Publications by authors named "Joachim K Krauss"

310 Publications

Prothrombotic immune thrombocytopenia after COVID-19 vaccination.

Blood 2021 Jul;138(4):350-353

Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

We report 5 cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis, splanchnic vein thrombosis, arterial cerebral thromboembolism, and thrombotic microangiopathy. All patients had thrombocytopenia and markedly elevated D-dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients, although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependent manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in 3 patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.
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http://dx.doi.org/10.1182/blood.2021011958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084604PMC
July 2021

Improvement of head and neck range of motion induced by chronic pallidal deep brain stimulation for cervical dystonia.

J Neural Transm (Vienna) 2021 Aug 6;128(8):1205-1213. Epub 2021 Jul 6.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become an accepted treatment for severe cervical dystonia (CD). Assessment of therapeutic efficacy of DBS mostly focused on head position at rest but hardly on limitations of head and neck mobility, which represent a functionally important impairment in CD.

Objective: We aimed to determine prospectively head and neck range of motion (ROM) preoperatively and during chronic bilateral GPi DBS in a series of 11 patients with idiopathic CD or segmental dystonia with prominent CD using a computerized motion analysis.

Methods: Maximum horizontal rotation of the head in the transverse plane and lateral inclination in the frontal plane were measured preoperatively and at a median of 7 months of chronic GPi DBS, using an ultrasound-based three-dimensional measuring system combined with surface electromyography of cervical muscles.

Results: Horizontal rotation of the head increased from 78.8° ± 31.5° (mean ± SD) preoperatively to 100.7° ± 24.7° with GPi DBS (p < 0.01), thereby improvement of head rotation to the anti-dystonic side (+ 14,2° ± 12,2°) was greater than to the pro-dystonic side (+ 7,8° ± 9,2°; p < 0.05). Movement-related agonistic-antagonistic EMG modulation during head rotation was enhanced with GPi DBS in both sternocleidomastoid (modulation index (MI) 35.8% ± 26.7% preoperatively vs. 67.3% ± 16.9% with GPi DBS, p < 0.01), and splenius capitis muscles (MI 1.9% ± 24.5% preoperatively vs. 44.8% ± 11.6% with GPi DBS, p < 0.01).

Conclusion: Chronic bilateral GPi DBS significantly improves head ROM in CD, likely due to enhanced agonist-antagonist EMG activity with reduced co-contraction. Computerized motion analysis provides an objective measurement to assess the improvement of head and neck mobility in CD.
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http://dx.doi.org/10.1007/s00702-021-02365-5DOI Listing
August 2021

Centromedian-Parafascicular and Somatosensory Thalamic Deep Brain Stimulation for Treatment of Chronic Neuropathic Pain: A Contemporary Series of 40 Patients.

Biomedicines 2021 Jun 25;9(7). Epub 2021 Jun 25.

Department of Neurosurgery, Hannover Medical School, 30625 Hannover, Germany.

The treatment of neuropathic and central pain still remains a major challenge. Thalamic deep brain stimulation (DBS) involving various target structures is a therapeutic option which has received increased re-interest. Beneficial results have been reported in several more recent smaller studies, however, there is a lack of prospective studies on larger series providing long term outcomes. Forty patients with refractory neuropathic and central pain syndromes underwent stereotactic bifocal implantation of DBS electrodes in the centromedian-parafascicular (CM-Pf) and the ventroposterolateral (VPL) or ventroposteromedial (VPM) nucleus contralateral to the side of pain. Electrodes were externalized for test stimulation for several days. Outcome was assessed with five specific VAS pain scores (maximum, minimum, average pain, pain at presentation, allodynia). The mean age at surgery was 53.5 years, and the mean duration of pain was 8.2 years. During test stimulation significant reductions of all five pain scores was achieved with either CM-Pf or VPL/VPM stimulation. Pacemakers were implanted in 33/40 patients for chronic stimulation for whom a mean follow-up of 62.8 months (range 3-180 months) was available. Of these, 18 patients had a follow-up beyond four years. Hardware related complications requiring secondary surgeries occurred in 11/33 patients. The VAS maximum pain score was improved by ≥50% in 8/18, and by ≥30% in 11/18 on long term follow-up beyond four years, and the VAS average pain score by ≥50% in 10/18, and by ≥30% in 16/18. On a group level, changes in pain scores remained statistically significant over time, however, there was no difference when comparing the efficacy of CM-Pf versus VPL/VPM stimulation. The best results were achieved in patients with facial pain, poststroke/central pain (except thalamic pain), or brachial plexus injury, while patients with thalamic lesions had the least benefit. Thalamic DBS is a useful treatment option in selected patients with severe and medically refractory pain.
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http://dx.doi.org/10.3390/biomedicines9070731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301341PMC
June 2021

Dystonia Management: What to Expect From the Future? The Perspectives of Patients and Clinicians Within DystoniaNet Europe.

Front Neurol 2021 3;12:646841. Epub 2021 Jun 3.

Expertise Centre Movement Disorders Groningen, Department of Neurology, University Medical Centre Groningen, Groningen, Netherlands.

Improved care for people with dystonia presents a number of challenges. Major gaps in knowledge exist with regard to how to optimize the diagnostic process, how to leverage discoveries in pathophysiology into biomarkers, and how to develop an evidence base for current and novel treatments. These challenges are made greater by the realization of the wide spectrum of symptoms and difficulties faced by people with dystonia, which go well-beyond motor symptoms. A network of clinicians, scientists, and patients could provide resources to facilitate information exchange at different levels, share mutual experiences, and support each other's innovative projects. In the past, collaborative initiatives have been launched, including the , the which however only existed for a limited time), and the Dutch project. The European Reference Network on Rare Neurological Diseases includes dystonia among other rare conditions affecting the central nervous system in a dedicated stream. Currently, we aim to broaden the scope of these initiatives to a comprehensive European level by further expanding the DystoniaNet network, in close collaboration with the ERN-RND. In line with the ERN-RND, the mission of DystoniaNet Europe is to improve care and quality of life for people with dystonia by, among other endeavors, facilitating access to specialized care, overcoming the disparity in education of medical professionals, and serving as a solid platform to foster international clinical and research collaborations. In this review, both professionals within the dystonia field and patients and caregivers representing Dystonia Europe highlight important unsolved issues and promising new strategies and the role that a European network can play in activating them.
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http://dx.doi.org/10.3389/fneur.2021.646841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211212PMC
June 2021

Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin.

Acta Neuropathol 2021 Jul 30;142(1):191-210. Epub 2021 Apr 30.

Department of Human Genetics OE 6300, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.
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http://dx.doi.org/10.1007/s00401-021-02307-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217027PMC
July 2021

Prothrombotic immune thrombocytopenia after COVID-19 vaccine.

Blood 2021 Apr 28. Epub 2021 Apr 28.

Hannover Medical School, Hannover, Germany.

We report five cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), arterial cerebral thromboembolism, and thrombotic microangiopathy (TMA). All patients had thrombocytopenia and markedly elevated D-Dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependant manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in three patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.
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http://dx.doi.org/10.1182/blood.2021011958DOI Listing
April 2021

Reply to: "Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus".

Mov Disord 2021 04;36(4):1043-1044

Department of Neurosurgery, Medical School Hannover, Hannover, Germany.

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http://dx.doi.org/10.1002/mds.28573DOI Listing
April 2021

Epigenetic Regulation of Neural Transmission after Cerebellar Fastigial Nucleus Lesions in Juvenile Rats.

Cerebellum 2021 Apr 8. Epub 2021 Apr 8.

Department of Psychiatry, Laboratory of Molecular Neuroscience, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.

Structural and functional abnormalities in the cerebellar midline region, including the fastigial nucleus, have been reported in neuropsychiatric disorders, also comprising the cerebellar cognitive affecting syndrome. In rats, early fastigial lesions reduce social interaction during development and lead to cognitive and emotional deficits in adults, accompanied by compromised neuronal network activity. Since epigenetic mechanisms are implicated in the etiology of neuropsychiatric disorders, we investigated whether fastigial nucleus lesions in juvenile rats would impact epigenetic regulation of neural transmission. The fastigial nucleus was lesioned bilaterally in 23-day-old male rats. Sham-lesion and naïve rats served as controls. DNA methylation was investigated for target genes of the GABAergic, dopaminergic, glutamatergic and oxytocinergic systems in brain regions with anatomic connections to the fastigial nucleus, i.e., medial prefrontal cortex, nucleus accumbens, striatum, thalamus, and sensorimotor cortex. Protein expression was examined for the respective target genes in case of altered DNA methylation between lesion and control groups. Lesioning of the fastigial nucleus led to significant differences in the epigenetic regulation of glutamate decarboxylase 1 and the oxytocin receptor in the nucleus accumbens and the prefrontal cortex. No differences were found for the other target genes and brain regions. Our findings indicate that epigenetic dysregulation after lesioning of the fastigial nucleus may influence long-term recovery and the emergence of behavioral changes. Together with previous behavioral and electrophysiological investigations of this rat model, these observations can play a role in the cerebellar cognitive affective syndrome and other neuropsychiatric disorders.
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http://dx.doi.org/10.1007/s12311-021-01264-5DOI Listing
April 2021

Auditory Stimulation Modulates Resting-State Functional Connectivity in Unresponsive Wakefulness Syndrome Patients.

Front Neurosci 2021 16;15:554194. Epub 2021 Feb 16.

BDH-Klinik Hessisch Oldendorf, Hessisch Oldendorf, Germany.

Passive listening to music is associated with several psychological and physical benefits in both, healthy and diseased populations. In this fMRI study, we examined whether preferred music has effects on the functional connectivity within resting-state networks related to consciousness. Thirteen patients in unresponsive wakefulness syndrome (UWS) and 18 healthy controls (HC) were enrolled. Both groups were exposed to different auditory stimulation (scanner noise, preferred music, and aversive auditory stimulation). Functional connectivity was analyzed using a seed-based approach. In HC, no differences were found between the three conditions, indicating that their networks are already working at high level. UWS patients showed impaired functional connectivity within all resting-state networks. In addition, functional connectivity of the auditory network was modulated by preferred music and aversive auditory stimulation. Hence, both conditions have the potential to modulate brain activity of UWS patients.
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http://dx.doi.org/10.3389/fnins.2021.554194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921457PMC
February 2021

When Fat Hits the Brain: Intraventricular and Subarachnoid Fat Migration Secondary to a Complex Sacropelvic Fracture-Diagnosis and Treatment.

J Neurol Surg A Cent Eur Neurosurg 2021 Feb 22. Epub 2021 Feb 22.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Massive migration of fat droplets in the ventricles and the subarachnoid space is a very rare sequel of spinal trauma. Owing to its rarity, knowledge about treatment and outcome remains limited. We report on the uncommon occurrence of massive subarachnoid and intraventricular fat dissemination in a 41-year-old man who suffered a complex sacropelvic fracture with spondylopelvic dissociation but who had no head injury. We show that early placement of an external ventricular drain with prolonged drainage for washout of the fat depots can prevent chronic hydrocephalus and subsequent shunt dependency.
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http://dx.doi.org/10.1055/s-0041-1722967DOI Listing
February 2021

Pseudotumor cerebri syndrome in a child with Alagille syndrome: intracranial pressure dynamics and treatment outcome after ventriculoperitoneal shunting.

Childs Nerv Syst 2021 Feb 8. Epub 2021 Feb 8.

Department of Neurosurgery, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, DE-30625, Hannover, Germany.

Alagille syndrome (AS) is a rare multisystem disease of the liver, heart, eyes, face, skeleton, kidneys, and vascular system. The occurrence of pseudotumor cerebri syndrome (PTCS) in patients with AS has been reported only exceptionally. Owning to its rarity and a mostly atypical presentation, the diagnosis and natural history of affected patients remain uncertain. We report an atypical case of PTCS in a 4-year-old boy with a known history of AS who presented with bilateral papilledema (PE) on a routine ophthalmological examination. Visual findings deteriorated after treatment with acetazolamide. Continuous intracranial pressure (ICP) monitoring was then utilized to investigate ICP dynamics. Successful treatment with resolution of PE was achieved after ventriculoperitoneal shunting but relapsed due to growth-related dislocation of the ventricular catheter. This report brings new insights into the ICP dynamics and the resulting treatment in this possibly underdiagnosed subgroup of PTCS patients. It also demonstrates that ventriculoperitoneal shunting can provide long-term improvement of symptoms for more than 10 years.
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http://dx.doi.org/10.1007/s00381-021-05043-9DOI Listing
February 2021

Primary and secondary gliosarcoma: differences in treatment and outcome.

Br J Neurosurg 2021 Feb 4:1-8. Epub 2021 Feb 4.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Introduction: There are only few studies comparing differences in the outcome of primary versus secondary gliosarcoma. This study aimed to review the outcome and survival of patients with primary or secondary gliosarcoma following surgical resection and adjuvant treatment. The data were also matched with data of patients with primary and secondary glioblastoma (GBM).

Patients And Methods: Treatment histories of 10 patients with primary gliosarcoma and 10 patients with secondary gliosarcoma were analysed and compared. Additionally, data of 20 patients with primary and 20 patients with secondary GBM were analysed and compared. All patients underwent surgical resection of the tumour in our department. Follow-up data, progression-free survival (PFS), and median overall survival (mOS) were evaluated.

Results: The median PFS in patients with primary gliosarcoma was significantly higher than in patients with secondary gliosarcoma ( = 0.037). The 6-month PFS rates were 80.0% in patients with primary and 30.0% in patients with secondary gliosarcoma. Upon recurrence, five patients with primary gliosarcoma and four patients with secondary gliosarcoma underwent repeat surgical resection. The mOS of patients with primary gliosarcoma was significantly higher than that of patients with secondary gliosarcoma ( = 0.031). The percentage of patients surviving at 1-year/2-year follow-up in primary gliosarcoma was 70%/20%, while it was only 10%/10% in secondary gliosarcoma. When PFS and mOS of primary gliosarcoma was compared to primary GBM, there were no statistically differences ( = 0.509;  = 0.435). The PFS and mOS of secondary gliosarcoma and secondary GBM were also comparable ( = 0.290 and  = 0.390).

Conclusion: Patients with primary gliosarcoma have a higher PFS and mOS compared to those with secondary gliosarcoma. In the case of tumour recurrence, patients with secondary gliosarcoma harbour an unfavourable prognosis with limited further options. The outcome of patients with primary or secondary gliosarcoma is comparable to that of patients with primary or secondary GBM.
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http://dx.doi.org/10.1080/02688697.2021.1872773DOI Listing
February 2021

Oscillatory activity in the BNST/ALIC and the frontal cortex in OCD: acute effects of DBS.

J Neural Transm (Vienna) 2021 02 3;128(2):215-224. Epub 2021 Feb 3.

Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.

Deep brain stimulation (DBS) of the bed nucleus of the stria terminalis/anterior limb of the internal capsule (BNST/ALIC) is successfully used for treatment of patients with obsessive-compulsive disorder (OCD). Clinical and experimental studies have suggested that enhanced network synchronization in the theta band is correlated with severity of symptoms. The mechanisms of action of DBS remain unclear in OCD. We here investigate the effect of acute stimulation of the BNCT/ALIC on oscillatory neuronal activity in patients with OCD implanted with DBS electrodes. We recorded the oscillatory activity of local field potentials (LFPs) from DBS electrodes (contact + 0/- 3; bipolar configuration; both hemispheres) from the BNST/ALIC parallel with frontal cortical electroencephalogram (EEG) one day after DBS surgery in four patients with OCD. BNST/ALIC and frontal EEG oscillatory activities were analysed before stimulation as baseline, and after three periods of stimulation with different voltage amplitudes (1 V, 2 V and 3.5 V) at 130 Hz. Overall, acute high frequency DBS reduced oscillatory theta band (4-8 Hz; p < 0.01) but increased other frequency bands in BNST/ALIC and the frontal cortex (p < 0.01). We show that stimulation of the BNST/ALIC in OCD modulates oscillatory activity in brain regions that are involved in the pathomechanisms of OCD. Our findings confirm and extend the findings that enhanced theta oscillatory activity in neuronal networks may be a biomarker for OCD.
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http://dx.doi.org/10.1007/s00702-020-02297-6DOI Listing
February 2021

The influence of the CRS-R score on functional outcome in patients with severe brain injury receiving early rehabilitation.

BMC Neurol 2021 Jan 30;21(1):44. Epub 2021 Jan 30.

Institute for Neurorehabilitative Research, Associated Institute of the Hannover Medical School, BDH-Clinic Hessisch Oldendorf, Hessisch Oldendorf, Germany.

Background: The aim of the study was to determine the role of the Coma Recovery Scale-Revised (CRS-R) in the prediction of functional status at the end of neurological early rehabilitative treatment.

Methods: Patients consecutively admitted to intensive or intermediate care units of a neurological rehabilitation center were enrolled in the study. Consciousness and functional status were assessed with the Coma Recovery Scale-Revised (CRS-R) and the Early Rehabilitation Barthel Index (ERBI), respectively. Both assessments were carried out weekly within the first month and at the end of early rehabilitation. Patient and clinical data were entered into a binary logistic regression model to predict functional status at discharge.

Results: 327 patients (112 females, 215 males) with a median age of 63 years (IQR = 53-75) and a median disease duration of 18 days (IQR = 12-28) were included. Most patients suffered from stroke (59 %), followed by traumatic brain injury (31 %), and hypoxic ischemic encephalopathy (10 %). Upon admission, 12 % were diagnosed as comatose, 31 % as unresponsive wakefulness syndrome (UWS), 35 % as minimally conscious state (MCS) and 22 % already emerged from MCS (eMCS). Of all patients undergoing complete early rehabilitative treatment (n = 180), 72 % showed improvements in level of consciousness (LOC). In this group, age, initial CRS-R score and gains in CRS-R score after four weeks independently predicted functional outcome at discharge.

Conclusions: The study confirms the relevance of the CRS-R score for functional outcome prediction. High CRS-R scores and young age facilitate functional improvements and increase the probability to continue treatment in subsequent rehabilitation phases. Moreover, results indicate that recovery might occur over a period of time that extends beyond acute care.
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http://dx.doi.org/10.1186/s12883-021-02063-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847163PMC
January 2021

The prognostic significance of clinicopathological features in meningiomas: Microscopic brain invasion can predict patient outcome in otherwise benign meningiomas.

Neuropathol Appl Neurobiol 2021 Jan 28. Epub 2021 Jan 28.

Department of Neuropathology, Institute of Pathology, Hannover Medical School, Hannover, Germany.

Aims: Brain invasion (BI) was firstly defined as a single criterion of atypia in otherwise benign meningiomas in the revised fourth edition of 2016 WHO classification of brain tumours after being previously inconsistently addressed. However, recent studies have raised doubts about the prognostic significance of BI in otherwise benign meningiomas. In our study, we investigate the reproducibility of such a prognostic effect.

Methods: We identified two cohorts one consisting of 483 patients with meningioma WHO grade I (M°I) or atypical meningioma WHO grade II (M°II) from Hannover Medical School and the other including atypical meningiomas defined according to the classical WHO criteria (M°IIb) from the University Hospital Heidelberg. Follow-up data with a median observation time of 38.2 months were available from 308 cases. These included 243 M°I and 65 M°II patients with the latter group consisting of 25 patients with otherwise benign meningiomas with BI (M°IIa) and 40 with M°IIb.

Results: A significant difference of progression-free interval (PFI) was found between patients with M°I and M°II, M°I and M°IIa and those with M°I and M°IIb of both cohorts and each separately. However, PFI of M°IIa and M°IIb patients showed no significant difference. In the multivariate regression analysis adjusted for M°I/M°IIa versus M°IIb, sex, age, extent of resection and tumour location, BI exhibited the strongest risk of relapse (Hazard ratio: 4.95) serving as an independent predictor of PFI (p = 0.002).

Conclusions: Our results clearly support the definition of BI as a single criterion of atypia in WHO classification of 2016.
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http://dx.doi.org/10.1111/nan.12700DOI Listing
January 2021

Effect of a bundle approach on external ventricular drain-related infection.

Acta Neurochir (Wien) 2021 04 11;163(4):1135-1142. Epub 2021 Jan 11.

Department of Neurosurgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.

Background: Emergency placement of an external ventricular drain (EVD) is one of the most frequently performed neurosurgical procedures. EVD-related infection continues to be a major challenge causing significant morbidity and costs. Bundle approaches have been shown to reduce infection rates; however, they are still not widely used, and observation periods often were rather short.

Methods: The present study evaluated the effect of a multi-item bundle approach for EVD placement and care on the occurrence of EVD-related infection. A before/after approach was used to compare groups of consecutive patients over 5-year epochs to control for bias and secondary confounding variables.

Results: The number of patients in the group before implementation of the bundle approach was 141 and 208 thereafter. There were no statistical differences in demographic and other variables. While 41/141 patients (29.1%) had an EVD-related infection before, this was the case in only 10/208 patients (4.8%) thereafter (p < 0.0001). The EVD-related infection rate was reduced from 13.7/1000 catheter days to 3.2/1000, and the 50% probability of an EVD-related infection in correlation to the mean duration of EVD placement was significantly lower (p < 0.0001). Routine EVD replacement was not helpful to reduce EVD-related infection. EVD-related infection rates remained low also over the next 8 years after the study was finished.

Conclusions: The introduction of a multi-item bundle approach for EVD insertion and care resulted in a marked reduction of EVD-related infection. Long observation periods over 5 years and beyond confirm that short-term changes are sustained with continued use of such protocols.
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http://dx.doi.org/10.1007/s00701-020-04698-8DOI Listing
April 2021

Operative findings and outcome of microvascular decompression/adhesiolysis for trigeminal neuralgia in multiple sclerosis without demyelinating brain stem lesions.

Clin Neurol Neurosurg 2021 01 18;200:106376. Epub 2020 Nov 18.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Objective: Trigeminal neuralgia (TN) in multiple sclerosis (MS) poses several challenges for treatment. Although these patients often have typical attacks, they may not be considered as candidates for microvascular decompression (MVD). Here we report on surgical findings and long term follow-up of MVD/ adhesiolysis in a series of patients with multiple sclerosis but without demyelinating brain stem lesions.

Methods: Fifteen patients with MS-related TN underwent MVD/ adhesiolysis. Demyelinating brain stem lesions were excluded radiologically. Outcome of the intervention was assessed according to the Barrow Neurological Institute (BNI) pain intensity score at 3, 12, 24 months follow-up and at the last available follow-up (mean 88.2 months, range 38-146).

Results: All 15 patients benefited from MVD/adhesiolysis and were pain free on the first day of surgery. Intraoperative findings included arterial contact in 7/15 (47 %) patients, venous contact in 9/15 (60 %), and prominent arachnoid thickening in 12/15 (80 %). The distribution of the BNI pain intensity scores showed marked improvement at all follow-up evaluations. Five patients underwent repeat MVD/adhesiolysis for pain recurrence at a mean of 43 months after the first surgery. Long term evaluation at the last available follow-up demonstrated favorable outcome in 13/15 patients (BNI I-IIIa) (87 %), while 2/15 patients had limited benefit (BNI IV).

Conclusions: MS-related TN in patients without demyelinating brain stem lesions may be related either to vascular conflicts or to focal arachnoiditis at the trigeminal nerve entry zone. MVD/ adhesiolysis may be considered as a useful treatment option in this subgroup of patients with regard to long term outcome.
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http://dx.doi.org/10.1016/j.clineuro.2020.106376DOI Listing
January 2021

Technology of deep brain stimulation: current status and future directions.

Nat Rev Neurol 2021 Feb 26;17(2):75-87. Epub 2020 Nov 26.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.
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http://dx.doi.org/10.1038/s41582-020-00426-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116699PMC
February 2021

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

Mol Psychiatry 2021 01 3;26(1):60-65. Epub 2020 Nov 3.

Department of Neurosurgery, Karolinska Institutet and University Hospital, Stockholm, Sweden.

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.
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http://dx.doi.org/10.1038/s41380-020-00933-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815503PMC
January 2021

Pallidal Deep Brain Stimulation in Patients with Prior Bilateral Pallidotomy and Selective Peripheral Denervation for Treatment of Dystonia.

Stereotact Funct Neurosurg 2021 20;99(1):1-5. Epub 2020 Oct 20.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Introduction: Deep brain stimulation (DBS) of the globus pallidus internus has become an accepted treatment for severe isolated idiopathic and inherited dystonia. Patients who had other forms of surgery earlier, such as radiofrequency lesioning or selective peripheral denervation, however, usually are not considered candidates for DBS.

Objective: The aim of this study was to evaluate the long-term outcome of pallidal DBS in a rare subgroup of patients who had undergone both pallidotomy and selective peripheral denervation previously with a waning effect over the years.

Methods: Pallidal DBS was performed according to a prospective study protocol in 2 patients with isolated idiopathic dystonia, and patients were followed for a period of at least 6 years.

Results: Both patients benefitted from long-lasting amelioration of dystonia after pallidal DBS, which was comparable to that of patients who did not have previous surgeries. In a 62-year-old female with cervical dystonia both the Burke-Fahn-Marsden (BFM) and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) motor scores were improved at follow-up 8 years after surgery (50 and 39%). In a 32-year-old male with generalized dystonia, the BFM motor and disability scores showed marked improvement at 6.5 years of follow-up (82 and 66%).

Conclusions: Pallidal DBS can yield marked and long-lasting improvement in patients who underwent both pallidotomy and selective peripheral denervation earlier. Therefore, such patients, in general, should not be excluded from DBS.
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http://dx.doi.org/10.1159/000509822DOI Listing
July 2021

Bilateral pallidal stimulation improves cervical dystonia for more than a decade.

Parkinsonism Relat Disord 2020 12 15;81:78-81. Epub 2020 Oct 15.

Department of Neurology, Inselspital, Berne University Hospital, Berne, Switzerland; Institute of Neurology, Konolfingen, Switzerland.

Introduction: Deep brain stimulation (DBS) is an effective treatment in medically resistant cervical dystonia (CD) with a documented therapeutic effect. Long term outcome beyond a decade, however, has not been studied systematically.

Methods: To investigate the impact of pallidal DBS beyond 10 years in CD we followed a series of five consecutive patients with severe medication-resistant CD. Severity of head and neck deviation, disability, and pain related to dystonia were assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in the frame of a prospective study. The primary endpoint of this study was a change in the TWSTRS total score. Secondary endpoints were changes in the subscores of the TWSTRS.

Results: The mean follow-up time was 11.5 years (range 10-12.8). Comparing baseline and the last follow-up, CD improved by 53% on the total TWSTRS score, by 54.1% on the severity score, and by 70.1% on the disability score, while pain did not improve significantly. Improvement was stable over time. Patients with a tonic pattern of CD responded less to DBS than patients with a phasic pattern. DBS had no significant effect on mood and cognition. Two patients underwent electrode revisions. One patient had an infection of the proximal cable two years after surgery.

Conclusions: Chronic bilateral pallidal stimulation improves severity of dystonia and disability over more than a decade in treatment resistant CD. Results may vary among individual patients.
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http://dx.doi.org/10.1016/j.parkreldis.2020.10.028DOI Listing
December 2020

Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus.

Mov Disord 2020 11 22;35(11):1945-1954. Epub 2020 Sep 22.

Department of Neurosurgery, Medical School Hannover, Hannover, Germany.

Idiopathic normal pressure hydrocephalus is considered common but remains underinvestigated. There are no uniformly accepted diagnostic criteria and therapeutic guidelines. We summarize the accumulated evidence regarding the definition, pathophysiology, diagnosis, and treatment of idiopathic normal pressure hydrocephalus, highlighting the many gaps and controversies, including diagnostic challenges, the frequent association with neurodegeneration and vascular disease, and the many unknowns regarding patient selection and outcome predictors. A roadmap to fill these gaps and solve the controversies around this condition is also proposed. More evidence is required with respect to diagnostic criteria, the value of ancillary testing, prospective population-based studies and novel trial designs. Furthermore, a need exists to develop new advanced options in shunt technology. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28251DOI Listing
November 2020

The dimensions of "failed back surgery syndrome": what is behind a label?

Acta Neurochir (Wien) 2021 01 1;163(1):245-250. Epub 2020 Sep 1.

Department of Neurosurgery, Medical School Hannover, MHH, Hannover, Germany.

Background: The term failed back surgery syndrome (FBSS) has been criticized for being too unspecific and several studies have shown that a variety of conditions may underlie this label. The aims of the present study were to describe the specific symptoms and to investigate the primary and secondary underlying causes of FBSS in a contemporary series of patients who had lumbar spinal surgery before.

Methods: We used a multilevel approach along three different axes defining symptomatic, morphological, and functional pathology dimensions.

Results: Within the study period of 3 years, a total of 145 patients (74 f, 71 m, mean age 51a, range 32-82a) with the external diagnosis of FBSS were included. Disk surgery up to 4 times and surgery for spinal stenosis up to 3 times were the commonest index operations. Most often, the patients complained of low back pain (n = 126), pseudoradicular pain (n = 54), and neuropathic pain (n = 44). Imaging revealed osteochondrosis (n = 61), spondylarthrosis (n = 48), and spinal misalignment (n = 32) as the most frequent morphological changes. The majority of patients were assigned at least to two different symptomatic subcategories and morphological subcategories, respectively. According to these findings, one or more functional pathologies were assigned in 131/145 patients that subsequently enabled a specific treatment strategy.

Conclusions: FBSS has become rather a vague and imprecisely used generic term. We suggest that it should be avoided in the future both with regard to its partially stigmatizing connotation and its inherent hindering to provide individualized medicine.
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http://dx.doi.org/10.1007/s00701-020-04548-7DOI Listing
January 2021

Deep Brain Stimulation for Chronic Cluster Headache: Meta-Analysis of Individual Patient Data.

Ann Neurol 2020 11 11;88(5):956-969. Epub 2020 Sep 11.

Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.

Objective: Deep brain stimulation (DBS) is a treatment option for refractory chronic cluster headache (CCH). Despite several recent prospective case series reporting a good outcome, the effectiveness and the optimal stimulation target of DBS for CCH remain unclear. We aimed to obtain precise estimates and predictors of long-term pain relief in an individual patient data meta-analysis. Furthermore, we aimed to construct a probabilistic stimulation map of effective DBS.

Methods: We invited investigators of published cohorts of patients undergoing DBS for CCH, identified by a systematic review of MEDLINE from inception to Febuary 15, 2019, to provide individual patient data on baseline covariates, pre- and postoperative headache scores at median (12-month) and long-term follow-up, in addition to individual imaging data to obtain individual electrode positions. We calculated a stimulation map using voxel-wise statistical analysis. We used multiple regression analysis to estimate predictors of pain relief.

Results: Among 40 patients from four different cohorts representing ~50% of all previously published cases, we found a significant 77% mean reduction in headache attack frequency over a mean follow-up of 44 months, with an overall response rate of 75%. Positive outcome was not associated with baseline covariates. We identified 2 hotspots of stimulation covering the midbrain ventral and retrorubral tegmentum.

Interpretation: This study supports the hypothesis that DBS provides long-term pain relief for the majority of CCH patients. Our stimulation map of the region of influence of therapeutic DBS identified an optimal anatomical target site that can help surgeons to guide their surgical planning in the future. ANN NEUROL 2020;88:956-969.
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http://dx.doi.org/10.1002/ana.25887DOI Listing
November 2020

Body Concept and Quality of Life in Patients with Idiopathic Dystonia.

Brain Sci 2020 Jul 28;10(8). Epub 2020 Jul 28.

Center for Systems Neuroscience, 30625 Hannover, Germany.

Patients with dystonia experience unusual postures and disfigurement. The aim of the study was to examine changes in the body concept in relation to quality of life and severity of dystonia. Our cohort consisted of 20 patients with idiopathic dystonia resistant to medical therapy who were planned for pallidal deep brain stimulation. The results were compared to 25 healthy controls. The patients were assessed with Frankfurt Body Concept Scale, Short Form 36 (SF-36) Health Survey, Hamilton Depression Scale, Beck Depression Inventory, Social Phobia Inventory and Social Interaction Anxiety Scale. The disease severity was evaluated with Burke-Fahn-Marsden Dystonia Rating Scale and Toronto Western Spasmodic Torticollis Rating Scale. Patients with dystonia had a significantly impaired body concept in eight out of nine subscales in comparison to healthy controls. The differences were most pronounced for the subscales general health, body care, physical efficacy, sexuality and physical appearance ( < 0.001). Furthermore, all eight subscales of SF-36 exhibited significantly lower values in patients with dystonia compared to controls. We also found significant positive correlations between SF-36 and body concept subscales. Impairment of body concept was not associated with disease severity or levels of social anxiety symptoms. However, there was a significant association between self-rated depression and disease severity. Our patients suffered from increased depression and social anxiety symptoms except social interaction anxiety. We conclude that patients with dystonia have significant body concept impairment that interferes with quality of life in both physical and emotional domains. Future studies should focus on assessing these symptoms after adequate therapeutic management of motor symptoms.
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http://dx.doi.org/10.3390/brainsci10080488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464975PMC
July 2020

Long-Term Deep Brain Stimulation in Treatment-Resistant Obsessive-Compulsive Disorder: Outcome and Quality of Life at Four to Eight Years Follow-Up.

Neuromodulation 2021 Feb 15;24(2):324-330. Epub 2020 Jul 15.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Background: Obsessive compulsive disorder (OCD) is a severe disabling disease, and around 10% of patients are considered to be treatment-resistant (tr) in spite of guideline-based therapy. Deep brain stimulation (DBS) has been proposed as a promising treatment for patients with trOCD. However, the optimal site for stimulation is still a matter of debate, and clinical long-term follow-up observations including data on quality of life are sparse. We here present six trOCD patients who underwent DBS with electrodes placed in the bed nucleus of the stria terminalis/anterior limb of the internal capsule (BNST/ALIC), followed for four to eight years after lead implantation.

Materials And Methods: In this prospective observational study, six patients (four men, two women) aged 32-51 years and suffering from severe to extreme trOCD underwent DBS of the BNST/ALIC. Symptom severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and quality of life using the World Health Organization Quality of Life assessment scale (WHO-QoL BREF). Follow-up was obtained at least for four years in all patients.

Results: With chronic DBS for four to eight years, four of the six patients had sustained improvement. Two patients remitted and two patients responded (defined as >35% symptom reduction), while the other two patients were considered nonresponders on long-term. Quality of life markedly improved in remitters and responders. We did not observe peri-interventional side effects or adverse effects of chronic stimulation.

Conclusions: Chronic DBS of ALIC provides long-term benefit up to four to eight years in trOCD, although not all patients take profit. Targeting the BNST was not particularly relevant since no patient appeared to benefit from direct stimulation of the BNST. Quality of life improved in DBS responders, documented by improved QoL scores and, even more important, by regaining of autonomy and improving psychosocial functioning.
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http://dx.doi.org/10.1111/ner.13232DOI Listing
February 2021

Lesion of the Fastigial Nucleus in Juvenile Rats Deteriorates Rat Behavior in Adulthood, Accompanied by Altered Neuronal Activity in the Medial Prefrontal Cortex.

Neuroscience 2020 08 1;442:29-40. Epub 2020 Jul 1.

Department of Neurosurgery, Hannover Medical School, Hannover, Lower Saxony, Germany. Electronic address:

The cerebellar cognitive affective syndrome may result from various cerebellar injuries. Although it is not exactly known which anatomical structures are involved, the fastigial nucleus has been thought to play a pivotal role according to recent studies. Here we investigate whether bilateral fastigial nucleus lesions in juvenile rats affect cognitive-associative and limbic related functions in adulthood. Furthermore, potential effects on the neuronal activity in the medial prefrontal cortex (mPFC) and local field coherence with the sensorimotor cortex (SMCtx) were evaluated. The fastigial nucleus was lesioned bilaterally by thermocoagulation via stereotaxically inserted electrodes in 23-day old male Sprague Dawley rats. Naïve and sham-lesioned rats (electrodes inserted above the nucleus and no electrical current applied) served as controls. As adults, all groups were tested for cognitive-associative function, social behavior, and anxiety. Thereafter, electrophysiological recordings were obtained under urethane anesthesia. Finally, lesions and recording sites were histologically verified. Spatial learning in a radial maze test and learning in an operant learning paradigm was disturbed in rats with fastigial lesions. Furthermore, in the elevated plus maze anxiety was enhanced, whereas social behavior was not affected. Electrophysiological recordings showed enhanced local field coherence between mPFC and SMCtx across all frequency bands. Impaired cognitive and affective functions together with enhanced coherence between mPFC and SMCtx after bilateral fastigial nucleus lesions indicate that the fastigial nucleus contribute to the development of the cerebellar cognitive affective syndrome and associated motor behavior.
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http://dx.doi.org/10.1016/j.neuroscience.2020.06.035DOI Listing
August 2020

Psychosurgery in the History of Stereotactic Functional Neurosurgery.

Stereotact Funct Neurosurg 2020 29;98(4):241-247. Epub 2020 Jun 29.

Department of Neurosurgery, Medical School Hannover, MHH, Hannover, Germany.

The paper invites to reappraise the role of psychosurgery for and within the development of functional stereotactic neurosurgery. It highlights the significant and long-lived role of stereotactic neurosurgery in the treatment of severe and chronic mental disorders. Stereotactic neurosurgery developed out of psychosurgery. It was leucotomy for psychiatric disorders and chronic pain that paved the way for stereotactic dorsomedial thalamotomy in these indications and subsequently for stereotactic surgery in epilepsy and movement disorders. Through the 1960s stereotactic psychosurgery continued to progress in silence. Due to the increased applications of stereotactic surgery in psychiatric indications, psychosurgery's renaissance was proclaimed in the early 1970s. At the same time, however, a public fearing mind control started to discredit all functional neurosurgery for mental disorders, including stereotactic procedures. In writing its own history, stereotactic neurosurgery's identity as a neuropsychiatric discipline became subsequently increasingly redefined as principally a sort of "surgical neurology," cut off from its psychiatric origin.
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http://dx.doi.org/10.1159/000508167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592934PMC
May 2021

Development and Validation of the Orthostatic Tremor Severity and Disability Scale (OT-10).

Mov Disord 2020 10 20;35(10):1796-1801. Epub 2020 Jun 20.

Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.

Background: Limited tools are available for the assessment of orthostatic tremor severity and disability.

Objectives: To develop and validate a self-administered orthostatic tremor scale.

Methods: After expert consensus and literature review generating a list of 42 items, the scale was developed and modified for validation after a patient focus group, multiple rounds of Delphi panels, and cognitive interviews. Clinimetric evaluations included assessing content validity, internal consistency, measurement error and reliability, construct validity, and concurrent validity anchored on the examiner's Clinical Global Impression score.

Results: Eleven items ranked on a Likert scale from 0 (no disability/severity) to 5 (maximal disability/severity) were evaluated in 54 orthostatic tremor patients (16 men and 38 women; mean age: 69.17 ± 9.64 years; disease duration: 13.83 ± 11.24 years) to probe severity and disability over the preceding 1-week period. The 11-item scale showed good internal consistency (Cronbach's alpha = 0.863) and acceptable (>0.40) item-to-total correlation. However, one item was removed at the final Delphi panel because of significant floor effect, poor item-to-total correlation, and poor factor-loading, leaving the scale with 10 items (10-item Orthostatic Tremor Severity and Disability Scale). Test-retest reliability at 2 weeks was excellent (two-way random intraclass correlation coefficient > 0.90), and the individual item test-retest reliability showed good agreement, with a threshold weighted kappa >0.60 for all items. Exploratory factor analyses revealed a parsimonious two-factor construct accounting for 57.7% of the scale's variance. The 10-item Orthostatic Tremor Severity and Disability Scale scores correlated with the CGI.

Conclusions: The self-administered 10-item Orthostatic Tremor Severity and Disability Scale scale is valid and reliable for capturing orthostatic tremor-related severity and disability. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28142DOI Listing
October 2020

Body weight algorithm predicts humane endpoint in an intracranial rat glioma model.

Sci Rep 2020 06 2;10(1):9020. Epub 2020 Jun 2.

Department of Neurosurgery, Hannover Medical School, Hannover, Lower Saxony, Germany.

Humane endpoint determination is fundamental in animal experimentation. Despite commonly accepted endpoint criteria for intracranial tumour models (20% body weight loss and deteriorated clinical score) some animals still die before being euthanized in current research. We here systematically evaluated other measures as surrogates for a more reliable humane endpoint determination. Adult male BDIX rats (n = 119) with intracranial glioma formation after BT4Ca cell-injection were used. Clinical score and body weight were assessed daily. One subgroup (n = 14) was assessed daily for species-specific (nesting, burrowing), motor (distance, coordination) and social behaviour. Another subgroup (n = 8) was implanted with a telemetric device for monitoring heart rate (variability), temperature and activity. Body weight and clinical score of all other rats were used for training (n = 34) and validation (n = 63) of an elaborate body weight course analysis algorithm for endpoint detection. BT4Ca cell-injection reliably induced fast-growing tumours. No behavioural or physiological parameter detected deteriorations of the clinical state earlier or more reliable than clinical scoring by experienced observers. However, the body weight course analysis algorithm predicted endpoints in 97% of animals without confounding observer-dependent factors. Clinical scoring together with the novel algorithm enables highly reliable and observer-independent endpoint determination in a rodent intracranial tumour model.
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http://dx.doi.org/10.1038/s41598-020-65783-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265476PMC
June 2020
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