Publications by authors named "Ralf Gold"

543 Publications

Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis.

J Neurol 2021 Oct 9. Epub 2021 Oct 9.

University of Bari, Bari, Italy.

Early intervention with high-efficacy disease-modifying therapy (HE DMT) may be the best strategy to delay irreversible neurological damage and progression of multiple sclerosis (MS). In European healthcare systems, however, patient access to HE DMTs in MS is often restricted to later stages of the disease due to restrictions in reimbursement despite broader regulatory labels. Although not every patient should be treated with HE DMTs at the initial stages of the disease, early and unrestricted access to HE DMTs with a positive benefit-risk profile and a reasonable value proposition will provide the freedom of choice for an appropriate treatment based on a shared decision between expert physicians and patients. This will further optimize outcomes and facilitate efficient resource allocation and sustainability in healthcare systems and society.
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http://dx.doi.org/10.1007/s00415-021-10836-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501364PMC
October 2021

Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.

Eur Heart J 2021 Oct 1. Epub 2021 Oct 1.

Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.

Aims: Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism.

Methods And Results: Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels.

Conclusion: Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.
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http://dx.doi.org/10.1093/eurheartj/ehab644DOI Listing
October 2021

Hospital Admissions for Neurodegenerative Diseases during the First Wave of the COVID-19 Pandemic: A Nationwide Cross-Sectional Study from Germany.

Brain Sci 2021 Sep 15;11(9). Epub 2021 Sep 15.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44801 Bochum, Germany.

(1) Background: The COVID-19 pandemic impacts healthcare utilization across all care settings and health conditions. The objective of this study was to determine changes in hospital admissions for neurodegenerative diseases (NDD) during the first COVID-19 wave in Germany; (2) Methods: This cross-sectional study used nationwide administrative claims data covering 1468 hospitals. The primary outcome was the year-to-year relative change in case numbers during a four-month study period (16 January-15 May 2020 vs. 2019) during the first pandemic wave. Secondary outcomes included year-to-year relative changes during a four-week peak phase (16 March-15 April) and changes between differential phases of the wave. The analyzed NDD comprised progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease; (3) Results: Hospital admissions for any reason decreased by 16.7% in 2020 during the study period and by 36.6% during the peak phase, whereas admissions for NDD decreased by 27.6% and 65.0%, respectively. PSP cases decreased during the study period (-34.7%) and the peak phase (-68.1%) and stayed reduced in a late phase with falling COVID-19 numbers. MSA and ALS cases increased strongest after the peak, with ALS cases being comparatively weakly reduced during the study period (-17.3%) and peak phase (-51.7%); (4) Conclusions: Inpatient care utilization for NDD changed differentially during the first wave of the COVID-19 pandemic in Germany and showed a greater reduction than overall and general neurological admissions. Mitigating long-term health deterioration of this vulnerable subgroup is important to reduce morbidity and mortality in the future.
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http://dx.doi.org/10.3390/brainsci11091219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466543PMC
September 2021

Report of a fulminant anti-pan-neurofascin-associated neuropathy responsive to rituximab and bortezomib.

J Peripher Nerv Syst 2021 Sep 5. Epub 2021 Sep 5.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

Inflammatory neuropathies with pathogenic involvement of the nodes of Ranvier through autoantibodies have been increasingly characterized in the past years. The so-called anti-pan-NF-associated neuropathies caused by the simultaneous existence of anti-Neurofascin-186/-140 and -155-antibodies are extremely rare and cause life-threatening symptoms. Therapeutic strategies are needed as symptoms may be life-threatening and may not respond to standard first-line CIDP treatment. We report a case of a 52-year-old male with a rare anti-pan-neurofascin (NF) (-155, -186/-140)-associated neuropathy. The initial presentation was subacute with mild paresthesia leading to a fulminant "locked-in"-like syndrome requiring mechanical ventilation within the first eight weeks despite treatment with intravenous immunoglobulins. Nerve conduction studies revealed non-excitable nerves with acute spontaneous activity in electromyography. High titers of anti-Neurofascin-155, -186/-140-antibodies were detected in serum and cerebrospinal fluid. A combination of aggressive immunotherapy consisting of intravenous immunoglobulins, plasma exchange, rituximab and bortezomib resulted in clinical improvement with ambulation and non-detectable anti-neurofascin-antibodies within the following 3 months. The follow-up nerve conduction studies showed normalized amplitudes of the peripheral nerves with signs of reinnervation in electromyography. We conclude that an early aggressive immunotherapy consisting of a combination of rituximab and bortezomib could be considered as a therapeutic option for anti-pan-NF-associated neuropathies.
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http://dx.doi.org/10.1111/jns.12465DOI Listing
September 2021

Maintenance therapy with subcutaneous immunoglobulin in a patient with immune-mediated neuropathic postural tachycardia syndrome.

J Transl Autoimmun 2021 14;4:100112. Epub 2021 Aug 14.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

Aims: We describe the disease course of a 35-year-old female with an autoimmune mediated neuropathic postural tachycardia syndrome (PoTS), who responded to immunoglobulin therapy and stabilized on maintenance therapy with subcutaneous immunoglobulin (SCIg).

Methods: We provide longitudinal data of clinical scores, tilt-table results and antibody titers.

Results: Initial treatment with intravenous immunoglobulin caused infusion-related side-effects whereas SCIg was well tolerated and improved clinical symptoms and quality of life. Clinical improvement correlated with the reduction of serum antibody titers 22 months after first infusion.

Conclusions: These findings suggest that autoimmune-mediated neuropathic PoTS can be treated sufficiently with IVIg whereas SCIg minimizes side-effects.
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http://dx.doi.org/10.1016/j.jtauto.2021.100112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387908PMC
August 2021

Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results.

Mult Scler 2021 Sep 1:13524585211037909. Epub 2021 Sep 1.

Biogen, Cambridge, MA, USA.

Background: Dimethyl fumarate (DMF) demonstrated favorable benefit-risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension.

Objective: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE.

Methods: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0-2), then DMF (Years 3-10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years.

Results: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04-10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF ( = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120-0.169)), while for PBO/DMF ( = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0-2 years, 0.330 (95% CI, 0.266-0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118-0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening.

Conclusion: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF's positive benefit/risk profile for long-term RRMS treatment.
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http://dx.doi.org/10.1177/13524585211037909DOI Listing
September 2021

Short- and long-term outcome of patients with spontaneous echo contrast or thrombus in the left atrial appendage in the era of the direct acting anticoagulants.

Clin Res Cardiol 2021 Aug 26. Epub 2021 Aug 26.

Cardiology and Rhythmology, University Hospital St. Josef Hospital, Ruhr-University Bochum, Gudrunstraße 56, 44791, Bochum, Germany.

Background: Thrombi and spontaneous echo contrast (SEC) in the left atrial appendage (LAA) are associated with thromboembolic events and poor prognosis. There are very few data on long-term outcome, especially with the use of direct acting anticoagulants (DOAC).

Methods: In this retrospective study, all transoesophageal echocardiographies performed at a tertiary care university hospital from 2015 to 2020 were analyzed. All patients with thrombus or SEC in the LAA were included. Medical history, laboratory, echocardiographic parameters and medication at discharge were documented. The primary endpoint of the study was a composite endpoint (all-cause mortality, non-fatal stroke or transient ischaemic attack [TIA], non-fatal systemic embolization, non-fatal major bleeding and non-fatal myocardial infarction).

Results: Of a total of 4062 transoesophageal echocardiographies, thrombi were detected in 51 patients (1.2%) and SEC in 251 patients (6.2%). These patients formed the final study cohort (n = 302). During a mean follow-up period of 956 ± 663 days, 87 patients (29%) suffered the primary point. The following baseline characteristics predicted the primary endpoint: age, haemoglobin, a previous coronary artery bypass grafting, dialysis and choice of anticoagulation. Prescription of apixaban at discharge was associated with lower rate of adverse events (hazard ratio 0.564, confidence interval 0.331-0.960; p = 0.035) while prescription of dabigatran was associated with higher rate of adverse events (hazard ratio 3.091, confidence interval 1.506-6.347; p = 0.002).

Conclusion: Even in the DOAC era, the occurrence of thrombus or SEC in the LAA is associated with a high rate of MACCE. Our study suggests that the choice of DOAC therapy may have an impact on long-term survival.
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http://dx.doi.org/10.1007/s00392-021-01926-8DOI Listing
August 2021

COVID-19 mRNA vaccine induced rhabdomyolysis and fasciitis.

J Neurol 2021 Aug 25. Epub 2021 Aug 25.

Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791, Bochum, Germany.

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http://dx.doi.org/10.1007/s00415-021-10768-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386679PMC
August 2021

[Immunotherapy and personalized treatment of multiple sclerosis].

Nervenarzt 2021 Oct 24;92(10):986-995. Epub 2021 Aug 24.

Neurologische Klinik, St. Josef-Hospital, Ruhr-Universität-Bochum, Bochum, Deutschland.

Personalized medicine requires a patient-oriented approach with the exact classification of the disease being determined by the underlying pathophysiological processes. In particular, the optimal treatment of multiple sclerosis (MS) requires personalized treatment that goes beyond the pure concept of precision medicine; however, due to the lack of robust biomarkers beyond cranial magnetic resonance imaging and a lacking detailed understanding of some aspects of MS pathogenesis, this approach is not yet fully implemented. Important questions for a better therapeutic stratification of MS patients are: (1) when does MS start? (2) Does the spectrum of MS really span multiple diseases? (3) When does the progressive phase of the disease begin? (4) In which phase of the disease is there a therapeutic window for immunotherapy? Recent findings indicate that MS represents a spectrum of diseases and that there is a therapeutic delay of several years, on which the optimal treatment effect of a disease-modifying treatment depends. For a personalized treatment of MS it is important to determine the exact disease stage of the patient and to react to the development or increase of focal inflammatory activity in a timely manner.
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http://dx.doi.org/10.1007/s00115-021-01176-zDOI Listing
October 2021

Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper).

Ther Adv Neurol Disord 2021 18;14:17562864211039648. Epub 2021 Aug 18.

Neurologie in Meerbusch, MS-Zentrum, Meerbusch, Germany.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).
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http://dx.doi.org/10.1177/17562864211039648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377320PMC
August 2021

Multiple sclerosis is not associated with an increased risk for severe COVID-19: a nationwide retrospective cross-sectional study from Germany.

Neurol Res Pract 2021 Aug 16;3(1):42. Epub 2021 Aug 16.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

Background: Since the coronavirus disease 2019 (COVID-19) has risen, several risk factors have been identified, predicting a worse outcome. It has been speculated that patients with Multiple sclerosis (MS) have an increased risk for a severe course of COVID-19 due to a suspected higher vulnerability. Therefore, we aimed to analyze the impact of comorbid MS on the outcome of patients with COVID-19 in Germany.

Methods: We conducted a retrospective cross-sectional study using the administrative database of all hospitalized patients diagnosed with PCR-confirmed COVID-19 (n = 157,524) in Germany during 2020. The cohort was stratified according to the presence (n = 551) or absence (n = 156,973) of comorbid MS, including discrimination of MS subtypes. Primary outcome measures were admission to the intensive care unit (ICU), use of invasive or non-invasive ventilation, and in-hospital mortality. Differences were investigated using rates and odds ratios as estimates. Pooled overall estimates, sex-stratified estimates, age-group stratified estimates, and MS subtype stratified estimates were calculated for all outcomes under the random-effects model.

Results: Among 157,524 patients hospitalized with COVID-19, 551 had a concurrent MS diagnosis (0.3%). Overall, univariate analysis showed lower rates of ICU admission (17.1% versus 22.7%, p < 0.001), lower use of ventilation (9.8% versus 14.5%, p < 0.001) and lower in-hospital mortality (11.1% versus 19.3%, p < 0.001) among COVID-19 patients with comorbid MS. This finding was stable across the subgroup analysis of sex and MS subtype but was attenuated by age-stratification, confirming equal odds of in-hospital mortality between COVID-19 patients with and without MS (log OR: 0.09 [95% CI: - 0.40, 0.59]).

Conclusions: Although there might be differences in risk within the MS patients' population, this large-scale nationwide analysis found no evidence for a worse outcome of COVID-19 in patients with comorbid MS compared to non-MS individuals.
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http://dx.doi.org/10.1186/s42466-021-00143-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364944PMC
August 2021

Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome in seven patients with sarcoidosis: a critical discussion of treatment and prognosis.

Ther Adv Neurol Disord 2021 31;14:17562864211035543. Epub 2021 Jul 31.

Department of Neurology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.

Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly progressive spastic hemi- or limb pareses as well as disturbances of vision, speech, and orientation. Cerebral magnetic resonance imaging showed T2-hyperintense, confluent, mainly supratentorial lesions. Four patients developed punctate contrast enhancement as a radiological sign of an immune reconstitution inflammatory syndrome (IRIS), three of them having a fatal course. In the cerebrospinal fluid, the initial JC virus load (8-25,787 copies/ml) did not correlate with interindividual severity; however, virus load corresponded to clinical dynamics. Brain biopsies ( = 2), performed 2 months after symptom onset, showed spotted demyelination and microglial activation. All patients had lymphopenia in the range of 270-1150/µl. To control JC virus, three patients received a combination of mirtazapine and mefloquine, another two patients additionally took cidofovir. One patient was treated with cidofovir only, and one patient had a combined regimen with mirtazapine, mefloquine, cidofovir, intravenous interleukin 2, and JC capsid vaccination. To treat sarcoidosis, the four previously untreated patients received prednisolone. Three patients had taken immunosuppressants prior to PML onset, which were subsequently stopped as a potential accelerator of opportunistic infections. After 6-54 months of follow up, three patients reached an incomplete recovery, one patient progressed, but survived so far, and two patients died. One further patient was additionally diagnosed with lung cancer, which he died from after 24 months. We conclude that the combination of PML and sarcoidosis is a diagnostic and therapeutic challenge. PML can occur as the first sign of sarcoidosis without preceding immunosuppressive treatment. The development of IRIS might be an indicator of poor outcome.
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http://dx.doi.org/10.1177/17562864211035543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326823PMC
July 2021

Multiple sclerosis therapy consensus group (MSTCG): answers to the discussion questions.

Neurol Res Pract 2021 Aug 6;3(1):44. Epub 2021 Aug 6.

Klinik und Poliklinik für Neurologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany.

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http://dx.doi.org/10.1186/s42466-021-00140-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344158PMC
August 2021

Corneal inflammatory cell infiltration predicts disease activity in chronic inflammatory demyelinating polyneuropathy.

Sci Rep 2021 07 26;11(1):15150. Epub 2021 Jul 26.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany.

The assessment of disease activity is fundamental in the management of chronic inflammatory demyelinating polyneuropathy (CIDP). Previous studies with small patient numbers found an increase of corneal immune cell infiltrates as a potential marker of inflammation in patients with CIDP. However, its clinical relevance remained unclear. The present study aimed to determine whether the amount of corneal inflammatory cells (CIC) measured by corneal confocal microscopy (CCM) detects disease activity in CIDP. CIC were measured in 142 CCM-investigations of 97 CIDP-patients. Data on clinical disease activity, disability (INCAT-ODSS) and need for therapy escalation at the timepoint of CCM, 3 and 6 months later were analyzed depending CIC-count. Pathological spontaneous activity during electromyography was examined as another possible biomarker for disease activity in comparison to CIC-count. An increased CIC-count at baseline was found in patients with clinical disease activity and disability progression in the following 3-6 months. An increase to more than 25 CIC/mm had a sensitivity of 0.73 and a specificity of 0.71 to detect clinical disease activity and a sensitivity of 0.77 and a specificity of 0.64 to detect disability progression (increasing INCAT-ODSS) in the following 6 months. An increase to more than 50 CIC/mm had a sensitivity of about 0.51 and a specificity of 0.91 to detect clinical disease activity and a sensitivity of 0.53 and a specificity of 0.80 to detect disability progression. CIC count is a non-invasive biomarker for the detection of disease activity in the following 6 months in CIDP.
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http://dx.doi.org/10.1038/s41598-021-94605-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313721PMC
July 2021

[Multiple sclerosis treatment consensus group (MSTCG): position paper on disease-modifying treatment of multiple sclerosis 2021 (white paper)].

Nervenarzt 2021 Aug 23;92(8):773-801. Epub 2021 Jul 23.

Multiple Sklerose Therapie Konsensus Gruppe (MSTKG), Münster, Deutschland.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).
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http://dx.doi.org/10.1007/s00115-021-01157-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300076PMC
August 2021

The impact of the COVID-19 pandemic on hospitalizations and plasmapheresis therapy in multiple sclerosis and neuromyelitis optica spectrum disorder: a nationwide analysis from Germany.

Ther Adv Neurol Disord 2021 7;14:17562864211030656. Epub 2021 Jul 7.

Department of Neurology, Ruhr University Bochum, St. Josef-Hospital Bochum, Gudrunstrasse 56, Bochum, 44791 Germany.

Background: Many countries worldwide reported side effects of the coronavirus disease 2019 (COVID-19) pandemic that have influenced the care of patients with other diseases in both acute and elective settings. Patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) represent the major patient population suffering from an autoimmune inflammatory demyelinating disease of the central nervous system. We aimed to analyze MS and NMOSD hospitalizations, the application of plasmapheresis therapy, and the dynamic during different periods of the COVID-19 pandemic in Germany.

Methods: We conducted a nationwide retrospective cross-sectional study using the administrative database of all hospitalized patients with the main diagnosis of MS and NMOSD, including the information on the application of plasmapheresis therapy. We included full-year data from 1463 hospitals of all MS and NMOSD patients hospitalized in 2019 and 2020 in Germany ( = 87,453). We compared case numbers and plasmapheresis therapy rates of the different pandemic periods in 2020 with the corresponding periods in 2019.

Results: We observed a substantial decline of MS and NMOSD patients' hospitalizations during the different pandemic periods, with the most remarkable decline during the first wave of the pandemic (First diagnosis of MS: -16.8%; relapsing-remitting MS: -34.0%; secondary progressive MS: -48.9%; primary progressive MS: -43.8%; NMOSD: -19.2%). Treatment rates with plasmapheresis increased for MS and NMOSD patients in 2020 compared to 2019 (1.8% 1.6%,  = 0.003; 14.0% 9.3%,  < 0.001), with a substantial increase during the first wave of the pandemic, especially in NMOSD patients (19.7% 8.4%,  < 0.001).

Conclusion: There was a marked decline of MS and NMOSD patients' hospitalizations during the different pandemic periods in 2020, with the most substantial reduction during the pandemic's first wave and in progressive MS patients. MS and NMOSD patients who needed rescue relapse treatment continued to receive plasmapheresis therapy in Germany.
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http://dx.doi.org/10.1177/17562864211030656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267031PMC
July 2021

An algorithm using clinical data to predict the optimal individual glucocorticoid dosage to treat multiple sclerosis relapses.

Ther Adv Neurol Disord 2021 17;14:17562864211020074. Epub 2021 Jun 17.

Department of Neurology, University Hospital Bern, Inselspital, Bern, Switzerland.

Background: Glucocorticoid (GC) pulse therapy is used for multiple sclerosis (MS) relapse treatment; however, GC resistance is a common problem. Considering that GC dosing is individual with several response-influencing factors, establishing a predictive model, which supports clinicians to estimate the maximum GC dose above which no additional therapeutic value can be expected presents a huge clinical need.

Method: We established two, independent retrospective cohorts of MS patients. The first was an explorative cohort for model generation, while the second was established for its validation. Using the explorative cohort, a multivariate regression analysis with the GC dose used as the dependent variable and serum vitamin D (25D) concentration, sex, age, EDSS, contrast enhancement on cranial magnetic resonance imaging (MRI), immune therapy, and the involvement of the optic nerve as independent variables was established.

Results: In the explorative cohort, 113 MS patients were included. 25-hydroxyvitamin D (25D) serum concentration and the presence of optic neuritis were independent predictors of the GC dose needed to treat MS relapses [(25D): -25.95 (95% confidence interval (CI)): -47.40 to -4.49;  = 0.018; optic neuritis: 2040.51 (95% CI: 584.64-3496.36),  = 0.006]. Validation of the multivariate linear regression model was performed within a second cohort. Here, the predicted GC dose did not differ significantly from the dose administered in clinical routine (mean difference: -843.54; 95% CI: -2078.08-391.00;  = 30,  = 0.173).

Conclusion: Our model could predict the GC dose given in clinical, routine MS relapse care, above which clinicians estimate no further benefit. Further studies should validate and improve our algorithm to help the implementation of predictive models in GC dosing.
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http://dx.doi.org/10.1177/17562864211020074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216377PMC
June 2021

Prevalence and Characteristics of Polyneuropathy in Atypical Parkinsonian Syndromes: An Explorative Study.

Brain Sci 2021 Jun 30;11(7). Epub 2021 Jun 30.

Department of Neurology, St. Josef-Hospital, Ruhr-University, D-44791 Bochum, Germany.

(1) Background: Peripheral nerve involvement is increasingly recognized in Parkinson's disease (PD). Although non-motor symptoms and postural instability are early features of atypical parkinsonian syndromes (APS), peripheral neuropathies in APS have not been addressed in detail thus far. Therefore, the aim of this study was to investigate the prevalence and characteristics of polyneuropathies (PNP) in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), as representative syndromes of APS. (2) Methods: In total, 8 MSA and 6 PSP patients were comprehensively analyzed regarding subjective, clinical (motor and non-motor) and paraclinical PNP features using nerve conduction studies and high resolution nerve ultrasounds (HRUS). (3) Results: A total of 87.5% of MSA and 66.7% of PSP patients complained of at least one neuropathic symptom, with electrophysiological confirmation of PNP in 50.0% of both, MSA and PSP patients. PNP symptom severity in PSP and motor nerve amplitude in MSA were associated with compromised motor function. Morphologic nerve examination by HRUS showed few alterations according to the axonal type of PNP. (4) Conclusions: The overall high PNP symptom burden may be partially credited to the significant prevalence of electrophysiologically diagnosed PNP, and impact motor aspects of APS. The findings of this exploratory study reinforce further investigations on a larger scale, in order to elucidate peripheral nerve involvement and the underlying pathophysiological mechanisms of APS.
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http://dx.doi.org/10.3390/brainsci11070879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301815PMC
June 2021

CMV meningitis associated with dimethyl fumarate therapy-induced lymphopenia in a multiple sclerosis patient.

J Neurol 2021 Nov 27;268(11):4374-4375. Epub 2021 Jun 27.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany.

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http://dx.doi.org/10.1007/s00415-021-10661-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505348PMC
November 2021

Propionic Acid Rescues High-Fat Diet Enhanced Immunopathology in Autoimmunity Effects on Th17 Responses.

Front Immunol 2021 1;12:701626. Epub 2021 Jun 1.

Department of Neurology, University Hospital Regensburg, Regensburg, Germany.

High-fat diets (HFD) are linked to obesity and associated comorbidities and induce pathogenic T helper (Th) 17 cells while decreasing regulatory T cells (Treg). This pro-inflammatory environment also aggravates immunopathology in experimental autoimmune encephalomyelitis (EAE) as a prototype model of T cell mediated autoimmunity. The strong association of HFD to obesity as well as the increasing risk of autoimmunity in the Western world stresses the importance to identify compounds that counteract this metabolically induced pro-inflammatory state in humans. One prominent candidate is the short-chain fatty acid propionate (PA) that was recently identified as potent therapy in the autoimmune disease multiple sclerosis by enhancing Treg cell frequencies and functionality. Mice were fed a HFD rich lauric acid (LA) and treated either with water or PA during MOG-EAE. We analyzed Treg and Th17 cell frequencies in different tissues, antigen-specific cell proliferation and cytokine secretion, investigated Treg cell functionality by suppression assays and IL-10 signaling blockade and employed Western blotting to investigate the involvement of p38-MAPK signaling. Finally, we performed an explorative study in obese and non-obese MS patients, investigating fecal PA concentrations as well as peripheral Th17 and Treg frequencies before and after 90 days of daily PA intake. As compared to controls, mice on a HFD displayed a more severe course of EAE with enhanced demyelination and immune cell infiltration in the spinal cord. PA treatment prevented this disease enhancing effect of HFD by inhibiting Th17 mediated inflammatory processes in the gut and the spleen. Blocking experiments and signaling studies revealed p38-MAPK and IL-10 signaling as important targets linking the beneficial effects of PA treatment and reduced inflammation due to enhanced Treg frequency and functionality. An explorative study in a small group of MS patients revealed reduced PA concentrations in fecal samples of obese MS patients compared to the non-obese group, coinciding with increased Th17 but decreased Treg cells in obese patients. Importantly, PA intake could restore the Treg-Th17 homeostasis. Our data thus identify Th17 responses as an important target for the beneficial effects of PA in HFD and obesity in addition to the recently identified potential of PA as a Treg inducing therapy in T cell mediated autoimmunity.
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http://dx.doi.org/10.3389/fimmu.2021.701626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204048PMC
June 2021

Usefulness of Computed Tomographic Perfusion Imaging for Appropriate Diagnosis of Acute Cerebral Vessel Occlusion in Case of Anatomic Variations of the Circle of Willis.

Neurointervention 2021 Jul 17;16(2):190-193. Epub 2021 Jun 17.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

Mechanical thrombectomy (MT) is an effective treatment in patients with acute ischemic stroke (AIS) due to emergent large-vessel occlusion in the anterior circulation. Occlusion of the anterior cerebral artery (ACA) affects up to 15% of these patients. Here we report a case of an elderly patient with an successful MT of an embolic A2-segment occlussion with the anatomic variation of a triplication. Triplication of ACA is a rare anatomical variation, and the occlusion could have been easily overlooked in case of not performing the CT-perfusion (CTP) sequences. As anatomical variations of the circle of Willis are present in most subjects, CTA alone might be limited in the acute setting, particularly for young residents performing the first view on call. This case highlights the importance of including CTP in the initial CT-diagnostic algorithm in AIS patients who are basically eligible for recanalization therapies, irrespective of inconspicuous initial findings in CTA.
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http://dx.doi.org/10.5469/neuroint.2021.00136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261118PMC
July 2021

Pain, Depression, and Quality of Life in Neuromyelitis Optica Spectrum Disorder: A Cross-Sectional Study of 166 AQP4 Antibody-Seropositive Patients.

Neurol Neuroimmunol Neuroinflamm 2021 05 20;8(3). Epub 2021 Apr 20.

From the Department of Neurology (I.A., D.R., E.H., K.H., R.G., I.K.), St. Josef-Hospital, Ruhr-University Bochum, Germany; Department of Neurology (I.A.), Sechenov First Moscow State Medical University, Russia; NeuroCure Clinical Research Center (S.A., F.P.), Charité Universitätsmedizin Berlin, Berlin Institute of Health, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Department of Neurology (C.T., M.W.H.), Hannover Medical School, Germany; Institute of Clinical Neuroimmunology (J.H., T.K., H.L.P.), University Hospital and Biomedical Center, Ludwig-Maximilians University Munich, Germany; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf, Germany; Molecular Neuroimmunology Group (B.W., S.J.), Department of Neurology, University of Heidelberg, Germany; Institut für Neuroimmunologie und Multiple Sklerose (INIMS) (V.H., J.-P.S.), Zentrum für Molekulare Neurobiologie, Hamburg, Germany; Klinik und Poliklinik für Neurologie (V.H., J.-P.S.), Universitätsklinikum Hamburg-Eppendorf, Germany; APHM (J.-P.S.), Hopital de la Timone, CEMEREM, Marseille, France; Aix Marseille Université (J.-P.S.), CRMBM, CNRS UMR 7339, Marseille, France; Department of Neurology (M.S.), University of Ulm, Germany; Münster Department of Neurology with Institute of Translational Neurology (L.K., M.P.), University Hospital Münster, Germany; Department of Neurology (H.L.P., M.S.W.), University Medical Center, Göttingen, Germany; Department of Neurology (M.P.), Otto-von-Guericke University, Magdeburg, Germany; Department of Neurology (P.S.R.), Medical University of Vienna, Austria; Neuroimmunology Section (P.S.R.), Department of Neurology, University of Rostock, Germany; Department of Neurology (A.B.), School of Medicine, Technical University of Munich, Germany; Charité-Universitätsmedizin Berlin, CRO SOSTANA GmbH Berlin (K.-D.W.), Germany; and Marianne-Strauß-Klinik (I.K.), Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gGmbH, Berg, Germany.

Objectives: To evaluate prevalence, clinical characteristics, and predictors of pain, depression, and their impact on the quality of life (QoL) in a large neuromyelitis optica spectrum disorder (NMOSD) cohort.

Methods: We included 166 patients with aquaporin-4-seropositive NMOSD from 13 tertiary referral centers. Patients received questionnaires on demographic and clinical characteristics, PainDetect, short form of Brief Pain Inventory, Beck Depression Inventory-II, and Short Form 36 Health Survey.

Results: One hundred twenty-five (75.3%) patients suffered from chronic NMOSD-associated pain. Of these, 65.9% had neuropathic pain, 68.8% reported spasticity-associated pain and 26.4% painful tonic spasms. Number of previous myelitis attacks (OR = 1.27, = 0.018) and involved upper thoracic segments (OR = 1.31, = 0.018) were the only predictive factors for chronic pain. The latter was specifically associated with spasticity-associated pain (OR = 1.36, = 0.002). More than a third (39.8%) suffered from depression, which was moderate to severe in 51.5%. Pain severity (OR = 1.81, < 0.001) and especially neuropathic character (OR = 3.44, < 0.001) were associated with depression. Pain severity and walking impairment explained 53.9% of the physical QoL variability, while depression and walking impairment 39.7% of the mental QoL variability. No specific medication was given to 70.6% of patients with moderate or severe depression and 42.5% of those with neuropathic pain. Two-thirds (64.2%) of patients with symptomatic treatment still reported moderate to severe pain.

Conclusions: Myelitis episodes involving upper thoracic segments are main drivers of pain in NMOSD. Although pain intensity was lower than in previous studies, pain and depression remain undertreated and strongly affect QoL. Interventional studies on targeted treatment strategies for pain are urgently needed in NMOSD.
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http://dx.doi.org/10.1212/NXI.0000000000000985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058953PMC
May 2021

Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?

J Neuroinflammation 2021 May 29;18(1):121. Epub 2021 May 29.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

Background: To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON).

Methods: All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation <18 years were included in the pediatric (MOGAD) cohort and patients with ≥18 years in the adult (MOGAD) cohort. For patients with MOGAD ON, examinations at least ≥6 months after ON onset were included in the analyses. Using spectral domain optical coherence tomography (SD-OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIPL). High- and 2.5% low-contrast visual acuity (HCVA, LCVA) and visual-evoked potentials (VEP) were obtained.

Results: Twenty MOGAD (10.3±3.7 years, 30 MOGAD ON eyes) and 39 MOGAD (34.9±11.6 years, 42 MOGAD ON eyes) patients were included. The average number of ON episodes per ON eye was similar in both groups (1.8±1.3 and 2.0±1.7). In both pediatric and adult MOGAD, ON led to pronounced neuroaxonal retinal atrophy (pRNFL: 63.1±18.7 and 64.3±22.9 μm; GCIPL: 0.42±0.09 and 0.44±0.13 mm, respectively) and moderate delay of the VEP latencies (117.9±10.7 and 118.0±14.5 ms). In contrast, visual acuity was substantially better in children (HCVA: 51.4±9.3 vs. 35.0±20.6 raw letters, p=0.001; LCVA: 22.8±14.6 vs. 13.5±16.4, p=0.028). Complete visual recovery (HCVA-logMAR 0.0) occurred in 73.3% of MOGAD and 31% MOGAD ON eyes, while 3.3% and 31% demonstrated moderate to severe (logMAR > 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome.

Conclusion: Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes.
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http://dx.doi.org/10.1186/s12974-021-02160-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164737PMC
May 2021

Clozapine Regulates Microglia and Is Effective in Chronic Experimental Autoimmune Encephalomyelitis.

Front Immunol 2021 3;12:656941. Epub 2021 May 3.

Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Bochum, Germany.

Objective: Progressive multiple sclerosis is characterized by chronic inflammation with microglial activation, oxidative stress, accumulation of iron and continuous neurodegeneration with inadequate effectiveness of medications used so far. We now investigated effects of iron on microglia and used the previously identified neuroprotective antipsychotic clozapine and in chronic experimental autoimmune encephalomyelitis (EAE).

Methods: Microglia were treated with iron and clozapine followed by analysis of cell death and response to oxidative stress, cytokine release and neuronal phagocytosis. Clozapine was investigated in chronic EAE regarding optimal dosing and therapeutic effectiveness in different treatment paradigms. Animals were scored clinically by blinded raters. Spinal cords were analyzed histologically for inflammation, demyelination, microglial activation and iron accumulation and for transcription changes of regulators of iron metabolism and inflammation. Effects on immune cells were analyzed using flow cytometry.

Results: Iron impaired microglial function regarding phagocytosis and markers of inflammation; this was regulated by clozapine, reflected in reduced release of IL-6 and normalization of neuronal phagocytosis. In chronic EAE, clozapine dose-dependently attenuated clinical signs and still had an effect if applied in a therapeutic setting. Early mild sedative effects habituated over time. Histologically, demyelination was reduced by clozapine and positive effects on inflammation strongly correlated with reduced iron deposition. This was accompanied by reduced expression of DMT-1, an iron transport protein.

Conclusions: Clozapine regulates microglial function and attenuates chronic EAE, even in a therapeutic treatment paradigm. This well-defined generic medication might therefore be considered as promising add-on therapeutic for further development in progressive MS.
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http://dx.doi.org/10.3389/fimmu.2021.656941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126707PMC
September 2021

Clinical Profiles and Mortality of COVID-19 Inpatients with Parkinson's Disease in Germany.

Mov Disord 2021 05 4;36(5):1049-1057. Epub 2021 May 4.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

Background: Comprehensive, nationwide data regarding Parkinson's disease (PD) hospitalizations, coronavirus disease 2019 (COVID-19) in-hospital frequency, and COVID-19-associated inpatient mortality during the first wave of the COVID-19 pandemic are not available.

Objective: To provide a nationwide analysis on hospitalized PD patients in Germany and evaluate the impact of the COVID-19 pandemic.

Methods: We conducted a cross-sectional study using an administrative claims database covering 1468 hospitals and 5,210,432 patient hospitalizations including a total of 30,872 COVID-19 cases between January 16 and May 15, 2020.

Results: Compared to 2019, hospitalizations for PD transiently decreased by up to 72.7% in 2020. COVID-19 frequency was significantly higher in the population of 64,434 PD patients (693 being COVID-19 ) than in non-PD patients (1.1% vs. 0.6%, P < 0.001), especially in subjects with advanced age (≥ 65 years). Regarding established COVID-19 risk comorbidities, COVID-19 inpatients with PD showed higher incidences than non-PD COVID-19 subjects, particularly hypertension and chronic kidney disease. Advanced age and male sex were significantly more frequent in COVID-19 than in COVID-19 PD patients. The COVID-19 inpatient mortality rate was much higher in PD patients than in non-PD patients (35.4% vs. 20.7%, P < 0.001), especially in patients aged 75-79 years. Of note, overall inpatient mortality of PD patients was significantly higher in 2020 than in 2019 (5.7% vs. 4.9%, P < 0.001).

Conclusions: PD inpatients are more frequently affected by COVID-19 and suffer from increased COVID-19-associated mortality in comparison to non-PD patients. More comprehensive studies are needed to assess the significance of associated comorbidities for COVID-19 risk and mortality in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207013PMC
May 2021

A Propagated Skeleton Approach to High Throughput Screening of Neurite Outgrowth for In Vitro Parkinson's Disease Modelling.

Cells 2021 04 17;10(4). Epub 2021 Apr 17.

Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44803 Bochum, Germany.

Neuronal models of neurodegenerative diseases such as Parkinson's Disease (PD) are extensively studied in pathological and therapeutical research with neurite outgrowth being a core feature. Screening of neurite outgrowth enables characterization of various stimuli and therapeutic effects after lesion. In this study, we describe an autonomous computational assay for a high throughput skeletonization approach allowing for quantification of neurite outgrowth in large data sets from fluorescence microscopic imaging. Development and validation of the assay was conducted with differentiated SH-SY5Y cells and primary mesencephalic dopaminergic neurons (MDN) treated with the neurotoxic lesioning compound Rotenone. Results of manual annotation using NeuronJ and automated data were shown to correlate strongly (R2-value 0.9077 for SH-SY5Y cells and R2-value 0.9297 for MDN). Pooled linear regressions of results from SH-SY5Y cell image data could be integrated into an equation formula (y=0.5410·x+1792; y=0.8789·x+0.09191 for normalized results) with depicting automated and depicting manual data. This automated neurite length algorithm constitutes a valuable tool for modelling of neurite outgrowth that can be easily applied to evaluate therapeutic compounds with high throughput approaches.
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http://dx.doi.org/10.3390/cells10040931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072564PMC
April 2021

Analysis of nationwide multimodal complex treatment and drug pump therapy in Parkinson's disease in times of COVID-19 pandemic in Germany.

Parkinsonism Relat Disord 2021 04 18;85:109-113. Epub 2021 Mar 18.

Department of Neurology, St. Josef-Hospital Bochum, Ruhr University Bochum, Germany; Medical Faculty, Ruhr University Bochum, Germany; Center for Protein Diagnostics (ProDi), Ruhr University Bochum, Bochum, Germany. Electronic address:

Introduction: During the first peak phase of the COVID-19 pandemic, the German Ministry of Health recommended that elective treatments should be postponed to increase hospital capacities. This has also compromised the capacity for application of specialized Parkinson's disease (PD) therapies to an unknown extent.

Methods: We conducted a nationwide cross-sectional study using administrative database of all hospitalized patients with main diagnosis of PD receiving multimodal complex treatment (PD-MCT), initial setup of levodopa/carbidopa intestinal gel (LCIG) or continuous subcutaneous apomorphine infusion (CSAI) in Germany. We compared case numbers and clinical characteristics of the pandemic (March 16th - May 15th, 2020) and post-lockdown (July 16th - September 15th, 2020) period with the pre-pandemic (January 16th - March 15th, 2020) and historical control period (March 16th - May 15th, 2019).

Results: We identified a strong decline for PD-MCT(-62.8%) and for the application of drug pump-based therapies (-69.4%) during the first peak phase of the pandemic as compared to the pre-pandemic period while specialized PD treatment procedures increased again in the post-lockdown phase. Advanced disease was a marker for PD-MCT patients during the pandemic period.

Conclusion: Besides the marked decline in specialized PD treatments during the first peak phase of the COVID-19 pandemic, we found recuperative effects for these procedures in the post-lockdown period without reaching pre-pandemic levels. Strengthening treatment capacities for PD patients, even in the event of a persistent pandemic, is urgently needed in order to maintain the quality of care.
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http://dx.doi.org/10.1016/j.parkreldis.2021.03.006DOI Listing
April 2021

Cross-sectional area reference values for peripheral nerve ultrasound in adults: A systematic review and meta-analysis-Part III: Cervical nerve roots and vagal nerve.

Eur J Neurol 2021 07 2;28(7):2319-2326. Epub 2021 May 2.

Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.

Background And Purpose: Measurement of the cross-sectional area (CSA) of cervical nerve roots using ultrasound is useful in the evaluation of inflammatory polyneuropathies, and measurement of CSA of the vagal nerve might give information about involvement of the autonomic nervous system. We performed a systematic review and meta-analysis of published CSA reference values for cervical nerve roots and vagal nerve.

Methods: We included available-to-date nerve ultrasound studies on healthy adults and provide meta-analysis for CSA of the following nerves: cervical nerve roots C5, C6, and C7 as well as vagal nerve in the carotid sheath at the carotid bifurcation level. We report regression and correlation analyses for age, gender, height, weight, and geographic continent.

Results: We included 11 studies with 885 healthy volunteers (mean age = 42.7 years) and 3149 examined nerve sites. Calculated mean pooled CSA of C5 root was 5.6 mm (95% confidence interval [CI] = 4.6-6.7 mm , n = 911), of C6 root was 8.8 mm (95% CI = 7.4-10.3 mm , n = 909), of C7 root was 9.5 mm (95% CI = 8.0-10.9 mm , n = 909), and of vagal nerve was 2.2 mm (95% CI = 1.5-2.9 mm , n = 420). No heterogeneity was found across studies for any site. Subgroup analysis revealed no significant effects of age, gender, height, weight, and geographic continent on CSA for any of these nerve sites.

Conclusions: We provide the first meta-analysis on CSA reference values for the cervical nerve roots and the vagal nerve, with no heterogeneity of reported CSA values at all nerve sites. Our data facilitate the goal of an international standardized evaluation protocol.
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http://dx.doi.org/10.1111/ene.14862DOI Listing
July 2021

Evaluation of the EFNS/PNS diagnostic criteria in a cohort of CIDP patients.

Ann Clin Transl Neurol 2021 05 7;8(5):1110-1121. Epub 2021 Apr 7.

Department of Neurology, St. Josef-Hospital, Ruhr-University, Bochum, Germany.

Objective: To evaluate the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) in a cohort of patients diagnosed and treated for CIDP in a tertiary university hospital.

Methods: In a monocentric retrospective study of 203 CIDP patients, diagnosed according to expert opinion, we evaluated the EFNS/PNS diagnostic criteria. Clinical course and nerve conduction studies (NCS) over 1 year from first referral were studied. Secondarily, we compared the clinical and paraclinical characteristics, including nerve ultrasound, of patients who failed with those who fulfilled the criteria in order to identify clinically relevant differences.

Results: At 1 year, 182 (89.7%) patients fulfilled the criteria (156/76.9% definite, 22/10.8% probable, and 4/2% possible). Twenty-one (10.3%) patients did not because the electrodiagnostic criteria remained negative. These still showed signs of demyelination but did not reach the cut-off values. They also presented typical, albeit less pronounced, multifocal nerve enlargement in ultrasonography. Mean disability at presentation and 1 year after was significantly lower. Most importantly, a relevant proportion of these patients also responded to therapy (6/21 = 28.6% vs. 82/182 = 45.3% of those fulfilling the criteria).

Interpretation: CIDP diagnosis could be established for 89.7% of patients over the course of 1 year using EFNS/PNS criteria. The remaining patients (10.3%) presented with milder disability, less accentuated demyelination, but otherwise similar characteristics and still considerable probability of treatment response. Failure to fulfill diagnostic criteria should not automatically preclude treatment. Nerve ultrasound should be considered as a complementary diagnostic tool to detect signs of inflammation in CIDP.
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http://dx.doi.org/10.1002/acn3.51357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108415PMC
May 2021
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