Prospective Evaluation of a Modified Apnea Test in Brain Death Candidates that Does Not Require Disconnection from the Ventilator.

BACKGROUND: The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from the ventilator followed by tracheal oxygen insufflation to ensure adequate oxygenation. To rate the test as positive, most international guidelines state that a lack of spontaneous breathing must be demonstrated when the arterial partial pressure of carbon dioxide (PaCO2) ≥ 60 mm Hg. However, the loss of positive end-expiratory pressure that is associated with disconnection from the ventilator may cause rapid desaturation. This, in turn, can lead to cardiopulmonary instability (especially in patients with pulmonary impairment and diseases such as acute respiratory distress syndrome), putting patients at increased risk. Therefore, this prospective study aimed to investigate whether a modified version of the AT (mAT), in which the patient remains connected to the ventilator, is a safer yet still valid alternative. METHODS: The mAT was performed in all 140 BD/DNC candidates registered between January 2019 and December 2022: after 10 min of preoxygenation, (1) positive end-expiratory pressure was increased by 2 mbar (1.5 mm Hg), (2) ventilation mode was switched to continuous positive airway pressure, and (3) apnea back-up mode was turned off (flow trigger 10 L/min). The mAT was considered positive when spontaneous breathing did not occur upon PaCO2 increase to ≥ 60 mm Hg (baseline 35-45 mm Hg). Clinical complications during/after mAT were documented. RESULTS: The mAT was possible in 139/140 patients and had a median duration of 15 min (interquartile range 13-19 min). Severe complications were not evident. In 51 patients, the post-mAT arterial partial pressure of oxygen (PaO2) was lower than the pre-mAT PaO2, whereas it was the same or higher in 88 cases. In patients with pulmonary impairment, apneic oxygenation during the mAT improved PaO2. In 123 cases, there was a transient drop in blood pressure at the end of or after the mAT, whereas in 12 cases, the mean arterial pressure dropped below 60 mm Hg. CONCLUSIONS: The mAT is a safe and protective means of identifying patients who no longer have an intact central respiratory drive, which is a critical factor in the diagnosis of BD/DNC. Clinical trial registration DRKS, DRKS00017803, retrospectively registered 23.11.2020, https://drks.de/search/de/trial/DRKS00017803.

Minimally invasive resection of a prominent transverse process in neurogenic thoracic outlet syndrome: new application for a primarily spinal approach. Illustrative case.

BACKGROUND: The optimal surgical approach to treat neurogenic thoracic outlet syndrome (nTOS) depends on the individual patient's anatomy as well as the surgeon's experience. The authors present a minimally invasive posterior approach for the resection of a prominent transverse process to reduce local muscular trauma. OBSERVATIONS: A 19-year-old female presented with painful sensations in the right arm and severe fine-motor skill dysfunction in the right hand, each of which had been present for several years. Further examination confirmed affected C8 and T1 areas, and imaging showed an elongated C7 transverse process displacing the lower trunk of the brachial plexus. Decompression of the plexus structures by resection of the C7 transverse process was indicated, owing to persistent neurological effects. Surgery was performed using a minimally invasive posterior approach in which the nuchal soft tissue was bluntly dissected by dilatators and resection of the transverse process was done microscopically through a tubular retractor. The postoperative course showed a sufficient reduction of pain and paresthesia. LESSONS: The authors describe a minimally invasive posterior approach for the treatment of nTOS with the aim of providing indirect relief of strain on brachial plexus structures. The advantages of this technique include a small skin incision and minor soft tissue damage.

Brain death determination in patients with veno-arterial extracorporeal membrane oxygenation: A systematic study to address the Harlequin syndrome.

PURPOSE: The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different paCO2-levels. The purpose of this study was to compare two variants of paCO2-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination. MATERIALS AND METHODS: Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in paCO2-levels were analysed for both variants. RESULTS: At the start of AT, median paCO2-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median paCO2-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, paCO2-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, paCO2-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002). CONCLUSIONS: Simultaneous paCO2-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study.

BACKGROUND: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. METHODS: This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. RESULTS: Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043). CONCLUSIONS: Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke (COTTIS): a pilot study.

BACKGROUND: To evaluate the feasibility and safety of a fast initiation of cooling to a target temperature of 35°C by means of transnasal cooling in patients with anterior circulation large vessel occlusion (LVO) undergoing endovascular thrombectomy (EVT). METHODS: Patients with an LVO onset of <24 hour who had an indication for EVT were included in the study. Transnasal cooling (RhinoChill) was initiated immediately after the patient was intubated for EVT and continued until an oesophageal target temperature of 35°C was reached. Hypothermia was maintained with surface cooling for 6-hour postrecanalisation, followed by active rewarming (+0.2°C/hour). The primary outcome was defined as the time required to reach 35°C, while secondary outcomes comprised clinical, radiological and safety parameters. RESULTS: Twenty-two patients (median age, 77 years) were included in the study (14 received additional thrombolysis, 4 additional stenting of the proximal internal carotid artery). The median time intervals were 309 min for last-seen-normal-to-groin, 58 min for door-to-cooling-initiation, 65 min for door-to-groin and 123 min for door-to-recanalisation. The target temperature of 35°C was reached within 30 min (range 13-78 min), corresponding to a cooling rate of 2.6 °C/hour. On recanalisation, 86% of the patients had a body temperature of ≤35°C. The median National Institutes of Health Stroke Scale at admission was 15 and improved to 2 by day 7, and 68% of patients had a good outcome (modified Rankin Scale 0-2) at 3 months. Postprocedure complications included asymptomatic bradycardia (32%), pneumonia (18%) and asymptomatic haemorrhagic transformation (18%). CONCLUSION: The combined application of hypothermia and thrombectomy was found to be feasible in sedated and ventilated patents. Adverse events were comparable to those previously described for EVT in the absence of hypothermia. The effect of this procedure will next be evaluated in the randomised COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke-2 trial.

[Prospective investigation of extracranial duplex sonography for the detection of cerebral circulatory arrest in patients with irreversible loss of brain function]. / Prospektive Untersuchung der extrakraniellen Duplexsonographie zum Nachweis des zerebralen Perfusionsstillstands bei Patienten mit irreversiblem Hirnfunktionsausfall.

BACKGROUND: A broader distribution of bedside color-coded duplex sonography (CCD) for detection of cerebral circulatory arrest (CCA) would be important to improve its use in the diagnosis of irreversible loss of brain function (ILBF-Dx). QUESTION: Is extracranial compared to the commonly applied transcranial CCD of the brain-supplying vessels (ECCD vs. TCCD) equivalent for the detection of CCA in ILBF-Dx regarding specificity and sensitivity? MATERIAL AND METHODS: Study period January 2019-June 2022, screening of 136 and inclusion of 114 patients with severe brain lesions > 24 h after onset of fixed and dilated pupils, apnea and completed ILBF-Dx. Exclusion of patients without brainstem areflexia and guideline-conform applicability of CCD. Complementary ECCD (and TCCD, if other method used for irreversibility detection). RESULTS: Detection of ILBF (ILBF+) in 86.8% (99/114), no ILBF (ILBF-) in 13.2% (15/114). ECCD was fully feasible in all patients; findings matching CCA were found in 94/99 ILBF+ cases (ECCD+) and not in 5 patients (ECCD-). All 15 patients with ILBF- showed ECCD- findings. Thus, the specificity of ECCD was 1.0, and the sensitivity was 0.949. TCCD showed CCA in 56 patients (TCCD+), and ECCD+ was also found in all of them. An inconclusive result of TCCD in ILBF+ was found in 38 cases, with parallel ECCD+ in all of these patients. In 20 cases, TCCD did not show CCA (TCCD-), these also showed ECCD-. Of these patients 15 were ILBF- and 5 were ILBF+. DISCUSSION: TCCD was not completely feasible or inconclusive in one third of the cases, whereas ECCD was always feasible. ECCD showed high validity with respect to the detection of CCA. Therefore, the possibility of using ECCD alone to detect CCA in ILBF-Dx should be discussed.

Minimally-invasive bedside catheter haematoma aspiration followed by local thrombolysis in spontaneous supratentorial intracerebral haemorrhage: a retrospective single-center study.

Background and purpose: The role of surgery in the treatment of intracerebral haemorrhage (ICH) remains controversial. Whereas open surgery has failed to show any clinical benefit, recent studies have suggested that minimal invasive procedures can indeed be beneficial, especially when they are applied at an early time point. This retrospective study therefore evaluated the feasibility of a free-hand bedside catheter technique with subsequent local lysis for early haematoma evacuation in patients with spontaneous supratentorial ICH. Methods: Patients with spontaneous supratentorial haemorrhage of a volume of >30 mL who were treated with bedside catheter haematoma evacuation were identified from our institutional database. The entry point and evacuation trajectory of the catheter were based on a 3D-reconstructed CT scan. The catheter was inserted bedside into the core of the haematoma, and urokinase (5,000 IE) was administered every 6 h for a maximum of 4 days. Evolution of haematoma volume, perihaemorrhagic edema, midline-shift, adverse events and functional outcome were analyzed. Results: A total of 110 patients with a median initial haematoma volume of 60.6 mL were analyzed. Haematoma volume decreased to 46.1 mL immediately after catheter placement and initial aspiration (with a median time to treatment of 9 h after ictus), and to 21.0 mL at the end of urokinase treatment. Perihaemorrhagic edema decreased significantly from 45.0 mL to 38.9 mL and midline-shift from 6.0 mm to 2.0 mm. The median NIHSS score improved from 18 on admission to 10 at discharge, and the median mRS at discharge was 4; the latter was even lower in patients who reached a target volume ≤ 15 mL at the end of local lysis. The in-hospital mortality rate was 8.2%, and catheter/local lysis-associated complications occurred in 5.5% of patients. Conclusion: Bedside catheter aspiration with subsequent urokinase irrigation is a safe and feasible procedure for treating spontaneous supratentorial ICH, and can immediately reduce the mass effects of haemorrhage. Additional controlled studies that assess the long-term outcome and generalizability of our findings are therefore warranted. Clinical trial registration: [www.drks.de], identifier [DRKS00007908].

Digital Patient-Reported Outcome Measures Assessing Health-Related Quality of Life in Skull Base Diseases-Analysis of Feasibility and Pitfalls Two Years after Implementation.

Health-related quality of life (HRQoL) assessment is becoming increasingly important in neurosurgery following the trend toward patient-centered care, especially in the context of skull base diseases. The current study evaluates the systematic assessment of HRQoL using digital patient-reported outcome measures (PROMs) in a tertiary care center specialized in skull base diseases. The methodology and feasibility to conduct digital PROMs using both generic and disease-specific questionnaires were investigated. Infrastructural and patient-specific factors affecting participation and response rates were analyzed. Since August 2020, 158 digital PROMs were implemented in skull base patients presenting for specialized outpatient consultations. Reduced personnel capacity led to significantly fewer PROMs being conducted during the second versus (vs.) the first year after introduction (mean: 0.77 vs. 2.47 per consultation day, p = 0.0002). The mean age of patients not completing vs. those completing long-term assessments was significantly higher (59.90 vs. 54.11 years, p = 0.0136). Follow-up response rates tended to be increased with recent surgery rather than with the wait-and-scan strategy. Our strategy of conducting digital PROMs appears suitable for assessing HRQoL in skull base diseases. The availability of medical personnel for implementation and supervision was essential. Response rates during follow-up tended to be higher both with younger age and after recent surgery.

Exclusive color-coded duplex sonography of extracranial vessels reliably confirms brain death: A prospective study.

Background: Transcranial color-coded duplex sonography (TCCD) can be used as an ancillary test for determining irreversible loss of brain function (ILBF) when demonstration of cerebral circulatory arrest (CCA) is required. However, visualization of the intracranial vessels by TCCD is often difficult, or even impossible, in this patient cohort due to elevated intracranial pressure, an insufficient transtemporal bone window, or warped anatomical conditions. Since extracranial color-coded duplex sonography (ECCD) can be performed without restriction in the aforementioned situations, we investigated the feasibility of omitting TCCD altogether, such that the ILBF examination would be simplified, without compromising on its reliability. Methods: A total of 122 patients were prospectively examined by two experienced neurointensivists for the presence of ILBF from 01/2019-12/2021. Inclusion criteria were (i) the presence of a severe cerebral lesion on cranial CT or MRI, and (ii) brainstem areflexia. Upon standardized clinical examination, 9 patients were excluded due to incomplete brainstem areflexia, and a further 22 due to the presence of factors with a potentially confounding influence on apnea testing, EEG or sonography. A total of 91 patients were enrolled and underwent needle-EEG recording for >30 min (= gold standard), as well as ECCD and TCCD. The sonographer was blinded to the EEG result. Results: All patients whose ECCD result was consistent with ILBF had this diagnosis confirmed by EEG (n = 77; specificity: 1). Both ECCD and EEG were not consistent with ILBF in a further 12 patients. In the remaining two patients, ECCD detected reperfusion due to long-lasting cerebral hypoxia; however, ILBF was ultimately confirmed by EEG (sensitivity: 0.975). This yielded a positive predictive value (PPV) of one and a negative predictive value of 0.857 for the validity of ECCD in ILBF confirmation. TCCD was not possible/inconclusive in 31 patients (34%). Conclusions: The use of ECCD for the confirmation of ILBF is associated with high levels of specificity and a high positive predictive value when compared to needle-electrode EEG. This makes ECCD a potential alternative to the ancillary tests currently used in this setting, but confirmation in a multi-center trial is warranted. Trial registration: https://www.drks.de, DRKS00017803.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

The Tourniquet Ischemia Test in the Diagnosis of Complex Regional Pain Syndrome.

BACKGROUND: The tourniquet ischemia test (IT) is a hitherto rarely used tool for the diagnostic work-up of patients with suspected complex regional pain syndrome (CRPS). This analysis aims to determine the sensitivity and specificity of this test, and elucidate factors that can influence the test result. METHODS: Consecutive data on clinical presentation, results of the IT and other diagnostic tests, and clinical characteristics were analyzed from patients presenting at our autonomic laboratory between 2000 and 2011. IT results were compared with the final clinical diagnosis at discharge, and statistical analysis was performed to determine specificity, sensitivity, and positive and negative predictive values of the IT. RESULTS: A total of 78 patients were assessed. IT results were positive (≥50% reduction in pain during ischemia) in 26 cases and negative in 52 cases. CRPS was the final diagnosis in 45 cases, and in 33 cases, a different diagnosis was made. This results in a test sensitivity of 49% and a specificity of 88%, with a positive predictive value of 85% and a negative predictive value of 56%. Age, sex, the type and stage of CRPS, and the affected extremity did not influence the test result in a statistically significant manner. Specificity worsened to 76% if any pain reduction was rated as a positive test result. CONCLUSIONS: A positive tourniquet IT has a high positive predictive value for the diagnosis of CRPS. It is thus useful as a confirmatory assay in patients with suspected CRPS. Low sensitivity rules out its use as a screening test. SIGNIFICANCE: This study retrospectively analyzed the clinical significance of the tourniquet IT that was routinely used in patients with suspected CRPS. It showed that a positive IT result is useful as a confirmatory assay in patients fulfilling the clinical criteria.

Thyroid Diseases Are an Underestimated Risk Factor for Cerebral Venous Sinus Thrombosis.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease that generally accounts for just 1% of all strokes. Of the multiple risk factors that have been identified, the most common are genetic or acquired thrombophilia and the use of oral contraceptives, while the less common include local infections and mechanical causes. Thyroid diseases have been described as rare risk factors for CVST (<2% of all cases), without exact knowledge of the underlying pathophysiology. This retrospective study aimed to re-evaluate the relevance of thyroid disease as risk factor for CVST, with particular emphasis on hyperthyroidism. Patients and Methods: Confirmed cases of CVST were (re-)evaluated in terms of risk factors including thyroid parameters. Results were compared to previous data from the International Study on CVST. Results: Between 1996 and 2016, 182 patients with confirmed CVST were treated in our hospital with a median age of 44 years and a female proportion of 74.7%. Genetic or acquired thrombophilia along with the use of oral contraceptives were found to be the most common risk factors. Thyroid diseases were present in 20.9% of CVST patients; this included patients with previous (9.9%) and current thyroid dysfunction (11%). Discussion and Conclusions: Thyroid diseases may represent a more common risk factor for CVST than previously described. This holds true even if patients with current thyroid dysfunction are purely taken into account. However, 58% of patients had more than one additional risk factor, suggesting a multifactorial hypercoagulability. Clinical Trials Register: Registered at the German Clinical Trials Register: http://www.drks.de, DRKS00017044.

Isolated Cervical Myelitis in Lyme Disease: A Rare Manifestation of Acute Neuroborreliosis.

Neuroborreliosis is the neurological manifestation of Lyme disease, a tick-borne infectious multi-system disease caused by Borrelia burgdorferi sensu lato. It appears in 3 to 15% of all cases of acute Lyme disease, and includes meningitis, cranial neuritis, and painful radiculoneuritis as the most common manifestations. We report a case of acute neuroborreliosis that manifested as extended isolated cervical myelitis. Not only the manifestation as isolated myelitis in the early stages of borreliosis represents a rarity, but also the strong contrast between mild clinical symptoms and pronounced imaging findings in this case is remarkable.

Cerebral amyloid angiopathy-related intracerebral hemorrhage: Feasibility and safety of bedside catheter hematoma evacuation with urokinase.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhage (ICH). However, data on surgical intervention in CAA-related ICH is very limited. In this retrospective study we assessed safety and efficacy of free-hand catheter aspiration followed by local thrombolysis in CAA-related large ICH. PATIENTS AND METHODS: Patients with CAA-related lobar ICH>30 ml that were treated with this catheter technique were identified from our prospective database. The catheter was inserted at the bedside in the core of the hematoma and urokinase (5000IE) was administered every 6 h for a maximum of 4 days. Evolution of hematoma volume, perihemorrhagic edema (PHE) and midline-shift (MLS) as well as adverse events and functional outcome were analyzed. RESULTS: Twenty-one patients (median age 79 years) were treated between 2013-2018. Hematoma volume decreased from 70 ml at admission (IQR 49-98 ml) to 52 ml (IQR 35-76 ml, p < 0.001) immediately after catheter aspiration, and to 23.5 ml (IQR 17-47 ml, p < 0.001) at the end of urokinase treatment. At day 4, PHE volume (from 45 ml [IQR 33-71 ml] to 36 ml [IQR 22-50 ml]; p = 0.001) and MLS (from 5 mm [IQR 3.5-7 mm] to 1 mm [IQR 0.5-3 mm]; p < 0.001) were reduced significantly. No infection was observed, rebleeding after administration of 4 × 5000IE urokinase occurred in one patient (5 %). At discharge, modified Rankin Scale was 3 in 33 %, 4 in 24 %, and 5 in 43 % of patients, and had further improved after rehabilitation to an mRS of 2 in 10 %, 3 in 38 %, 4 in 19 %, and 5 in 33 % (median 9 weeks after ictus). There were no patient deaths during this time. CONCLUSIONS: Bedside catheter hematoma evacuation in large CAA-related ICH seemed feasible and safe and could immediately decrease mass effect. Further studies assessing functional outcome are warranted.

A new approach to characterize postural deficits in chemotherapy-induced peripheral neuropathy and to analyze postural adaptions after an exercise intervention.

BACKGROUND: Postural instability presents a common and disabling consequence of chemotherapy-induced peripheral neuropathy (CIPN). However, knowledge about postural behavior of CIPN patients is sparse. With this pilot study, we used a new approach to i) characterize postural impairments as compared to healthy subjects, ii) allocate possible abnormalities to a set of parameters describing sensorimotor function, and iii) evaluate the effects of a balance-based exercise intervention. METHODS: We analyzed spontaneous and externally perturbed postural control in eight CIPN patients before and after a balance-based exercise intervention by using a modification of an established postural control model. These findings were compared to 15 matched healthy subjects. RESULTS: Spontaneous sway amplitude and velocity were larger in CIPN patients compared to healthy subjects. CIPN patients' reactions to external perturbations were smaller compared to healthy subjects, indicating that patients favor vestibular over proprioceptive sensory information. The balance-based exercise intervention up-weighted proprioceptive information in patients. CONCLUSIONS: CIPN patients' major postural deficit may relate to underuse of proprioceptive information that results in a less accurate posture control as spontaneous sway results indicate. The balance-based exercise intervention is able to partially correct for this abnormality. Our study contributes to a better understanding of postural impairments in CIPN patients and suggests an effective treatment strategy. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00004340, retrospectively registered 04 January 2013.

Hemodynamics of cerebral veins analyzed by 2d and 4d flow mri and ultrasound in healthy volunteers and patients with multiple sclerosis.

BACKGROUND: Hemodynamic alterations of extracranial veins are considered an etiologic factor in multiple sclerosis (MS). However, ultrasound and MRI studies could not confirm a pathophysiological link. Because of technical challenges using standard diagnostics, information about the involvement of superficial intracranial veins in proximity to the affected brain in MS is scarce. PURPOSE: To comprehensively investigate the hemodynamics of intracranial veins and of the venous outflow tract in MS patients and controls. STUDY TYPE: Prospective. POPULATION: Twenty-eight patients with relapsing-remitting MS (EDSS1.9 ± 1.1; range 0-3) and 41 healthy controls. FIELD STRENGTH/SEQUENCE: 3T/2D phase-contrast and time-resolved 4D flow MRI, extra- and transcranial sonography. ASSESSMENT: Hemodynamics within the superficial and deep intracranial venous system and outflow tract including the internal, basal, and great cerebral vein, straight, superior sagittal, and transverse sinuses, internal jugular and vertebral veins. Sonography adhered to the chronic cerebrospinal venous insufficiency (CCSVI) criteria. STATISTICAL TESTS: Multivariate repeated measure analysis of variance, Student's two-sample t-test, chi-square, Fisher's exact test; separate analysis of the entire cohort and 32 age- and sex-matched participants. RESULTS: Multi- and univariate main effects of the factor group (MS patient vs. control) and its interactions with the factor vessel position (lower flow within dorsal superior sagittal sinus in MS, 3 ± 1 ml/s vs. 3.8 ± 1 ml/s; P < 0.05) in the uncontrolled cohort were attributable to age-related differences. Age- and sex-matched pairs showed a different velocity gradient in a single segment within the deep cerebral veins (great cerebral vein, vena cerebri magna [VCM] 7.6 ± 1.7 cm/s; straight sinus [StS] 10.5 ± 2.2 cm/s vs. volunteers: VCM 9.2 ± 2.3 cm/s; StS 10.2 ± 2.3 cm/s; P = 0.01), reaching comparable velocities instantaneously downstream. Sonography was not statistically different between groups. DATA CONCLUSION: Consistent with previous studies focusing on extracranial hemodynamics, our comprehensive analysis of intracerebral venous blood flow did not reveal relevant differences between MS patients and controls. Level of Evidence 1. Technical Efficacy Stage 3. J. Magn. Reson. Imaging 2020;51:205-217.