Pain-Related Vertex Evoked Potentials. Comparison of Surface Electrical to Heat Stimulation.

INTRODUCTION: Demonstration of nociceptive fiber abnormality is important for diagnosing neuropathic pain and small fiber neuropathies. This is usually assessed by brief heat pulses using lasers, contact heat, or special electrodes. We hypothesized that pain-related evoked potentials to conventional surface electrical stimulation (PREPse) can index Aδ afferences despite tactile Aß fibers coactivation. PREPse may be more readily used clinically than contact heat evoked potentials (CHEPS). METHODS: Twenty-eight healthy subjects. Vertex (Cz-A1/A2) recordings. Electrical stimulation of middle finger and second toe with conventional ring, and forearm/leg skin with cup, electrodes. Contact heat stimulation to forearm and leg. Compression ischemic nerve blockade. RESULTS: PREPse peripheral velocities were within the midrange of Aδ fibers. N1-P1 amplitude increased with pain numerical rating scale graded (0-10) electrical stimulation (n = 25) and decreased with increasing stimulation frequency. Amplitudes were unchanged by different presentation orders of four stimulation intensities. PREPse N1 (∼130 milliseconds) and N2 (∼345 milliseconds) peaks were approximately 40 milliseconds earlier than that with CHEPS. PREPse and CHEPS N1-N2 interpeak latency (∼207 milliseconds) were similar. PREPse became unrecordable with nerve blockade of Aδ fibers. CONCLUSIONS: PREPse earlier N1 and N2 peaks, and similar interpeak N1-N2 latencies and central conduction velocities, or synaptic delays, to CHEPS are consistent with direct stimulation of Aδ fibers. The relation of vertex PREPse amplitude and pain, or the differential effects of frequency stimulation, is similar to pain-related evoked potential to laser, special electrodes, or contact heat stimulation. The relationship to Aδ was validated by conduction velocity and nerve block. Clinical utility of PREPse compared with CHEPS needs validation in somatosensory pathways lesions.

Distinguishing Gastrointestinal Leiomyomas From Muscularis Propria in Biopsy Specimens by Differential Expression of S100 Immunohistochemical Stain.

OBJECTIVES: Interpreting small biopsy specimens or fine-needle aspirations of gastrointestinal tract (GI) smooth muscle lesions may be challenging when the differential diagnosis includes leiomyoma vs muscularis propria (MP). We evaluated the utility of S100 staining in distinguishing GI leiomyomas from MP. METHODS: A search was conducted in our laboratory information system for cases of leiomyomas arising within the GI tract (2004-2021). Site-matched controls containing MP were selected (2018-2020). Five high-power fields (hpf) were counted on S100 immunohistochemical stains by two pathologists in the resections and by three different blinded pathologists in the biopsy specimens and analyzed. RESULTS: The median S100 count was 2.5/5 hpf in leiomyoma resection cases (n = 38), which was significantly lower than the median count of 548/5 hpf in MP (n = 19) with a P value of <.0001. The median S100 count in biopsy specimens (n = 16) was 1.2/5 hpf and within the expected range of 1 to 104/5 hpf (minimum-maximum value) established by the leiomyoma resections. S100 counts in the normal MP were significantly higher than those observed in leiomyomas (P < .001). CONCLUSIONS: S100 staining can aid in distinguishing a leiomyoma from MP in the GI tract, which is especially helpful when evaluating cases with limited sampling.

Comparison of Diagnostic Sensitivity and Procedure-Related Pain of Concurrent Ultrasound-guided Fine-needle Aspiration and Core-needle Biopsy of Axillary Lymph Nodes in Patients with Suspected or Known Breast Cancer.

OBJECTIVE: Conflicting data exist on the diagnostic sensitivity of core-needle biopsy (CNB) compared to fine-needle aspiration (FNA) in the evaluation of axillary lymph node metastasis from breast cancer. Our purpose was to evaluate the sensitivity of CNB and FNA using subsequent axillary surgery as the gold standard and to compare the patients' subjective pain levels for each biopsy method. METHODS: This IRB-approved prospective study enrolled 140 patients from February 2014 to May 2019 with known or suspected breast cancer. Patients underwent both US-guided FNA and 14-gauge CNB of the same node with clip placement and rated their pain level using a verbal numerical rating scale of 0 to 10. The diagnostic sensitivities were determined by pathology of the surgically excised lymph node using the McNemar test of correlated proportions. Changes in pain scores for CNB and FNA were determined using the Wilcoxon rank sum test. RESULTS: A total of 94 patients had confirmatory excision of the biopsied node with nodal metastasis detected in 71.3% (67/94). The sensitivity of CNB for detection of nodal metastasis was 95.5% (64/67), while the sensitivity of FNA was 67.2% (45/67) (P < 0.05). Overall pain score ratings for CNB increased by 0.6 from baseline on an 11-point numerical rating scale, while overall pain score rating for FNA decreased by 0.2 from baseline (P < 0.05). CONCLUSION: Our study demonstrates that 14-gauge CNB has superior sensitivity for detection of axillary nodal metastases and mildly increased pain compared with 25-gauge FNA in patients with breast cancer.

Neurologic Features Associated With SARS-CoV-2 Infection in Children: A Case Series Report.

INTRODUCTION: Although multiple neurologic manifestations associated with SARS-CoV-2 infection have been described in adults, there is little information about those presented in children. Here, we described neurologic manifestations associated with COVID-19 in the pediatric population. METHODS: Retrospective case series report. We included patients younger than 18 years, admitted with confirmed SARS-CoV-2 infection and neurologic manifestations at our hospital in Santiago, Chile. Demographics, clinical presentations, laboratory results, radiologic and neurophysiological studies, treatment, and outcome features were described. Cases were described based on whether they presented with predominantly central or peripheral neurologic involvement. RESULTS: Thirteen of 90 (14.4%) patients admitted with confirmed infection presented with new-onset neurologic symptoms and 4 patients showed epilepsy exacerbation. Neurologic manifestations ranged from mild (headache, muscle weakness, anosmia, ageusia), to severe (status epilepticus, Guillain-Barré syndrome, encephalopathy, demyelinating events). CONCLUSIONS: We found a wide range of neurologic manifestations in children with confirmed SARS-CoV-2 infection. In general, neurologic symptoms were resolved as the systemic presentation subsided. It is essential to recognize and report the main neurologic manifestations related to this new infectious disease in the pediatric population. More evidence is needed to establish the specific causality of nervous system involvement.

Imaging in Pediatric Multiple Sclerosis : An Iconographic Review.

Pediatric-onset multiple sclerosis (POMS) is defined by a first multiple sclerosis (MS) attack occurring before 18 years old and is diagnosed by demonstration of dissemination in time (DIT) and space (DIS). Although guidelines evolved over the years, they always recognized the importance of magnetic resonance imaging (MRI) for diagnosis. The 2017 McDonald criteria are increasingly used and have been validated in several cohorts. The use of MRI is the most important tool for the early diagnosis, monitoring, and assessment of treatment response of MS and standard protocols include precontrast and postcontrast T1, T2, fluid attenuation inversion recovery (FLAIR) and diffusion sequences. A distinctive MS lesion compromises white matter and it is well-demarcated and confluent, showing demyelination, inflammation, gliosis, and relative axonal preservation. Considering the growing recognition of pediatric MS as a differential diagnosis for children presenting with a clinical central nervous system event, we present a POMS lesions guide (periventricular, juxtacortical, infratentorial, spinal cord, cortical, tumefactive, black hole, contrast-enhanced). Owing to its rareness, POMS is a diagnosis by exclusion and MRI plays a fundamental role in distinguishing POMS from other demyelinating and non-demyelinating conditions. Three main groups of disorders can mimic POMS: inflammatory, metabolic and tumoral; however, imaging patterns earlier described lower the possibilities of alternative diagnoses and strongly suggest POMS when likely.

First-line pembrolizumab therapy in a cisplatin-ineligible patient with plasmacytoid urothelial carcinoma: A case report.

BACKGROUND: Plasmacytoid urothelial carcinoma (PUC) is a rare but aggressive variant of transitional cell carcinoma. In patients with unresectable disease, cisplatin-based combination chemotherapy is the most commonly used treatment. However, many patients are cisplatin-ineligible due to poor performance status or other comorbidities. We report a case of a cisplatin-ineligible patient with metastatic PUC who was treated with pembrolizumab. CASE REPORT: A 71-year-old man with 30 pack-year smoking history and schizoaffective disorder was found to have multiple right-sided lung nodules after presenting with atypical chest pain. Staging CT showed bilateral adrenal masses and a large soft tissue mass in the right iliac fossa. Tissue pathology and immunohistochemical staining was consistent with PUC. As the patient was cisplatin-ineligible due to poor performance status and multiple medical comorbidities, the decision was made to treat with pembrolizumab. Repeat CT chest and abdomen showed partial response at three months and stable disease at six months. DISCUSSION: The KEYNOTE-052 study found that first-line pembrolizumab in cisplatin-ineligible patients with urothelial cancer resulted in complete or partial response in 24% of patients with few adverse effects. However, it is unclear if patients with plasmacytoid variant were included. To our knowledge, this is the first case report of a patient with metastatic PUC not only treated with pembrolizumab but shown to have clinical response. CONCLUSION: Given our patient's clinical response, pembrolizumab is a promising first-line agent for treating cisplatin-ineligible patients with metastatic PUC. Further evaluation is warranted to confirm the benefit of treating this patient population with pembrolizumab.

Peutz-Jeghers Type Polyp of the Appendix with Review of Literature.

Hamartomatous polyps of Peutz-Jeghers type are strongly associated with Peutz-Jeghers polyposis syndrome and are predominantly encountered in the small intestine. Sporadic cases are uncommonly reported. We report a case of a polyp identified incidentally in the appendix of a patient undergoing diagnostic imaging due to a history of hepatitis C infection. Histopathologic evaluation after appendectomy showed a polyp with bands of muscularis mucosae bundles with arborizing architecture and variable amounts of inspissated mucin, morphologically indistinguishable from Peutz-Jeghers type hamartomatous polyp. A family or personal history of abdominal cancers was not reported by the patient, suggesting a sporadic occurrence. Next generation sequencing revealed only two pathogenic low-level STK11 mutations, presumed to be somatic. In conclusion, this is an unusual case of a sporadic Peutz-Jeghers type polyp occurring in the appendix.

Reporte de cuestiones relativas a los estudios de precisión diagnóstica de la citología de aspiración con aguja fina / Reporting issues in diagnostic accuracy studies for fine-needle aspiration cytology

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Impact of rapid on-site evaluation on the adequacy of endoscopic-ultrasound guided fine-needle aspiration of solid pancreatic lesions: a systematic review and meta-analysis.

BACKGROUND: Rapid on-site evaluation (ROSE) has the potential to improve adequacy rates for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic lesions, but its impact is context-dependent. No studies exist that summarize the relationship between ROSE, number of needle passes, and resulting adequacy rates. AIMS: To analyze data from previous studies to establish if ROSE is associated with improved adequacy rates; to evaluate the relationship between ROSE, number of needle passes, and the resulting adequacy rates of EUS-FNA for solid pancreatic lesions. METHODS: Systematic review and meta-analysis of studies reporting the adequacy rates for EUS-FNA of solid pancreatic lesions. RESULTS: The search produced 3822 original studies, of which 70 studies met our inclusion criteria. The overall average adequacy rate was 96.2% (95% confidence interval: 95.5, 96.9). ROSE was associated with a statistically significant improvement of up to 3.5% in adequacy rates. There was heterogeneity in adequacy rates across all subgroups. No association between the assessor type and adequacy rates was found. Studies with ROSE have high per-case adequacy and a relatively high number of needle passes in contrast to non-ROSE studies. ROSE is an effect modifier of the relationship between number of needle passes and adequacy. CONCLUSIONS: ROSE is associated with up to 3.5% improvement in adequacy rates for EUS-FNA of solid pancreatic lesions. ROSE assessor type has no impact on adequacy rates. ROSE is an effect modifier on the relationship between needle passes and per-case adequacy for EUS-FNA of solid pancreatic lesions.

Disturbed sensory perception of changes in thermoalgesic stimuli in patients with small fiber neuropathies.

The assessment of functional deficits in small fibre neuropathies (SFN) requires using ancillary tests other than conventional neurophysiological techniques. One of the tests with most widespread use is thermal threshold determination, as part of quantitative sensory testing. Thermal thresholds typically reflect one point in the whole subjective experience elicited by a thermal stimulus. We reasoned that more information could be obtained by analyzing the subjective description of the ongoing sensation elicited by slow temperature changes (dynamic thermal testing, DTT). Twenty SFN patients and 20 healthy subjects were requested to describe, by using an electronic visual analog scale system, the sensation perceived when the temperature of a thermode was made to slowly change according to a predetermined pattern. The thermode was attached to the left ventral forearm or the distal third of the left leg and the stimulus was either a monophasic heat or cold stimuli that reached 120% of pain threshold and reversed to get back to baseline at a rate of 0.5 °C/s. Abnormalities seen in patients in comparison to healthy subjects were: (1) delayed perception of temperature changes, both at onset and at reversal, (2) longer duration of pain perception at peak temperature, and (3) absence of an overshoot sensation after reversal, ie, a transient perception of the opposite sensation before the temperature reached again baseline. The use of DTT increases the yield of thermal testing for clinical and physiological studies. It adds information that can be discriminant between healthy subjects and SFN patients and shows physiological details about the process of activation and inactivation of temperature receptors that may be abnormal in SFN.

Rapid on-site evaluation increases endoscopic ultrasound-guided fine-needle aspiration adequacy for pancreatic lesions.

BACKGROUND: Rapid on-site evaluation (ROSE) has the potential to improve adequacy rates and affect other outcomes; however, there have been few comparative studies to assess the impact of ROSE in the setting of ultrasound-guided endoscopic fine-needle aspiration cytology for pancreatic lesions. AIMS: To determine whether ROSE improves adequacy rates of endoscopic fine-needle aspiration cytology for pancreatic lesions. METHODS: Systematic review and meta-analysis of studies reporting a head-to-head comparison of adequacy or diagnostic accuracy (with ROSE vs. without ROSE) at a single site. RESULTS: ROSE was associated with a statistically significant (p < 0.001) improvement in the adequacy rate (average 10 %, 95 % CI: 5-24 %). The impact of ROSE depends on the per-pass adequacy rate without ROSE. ROSE had no impact on diagnostic yield (p < 0.76). CONCLUSIONS: ROSE is associated with an improvement in adequacy rates when implemented at sites where the per-case adequacy rate without ROSE is low (<90 %). It is unclear whether the type of assessor (pathologist vs. non-pathologist) has a significant impact on the success rate of ROSE. ROSE has no impact on diagnostic yield. Studies should employ head-to-head comparisons of cohorts with and without ROSE at a single location.

Brainstem dysfunction in variegate porphyria.

INTRODUCTION: Variegate porphyria (VP) is a rare metabolic disorder that may present as an acute predominantly motor neuropathy. Cranial nerves and brainstem functions have been only scarcely studied. METHODS: Brainstem reflexes were examined in symptomatic and non-symptomatic VP mutation carriers of a single family. RESULTS: Similar results were found in the 2 patients with a history of porphyric crises. The blink reflex showed an absence of late responses (R2 and R2c) to stimulation of both sides. The masseter inhibitory reflex showed reduced inhibition of the second phase. The jaw jerk was normal. The asymptomatic carriers did not show any of the abnormalities just noted. CONCLUSIONS: Our results are compatible with a central lower pons-upper medulla disorder in the brainstem. We hypothesize that brainstem dysfunction in VP patients with a history of porphyric crises may be due to neurotoxic effects of porphyrin precursors as well as subclinical osmolarity changes due to hyponatremia.

The effects of transcranial magnetic stimulation on vibratory-induced presynaptic inhibition of the soleus H reflex.

A single-pulse transcranial magnetic stimulus (TMS) may induce contraction in many muscles of the body at the same time. This is specially the case when using the double-cone coil to obtain the motor evoked potentials in leg muscles. Even if intensity is kept below threshold for the soleus muscle, TMS induces facilitation of the soleus H reflex that is separated into two phases: the first, peaking at 10-20 ms and the second, peaking at 70-90 ms. We investigated the possibility that TMS-induced facilitation of the H reflex was related, at least in part, to the reafferentation volley reaching the alpha motoneuron after synchronized contraction of other muscles in the body. To test this hypothesis, we examined the effects of vibration on the TMS-induced facilitation of the soleus H reflex. As expected, vibration applied over the triceps tendon caused a significant reduction in H reflex amplitude: 42.4 ± 6.4 % of control values. When conditioned by TMS at intervals corresponding to the first phase, the H reflex was facilitated to the same extent in both conditions: with and without vibration. However, at intervals corresponding to the second facilitation phase, there was a significantly reduced facilitation with vibration. These differential effects of vibration on the two phases of the TMS-induced facilitation of the H reflex indicate a different mechanism for each facilitation phase. The first phase could result from direct corticospinal excitatory input, while the second phase might depend on inputs via Ia afferents from heteronymous muscles.