The current and upcoming era of radiomics in phaeochromocytoma and paraganglioma.

The topic of the diagnosis of phaeochromocytomas remains highly relevant because of advances in laboratory diagnostics, genetics, and therapeutic options and also the development of imaging methods. Computed tomography still represents an essential tool in clinical practice, especially in incidentally discovered adrenal masses; it allows morphological evaluation, including size, shape, necrosis, and unenhanced attenuation. More advanced post-processing tools to analyse digital images, such as texture analysis and radiomics, are currently being studied. Radiomic features utilise digital image pixels to calculate parameters and relations undetectable by the human eye. On the other hand, the amount of radiomic data requires massive computer capacity. Radiomics, together with machine learning and artificial intelligence in general, has the potential to improve not only the differential diagnosis but also the prediction of complications and therapy outcomes of phaeochromocytomas in the future. Currently, the potential of radiomics and machine learning does not match expectations and awaits its fulfilment.

Interhemispheric parietal cortex connectivity reflects improvement in post-stroke spasticity due to treatment with botulinum toxin-A.

In post-stroke spasticity (PSS), effective treatment with botulinum neurotoxin (BoNT) is associated with transient decrease in activation of the ipsilesional superior parietal lobule (SPL) and intraparietal sulcus (IPS). We hypothesized that this would be reflected in changes in resting-state functional connectivity (rsFC) of the SPL/IPS. Our aim was therefore to assess rsFC of the ipsilesional SPL/IPS in chronic stroke patients with hemiparesis both with and without PSS and to explore the relationship between SPL/IPS rsFC and PSS severity. To this end, fourteen chronic stroke patients with upper limb weakness and PSS (the PSS group) and 8 patients with comparable weakness but no PSS (the control group) underwent clinical evaluation and 3 fMRI examinations, at baseline (W0) and 4 and 11 weeks after BoNT (W4 and W11, respectively). Seed-based rsFC of the atlas-based SPL and IPS was evaluated using a group×time interaction analysis and a correlation analysis with PSS severity (modified Ashworth scale), integrity of the ipsilesional somatosensory afferent pathway (evoked potential N20 latency), and age. In the PSS group, transient improvement in PSS was associated with increase in rsFC between the ipsilesional IPS and the contralesional SPL at W4. The interhemispheric connectivity was negatively correlated with PSS severity at baseline and with PSS improvement at W4. We propose adaptation of the internal forward model as the putative underlying mechanism and discuss its possible association with increased limb use, diminished spastic dystonia, or improved motor performance, as well as its potential contribution to the clinical effects of BoNT.

Effect of Peritoneal Fixation (PerFix) on Lymphocele Formation in Robot-assisted Radical Prostatectomy with Pelvic Lymphadenectomy: Results of a Randomized Prospective Trial.

BACKGROUND: Symptomatic lymphoceles present the most common complication of robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (ePLND). No surgical technique has so far shown success in reducing the incidence rate, but several retrospective studies have shown the beneficial effect of the fixation of the peritoneum. OBJECTIVE: To introduce a modification in the technique of fixing the peritoneum to the pubic bone and to confirm whether this intervention reduces the incidence of lymphoceles. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized (1:1) single-center one-sided blind study was conducted in patients with localized prostate cancer (cT1-2cN0M0) indicated for RARP with ePLND operated between December 2019 and June 2021. In the intervention group, the free flap of the peritoneum was fixed to the pubic bone. In the control group, the peritoneal flap was left free without fixation. SURGICAL PROCEDURE: In the intervention group, the free flap of the peritoneum was fixed to the pubic bone (PerFix) so that lateral holes were left, allowing drainage of lymph from the pelvis into the abdominal cavity, where it would be resorbed. The iliac vessels and obturator fossa remained uncovered by the peritoneum and the bladder. MEASUREMENTS: The primary objective was to evaluate the frequency of symptomatic lymphoceles during follow-up. The secondary endpoints were the radiological presence of lymphoceles on computed tomography of the pelvis carried out 6 wk after surgery, the volume of the lymphoceles, and the degree of severe (Clavien-Dindo ≥3) complications. RESULTS AND LIMITATIONS: Of the 260 randomized patients, 245 were evaluated in the final analysis-123 in the intervention and 122 in the control group. The median follow-up was 595 d. There were no differences between the groups regarding clinical and pathological variables. The median of 17 nodes removed was the same in both groups (p = 0.961). Symptomatic lymphoceles occurred in 17 patients (6.9%), while in the intervention group these were found in three (2.4%) versus 14 (11.5%) in the control group (p = 0.011). The number of radiologically detected asymptomatic lymphoceles did not differ (p = 0.095). There was no significant difference in lymphocele volume between the two groups (p = 0.118). The rate of serious complications (Clavien 3a and 3b) was 4.8% in the intervention group and 9.1% in the control group (p = 0.587). A multivariate logistic regression model of symptomatic lymphocele occurrence was created with significant factors: body mass index (odds ratio [OR] = 1.1, 95% confidence interval [CI] = [1.03, 1.26], p = 0.012) and intervention (OR = 4.6, 95% CI = [1.28, 16.82], p = 0.02). CONCLUSIONS: Fixation of the peritoneum (PerFix) reduced the incidence of symptomatic lymphoceles in RARP with ePLND. We found no difference in the frequency of asymptomatic lymphocele development. The volume of the detected lymphoceles was similar. PATIENT SUMMARY: In this study, we compared the rate of development of postoperative complications using the peritoneal fixation technique with that of a nonfixation control group for robot-assisted radical prostatectomy with extended pelvic lymphadenectomy. Fixation of the peritoneum should obviate the development of severe complications in the postoperative period.

Determination of the prevalence and predictors of ventricular thrombus with assessment of the risk of systemic embolization to the CNS in patients after acute myocardial infarction using magnetic resonance imaging, echocardiography and cardiac markers - a prospective, unicentric, observational study.

BACKGROUND: Left ventricular thrombus (LVT) formation is one of the well-known and serious complications of acute myocardial infarction (AMI) due to the risk of systemic arterial embolization (SE). To diagnose LVT, echocardiography (TTE) is used. Late gadolinium-enhanced cardiovascular magnetic resonance (DE-CMR) is the gold standard for diagnosing LVT. OBJECTIVES: The aim of this observational study was to determine the role of transthoracic echocardiography and cardiac markers in predicting the occurrence of LVT compared with a reference cardiac imaging (DE-CMR) and to determine the risk of systemic embolization to the CNS using brain MRA. METHODS: Seventy patients after MI managed by percutaneous coronary intervention (localization: 92.9% anterior wall, 7% other; median age 58.7 years) were initially examined by transthoracic echocardiography (TTE, n=69) with a focus on LVT detection. Patients were then referred for DE-CMR (n=55). Laboratory determination of cardiac markers (Troponin T and NTproBNP) was carried out in all. Brain MRA was performed 1 year apart (n=51). RESULTS: The prevalence of LVT detected by echocardiography: (n=11/69, i.e. 15.9%); by DE-CMR: (n=9/55, i.e. 16.7%). Statistically significant parameters to predict the occurrence of LVT after AMI (cut off value): (a) detected by echocardiography: anamnestic data - delay (≥ 5 hours), echocardiographic parameters - left atrial volume index (LAVI≥ 32 mL/m2), LV EF Simpson biplane and estimated (≤ 42%), tissue Doppler determination of septal A wave velocity (≤ 7.5cm/s); (b) detected by DE-CMR: anamnestic data - delay (≥ 13 hours), DE-CMR parameters - left ventricular end-diastolic diameter (≥ 54mm). The value of cardiac markers (Troponin T and NTproBNP in ng/L) in LVT detected by echocardiography did not reach statistical significance. In LVT detected by DE-CMR, NTproBNP was statistically significantly increased at 1 month after AMI onset (no optimal cut-off value could be determined). There was no statistically significant association between the LVT detection (both modalities) and the occurrence of clinically manifest and silent cardioembolic events. CONCLUSION: Our study confirmed a relatively high prevalence of LVT in the high-risk group of patients with anterior wall STEMI. Due to the low prevalence of thromboembolic complications, no significant association between the LVT detection and the occurrence of a cardioembolic event was demonstrated.

Karyotyping of Lymphocytes and Epithelial Cells of Distinct Embryonic Origin Does Not Help to Predict the Turner Syndrome Features.

BACKGROUND: In Turner syndrome (TS), fluorescent in situ hybridization (FISH) karyotyping offers an alternative to classical karyotyping. OBJECTIVE: We tested the added value of FISH karyotyping from lymphocytes (mesodermal origin), buccal cells (ectodermal origin), and a rear-tongue smear (endodermal origin) to determine the 45,X cell line fraction and its impact on patient phenotype. DESIGN AND PATIENTS: Classical karyotyping and three FISH assays were done in 153 girls and women previously diagnosed with TS in four university hospitals. The 45,X cell line fraction was determined for each method and correlated with the major phenotypic signs. RESULTS: Classical karyotyping identified 45,X/46,XX mosaicism in 77/153 subjects (50%), 45,X monosomy in 52/153 (34%), and other karyotypes in 24/153 (16%). FISH from lymphocytes verified 45,X in 47/52 original cases, whereas 4/52 had 45,X/46,XX and 1/52 45,X/47,XYY mosaicism. The 45,X cell line fraction was higher in FISH from lymphocytes compared to classical karyotyping (median 86.4% vs. 70.0%; p < 0.001), while there was no difference for FISH from buccal or rear-tongue smear cells. The mean 45,X cell line fraction was more abundant in patients with several of the characteristic phenotypic signs compared to patients without them (p < 0.01), but the predictive power was insufficient. CONCLUSION: FISH analysis confirmed the findings of classical karyotyping; only a few 45,X monosomy cases were reclassified as mosaics. The 45,X cell line fraction did not show clinically meaningful prediction of the phenotype. FISH analysis of buccal or rear-tongue epithelial cells may be a non-inferior, less invasive alternative to classical karyotyping.

A Pathological Complete Response to the Combination of Ipilimumab and Nivolumab in a Patient with Metastatic Renal Cell Carcinoma.

Background and Objectives: Complete pathological response after ipilimumab and nivolumab combination therapy in a patient with intermediate prognosis renal cell carcinoma is an uncommon finding. Case presentation: A 60-year-old man presented with synchronous solitary metastatic bone lesion and renal cell carcinoma and achieved a complete pathological response after surgical resection of the bone lesion, followed by ipilimumab and nivolumab combination therapy and nephrectomy. The treatment was complicated by hypophysitis and oligoarthritis more than a year after the initiation of the therapy. Conclusions: Currently, the combination therapy based on immune checkpoint inhibitors represents the treatment of choice in patients with intermediate- and poor-risk prognosis metastatic renal cell carcinoma. In the present case, preoperative therapy with ipilimumab and nivolumab resulted in a complete pathological response in the renal tumor. Vigilance concerning potential immune-related side effects is warranted throughout the course of therapy and the subsequent follow-up.

Hypertension outcomes of adrenalectomy for unilateral primary aldosteronism.

PURPOSE: To evaluate laboratory and clinical results after unilateral adrenalectomy in patients with primary aldosteronism (PHA). METHODS: A cross-sectional analysis was performed using data from patients who underwent transperitoneal laparoscopic adrenalectomy for PHA, between January 2008 and December 2019. Surgical indications were based on adrenal venous sampling without ACTH stimulation. Analyses included patient demographics; preoperative clinical, pharmacological, laboratory, and radiological data; and postoperative results assessed after a median of 4 months. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication, thus enabling standardized comparison of dosage between the drug classes. Statistical assessments included univariable and multivariable logistic regression analysis. RESULTS: This study enrolled 87 patients. The patients were taking 5.4 DDD of antihypertensive medication before surgery, and 3.0 DDD after surgery. Complete biochemical success of surgery was reached 67 patients (77%), 19 patients (22%) had partial biochemical success. Complete clinical success with normalization of blood pressure and withdrawal of all antihypertensive drugs was achieved in 19 patients (22%). 57 patients (65%) exhibited a reduction of DDD after surgery and/or improvement of blood pressure-partial clinical success. Thus, in 76 (87%) of all enrolled patients, surgery had an overall positive effect on hypertension control. Multivariable logistic regression showed that complete clinical success was independently associated with female gender and baseline sum of antihypertensive drugs DDD < 4. CONCLUSION: A majority of patients undergoing unilateral adrenalectomy for PHA achieved markedly improved hypertension control, despite almost halving their antihypertensive medication. Almost a quarter of patients were cured and able to cease using all antihypertensive drugs.

Botulinum toxin injection changes resting state cerebellar connectivity in cervical dystonia.

In cervical dystonia, functional MRI (fMRI) evidence indicates changes in several resting state networks, which revert in part following the botulinum neurotoxin A (BoNT) therapy. Recently, the involvement of the cerebellum in dystonia has gained attention. The aim of our study was to compare connectivity between cerebellar subdivisions and the rest of the brain before and after BoNT treatment. Seventeen patients with cervical dystonia indicated for treatment with BoNT were enrolled (14 female, aged 50.2 ± 8.5 years, range 38-63 years). Clinical and fMRI examinations were carried out before and 4 weeks after BoNT injection. Clinical severity was evaluated using TWSTRS. Functional MRI data were acquired on a 1.5 T scanner during 8 min rest. Seed-based functional connectivity analysis was performed using data extracted from atlas-defined cerebellar areas in both datasets. Clinical scores demonstrated satisfactory BoNT effect. After treatment, connectivity decreased between the vermis lobule VIIIa and the left dorsal mesial frontal cortex. Positive correlations between the connectivity differences and the clinical improvement were detected for the right lobule VI, right crus II, vermis VIIIb and the right lobule IX. Our data provide evidence for modulation of cerebello-cortical connectivity resulting from successful treatment by botulinum neurotoxin.

Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background.

Foci of splenic tissue separated from the spleen can occur as a congenital anomaly. Isolated nodules of splenic tissue are called accessory spleens or spleniculli. However, nodules of splenic tissue can merge with other organs during embryonic development, in which case we speak of spleno-visceral fusions: most often, they merge with the tail of the pancreas (thus forming spleno-pancreatic fusion or an intrapancreatic accessory spleen), with the reproductive gland (i.e., spleno-gonadal fusion), or with the kidney (i.e., spleno-renal fusion). Our case report describes the fusion of heterotopic splenic tissue with the right adrenal gland, which was misinterpreted as a metastasis of a renal cell carcinoma. To the best of our knowledge, this is the first reported case of spleno-adrenal fusion. Spleno-visceral fusions usually represent asymptomatic conditions; their main clinical significance lies in the confusion they cause and its misinterpretation as tumors of other organs. We believe that the cause of retroperitoneal spleno-visceral fusions is the anomalous migration of splenic cells along the dorsal mesentery to the urogenital ridge, together with primitive germ cells, at the end of the fifth week and during the sixth week of embryonic age. This theory explains the possible origin of spleno-visceral fusions, their different frequency of occurrence, and the predominance of findings on the left side.

General anesthesia or conscious sedation in paroxysmal atrial fibrillation catheter ablation.

BACKGROUND: Catheter ablation of paroxysmal atrial fibrillation (AF) can be performed under general anesthesia or conscious sedation. The influence of type of anesthesiology care on procedural characteristics and ablation outcome in patients in whom intracardiac echocardiography (ICE) and elimination of adenosine-mediated dormant conduction (DC) is used is not entirely known. METHODS: 150 patients with paroxysmal AF were randomized to point-by-point radiofrequency catheter isolation of pulmonary veins (PVI) under general anesthesia (n=77) or conscious sedation (n=73). Adenosine-mediated dormant conduction was eliminated in all patients. Antiarrhythmic medication was discontinued after PVI. During twelve months of follow-up, all patients underwent four times 7-day ECG monitorings. RESULTS: There was no difference between groups in AF recurrence (28.6% vs. 31.5%, P=0.695). Patients in conscious sedation had longer procedure times (160 ± 32.1 vs. 132 ± 31.5 min, P<0.001), longer RF energy application times (40 ± 15 vs. 29 ± 11 min, P<0.001) and longer fluoroscopy times (6.2 min ± 5.3 vs. 4.3 min ± 2.2, P<0.001) with similar complication rates. CONCLUSION: Conscious sedation is not inferior to general anesthesia in regard to arrhythmia recurrence or complication rates of catheter ablation of paroxysmal atrial fibrillation. However, it is associated with longer procedure times, longer time of radiofrequency energy application and longer fluoroscopy times.

Diagnostic Value of Unenhanced CT Attenuation and CT Histogram Analysis in Differential Diagnosis of Adrenal Tumors.

Background and Objectives: Our aim was to verify the optimal cut-off value for unenhanced CT attenuation and the percentage of negative voxels in the volume CT histogram analysis of adrenal masses. Materials and Methods: We retrospectively analyzed the CT data of patients who underwent an adrenalectomy in the period 2002-2019. In total, 413 adrenalectomies were performed. Out of these, 233 histologically verified masses (123 adenomas, 58 pheochromocytomas, 18 carcinomas, and 34 metastases) fulfilled the inclusion criteria and were selected for analysis. The mean unenhanced attenuation in Hounsfield units (HU) and the percentage of voxels with attenuation less than 0 HU (negative voxels) were measured in each mass. Results: The mean unenhanced attenuation with a cut-off value of 10 HU reached a sensitivity of 59.4% and a specificity of 99.1% for benign adenomas. The mean unenhanced attenuation with a cut-off value of 15 HU reached a sensitivity of 69.1% and a specificity of 98.2%. For the histogram analysis, a cut-off value of 10% of negative pixels reached a sensitivity of 82.9% and a specificity of 98.2%, whereas a cut-off value of 5% of negative pixels reached a sensitivity of 87.8% and a specificity of 75.5%. The percentage of negative voxels reached a slightly better area under the curve (0.919) than unenhanced attenuation (0.908). Conclusion: Mean unenhanced attenuation with a cut-off value of 10 HU represents a simple tool, and the most specific one, to distinguish adrenal adenomas from non-adenomas. CT histogram analysis with cut-off values of 10% of negative voxels improves sensitivity without any loss of specificity.

Acute myocardial infarction, intraventricular thrombus and risk of systemic embolism.

The development of left ventricular thrombus (LVT) is a well-known and serious complication of acute myocardial infarction (AMI) due to the risk of systemic arterial embolism (SE), which is variable in its clinical picture and has potentially serious consequences depending on the extent of target organ damage. SE results in an increase in mortality and morbidity in these patients. LVT is one of the main causes of the development of ischaemic cardio-embolic cardiovascular events (CVE) after MI and the determination of the source of cardiac embolus is crucial for the initiation of adequate anticoagulant therapy in secondary prevention. Echocardiography holds an irreplaceable place in the diagnosis of LVT, contrast enhancement provides higher sensitivity. The gold standard for LVT diagnosis is cardiac magnetic resonance imaging, but it is not suitable as a basic screening test. In patients with already diagnosed LVT, it is necessary to adjust antithrombotic therapy by starting warfarin anticoagulation for at least 6 months with the need for echocardiographic follow-up to detect thrombotic residues. The effect of prophylactic administration of warfarin in high-risk patients after anterior AMI does not outweigh the risk of severe bleeding complications and does not result in a decrease in mortality and morbidity. At the present time, there is not enough evidence to use direct oral anticoagulants in this indication.

Long-term outcome of paroxysmal atrial fibrillation catheter ablation with and without pulmonary vein dormant conduction after adenosine challenge.

OBJECTIVES: The prognostic significance of adenosine-mediated pulmonary vein (PV) dormant conduction is unclear. We prospectively followed patients with adenosine-mediated PV reconduction with a subsequent repeated ablation until there was no reconduction inducible with patients without reconduction after PV isolation. METHOD AND RESULTS: Consecutive patients (n=179) with paroxysmal atrial fibrillation (AF) without prior catheter ablation (CA) were enlisted in the study. We used a point-by-point CA and general anesthesia in all patients. Twenty minutes after PV isolation we administered adenosine in a dose sufficient to produce an atrioventricular block. If a dormant conduction was present (n=54) we performed additional ablation until there was no adenosine mediated reconduction inducible. During 36 months of follow-up, all patients were examined for eight 7-day ECG recordings. There was no difference in arrhythmia recurrence rate between patients with and without dormant conduction (29.6 vs. 24.8% at 12 months, P=0.500; 31.5 vs. 30.4% at 36 months, P=1.000), for any echocardiographic parameter or any parameter of the ablation procedure. CONCLUSION: The patients with dormant conduction after adenosine during catheter ablation of paroxysmal atrial fibrillation with complete elimination of the dormant conduction by additional extensive ablation have the same outcome in the long term as patients without a dormant conduction.

Atrial fibrillation inducibility after pulmonary vein isolation under general anaesthesia.

AIMS: Atrial fibrillation (AF) inducibility with rapid atrial pacing following AF ablation is associated with higher risk of AF recurrence. The predictive value of AF inducibility in paroxysmal AF patients after pulmonary vein isolation (PVI), done under general anaesthesia (GA), remains questionable since GA might alter AF inducibility and/or sustainability. METHODS: Consecutive patients (n = 120) with paroxysmal AF without prior catheter ablation (CA) were enlisted in the study. All patients were ablated under GA. We have used a point-by-point CA and elimination of dormant conduction after adenosine in all patients. A predefined stimulation protocol was used to induce arrhythmias after PVI. Regular supraventricular tachycardias were mapped and ablated. Patients were divided into 3 subgroups - noninducible, inducible AF with spontaneous termination in five minutes, inducible AF without spontaneous termination. During 12 months of follow-up, all patients were examined four-times with 7-day ECG recordings. RESULTS: There was no statistical difference between the three subgroups in a rate of arrhythmia recurrence (11.1 vs. 27.5 vs. 27.3%, P=0.387), despite a clear trend to a better success rate in the non-inducible group. The subgroups did not differ in left atrial (LA) diameter (41.0±6, 43.0±7, 42.0±5 mm, P=0.962) or in any other baseline parameter. CONCLUSION: AF inducibility as well as presence or absence of its early spontaneous termination after PVI done under general anaesthesia in paroxysmal AF patients were not useful as predictors of procedural failure.

Hypoglycemia as a Symptom of Neoplastic Disease, with a focus on Insulin-like Growth Factors Producing Tumors.

This article reviews the current knowledge of uncommon causes of hypoglycemia, with a focus on neoplastic disease. However, these situations are rare. They commonly accompany severely ill patients and therefore a proper diagnosis is the basis for relevant treatment. Here we discuss the pathophysiological foundation of hypoglycemia - situations caused by increased insulin production or sensitivity - but we also focus on different cytokines which could cause hypoglycemia, especially IGF-II production in what are called nonislet cell tumors. From the clinical perspective we can divide the patients who are affected into "seemingly ill" or "healthy patients" and lead the diagnostic process accordingly.

Characteristic CT features of pheochromocytomas - probability model calculation tool based on a multicentric study.

OBJECTIVES: The aim of the study was to evaluate the CT features of adrenal tumors in an effort to identify features specific to pheochromocytomas and second, to define a feasible probability calculation model. METHODS: This multicentric retrospective study included patients from the period 2003 to 2017 with an appropriate CT examination and a histological diagnosis of an adrenal adenoma, pheochromocytoma, adrenocortical carcinoma, or metastasis. In total, 346 patients were suitable for the CT image analysis, which included evaluation of the largest diameter, the shape of the lesion, the presence of central necrosis and its margins, and the presence of an enhancing peripheral rim ("ring sign"). RESULTS: Pheochromocytomas have a significantly more spherical shape (P<0.001), whereas an elliptical shape significantly reduces the probability of a pheochromocytoma (odds ratio = 0.015), as does another shape (odds ratio = 0.006). A "ring sign" is also more frequent in pheochromocytomas compared to other adrenal tumors (P=0.001, odds ratio = 6.49). A sharp necrosis also increases the probability of a pheochromocytoma more than unsharp necrosis (odds ratio 231.6 vs. 20.2). The probability calculation model created on the basis of the results confirms a high sensitivity and specificity (80% and 95%). CONCLUSION: This study confirms the value of anatomical features in the assessment of adrenal masses with the ability to significantly improve the identification of pheochromocytomas. Advanced assessment of the tumor shape was defined and a original comprehensive calculating tool of the pheochromocytoma probability was created on the basis of the results presented here and could be used in clinical routine.

Differential Effects of Sustained Manual Pressure Stimulation According to Site of Action.

Sustained pressure stimulation of the body surface has been used in several physiotherapeutic techniques, such as reflex locomotion therapy. Clinical observations of global motor responses and subsequent motor behavioral changes after stimulation in certain sites suggest modulation of central sensorimotor control, however, the neuroanatomical correlates remain undescribed. We hypothesized that different body sites would specifically influence the sensorimotor system during the stimulation. We tested the hypothesis using functional magnetic resonance imaging (fMRI) in thirty healthy volunteers (mean age 24.2) scanned twice during intermittent manual pressure stimulation, once at the right lateral heel according to reflex locomotion therapy, and once at the right lateral ankle (control site). A flexible modeling approach with finite impulse response basis functions was employed since non-canonical hemodynamic response was expected. Subsequently, a clustering algorithm was used to separate areas with differential timecourses. Stimulation at both sites induced responses throughout the sensorimotor system that could be mostly separated into two anti-correlated subsystems with transient positive or negative signal change and rapid adaptation, although in heel stimulation, insulo-opercular cortices and pons showed sustained activation. In direct voxel-wise comparison, heel stimulation was associated with significantly higher activation levels in the contralateral primary motor cortex and decreased activation in the posterior parietal cortex. Thus, we demonstrate that the manual pressure stimulation affects multiple brain structures involved in motor control and the choice of stimulation site impacts the shape and amplitude of the blood oxygenation level-dependent response. We further discuss the relationship between the affected structures and behavioral changes after reflex locomotion therapy.