Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking. Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies. Design: Case study. Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA. Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories. Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics.

Introduction: In patients with SARS-CoV-2, innate immunity is playing a central role, depicted by hyperinflammation and longer lasting inflammatory response. Reliable inflammatory markers that cover both acute and long-lasting COVID-19 monitoring are still lacking. Thus, we investigated one specific inflammatory marker involved as one key player of the immune system, kynurenine (Kyn), and its use for diagnosis/detection of the Long-/Post-COVID syndrome in comparison to currently used markers in both serum and saliva samples. Material and methods: The study compromised in total 151 inpatients with a SARS-CoV-2 infection hospitalized between 03/2020 and 09/2021. The group NC (normal controls) included blood bank donors (n=302, 144f/158m, mean age 47.1 ± 18.3 years (range 18-75)). Two further groups were generated based on Group A (n=85, 27f/58m, mean age 63.1 ± 18.3 years (range 19-90), acute admission to the hospital) and Group B (n=66, 22f/44m, mean age 66.6 ± 17.6 years (range 17-90), admitted either for weaning or for rehabilitation period due to Long-COVID symptoms/syndrome). Plasma concentrations of Kyn, C-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured on admission. In Group B we determined Kyn 4 weeks after the negative PCR-test. In a subset of patients (n=11) concentrations of Kyn and CRP were measured in sera and saliva two, three and four months after dismission. We identified 12 patients with Post-COVID symptoms >20 weeks with still significant elevated Kyn-levels. Results: Mean values for NC used as reference were 2.79 ± 0.61 µM, range 1.2-4.1 µM. On admission, patients showed significantly higher concentrations of Kyn compared to NC (p-values < 0.001). Kyn significantly correlated with IL-6 peak-values (r=0.411; p-values <0.001) and CRP (r=0.488, p-values<0.001). Kyn values in Group B (Long-/Post-COVID) showed still significant higher values (8.77 ± 1.72 µM, range 5.5-16.6 µM), whereas CRP values in Group B were in the normal range. Conclusion: Serum and saliva Kyn are reflecting the acute and long-term pathophysiology of the SARS-CoV-2 disease concerning the innate immune response and thus may serve a useful biomarker for diagnosis and monitoring both Long- and Post-COVID syndrome and its therapy.

Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease.

BACKGROUND: Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons. OBJECTIVE: To determine whether nanoparticular CoQ(10) is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial. SETTING: Academic and nonacademic movement disorder clinics. PATIENTS: One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable antiparkinsonian treatment. Intervention Random assignment to placebo or nanoparticular CoQ(10) (100 mg 3 times a day) for a treatment period of 3 months. Stratification criterion was levodopa treatment. MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of the sum score of the UPDRS parts II and III between the baseline and 3-month visits. RESULTS: One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the sum UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the CoQ(10) group (P = .82). Statistical analysis according to the stratification did not result in significant changes of the primary outcome variable. No secondary outcome measure showed a significant change between the placebo group and the CoQ(10) group. The frequency and quality of adverse events were similar in both treatment groups. CONCLUSIONS: Nanoparticular CoQ(10) at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on CoQ(10) does not display symptomatic effects in midstage Parkinson disease.

24/7 Live Stream Telemedicine Home Treatment Service for Parkinson's Disease Patients.

BACKGROUND: Treatment of advanced-stage idiopathic Parkinson's disease (PD) is a demanding challenge, and in Germany, medication regimen adjustments are often made during inpatient stays. Admissions often follow an acute worsening of symptoms and functioning. In order to reduce long and expensive inpatient stays, and to provide more frequent consultations, a 24/7 live stream telemedicine home treatment service was established. METHODS: A pilot study was conducted in which laptops were distributed to 50 patients for 1 year to see whether such a service was feasible (in terms of patient participation and compliance) and whether this intervention affected the patient's condition, measured in UPDRS, Mini-Mental Status Examination (MMSE), 39-item Parkinson's Disease Questionnaire (PDQ39), and H & Y Scale. RESULTS: Seventy-two percent (36) of the patients were compliant and did not experience technical issues. Patients lived, on average, 198 ± 183 km away from the specialist clinic. In total, 264 video conversations took place with 6.9 ± 7.2 (0-29) calls per patient. We found a significant improvement in PDQ39 scores, but not in UPDRS, MMSE, or H & Y scores, at 1 year. CONCLUSIONS: Our data shows that 24/7 live stream telemedicine is feasible and can help to improve quality of life. However, a detailed preliminary review of the patient's willingness to use such a service should be made to obtain the best results. Improvement of the technical setup and network coverage would facilitate an improved service and increase efficiency.

Immunoadsorption in steroid-refractory multiple sclerosis: clinical experience in 60 patients.

BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system with a frequently relapsing or progressive course. For steroid-resistant relapse, plasma exchange (PE) has been established as guidelines-recommended treatment option. While PE is a non-selective extracorporeal blood purification process with elimination of plasma and subsequent substitution, immunoadsorption (IA) is a selective technique for the removal of autoantibodies and immune complexes with less adverse effects. So far there are only few reports on the treatment of MS by IA. The aim of this retrospective study was to assess the efficacy and safety of IA as an escalation therapy in MS patients. PATIENTS AND METHODS: A total of 60 patients with steroid-refractory MS relapse were treated by IA and analyzed retrospectively. Patients received six standardized IA sessions using a non-regenerable tryptophan immunoadsorber, at average 58 days after first indications of relapse. The treated plasma volume was two liters per IA session. Outcome was measured as improvement in relapse symptoms. From the pilot phase of the study comprising the first fourteen patients, detailed neurological examinations before and after IA such as Expanded Disability Status Scale (EDSS), Functional System Score (FS) and visual acuity are reported. Of the following 46 patients, only qualitative data regarding the therapeutic success, and in addition clinical data on tolerability, are presently available. RESULTS: In 53 of 60 patients clinically relevant improvement of the main symptom of MS relapse was noted after IA, there was no change in six patients, deterioration in one. This corresponds to a response rate of 88%. Symptomatic improvement was first registered on average after the third IA. 87.5% of patients could be treated through a peripheral venous access. Only 12.5% needed a central venous catheter. In four of 396 single treatments (1%) significant complications occurred, mild side effects or discomfort were registered 16 times (4%). If peripheral venous access was chosen, missed puncture or puncture hematoma occurred in 22 cases (5.5%). CONCLUSION: Immunoadsorption for the treatment of steroid-refractory MS relapse is safe and effective. The response rate was 88% and non-inferior to previous results with plasma exchange. Due to good tolerability, the treatment with immunoadsorption, which is usually possible through a peripheral venous access, can be performed on an outpatient basis.