First known case of catatonia due to cyclosporine A-related neurotoxicity in a pediatric patient with steroid-resistant nephrotic syndrome.

BACKGROUND: Catatonia is a neuropsychiatric syndrome characterized by diverse psychomotor abnormalities, including motor dysregulation and behavioral and affective disturbances. Once thought to occur primarily in the context of schizophrenia, recent data suggest most cases of catatonia develop in individuals with depressive or bipolar disorders. Moreover, catatonia may ensue in general medical and neurological conditions, as well as due to a variety of pharmaceuticals, drugs of abuse, and toxic agents. At one time considered rare in pediatric patients, evidence now suggests catatonia is both underrecognized and undertreated in this population, where it carries an elevated risk of morbidity and mortality. Here we present the case of a child with steroid-resistant nephrotic syndrome who developed catatonia due to cyclosporine A-related neurotoxicity. CASE PRESENTATION: A 9-year-old African-American boy with no psychiatric history and a 9-month history of nephrotic syndrome due to focal segmental glomerulosclerosis was admitted to the local children's hospital for management of mutism, posturing, insomnia, gait abnormalities, and somatic delusions. Seven days prior to admission, his cyclosporine plasma concentration was elevated at 1224 ng/mL (therapeutic range: 100-200 ng/mL). Upon admission, cyclosporine was discontinued and psychiatry was consulted, diagnosing catatonia. The patient subsequently received propofol 80 mg IV resulting in a transient lysis of catatonia. Over a lengthy hospitalization, the patient's catatonia was initially treated with lorazepam, quetiapine being added later to target psychosis. All signs and symptoms of catatonia resolved, and the patient was eventually tapered off both lorazepam and quetiapine with no return of symptoms more than 6 months later. CONCLUSIONS: To our knowledge, this case represents the first reported instance of cyclosporine A-induced catatonia in a patient with steroid-resistant nephrotic syndrome. It illustrates the importance of maintaining vigilance for signs and symptoms of cyclosporine A-related neurotoxicity (including catatonia) in patients with steroid-resistant nephrotic syndrome. In addition, it highlights the challenges faced by clinicians in jurisdictions that prohibit the use of electroconvulsive therapy in pediatric patients.

Current status and future prospects for the development of substance abuse vaccines.

INTRODUCTION: Substance use disorders (SUD) are a significant threat to both individual and public health. To date, SUD pharmacotherapy has focused primarily on agonist medications (i.e. nicotine replacement therapy for tobacco use disorder; methadone and buprenorphine for opioid use disorder), antagonist medications (i.e. naltrexone for opioid use disorder), and aversive therapy (i.e. disulfiram for alcohol use disorder). Pharmacotherapeutic approaches utilizing an immunological framework for medication development represent an important focus of study for treatment of these illnesses. Areas covered: This review discusses vaccines for treatment of substance use disorders. Using PubMed ( https://www.ncbi.nlm.nih.gov/pubmed/ ), we searched both preclinical and human clinical trials of vaccines for treatment of nicotine, cocaine, methamphetamine, and opioid use disorders. In addition, we searched for recently developed strategies for enhancement of the immunologic response through alteration of conjugate molecules and adjuvants. Expert commentary: Despite challenges in human clinical trials of SUD vaccines, a number of strategies have been introduced which may ultimately improve efficacy. These challenges, as well as their implications for vaccine development, are discussed. Additionally, the optimal conditions for research study and treatment are considered.

Anti-NMDA Receptor Encephalitis in a Patient with Previous Psychosis and Neurological Abnormalities: A Diagnostic Challenge.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by IgG autoantibodies directed against the NR1 subunit of the NMDA glutamate receptor. Psychiatric symptoms are common and include psychosis, mania, depressed mood, aggression, and speech abnormalities. Neurological symptoms such as seizures, decreased responsiveness, dyskinesias, and other movement abnormalities and/or autonomic instability are frequently seen as well. We present the case of a woman who was followed up at our facility for over 14 years for the treatment of multiple neuropsychiatric symptoms. Initially, she presented with paresthesias, memory loss, and manic symptoms. Nine years later, she presented to our facility again, this time with left sided numbness, left eyelid droop, and word finding difficulties. Finally, five years later, she presented with manic symptoms, hallucinations, and memory impairment. During her hospitalization, she subsequently developed catatonic symptoms and seizures. During her stay, it was discovered that she was positive for anti-NMDA receptor antibodies and her symptoms responded well to appropriate therapy. This case demonstrates that it may be useful for clinicians to consider screening for anti-NMDA receptor antibodies in long-term patients with neuropsychiatric symptoms that have not adequately responded to therapy.

Joint line restoration in a contemporary revision knee system.

We investigated a new revision total knee arthroplasty device and associated instrumentation to determine if it could reduce intraoperative complexity and restore the joint line through the arc of motion. In a prospective multicenter study, a total of 95 consecutive patients undergoing a revision knee arthroplasty were evaluated. Medical history, functional health scores, and intraoperative data were collected. The joint line was restored to 28 mm ± 5 mm in full extension and 90-degree flexion. Significant improvements were noted in all functional and general health scores. The anatomic boss position may allow for a reduction in instrumentation, as the need for femoral offset adapters was limited. Joint line restoration with proper posterior condylar offset correlated with positive functional outcomes.

Development of a scale to assess performance following primary total knee arthroplasty.

BACKGROUND: Quantitative assessment of postsurgical knee motion provides sensitive measurements, but results are technical and may not be meaningful to patients. Although several knee-specific instruments exist, no patient-reported outcome (PRO) measure correlates function with improved stability, motion, satisfaction, and confidence. OBJECTIVE: To address both the above limitations by developing a PRO measure to assess the phenomenon of a "normal" knee after primary total knee arthroplasty (TKA). METHODS: A draft conceptual model linking the impact of clinical mechanics to hypothesized functional outcomes was generated after a literature review of available assessment tools. Participants aged 18 to 80 years having undergone TKA within the past 10 to 18 months were identified and screened by clinical sites to participate in phase 1 focus groups or phase 2 in-depth interviews. Participants were asked to describe their TKA experiences, including how their knee feels now, followed by cognitive debriefing of Patient's Knee Implant Performance (PKIP) draft items. RESULTS: Phase 1 results indicated that concepts of confidence, stability, and satisfaction in patients' replacement knee when performing certain activities were distinct and important in the patients' assessment of their TKA. Phase 2 efforts yielded a final version of the PKIP measure containing nine items assessing the broader concepts of stability, confidence, and satisfaction in association with activities. Presurgical and postsurgical versions of the measure were created. CONCLUSIONS: Results of this qualitative study support use of the PKIP as a complementary PRO measure to assess performance after primary TKA. Psychometric evaluation of the PKIP is planned.

Mini-midvastus versus mini-medial parapatellar approach for minimally invasive total knee arthroplasty: outcomes pendulum is at equilibrium.

Comparisons between mini-midvastus (mMV) and mini-medial parapatellar approach (mMPP) for total knee arthroplasty (TKA) have reported variable results. We compared two approaches with minimum two year follow up. Forty consecutive patients who underwent staged bilateral TKA were prospectively randomized for mMPP approach in one knee and mMV approach in the other. Clinical parameters (muscle strength, pain, ROM, Knee Society Score) and surgic.l parameters (duration of surgery, blood loss, lateral releases) were assessed at 2, 6, 12 weeks and 6, 12, 24 months postoperatively. Clinical outcomes revealed inconsistent pattern of differences at various intervals. Surgical outcomes were not different. There were no major differences in outcomes between the two approaches. We recommend someone use surgical approach with which they are most familiar.

Effect of implant design on knee flexion.

From March 2006 to August 2008, 93 subjects (186 knees) underwent simultaneous bilateral total knee arthroplasty performed by eight surgeons at North American centers. This randomized study was conducted to determine whether non-weight-bearing passive flexion was superior for knees receiving a posterior stabilized high flexion device compared to a posterior stabilized standard device in the contra-lateral knee. Weight-bearing single leg active flexion was one secondary endpoint. Follow-up compliance was 92.5%. Results show small, but significant superiority in the motion metrics for the high flexion device compared to the standard device 12 months after surgery, especially for a subgroup of patients with pre-operative flexion less than 120° in both knees. Thus, the ideal candidate for the high flexion device may be one with lesser pre-operative flexion.

Function related specifications for total knee arthroplasty implant devices.

Current specifications for total knee implant devices reflect components' properties separate from each other and often in noncomparable units. We can recognize the tibial base plate thickness, size of femoral component, etc. How does it reflect the functional capabilities of the whole assembly, particularly in relation to wear and survivorship? Such approach does not take into account the fact that the individual components interact with each other, which in turn defines the final evaluation. We suggest a new function related approach to specifications which will help to develop clinically relevant standardization methodology. We propose an Index of Congruence to be added in the future as a required specification for implants of all designs. This universal standardization will help surgeons in preoperative planning and may also serve as a common denominator to enable comparative studies between diverse designs and different manufacturers.