestan province in south-east of Iran

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mahmoud Hashemzaei ◽  
Mahdi Afshari ◽  
Zahra Koohkan ◽  
Ali Bazi ◽  
Ramin Rezaee ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Medical Students ◽  
Side Effects ◽  
Drug Information ◽  
Significant Risk ◽  
Disease Recurrence ◽  
Medical Sciences ◽  
Self Medication ◽  
Attitude And Practice ◽  
Knowledge Attitude And Practice

Abstract Background Self-medication is defined as using medicinal products to treat the disorders or symptoms diagnosed by oneself. Although informed self-medication is one of the ways to reduce health care costs, inappropriate self-treatment can pose various risks including drug side effects, recurrence of symptoms, drug resistance, etc. The purpose of this study was to investigate the knowledge, attitude, and practice of pharmacy and medical students toward self-medication. Methods This study was conducted in Zabol University of Medical Sciences in 2018. Overall, 170 pharmacy and medical students were included. A three-part researcher-made questionnaire was designed to address the students’ knowledge, attitude, and practice. Statistical analysis was performed in SPSS 25 software. Results According to the results, 97 (57.1%) students had carried out self-medication within the past 6 months. Overall, the students self-medicated on average 4.2 ± 2.9 times per year. Self-medication was more common in male students (65.4%, P = 0.043). Cold was the most common ailment treated with self-medication (93.2%), and antibiotics (74.4%) were the most commonly used drugs. The primary information sources used by the students were their previous prescriptions (47.4%). Pharmacy students had a higher level of drug information (P < 0.001). There was a statistically significant association between the level of drug information and the tendency for self-medication (P = 0.005). Disease recurrence was the most common negative complication of self-medication. Conclusion There is a need to educate pharmacy and medical students regarding self-medication and its side effects. The high prevalence of self-medication and the overuse of antibiotics can pose a significant risk of drug resistance.

scholarly journals Risk Factors Associated with Retinopathy of Prematurity in Very and Extremely Preterm Infants

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 420
Author(s):  
Claudia Ioana Borțea ◽  
Florina Stoica ◽  
Marioara Boia ◽  
Emil Radu Iacob ◽  
Mihai Dinu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Preterm Infants ◽  
Gestational Age ◽  
Retinopathy Of Prematurity ◽  
Univariate Analysis ◽  
Significant Risk ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Surfactant Administration ◽  
Stage 1

Background and Objectives: Retinopathy of prematurity (ROP) is the leading cause of blindness in preterm infants. We studied the relationship between different perinatal characteristics, i.e., sex; gestational age (GA); birth weight (BW); C-reactive protein (CRP) and lactate dehydrogenase (LDH) concentrations; ventilation, continuous positive airway pressure (CPAP), and surfactant administration; and the incidence of Stage 1–3 ROP. Materials and Methods: This study included 247 preterm infants with gestational age (GA) < 32 weeks that were successfully screened for ROP. Univariate and multivariate binary analyses were performed to find the most significant risk factors for ROP (Stage 1–3), while multivariate multinomial analysis was used to find the most significant risk factors for specific ROP stages, i.e., Stage 1, 2, and 3. Results: The incidence of ROP (Stage 1–3) was 66.40% (164 infants), while that of Stage 1, 2, and 3 ROP was 15.38% (38 infants), 27.53% (68 infants), and 23.48% (58 infants), respectively. Following univariate analysis, multiple perinatal characteristics, i.e., GA; BW; and ventilation, CPAP, and surfactant administration, were found to be statistically significant risk factors for ROP (p < 0.001). However, in a multivariate model using the same characteristics, only BW and ventilation were significant ROP predictors (p < 0.001 and p < 0.05, respectively). Multivariate multinomial analysis revealed that BW was only significantly correlated with Stage 2 and 3 ROP (p < 0.05 and p < 0.001, respectively), while ventilation was only significantly correlated with Stage 2 ROP (p < 0.05). Conclusions: The results indicate that GA; BW; and the use of ventilation, CPAP, and surfactant were all significant risk factors for ROP (Stage 1–3), but only BW and ventilation were significantly correlated with ROP and specific stages of the disease, namely Stage 2 and 3 ROP and Stage 2 ROP, respectively, in multivariate models.

scholarly journals Direct Versus Calculated LDL Cholesterol and C-Reactive Protein in Cardiovascular Disease Risk Assessment in the Framingham Offspring Study

2019 ◽  
Vol 65 (9) ◽  
pp. 1102-1114 ◽  
Author(s):  
Hiroaki Ikezaki ◽  
Virginia A Fisher ◽  
Elise Lim ◽  
Masumi Ai ◽  
Ching-Ti Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Ldl Cholesterol ◽  
Disease Risk ◽  
Univariate Analysis ◽  
Significant Risk ◽  
C Reactive Protein ◽  
Cox Regression Analysis ◽  
Reactive Protein ◽  
Standard Risk

AbstractBACKGROUNDIncreases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study.METHODSWe used stored frozen plasma samples (−80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods.RESULTSConsidering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death).CONCLUSIONSOur data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C.

scholarly journals Neutralizing Antibodies Titers and Side Effects in Response to BNT162b2 Vaccine in Healthcare Workers with and without Prior SARS-CoV-2 Infection

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 742
Author(s):  
José Javier Morales-Núñez ◽  
José Francisco Muñoz-Valle ◽  
Carlos Meza-López ◽  
Lin-Fa Wang ◽  
Andrea Carolina Machado Sulbarán ◽  
...  
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Adverse Effects ◽  
Antibody Production ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Vaccination Program ◽  
Expected Result ◽  
Neutralizing Capacity ◽  
The Usa

The main expected result of a vaccine against viruses is the ability to produce neutralizing antibodies. Currently, several vaccines against SARS-CoV-2 are being applied to prevent mortal complications, being Pfizer-BioNTech (BNT162b2) one of the first to be authorized in the USA and Mexico (11 December 2020). This study evaluated the efficacy of this vaccine on antibody production with neutralizing capacity and its side effects in healthcare workers with and without prior SARS-CoV-2 infection and in a group of unvaccinated individuals with prior COVID-19. The main findings are the production of 100% neutralizing antibodies in both groups after the second dose, well-tolerated adverse effects, the possible presence of immunosenescence, and finally, we support that a single dose of this vaccine in individuals with prior COVID-19 would be sufficient to achieve an immunization comparable to people without prior COVID-19 with a complete vaccination program (2 doses).

Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test

2018 ◽  
Vol 31 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Andrea Albrecht ◽  
Theresa Penger ◽  
Michaela Marx ◽  
Karin Hirsch ◽  
Helmuth G. Dörr
Keyword(s):  
Growth Hormone ◽  
Side Effects ◽  
Adverse Effects ◽  
Side Effect ◽  
Serum Testosterone ◽  
Low Flow ◽  
Effect Rate ◽  
Testosterone Levels ◽  
Testicular Pain ◽  
Prepubertal Boys

AbstractBackground:Despite the fact that priming with sex steroids in prepubertal children before growth hormone (GH) provocative tests is recommended, there is an ongoing controversial discussion about the appropriate age of the children, the drug used for priming, the dose and the period between priming and the GH test. Interestingly, there is no discussion on the safety of this procedure. To date, only little data have been available on the possible side effects of priming with testosterone.Methods:We analyzed the outcome in 188 short-statured prepubertal boys who had been primed with testosterone enanthate (n=136: 50 mg; n=51: 125 mg, and accidentally one boy with 250 mg) 7 days prior to the GH test. Serum testosterone levels were measured on the day of the GH test in 99 boys.Results:Overall, only five boys developed adverse side effects. Two boys (dose 125 mg) showed severe low-flow priapism and had to undergo decompression of the corpora cavernosa. One boy suffered from self-limiting priapism and testicular pain (dose 50 mg). Two patients reported testicular pain (each dose 50 mg). The single patient with 250 mg testosterone did not show any adverse effects. The total side effect rate was 2.7%. The serum testosterone levels of the boys with side effects were not different from the testosterone levels of the boys without any side effects.Conclusions:Parents and patients should be informed about the possible side effects of priming with testosterone such as priapism and testicular pain. However, the overall side effect rate is low. We found no correlation between the outcome and the testosterone dose used and/or the level of serum testosterone.

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