scholarly journals Contactin-1 autoimmunity

2020 ◽  
Vol 7 (4) ◽  
pp. e771
Author(s):  
Divyanshu Dubey ◽  
Josephe A. Honorat ◽  
Shahar Shelly ◽  
Christopher J. Klein ◽  
Lars Komorowski ◽  
...  

ObjectiveTo determine serologic characteristics, frequency, phenotype, paraneoplastic associations, and electrodiagnostic and histopathologic features accompanying contactin-1 autoimmunity.MethodsArchived sera known to produce synaptic tissue-based immunofluorescence patterns were reevaluated, and contactin-1 specificity was confirmed by recombinant protein assays. Screening of 233 chronic/relapsing demyelinating neuropathies for additional cases was performed.ResultsWe identified 10 contactin-1 IgG seropositive cases. Frequency of contactin-1 immunoglobulin (Ig) G among tested Mayo Clinic chronic/relapsing demyelinating neuropathies was 2%. Sensory predominant presentations (n = 9, 90%), neuropathic pain (n = 6, 60%), and subacute progression (n = 5, 50%) were commonly encountered among contactin-1 neuropathies. Two patients had chronic immune sensory polyradiculopathy-like phenotype at presentation. Electrodiagnostic studies were consistent with demyelination (slowed conduction velocities and/or prolonged distal latencies) without conduction block. Markedly elevated CSF protein (median 222 mg/dL, range 69–960 mg/dL), thickening/gadolinium enhancement of nerve roots (4/5), and subperineural edema on nerve biopsy (4/4) were other characteristic features. Three cases were diagnosed with paraneoplastic demyelinating neuropathies (thymoma, n = 1; breast cancer, n = 1; plasmacytoma, n = 1). Four of the 9 patients treated with IV immunoglobulin demonstrated initial clinical improvement, but the favorable response was sustained in only 1 case (median follow-up, 60 months). Sustained clinical stabilization or improvement was observed among 3 of the 6 cases in whom second-line therapies (rituximab, cyclophosphamide, and azathioprine) were used.ConclusionContactin-1 IgG has a distinct sensory predominant presentation commonly associated with neuropathic pain, with demyelinating changes on electrophysiologic studies. A paraneoplastic cause should be considered. Testing of contactin-1 IgG among cases with similar presentations may guide immunotherapy selection, especially second-line immunotherapy consideration.

2020 ◽  
Vol 133 (3) ◽  
pp. 830-838 ◽  
Author(s):  
Andrea Franzini ◽  
Giuseppe Messina ◽  
Vincenzo Levi ◽  
Antonio D’Ammando ◽  
Roberto Cordella ◽  
...  

OBJECTIVECentral poststroke neuropathic pain is a debilitating syndrome that is often resistant to medical therapies. Surgical measures include motor cortex stimulation and deep brain stimulation (DBS), which have been used to relieve pain. The aim of this study was to retrospectively assess the safety and long-term efficacy of DBS of the posterior limb of the internal capsule for relieving central poststroke neuropathic pain and associated spasticity affecting the lower limb.METHODSClinical and surgical data were retrospectively collected and analyzed in all patients who had undergone DBS of the posterior limb of the internal capsule to address central poststroke neuropathic pain refractory to conservative measures. In addition, long-term pain intensity and level of satisfaction gained from stimulation were assessed. Pain was evaluated using the visual analog scale (VAS). Information on gait improvement was obtained from medical records, neurological examination, and interview.RESULTSFour patients have undergone the procedure since 2001. No mortality or morbidity related to the surgery was recorded. In three patients, stimulation of the posterior limb of the internal capsule resulted in long-term pain relief; in a fourth patient, the procedure failed to produce any long-lasting positive effect. Two patients obtained a reduction in spasticity and improved motor capability. Before surgery, the mean VAS score was 9 (range 8–10). In the immediate postoperative period and within 1 week after the DBS system had been turned on, the mean VAS score was significantly lower at a mean of 3 (range 0–6). After a mean follow-up of 5.88 years, the mean VAS score was still reduced at 5.5 (range 3–8). The mean percentage of long-term pain reduction was 38.13%.CONCLUSIONSThis series suggests that stimulation of the posterior limb of the internal capsule is safe and effective in treating patients with chronic neuropathic pain affecting the lower limb. The procedure may be a more targeted treatment method than motor cortex stimulation or other neuromodulation techniques in the subset of patients whose pain and spasticity are referred to the lower limbs.


Hand ◽  
2021 ◽  
pp. 155894472199246
Author(s):  
David D. Rivedal ◽  
Meng Guo ◽  
James Sanger ◽  
Aaron Morgan

Targeted muscle reinnervation (TMR) has been shown to improve phantom and neuropathic pain in both the acute and chronic amputee population. Through rerouting of major peripheral nerves into a newly denervated muscle, TMR harnesses the plasticity of the brain, helping to revert the sensory cortex back toward the preinsult state, effectively reducing pain. We highlight a unique case of an above-elbow amputee for sarcoma who was initially treated with successful transhumeral TMR. Following inadvertent nerve biopsy of a TMR coaptation site, his pain returned, and he was unable to don his prosthetic. Revision of his TMR to a more proximal level was performed, providing improved pain and function of the amputated arm. This is the first report to highlight the concept of secondary neuroplasticity and successful proximal TMR revision in the setting of multiple insults to the same extremity.


Author(s):  
Giorgi Kuchukhidze ◽  
Davit Baliashvili ◽  
Natalia Adamashvili ◽  
Ana Kasradze ◽  
Russell R Kempker ◽  
...  

Abstract BACKGROUND High rates of loss to follow-up (LFU) exist among patients with multi-drug and extensively drug-resistant tuberculosis (M/XDR TB); We aimed to identify long-term clinical outcomes of patients who were LFU during second-line TB treatment. METHODS We conducted a follow-up study among adults who received second-line TB treatment in the country of Georgia during 2011-2014 with a final outcome of LFU. We attempted to interview all LFU patients, administered a structured questionnaire and obtained sputum samples. Active TB at follow-up was defined by positive sputum Xpert-TB/RIF or culture. RESULTS Follow-up information was obtained for 461 patients, among these patients, 107 (23%) died and 177 (38%) were contacted, of those contacted 123 (69%) consented to participate and 92 provided sputum samples. Thirteen (14%) had active TB with an estimated infectious time-period for transmitting drug-resistant TB in the community of 480 days (IQR=803). In multivariable analysis, positive culture at the time of LFU was associated with active TB at the time of our study (adjusted risk ratio=13.3, 95% CI: 4.2, 42.2) CONCLUSIONS Nearly one-quarter of patients on second-line TB treatment who were LFU died. Among those LFU evaluated in our study, one in seven remained in the community with positive sputum cultures. To reduce death and transmission of disease, additional strategies are needed to encourage patients to complete treatment.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Rie Ishikawa ◽  
Masako Iseki ◽  
Rie Koga ◽  
Eiichi Inada

Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. Seventy-six patients were able to complete follow-up surveys. The prevalence of PHI was 47/76 (62%), 28/76 (37%), and 34/76 (45%) at the acute, subacute, and chronic stages, respectively. PHI manifestation times and patterns varied. We investigated the relationship of PHI with neuropathic pain using the visual analog scale (VAS), which is a measure of pain intensity, and the PDQ, which is a questionnaire used to evaluate the elements of neuropathic pain. The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.


Neurosurgery ◽  
2010 ◽  
Vol 66 (5) ◽  
pp. 986-990 ◽  
Author(s):  
Dirk De Ridder ◽  
Sven Vanneste ◽  
Mark Plazier ◽  
Elsa van der Loo ◽  
Tomas Menovsky

Abstract INTRODUCTION Spinal cord stimulation is commonly used for neuropathic pain modulation. The major side effect is the onset of paresthesia. The authors describe a new stimulation design that suppresses pain as well as, or even better than, the currently used stimulation, but without creating paresthesia. METHODS A spinal cord electrode (Lamitrode) for neuropathic pain was implanted in 12 patients via laminectomy: 4 at the C2 level and 7 at the T8–T9 level for cervicobrachialgia and lumboischialgia, respectively (1 at T11 at another center). During external stimulation, the patients received the classic tonic stimulation (40 or 50 Hz) and the new burst stimulation (40-Hz burst with 5 spikes at 500 Hz per burst). RESULTS Pain scores were measured using a visual analog scale and the McGill Short Form preoperatively and during tonic and burst stimulation. Paresthesia was scored as present or not present. Burst stimulation was significantly better for pain suppression, by both the visual analog scale score and the McGill Short Form score. Paresthesia was present in 92% of patients during tonic stimulation, and in only 17% during burst stimulation. Average follow-up was 20.5 months. CONCLUSION The authors present a new method of spinal cord stimulation using bursts that suppress neuropathic pain without the mandatory paresthesia. Pain suppression seems as good as or potentially better than that achieved with the currently used stimulation. Average follow-up after nearly 2 years (20.5 months) suggests that this stimulation design is stable.


1992 ◽  
Vol 50 (3) ◽  
pp. 313-318 ◽  
Author(s):  
Joaquim P. Brasil-Neto

The author reviews the literature on electromyography and nerve conduction velocity studies in leprosy. It is concluded that these studies can be helpful in the early diagnosis of neural involvement, in the elucidation of pathophysiological mechanisms, and in the follow-up of patients under medical and/or surgical treatment.


2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
V Schillaci ◽  
G Stabile ◽  
G Shopova ◽  
A Arestia ◽  
A Agresta ◽  
...  

Abstract Background Isthmus-dependent right atrial flutter is the most frequently encountered atrial flutter in clinical practice (80–90% of atrial flutters). Purpose The aim of our study was to assess as first experience the feasibility and safety of radiofrequency catheter ablation (RFCA) of cavo-tricuspid isthmus (CTI) guided by KODEX-EPD imaging system in patients presenting with typical atrial flutter (AFL). Methods 16 consecutive patients (mean age 68,46±7,8 years, 80% males) with diagnosis of AFL underwent RFCA guided by KODEX-EPD imaging system. In 15 patients the analysis performed during tachycardia showed a counter-clockwise activation. In 1 patient no tachycardia could be induced and the ablation was performed in sinus rhythm with fixed pacing from the coronary sinus. The KODEX-EPD imaging system was also used to guide ablation and to confirm persistent bidirectional block after ablation. Results Mean procedural time was 37,6±8,2 min, mean radiofrequency ablation time was 7,8±3,4 min, and mean fluoroscopy time was 2,1±1,2 min. All procedures were acutely successful with interruption of AFL during RFCA along the inferior CTI in 15 patients and achievement of the bidirectional conduction block in 16 patients proven by atrial pacing medial and lateral to the ablation line. There were no major procedural and 30-day complications. Over a mean follow-up of 18 months, we observed no recurrence of arrhythmia and no complications. Conclusions Our study shows that RFCA for AFL using the KODEX-EPD imaging system is feasible, safe, and effective. FUNDunding Acknowledgement Type of funding sources: None.


2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 51-51
Author(s):  
Xiaoyun Pan ◽  
Lincy S. Lal ◽  
John White ◽  
Seyed Hamidreza Mahmoudpour ◽  
Christian Valencia

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Julian Andres Marin-Acevedo ◽  
Bethany Withycombe ◽  
Youngchul Kim ◽  
Zeynep Eroglu ◽  
Joseph Markowitz ◽  
...  

9562 Background: Anti-PD1 (aPD1) monotherapy with cemiplimab-rwlc or pembrolizumab is now considered standard of care for first-line management of advanced CSCC not amenable to surgery or curative radiotherapy. Previously chemotherapy or anti-EGFR agents were commonly used for these patients albeit with modest efficacy and limited duration of response. In prospective evaluation, the overall response rate (ORR) to cetuximab was 28% with disease control rate (DCR) of 69% at 6 weeks. The efficacy of second-line treatment following primary or acquired resistance to aPD1 therapy is not known. We investigated the activity of cetuximab in patients who progressed on previous IO therapy. Methods: We performed a single institution retrospective review from 9/28/18 (US approval date of cemiplimab-rwlc for CSCC) through 11/30/20 of patients with locally advanced or metastatic CSCC who received cetuximab after prior IO therapy. We identified patients who received cetuximab either immediately following IO therapy (cohort A) or as a subsequent line not immediately following IO therapy (cohort B). Primary endpoint was ORR with secondary endpoints of DCR, survival and toxicity. Median follow-up and survival times were calculated using the Kaplan-Meier method. Results: Thirteen patients, median age 72 years (62-82), all Caucasian, and 11 males (85%) were included in this study. Eleven pts received cetuximab immediately post-IO progression; two had additional intervening therapy post-IO before receiving cetuximab. Three patients received concurrent radiotherapy (palliative or definitive) with cetuximab. The ORR to cetuximab was 54% (7/13) including 1 complete and 6 partial responses. The cumulative 6-month DCR was 77%. All responses were observed in cohort A; both patients in cohort B had progressive disease as best response. Six of 7 initial responses are ongoing, including 3 in whom cetuximab was discontinued. At a median follow-up of 9.1 months, the median PFS has not been reached for the entire cohort. There were no unanticipated toxicities to cetuximab with rash (77%) and hypomagnesemia (54%) being the most common adverse events. Conclusions: In advanced CSCC, cetuximab used immediately after progression on aPD1 therapy yields notably higher and durable overall response than previously reported in the pre-IO therapy era. If validated in a larger dataset, this should be the preferred therapy for second-line treatment in advanced CSCC. Further exploration into the mechanism of this high efficacy of anti-EGFR therapy post aPD1 therapy is warranted.


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