L-Serine Treatment is Associated with Improvements in Behavior,EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants

Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01173-9.     

Small bowel obstruction in pregnancy

Background Intestinal obstruction in pregnancy is rare. Symptoms are often unspecific and a high level of suspicion is essential for early diagnosis. Fetal and maternal mortality rates are higher during pregnancy due to delay in diagnosis. Case A 31-year-old primigravida with a history of abdominal surgery was admitted because of worsening abdominal pain, abdominal distension and elevated pancreatic enzymes. Ultrasound showed dilated small bowel loops. Explorative laparotomy revealed a small bowel obstruction with partial bowel necrosis caused by a single adhesion. A jejuno-jejunostomy was performed. Five days later, she developed peritonitis. A secondary laparotomy and caesarean section were done. Conclusion In spite of timely diagnosis and prompt surgical intervention, our case was still complicated by peritonitis and early delivery. This underlines the necessity of immediate clinical suspicion. Small bowel obstruction should be considered in differential diagnosis of pregnant patients with a history of abdominal surgery.     

Pelvic Ring Fractures: Utility of Clinical Examination in Patients with Impaired Consciousness or Tracheal Intubation

Abstract Objective: To define the diagnostic accuracy of clinical examination in patients with impaired consciousness or endotracheal intubation to detect pelvic ring fractures and to identify those with severe bleeding. Methods: Included in this prospective data collection with retrolective data analysis were a consecutive series of blunt trauma victims with either a Glasgow Coma Scale ≤ 13 or tracheal intubation. Clinical examination comprised testing for stability of the iliac wings. Results: From 784 subjects (injury severity score 23.3 ± 17.4) 93 patients (11.9%) were found to have a pelvic ring fracture. Clinical instability of the pelvic ring was found in 42 patients. There was only one false positive. Fifty-two fractures could not be identified by clinical examination, including nine fractures (17%) that required surgical fracture stabilization (sensitivity of clinical examination 44.1%). Seventeen fractures (18.3%) were associated with a blood loss larger than 20% of circulating blood volume. Sixteen of those were identified by clinical instability of the pelvic ring (sensitivity 94.1%, specificity 97.0%, positive predictive value 38.1%, negative predictive value 99.9%). Conclusions: Clinical examination for stability of the pelvis in this selected group of patients missed a significant number of pelvic ring fractures including fractures that require surgical stabilization. The finding of a clinically unstable identifies most of the patients with the pelvic ring fracture being a major source of bleeding. A stable pelvis makes pelvic ring fracture as being the source of bleeding quite unlikely.     

Five-year results from chemonucleolysis with chymopapain or collagenase: a prospective randomized study

STUDY DESIGN: A 5-year clinical follow-up assessment of a prospective randomized study of chemonucleolysis using chymopapain (4000 IU) or collagenase (400 ABC units) was performed. SUMMARY OF BACKGROUND DATA: Intradiscal therapy can be performed for patients with contained discs by chemonucleolysis, percutaneous discectomy, or laser ablation. The oldest intradiscal therapy is chemonucleolysis with chymopapain. OBJECTIVE: The purpose of this study was to compare prospectively the efficacy of chymopapain and collagenase for intradiscal injection. METHODS: In this study, 100 patients with indication for intradiscal therapy were prospectively randomized to treatment with either chymopapain or collagenase. All the injections were performed by the double-needle technique with the patient under general anesthesia. The mean age of the patients was 35.5 years in the chymopapain group and 38 years in the collagenase group. An equal number of injections was performed at L4-L5 and L5-S1. RESULTS: After 5 years, good and excellent results were observed in 72% of the chymopapain group and 52% of the collagenase group when the surgically treated and lost patients were graded as poor. Using a scale of 0 (no pain) to 10 (intractable pain), the pain level dropped from 8.5 to 0.7 in the chymopapain group and from 8.6 to 0.9 in the collagenase group. Microdiscectomy at the injected level was required for 23 patients (14 in the collagenase group and 9 in the chymopapain group). CONCLUSIONS: After 5 years, no deterioration had occurred, as compared with the 1-year follow-up assessment. Chymopapain has proved to be safe, with one minor anaphylactic reaction, and effective even over the long term. Collagenase may need further study and cannot be recommended at this time.     

椎间盘源性腰痛的诊断与治疗

目的探讨腰椎间盘源性疼痛的诊断方法及采用前路经腹膜外入路椎间盘切除人工椎间盘置换或椎间cage植骨融合的临床疗效。方法35例经保守治疗无效的椎间盘源性腰痛患者接受手术治疗。椎间盘源性腰痛的诊断标准为：（1）腰部及下肢疼痛的部位与神经根定位不符；（2）症状反复发作，病程在半年以上；（3）MRI病变椎间盘T2加权像低信号；（4）椎间盘造影阳性，相邻节段为阴性对照；（5）关节突关节封闭除外关节突关节退变引起的疼痛。患者年龄25-67岁，平均43．6岁。L4-5 14例，L5S1 16例，L4-5和L5S1双间隙5例。前路经腹膜外入路椎间盘切除后行人工椎间盘置换13例16个椎间盘，椎间cage融合22例24个椎间盘。术后3-7天下地活动。腰围固定3个月。结果所有患者随访6～26个月，平均18个月。术后腰痛及下肢痛症状明显缓解，均恢复正常生活或工作。VAS评分由术前平均72分，降至术后18分，随访6个月时6．5分。ODI评分由术前平均21．5分。降至随访6个月时3分。椎间隙高度从术前平均9．5mm增加至术后13．5mm。手术时间70-120min，出血量100-400ml。随访时未发现肠梗阻、逆行射精和假体位置移动。结论椎间盘源性腰痛由于临床和影像学表现不典型，常被误诊或漏诊，可结合腰椎MRI及椎间盘造影进行诊断。腰椎前路椎间盘切除人工椎间盘置换或椎间cage融合是治疗椎间盘源性腰痛的有效选择。