Venous 3D Phase Contrast Magnetic Resonance Angiography Increases Diagnostic Certainty in Children with Ventriculoperitoneal Shunt and Suspected Shunt Failure.

BACKGROUND: Clinical symptoms in children with suspected malfunction of ventriculoperitoneal shunt may not be specific and difficult to interpret. The presence or absence of ventricular enlargement on magnetic resonance imaging (MRI) does not reliably predict raised intracranial pressure (ICP) in these patients. Therefore, the aim was to investigate the diagnostic utility of 3D venous phase-contrast MR angiography (vPCA) in these patients. MATERIALS: The MR studies of two groups of patients at two different examination dates were retrospectively analyzed; one group without clinical symptoms on both examinations and one with symptoms of shunt dysfunction on one examination receiving surgery. Both MRI examinations had to have been performed including axial T2 weighted (T2-w) images and 3D vPCA. Two (neuro)radiologists evaluated T2-w images alone and in combination with 3D vPCA in terms of suspected elevated ICP. Interrater reliability, sensitivity and specificity were assessed. RESULTS: Compression of venous sinuses was seen significantly more often in patients with shunt failure (p = 0.00003). Consequently, evaluation of 3D vPCA and T2-w images increases sensitivity to 0.92/1.0 compared to T2-w images alone with 0.69/0.77, the interrater agreement for the diagnosis of shunt failure rises from κ = 0.71 to κ = 0.837. Concerning imaging markers, three groups could be identified in children with shunt failure. CONCLUSION: In accordance with the literature, the results show that ventricular morphology alone is an unreliable marker for elevated ICP in children with shunt malfunction. The findings confirmed 3D vPCA as a valuable supplemental diagnostic tool improving diagnostic certainty for children with unchanged ventricular size in cases of shunt failure.

Iodine uptake of adrenal glands: A novel and reliable spectral dual-layer computed tomographic-derived biomarker for acute septic shock.

OBJECTIVES: Septic shock is a potentially fatal condition. This study aims to assess whether iodine uptake and iodine density of abdominal organs on dual-layer spectral detector computed tomography (SDCT) could serve as a new imaging biomarker for patients in septic shock. METHODS: Here, 95 patients who received contrast-enhanced abdominal CT examinations were included and separated into two groups: group A - septic shock; group B - no shock condition. Preselected abdominal (right and left adrenal gland, right and left kidney, infrarenal inferior vena cava (IVC), pancreas, spleen, and liver) localizations were independently evaluated by two radiologists, who measured iodine concentrations (mg/ml) and Hounsfield units (HU). RESULTS: In all, 1520 measurements of iodine concentrations in mg/ml and HU were performed, with 27 patients in group A and 68 in group B. Iodine concentrations in mg/ml and HU correlated significantly in all organs measured. The corresponding correlation coefficient (r) ranged from 0.809 (pancreas) to 0.963 (right kidney). Inter-rater reliability (IRR) was very good for mg/ml (κ = 0.8; p < 0.01) and good for HU (κ = 0.773; p < 0.01) measurements. The mean iodine concentration and HU of the adrenal glands in septic and nonseptic patients was 4.88 ± 1.16 mg/ml/153 ± 36 HU and 2.67 ± 1.07 mg/ml/112 ± 41 HU, respectively. Iodine concentrations in the adrenal glands were significantly higher in group A than in group B patients (p < 0.01). The other organs remained unaffected and no significant difference was observed between patients in group A and B. Patients in group A presented significantly more often with an iodine uptake of >3.5 mg/ml of one adrenal gland (sensitivity = 0.926, specificity = 0.849, AUC = 0.951) or/and a combined concentration of >7 mg/ml of both adrenal glands (sensitivity = 0.889, specificity = 0.836, AUC = 0.928). CONCLUSION: SDCT-derived iodine concentration of the adrenal glands could serve as a novel imaging biomarker for patients in acute septic shock. Our data suggest that an iodine uptake of >3.5 mg/ml of at least one adrenal gland or a combined iodine uptake of >7 mg/ml in both adrenal glands identifies patients in this condition.

Central vein sign in patients with inflammatory lesion of the upper cervical spinal cord on susceptibility weighted imaging at 3 tesla. Preliminary results.

BACKGROUND: The central vein sign (CVS) has been described in vivo in patients with MS but also in other inflammatory lesion of the brain such as neuromyelits optica spectrum disease and others. Recently, it has been used to differentiate patients with MS from other inflammatory lesions of the brain. OBJECTIVE: It was the goal of this study to demonstrate the feasibility of the depiction of the CVS in patients with inflammatory lesion of the upper cervical spinal cord using susceptibility weighted imaging (SWI). METHODS: Consecutive patients with inflammatory lesions of the upper cervical spinal cord were included. Patients were scanned using a 3 T Philips Ingenia CX. The presence of the CVS was assessed by two raters. Demographic and clinical parameters were compared between patients with and those without a CVS. RESULTS: 20 patients could be included. 15 patients had a diagnosis of MS. A CVS was present in 8 patients (40%). Agreement between the two raters was substantial (κ = 0.79). Time from first manifestation was significantly different (14 vs. 2 years, p = 0.021) between patients with CVS and without CVS. CONCLUSION: The depiction of the CVS in the upper cervical spine is feasible. More research is necessary to evaluate these preliminary results and the value of the CVS in the spinal cord.

Survival among patients with severe high cervical spine injuries - a TraumaRegister DGU® database study.

BACKGROUND: Trauma is a significant cause of death and impairment. The Abbreviated Injury Scale (AIS) differentiates the severity of trauma and is the basis for different trauma scores and prediction models. While the majority of patients do not survive injuries which are coded with an AIS 6, there are several patients with a severe high cervical spinal cord injury that could be discharged from hospital despite the prognosis of trauma scores. We estimate that the trauma scores and prediction models miscalculate these injuries. For this reason, we evaluated these findings in a larger control group. METHODS: In a retrospective, multi-centre study, we used the data recorded in the TraumaRegister DGU® (TR-DGU) to select patients with a severe cervical spinal cord injury and an AIS of 3 to 6 between 2002 to 2015. We compared the estimated mortality rate according to the Revised Injury Severity Classification II (RISC II) score against the actual mortality rate for this group. RESULTS: Six hundred and twelve patients (0.6%) sustained a severe cervical spinal cord injury with an AIS of 6. The mean age was 57.8 ± 21.8 years and 441 (72.3%) were male. 580 (98.6%) suffered a blunt trauma, 301 patients were injured in a car accident and 29 through attempted suicide. Out of the 612 patients, 391 (63.9%) died from their injury and 170 during the first 24 h. The group had a predicted mortality rate of 81.4%, but we observed an actual mortality rate of 63.9%. CONCLUSIONS: An AIS of 6 with a complete cord syndrome above C3 as documented in the TR-DGU is survivable if patients get to the hospital alive, at which point they show a survival rate of more than 35%. Compared to the mortality prognosis based on the RISC II score, they survived much more often than expected.

[Interdisciplinary neurovascular networks: state of the art]. / Interdisziplinäre neurovaskuläre Netzwerke: eine Standortbestimmung.

BACKGROUND: In order to treat the complete spectrum of neurovascular diseases at a high level of quality, which goes beyond the purely acute treatment of stroke, the German Stroke Society (DSG) together with the German Societies for Neurosurgery and Neuroradiology developed a certification procedure for neurovascular networks (NVN). Structurally, a NVN consists of a coordinating center with at least three neurovascular network partners with a certified stroke unit. From 2018 to 2020 a total of 15 NVN have so far been audited and certified according to this new standard. OBJECTIVE: How efficient are the NVN? Are high standards maintained? MATERIAL AND METHODS: The reports of the audits were analyzed. The data were taken from the period 2017-2019. RESULTS: The 15 NVN treated a total of 86,510 stroke patients in the years examined and were networked with a total of 107 partner clinics, which were situated an average of 25 km from the coordinating center and transferred a total of 2726 patients. The coordinating centers performed 2463 thrombectomies and treated 2383 patients with nontraumatic intracerebral bleeding. In 712 patients with acute aneurysmatic subarachnoid hemorrhages endovascular treatment was carried out and clipping in 401. The audit was successful in the majority of the NVN. CONCLUSION: The certification process of NVN has been successfully established and the audits proved to be a useful instrument for quality control and improvement. The 15 NVN are highly efficient and treat more than one quarter of stroke patients in German stroke units.

Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

ANTECEDENTES: La efectividad de la endarterectomía carotídea (carotid endarterectomy, CEA) en la prevención de un accidente cerebrovascular depende de que este procedimiento tenga pocos riesgos. El objetivo de este estudio fue evaluar la frecuencia y el momento de aparición de las complicaciones tras una CEA, lo que podría clarificar los mecanismos subyacentes y ayudar a establecer una política de altas hospitalarias segura. MÉTODOS: Se utilizaron los datos de los pacientes incluidos en cuatro grandes ensayos de intervención carotídea (VACS, ACAS, ACST-1 y GALA; 1983-2007). Para el presente análisis se utilizaron los datos de pacientes sometidos a CEA por estenosis de la arteria carótida asintomática recogidos inmediatamente tras la aleatorización. Se consideraron diferentes intervalos entre el procedimiento, la muerte o el accidente cerebrovascular: intraoperatorio día 0, postoperatorio día 0, postoperatorio días 1-3 y postoperatorio días 4-30. RESULTADOS: En el análisis se incluyeron 3.694 pacientes. Se detectaron complicaciones graves relacionadas con el procedimiento en 103 (2,8%) pacientes (18 accidentes cerebrovasculares fatales, 68 accidentes cerebrovasculares no fatales, 11 infartos de miocardio fatales y 6 muertes por otras causas). De los 86 accidentes cerebrovasculares, 67 (78%) fueron ipsilaterales, 17 (20%) contralaterales y dos (2%) vertebrobasilares. Los accidentes cerebrovasculares fueron isquémicos en 45 (52%) casos, hemorrágicos en 9 (10%) y no se pudo determinar el subtipo de ictus en 32 (37%). La mitad de los accidentes cerebrovasculares ocurrieron el día de la CEA. De todas las complicaciones graves registradas, 44 (43%) ocurrieron en el día 0 (20 intraoperatorias, 17 postoperatorias y 7 en períodos poco definidos), 23 (22%) entre los días 1-3 y 36 (35%) entre los días 4-30. CONCLUSIÓN: En este estudio, al menos la mitad de los accidentes cerebrovasculares relacionados con la CEA fueron isquémicos e ipsilaterales respecto a la arteria tratada. La mitad de todas las complicaciones de la CEA ocurrieron el día de la cirugía, pero un tercio de los casos se presentaron después del día 3, cuando muchos pacientes ya habían sido dados de alta.

Non-Contrast-Enhanced Carotid MRA: Clinical Evaluation of a Novel Ungated Radial Quiescent-Interval Slice-Selective MRA at 1.5T.

BACKGROUND AND PURPOSE: Non-contrast-enhanced MRA techniques have experienced a renaissance due to the known correlation between the use of gadolinium-based contrast agents and the development of nephrogenic systemic fibrosis and the deposition of gadolinium in some brain regions. The purpose of this study was to assess the diagnostic performance of ungated non-contrast-enhanced radial quiescent-interval slice-selective MRA of the extracranial supra-aortic arteries in comparison with conventional contrast-enhanced MRA in patients with clinical suspicion of carotid stenosis. MATERIALS AND METHODS: In this prospective study, both MRA pulse sequences were performed in 31 consecutive patients (median age, 68.8 years; 19 men). For the evaluation, the cervical arterial system was divided into 35 segments (right and left side). Three blinded reviewers separately evaluated these segments. An ordinal scoring system was used to assess the image quality of arterial segments and the stenosis grading of carotid arteries. RESULTS: Overall venous contamination in quiescent-interval slice-selective MRA was rated as "none" by all readers in 84.9% of cases and in 8.1% of cases in contrast-enhanced MRA (P < .0001). The visualization quality of arterial segments was considered good to excellent in 40.2% for the quiescent-interval slice-selective MRA and in 52.2% for the contrast-enhanced MRA (P < .0001). The diagnostic accuracy of ungated quiescent-interval slice-selective MRA concerning the stenosis grading showed a total sensitivity and specificity of 85.7% and 90.0%, respectively. CONCLUSIONS: Ungated quiescent-interval slice-selective MRA can be used clinically as an alternative to contrast-enhanced MRA without a significantly different image quality or diagnostic accuracy for the detection of carotid stenosis at 1.5T.

Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

The spectrum of progressive multifocal leukoencephalopathy: a practical approach.

John Cunningham virus (JCV) infection of the central nervous system causes progressive multifocal leukoencephalopathy (PML) in patients with systemic immunosuppression. With the increased application of modern immunotherapy and biologics in various immune-mediated disorders, the PML risk spectrum has changed. Thus, new tools and strategies for risk assessment and stratification in drug-associated PML such as the JCV antibody indices have been introduced. Imaging studies have highlighted atypical presentations of cerebral JCV disease such as granule cell neuronopathy. Imaging markers have been developed to differentiate PML from new multiple sclerosis lesions and to facilitate the early identification of pre-clinical manifestations of PML and its immune reconstitution inflammatory syndrome. PML can be diagnosed either by brain biopsy or by clinical, radiographic and virological criteria. Experimental treatment options including immunization and modulation of interleukin-mediated immune response are emerging. PML should be considered in any patient with compromised systemic or central nervous system immune surveillance presenting with progressive neurological symptoms.

Vessel Wall Enhancement in Unruptured Intracranial Aneurysms: An Indicator for Higher Risk of Rupture? High-Resolution MR Imaging and Correlated Histologic Findings.

BACKGROUND AND PURPOSE: Recent studies have suggested that wall enhancement of unruptured intracranial aneurysms in high-resolution MR imaging might serve as an imaging biomarker for higher risk of rupture. Histologic studies have revealed a possible association among inflammatory processes, degeneration, and destabilization of the aneurysm wall preceding rupture. Understanding the histologic condition underlying aneurysm wall enhancement could be an important step toward assessing the value of this method for risk stratification. We present our observations of aneurysm wall enhancement in MR vessel wall imaging and underlying histologic changes. MATERIALS AND METHODS: We reviewed records of patients with an unruptured middle cerebral artery aneurysm who underwent MR vessel wall imaging before aneurysm clipping. Contrast enhancement of the aneurysm wall was dichotomized into either none/faint or strong. Histologic analysis included myeloperoxidase stain for detection of inflammatory cell invasion and CD34 stain for assessment of neovascularization and vasa vasorum. RESULTS: Thirteen aneurysms were included. Five aneurysms showed strong wall enhancement. Among these, myeloperoxidase staining revealed inflammatory cell infiltration in 4. Three showed neovascularization. In 2 aneurysms, vasa vasorum were present. Seven aneurysms did not show wall enhancement; 1 had only mild enhancement. None of these bore evidence of inflammatory cell invasion or neovascularization, and they all lacked vasa vasorum. CONCLUSIONS: Wall enhancement in MR vessel wall imaging is associated with inflammatory cell invasion, neovascularization, and the presence of vasa vasorum. Enhancement does not occur when histologic signs of inflammation are absent. Our results support the hypothesis that MR vessel wall imaging could provide valuable information for risk stratification.

Quantitative Phase-Contrast MR Angiography to Measure Hemodynamic Changes in Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a syndrome of raised intracranial pressure of unknown etiology. Few MR imaging-based studies have investigated arterial and venous blood flow in these patients. Results are inconclusive, and to our knowledge, no comparison of the hemodynamic parameters before and after CSF pressure reduction has been published. The aim of this study was to assess the short-term effects of normalizing CSF pressure on intracranial flow to better understand the pathophysiology of idiopathic intracranial hypertension. MATERIALS AND METHODS: In this study, we performed quantitative MR imaging-derived flow measurements of brain-supplying arteries and draining veins/dural sinuses to visualize hemodynamic changes in patients with idiopathic intracranial hypertension before and after therapy by lumbar puncture in comparison with a healthy control group. RESULTS: We found differences in patients before and after lumbar puncture in the calculated resistance and pulsatility indices in the superior sagittal sinus. Venous pulsatility showed a negative correlation with CSF pressure in untreated patients. Additionally, there was a trend toward lower flow in the superior sagittal sinus in patients compared with healthy controls. Flow in the internal jugular veins was significantly reduced by lumbar puncture, and the resistance and pulsatility indices differed in patients and controls. The arterial flow was not influenced by pressure normalization. CONCLUSIONS: The results of the present study indicate that venous but not arterial blood flow differs in patients compared with controls and that calculating resistance and pulsatility indices may contribute to assessing short-term hemodynamic changes in patients with diagnosed idiopathic intracranial hypertension before and after CSF diversion.

In-hospital outcomes following single-dose radiation therapy in the treatment of heterotopic ossification of the hip following spinal cord injury-an analysis of 444 cases.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: The objective of the study was to analyse the efficacy of single-dose radiation therapy in the treatment of heterotopic ossification (HO) following spinal cord injury (SCI). SETTING: Department of Spinal Cord Injury and Department of General and Trauma Surgery, BG-University Hospital Bergmannsheil Bochum, Ruhr-University Bochum, Germany. METHODS: Patients who were treated for HO around the hips following SCI at our institution between January 2003 and December 2013 were included in this retrospective cohort study. A total of 444 HO cases around the hip were treated with single-dose radiation therapy after a mean time interval of 4.9 days (0-97 days; s.d.=8.1) after HO diagnosis. Primary outcome measures were the number of HO relapses and the occurrence of adverse side effects related to the radiation therapy. RESULTS: After a mean time interval of 63.2 days (8-295 days; s.d.=39.6) subsequent to SCI HO occurred in 207 male (84.8%) and 37 female (15.2%) patients with a mean age of 46.4 years (18-81 years, s.d.=18.2). In 200 patients both hips were affected, whereas the remaining 44 HO occurred unilateral. None of the patients suffered primary side effects due to the radiation therapy. However, in 13 out of 244 patients (5.3%), HO relapse occurred. After repeated single-dose radiotherapy, one patient suffered joint ankylosis and therefore required surgical resection. CONCLUSION: Our results present that single-dose radiation therapy is a safe option in the treatment for spinal cord-injured patients suffering from HOs of the hips.

Antiplasmodial activity of Heinsia crinita (Rubiaceae) and identification of new iridoids.

ETHNOPHARMACOLOGICAL RELEVANCE: Heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. Its stem bark powder is found in some peripheral markets in the Democratic Republic of the Congo (DRC) as a remedy against malaria. Investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties. MATERIALS AND METHODS: Different plant parts were extracted with methanol, ethanol and dichloromethane. Based on the preliminary assays, the dichloromethane extract of the stem bark was subjected to fractionation using preparative HPLC system and column chromatography. This step led to the isolation of two new iridoids which had their structures elucidated by NMR, UV, MS and FT-IR spectroscopic techniques. Extracts and pure compounds were tested in vitro against the 3D7 strain of Plasmodium falciparum. The inhibition of the parasite growth was evaluated in vitro by colorimetric method (p-LDH assay) and their cytotoxicity evaluated in vitro against the human non-cancer fibroblast cell line (WI38) through WST1 assay. The in vivo antiplasmodial activity was assessed by the inhibition of Plasmodium berghei growth in infected mice treated with the ethanol extract of H. crinita stem bark at the concentrations of 200 and 300mg/Kg/day per os, using a protocol based on the 4-d suppressive test of Peters and compared to a non-treated negative control group of mice (growth =100%). Finally the antioxidant activity of the same extract was evaluated using ABTS, DPPH and cell-based assays. RESULTS: A moderate in vitro antiplasmodial activity was observed for the dichloromethane extract of the stem bark of H. crinita (IC50 =29.2±1.39µg/mL) and for the two new iridoids, lamalbide 6, 7, 8- triacetate (IC50 =16.39±0.43µg/mL) as well as for its aglycone lamiridosin 6, 7, 8-triacetate (IC50 =0.44.56±1.12µg/mL). The ethanolic stem bark extract (200 and 300mg/kg/day, oral route) showed a moderate in vivo antimalarial activity in Plasmodium berghei-infected mice with 27.84±2.75% and 48.54±3.76% of inhibition of the parasite growth, respectively (p<0.01).). This extract displayed high cellular antioxidant activity using dichlorofluorescein-diacetate (DCFDA) on HL-60 monocytes. These crude extracts and pure compounds tested at the higher concentration of 100µg/mL did not show any cytotoxicity against WI38 cells. CONCLUSIONS: The results showed that H. crinita extracts possess antimalarial activity and contain some unusual iridoids with moderate antiplasmodial activity, therefore justifying to some extent its traditional use by the local population in DRC for this purpose. This is the first report of the isolation and antiplasmodial activity of these two new iridoids.

Fingerprinting and validation of a LC-DAD method for the analysis of biflavanones in Garcinia kola-based antimalarial improved traditional medicines.

African populations use traditional medicines in their initial attempt to treat a range of diseases. Nevertheless, accurate knowledge of the composition of these drugs remains a challenge in terms of ensuring the health of population and in order to advance towards improved traditional medicines (ITMs). In this paper chromatographic methods were developed for qualitative and quantitative analyses of a per os antimalarial ITM containing Garcinia kola. The identified analytical markers were used to establish TLC and HPLC fingerprints. G. kola seeds were analysed by HPLC to confirm the identity of the extract used by the Congolese manufacturer in the ITM. The main compounds (GB1, GB2, GB-1a and Kolaflavanone) were isolated by preparative TLC and identified by UPLC-MS and NMR. For the quantification of the major compound GB1, a simple and rapid experimental design was applied to develop an LC method, and then its validation was demonstrated using the total error strategy with the accuracy profile as a decision tool. The accurate results were observed within 0.14-0.45mg/mL range of GB1 expressed as naringenin. The extracts used in several batches of the analysed oral solutions contained GB1 (expressed as naringenin) within 2.04-2.43%. Both the fingerprints and the validated LC-DAD were found suitable for the quality control of G. kola-based raw material and finished products, respectively.