Citations

Erythromelalgia is a rare disorder characterized by episodic burning pain with redness and warmth of the extremities. Topical and systemic medications are the mainstay of management. We reviewed the published evidence for using procedural interventions to manage erythromelalgia, including their proposed mechanism of action and possible adverse effects, and included information in this review on epidural infusion, sympathetic ganglion block, sympathectomy, pulsed radiofrequency, spinal cord stimulation, dorsal root ganglion stimulation, brain stimulation, transcranial magnetic stimulation, and botulinum toxin injections. Both successful and unsuccessful outcomes have been reported. Although these procedural interventions extend the therapeutic options for erythromelalgia, the evidence for their use is limited. Case reports and small case series comprise most of the evidence. Based on our review, a multidisciplinary approach to management may be needed for patients with erythromelalgia.

Abstract Objective Randomized trials have demonstrated efficacy of spinal cord stimulation (SCS) for treatment of painful diabetic neuropathy (PDN). Preliminary data suggested that treatment of PDN with high-frequency SCS resulted in improvements on neurological examination. The purpose of the present study was to explore whether patients with PDN treated with high-frequency SCS would have improvements in lower-extremity peripheral nerve function. Design Prospective cohort study in an outpatient clinical practice at a tertiary care center. Methods Patients with PDN were treated with high-frequency SCS and followed up for 12 months after SCS implantation with clinical outcomes assessments of pain intensity, neuropathic symptoms, and neurological function. Small-fiber sudomotor function was assessed with the quantitative sudomotor axon reflex test (QSART), and large-fiber function was assessed with nerve conduction studies (NCS). Lower-extremity perfusion was assessed with laser Doppler flowmetry. Results Nine patients completed 12-month follow-up visits and were observed to have improvements in lower-extremity pain, weakness, and positive sensory symptoms. Neuropathy impairment scores were improved, and 2 patients had recovery of sensory responses on NCS. A reduction in sweat volume on QSART was observed in the proximal leg but not at other sites. No significant differences were noted in lower-extremity perfusion or NCS as compared with baseline. Conclusions The improvement in pain relief was concordant with improvement in neuropathy symptoms. The findings from this study provide encouraging preliminary data in support of the hypothesis of a positive effect of SCS on peripheral neuropathy, but the findings are based on small numbers and require further evaluation. Trial registration ClinicalTrials.gov ID NCT03769675.

Abstract Rationale Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. Objectives To characterize the clinical features and metabolic risk factors for prostacyclin-associated leg pain. Methods At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain. Measurements and Main Results Over a period of 2 years, we identified 11 patients with PAH and prostacyclin-associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20–96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14–36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small-fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small-fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin B12 deficiency in six (55%), uncompensated hypothyroidism in three (27%), and diabetes mellitus in one (9%). Conclusions Chronic prostacyclin-associated leg pain is associated with a small-fiber neuropathy. Treatable metabolic contributors (vitamin B12 deficiency, thyroid dysfunction, or diabetes) appear to be common possible “second hits” that may be underrecognized. We recommend screening for possible metabolic contributors in patients who have otherwise unexplained leg pain in the setting of PAH and current or anticipated prostacyclin therapy.

Objectives: The purpose of this single center, prospective randomized controlled trial was to compare clinical outcomes between an ultrasound-guided greater occipital nerve block (GONB) at the C2 vertebral level versus landmark-based GONB at the superior nuchal line. Methods: Patients with occipital neuralgia or cervicogenic headache were randomized to receive either a landmark-based GONB with sham ultrasound at the superior nuchal line or ultrasound-guided GONB at the C2 vertebral level with blinding of patients and data analysis investigators. Clinical outcomes were assessed at 30 minutes, 2 weeks, and 4 weeks postinjection. Results: Thirty-two patients were recruited with 16 participants in each group. Despite randomization, the ultrasound-guided GONB group reported higher numeric rating scale (NRS) scores at baseline. Those in the ultrasound-guided GONB group had a significant decrease in NRS from baseline compared with the landmark-based GONB group at 30 minutes (change of NRS of 4.0 vs. 2.0) and 4-week time points (change of NRS of 2.5 vs. −0.5). Both groups were found to have significant decreases in Headache Impact Test-6. The ultrasound-guided GONB had significant improvements in NRS, severe headache days, and analgesic use at 4 weeks when compared with baseline. No serious adverse events occurred in either group. Conclusions: Ultrasound-guided GONBs may provide superior pain reduction at 4 weeks when compared with landmark-based GONBs for patients with occipital neuralgia or cervicogenic headache.

Abstract The primary aim of this randomized clinical trial is to investigate the effects of ultrasound-guided transversus abdominis plane (TAP) vs ultrasound-guided trigger point injections (TPIs) on numerical rating scale pain scores at month 3 follow-up in patients with a chronic abdominal wall pain. The primary outcome measure was the difference in mean numeric rating scale pain scores between the TAP and TPI groups at month 3 in an intent-to-treat (ITT) analysis. A total of 60 patients were randomized 1:1 to receive an ultrasound-guided TAP block (n = 30) or an ultrasound-guided TPI (n = 30). No significant group differences in baseline demographic or clinical characteristics were observed. The mean baseline pain score for the TAP and TPI groups was 5.5 and 4.7, respectively. In the ITT analysis at month 3, the between-group difference in pain scores was 1.7 (95% confidence interval, 0.3-3.0) favoring the TPI group. In a secondary per-protocol analysis, the between-group difference in pain scores was 1.8 (95% confidence interval, 0.4-3.2) favoring the TPI group. For the ITT and per-protocol analyses, the group differences in pain scores were consistent with a medium effect size. The main finding of this randomized clinical trial is that adults with chronic abdominal wall pain who received a TPI reported significantly lower pain scores at month 3 follow-up compared with patients who received a TAP block.

Abstract 1. Combinations of effective agents produce at least an additive increase in complete remission rates over that which can be achieved when the agents are used individually. 2. Patients who do not achieve complete remission with initial treatment have a significantly shorter survival. 3. Alternating MTX and 6-MP at 28-day intervals during remission does not prolong the duration of remission over that of combined concurrent 6-MP and MTX. 4. The administration of folic acid antagonists intrathecally at 28-day intervals during antimetabolite maintained remission did not prolong the duration of remission. Meningeal leukemia, however, occurred significantly less frequently in these patients. 5. The duration of combined 6-MP and MTX maintained remission is not greater than that of 6-MP maintained remission. 6. The toxicity of 6-MP and MTX in combination in patients in remission is additive. The above conclusions were drawn from this comparative study of combinations of chemotherapeutic agents in children with acute lymphocytic leukemia.

Abstract The efficacy of three therapeutic programs for acute leukemia were compared. These programs included (1) Methotrexate (Phase I) followed by 6-mercaptopurine (Phase II); (2) 6-mercaptopurine (Phase I) followed by Methotrexate (Phase II); and (3) Combination Therapy, i.e., 6-mercaptopurine given in combination with Methotrexate. In children with acute lymphocytic leukemia the remission rate was 59 per cent for combination therapy, 47 per cent for 6-mercaptopurine, and 29 per cent for Methotrexate. The better remission rate for combination therapy is consistent with that predicted if it is assumed that 6-mercaptopurine and Methotrexate act independently. The median duration of complete remissions for the three treatments was not different (4 to 5 months). However, long lasting remissions were more frequent in patients receiving combination therapy. The median survival from the onset of therapy to death was 9 months. There were no differences between the three treatment programs as regards survival. In adults the remission rate was 15 per cent for combination therapy, 21 per cent for 6-mercaptopurine and 7 per cent for Methotrexate. As regards survival in adults, early deaths were more common in patients who received MTX as initial therapy, whereas after 5 months survival was somewhat better in those patients receiving combination therapy. In both children and adults there was no evidence that prior treatment with one of the antimetabolites altered response to the other antimetabolite. This result differs from those in animal models, and its effect on our concept of the mechanism of resistance is discussed. Responsiveness to the second course of antimetabolite therapy (Phase II) was as good as that to the first course of treatment. This was true for the remission rate, remission duration, and even for survival when appropriate corrections were made. Thus, responsiveness to drug therapy is maintained as the disease progresses temporally. It may be concluded therefore that new agents can be effectively studied in patients with "late" disease. Responsiveness to Phase II therapy was independent of responsiveness to Phase I. The most common and severe toxic manifestations related to the bone marrow and gastrointestinal tract. There were no major differences quantitatively in the toxicity for the three treatment programs in children in spite of the fact that the drugs were given in full dosage in the combination program. Oral ulcers and a generalized erythematous rash occurred significantly more frequently in patients receiving Methotrexate. Jaundice was significantly more frequent in adults and in patients receiving 6-MP.

Background and objective Epidural blood patch (EBP) is a safe and effective treatment for spontaneous intracranial hypotension (SIH), but clinical and procedural variables that predict EBP efficacy remain nebulous. Methods This study is an institutional review board-approved retrospective case series with dichotomized EBP efficacy defined at 3 months. The study included 202 patients receiving 604 EBPs; iatrogenic cerebrospinal fluid leaks were excluded. Results Of the EBPs, 473 (78%) were single-level, 349 (58%) lumbar, 75 (12%) bilevel, and 56 (9%) multilevel (≥3 levels). Higher volume (OR 1.64; p<0.0001), bilevel (3.17, 1.91–5.27; p<0.0001), and multilevel (117.3, 28.04–490.67; p<0.0001) EBP strategies predicted greater efficacy. Only volume (1.64, 1.47–1.87; p<0.0001) remained significant in multivariate analysis. Site-directed patches were more effective than non-targeted patches (8.35, 0.97–72.1; p=0.033). Lower thoracic plus lumbar was the most successful bilevel strategy, lasting for a median of 74 (3–187) days. Conclusions In this large cohort of EBP in SIH, volume, number of spinal levels injected, and site-directed strategies significantly correlated with greater likelihood of first EBP efficacy. Volume and leak site coverage likely explain the increased efficacy with bilevel and multilevel patches. In patients with cryptogenic leak site, and either moderate disability, negative prognostic brain MRI findings for successful EBP, or failed previous lumbar EBP, a low thoracic plus lumbar bilevel EBP strategy is recommended. Multilevel EBP incorporating transforaminal administration and fibrin glue should be considered in patients refractory to bilevel EBP. An algorithmic approach to treating SIH is proposed.