Experimental Study of the Course of Threshold Current,Voltage and Electrode Impedance During Stepwise Stimulation From the Skin Surface to the Human Cortex

BackgroundTranscranial electric stimulation as used during intraoperative neurostimulation is dependent on electrode and skull impedances.ObjectiveThreshold currents, voltages and electrode impedances were evaluated with electrical stimulation at 8 successive layers between the skin and the cerebral cortex.Patients and MethodsData of 10 patients (6f, 53 ± 11 years) were analyzed. Motor evoked potentials were elicited by constant current stimulation with corkscrew type electrodes (CS) at C3 and C4 in line with standard transcranial electric stimulation. A monopolar anodal ball tip shaped probe was used for all other measurements being performed at the level of the skin, dura and cortex, as well as within the skull by stepwise performed burr holes close to C3 resp. C4.ResultsAverage stimulation intensity, corresponding voltage and impedance for muscle MEPs at current motor threshold (CMT) were recorded: CS 54 ± 23 mA (mean ± SD), 38 ± 21 V, 686 ± 146 Ω; with the monopolar probe on skin 55 ± 28 mA, 100 ± 44 V, 1911 ± 683 Ω and scalp 59 ± 32 mA, 56 ± 28 V, 1010 ± 402 Ω; within the skull bone: outer compact layer 33 ± 23 mA, 91 ± 53 V, 3734 ± 2793 Ω; spongiform layer 33 ± 23 mA, 70 ± 44 V, 2347 ± 1327 Ω; inner compact layer (ICL) 28 ± 19 mA, 48 ± 23 V, 2103 ± 1498 Ω; on dura 25 ± 12 mA, 17 ± 12 V, 643 ± 244 Ω and cortex 14 ± 6 mA, 11 ± 5 V, 859 ± 300 Ω. CMTs were only significantly different for CS (P = 0.02) and for the monopolar probe between the cortex and ICL (P = 0.03), scalp (P = 0.01) or skin (P = 0.01) and between ICL and CS (P ≤ 0.01) or skin (P ≤ 0.01).ConclusionThe mean stimulation current of the CMT along the extracranial to intracranial anodal trajectory followed a stepwise reduction. VMT was strongly dependent on electrode impedance. CMT within the skull layers was noted to have relative strong shunting currents in scalp layers.     

Klinische Beiträge zur neurovegetativen Regulation des Kohlehydrathaushalts

Résumé Le métabolisme glucosique est réglé de façon diverse (anervale-fermentative, hormonale, hypothalamique, limbique et corticale). Déjà l'entrée de la glucose à travers le tube digestif peut être influencée nervalement. Ainsi la tendance en direction pyrovatique du métabolisme intermédiaire des sucres est-elle favorisée par des psychoanaleptiques et des psychotoniques, inhibée au contraire par des neuroplégiques et des sympathicolytiques qui, en même temps, favorisent la tendance en direction des pentoses. Le psychisme se trouve par de telles modifications métaboliques influencé soit dans le sens de l'excitation, de l'augmentation de la vigilance, soit dans le sens de l'apaisement, de l'atténuation des sensations douloureuses etc.Dans le dualisme hormonal régulateur insuline/glucagone la stimulation parasympathique provoque une sécrétion de l'insuline. L'équilibre établi dans le sang en circulation entre de l'insuline libre et de l'insuline liée aux protéines peut être influencé par la réserpine en cas de stress. La situation de stress aiguë mène par l'excitation hypothalamique-sympathique à une libération d'adrénaline et en même temps à l'enrichissement de noradrénaline hypothalamique. Ainsi le circuit régulateur glandotrope adénohypophysaire se trouve stimulé de façon non spécifique. L'excitation spécifique de ces circuits régulateurs s'effectue par les releasing-factors CRF, TRF et LRF constituant l'expression d'une sécrétion neurohormonale de la partie microcellulaire hypophysotrope de la base du troisième ventricule; de là résulte la constitution adénohypophysaire d'ACTH, TSH et LH avec ses effets correspondants au niveau des glandes hormonales périphériques: sécrétion des glucocorticoïdes par le cortex pararénal, sécrétion de thyroxine par la glande thyréoïdienne, de progestérone ou de testostérone par des ovaires resp. des testicules. En cas de stress le Nucleus ventromedialis hypothalami permet un réglage inverse compensateur.STH et insuline se trouvent dans un antagonisme corrélatif. Le système limbique possède une position clé dans la régulation du maintien du taux de la glucose sanguine; ici le cycle de Papez joue un grand rôle: fornix—hippocampus—corpus mammillare—tractus mammillo-thalamicus—cingulum—hippocampus.L'ensemble du problème de la régulation neurovégétative du métabolisme de la glucose a été reconnu bien avant son fondement expérimental par les cliniciens, par leurs observations sur des malades (perturbations du métabolisme des glucoses en cas de maladie de Cushing, d'acromégalie, d'angoisse de la mort imminente, diabète par traumatisme cérébral etc.). De la manifestation clinique d'un trouble métabolique diabétique endogène, resté des années durant en latence, sont responsables dans la plupart des cas des stress neurovégétatifs (des émotions psychiques, des accidents, des brûlures, des opérations, des maladies infectieuses etc.). 70% de toutes les hyperglycémies fonctionnelles se développent sur la base neurovégétative. La symptomatologie neurovégétative des hyperglycémies pourtant est à considérer comme conséquence et non pas comme cause de celles-ci. L'insuline déclenche physiologiquement non seulement des mécanismes chimiques mais aussi nerveux (de là des réflexes conditionnés hypoglycémiques, suppression de l'hyperglycémie initiale après injection intraveineuse d'insuline par dihydroergotamine).

---

---

Mit 7 Textabbildungen     

Influence of multisystemic affection on health-related quality of life in patients with myotonic dystrophy type 1

Aim

To assess health-related quality of life (HRQoL) in patients with DM1, to identify muscular, multisystemic, central and social factors that may affect QoL and to define a DM1 patient in risk of poor QoL.

Patients and method

This cross-sectional study comprised 120 DM1 consecutive patients. The following scales were used: Multidimensional Scale of Perceived Social Support (MSPSS), Muscular Impairment Rating Scale (MIRS), battery of neuropsychological tests, acceptance of illness scale (AIS), Hamilton rating scale for depression (Ham-D), Krupp's Fatigue Severity Scale (FSS), Daytime Sleepiness Scale (DSS) and SF-36 questionnaire.

Results

HRQoL was impaired in DM1 patients in both physical and mental domains (PCS was 41.8 ± 23.5, MCS 47.0 ± 24.3 and total SF-36 score 45.6 ± 24.0). The most significant factors correlating with better SF-36 total score were younger age (β = −0.45, p < 0.001), shorter duration of disease (β = −0.27, p = 0.001), higher education (β = 0.20, p = 0.009), less severe muscular weakness (β = −0.52, p < 0.001), normal swallowing (β = 0.22, p = 0.005), absence of fainting (β = 0.31, p = 0.002), absence of snoring (β = 0.21, p = 0.036), better acceptance of disease (β = −0.17, p = 0.036), lower depressiveness (β = −0.46, p = 0.001), lower fatigue (β = −0.32, p = 0.001), absence of cataract (β = −0.21, p = 0.034), absence of kyphosis (β = 0.31, p = 0.004) and absence of constipation (β = 0.24, p = 0.016). Second linear regression analysis revealed that depressed (β = −0.38, p < 0.001) and elder patients (β = −0.27, p = 0.007) and as well as those with poor acceptance of illness (β = −0.21, p = 0.006) were in especially higher risk of having poor HRQoL (R² = 0.68).

Conclusion

We identified different central, social, muscular, cardiorespiratory and other factors correlating with HRQoL. It is of great importance that most of these factors are amenable to treatment.     

Verbal Fluency in Essential Tremor Patients: The Effects of Deep Brain Stimulation

ObjectiveTo assess the effects of different frequencies of thalamic Deep-Brain-Stimulation (DBS) on cognitive performance of patients suffering from Essential Tremor (ET).MethodsIn 17 ET-patients with thalamic-DBS, Tremor-Rating-Scale (TRS), standardized phonemic and semantic verbal fluency (VF), Stroop-Color-Word-Test and Digit-span-test were investigated in three randomized stimulation-settings: i) high-frequency stimulation (HFS), ii) low-frequency stimulation (LFS) and iii) OFF-stimulation (DBS-OFF). Paired-samples t-test for TRS and one-way repeated measures analysis of variance for cognitive performance were calculated.ResultsTremor was reduced during HFS (Mean_TRS-HFS = 12.9 ± 9.6) compared to DBS-OFF (Mean_TRS-OFF = 44.4 ± 19.8, P < .001) and to LFS (Mean_TRS-10Hz = 50.0 ± 24.2; P < .001). While performance of Stroop-task and digit-span remained unaffected by stimulation-settings (P > .05), phonemic and semantic VF differed significantly between the three conditions (F_Pvf = 5.28, F_Svf = 3.41, both P < .05). Post-hoc comparisons revealed significant differences for both phonemic and semantic VF between LFS (Mean_Pvf-10Hz = 54.6 ± 9.2, Mean_Svf-10Hz = 56.4 ± 7.9) and HFS (Mean_Pvf-ON = 48.3 ± 11.4, Mean_Svf-ON = 51.1 ± 11.0, both P < .05), while DBS-OFF (Mean_Pvf-OFF = 51.2 ± 9.3, Mean_Svf-OFF = 53.6 ± 12.9) and HFS and DBS-OFF and LFS did not differ significantly (P > .05).ConclusionsHFS compared to LFS or DBS-OFF significantly reduced tremor but simultaneously worsened VF while working memory and cognitive inhibition remained unaffected. In contrast, LFS enhanced VF but did not ameliorate tremor. The data emphasize the relevance of thalamocortical loops for verbal fluency but also suggest that more sophisticated DBS-regimes in ET may improve both motor and cognitive performance.     

Short-course whole-brain radiotherapy (WBRT) for brain metastases due to small-cell lung cancer (SCLC)

Objective

Many patients with brain metastases due to SCLC have a poor survival prognosis. The most common treatment is whole-brain radiotherapy (WBRT). This retrospective study compares short-course WBRT with 5 × 4 Gy in 1 week to standard WBRT with 10 × 3 Gy in 2 weeks.

Methods

Forty-four SCLC patients receiving WBRT with 5 × 4 Gy were compared to 102 patients receiving 10 × 3 Gy for survival (OS) and local (intracerebral) control (LC). Seven further potential prognostic factors were investigated: age, gender, Karnofsky Performance Score (KPS), number of brain metastases, extracerebral metastases, interval from tumor diagnosis to WBRT, RPA (Recursive Partitioning Analysis) class.

Results

After 5 × 4 Gy, 12-month OS was 15%, versus 22% after 10 × 3 Gy (p = 0.69). On multivariate analysis, improved OS was associated with age ≤60 years (p = 0.013), KPS ≥70 (p < 0.001), <4 brain metastases (p = 0.011), and RPA class 1 (p < 0.001). 12-month LC was 34% after 5 × 4 Gy versus 25% after 10 × 3 Gy (p = 0.32). On multivariate analysis, improved LC was associated with KPS ≥70 (p < 0.001), <4 brain metastases (p = 0.027), and RPA class 1 (p < 0.001).

Conclusion

In patients with brain metastases due to SCLC, short-course WBRT with 5 × 4 Gy provided similar outcomes as 10 × 3 Gy and appears preferable, particularly for patients with poor estimated survival.     

修订的阿尔茨海默病诊断标准适用于中低收入国家吗?（英文）

阿尔茨海默病(Alzheimer’s Disease,AD)是老年人主要疾病负担之一。在中等收入国家,如中国,整体健康状况改善、寿命延长以及其他一些因素使得人口迅速老龄化,AD所致的负担日益加重。近来AD诊断标准的修订,则反映了过去三十年中对该病认识的新进展。不同国际组织提出不同的AD诊断标准,这些标准都将AD疾病谱细分为若干阶段,所分的阶段彼此有些重叠。某些情况下,诊断标准要求同时存在记忆受损的表现以及特定的生物标记物。然而,这些修订的标准有几大不足:需要有训练有素的临床医生才能明确区分不同的阶段;诊断标准提及的生物标记物在AD的发生和发展中的作用仍然不明确;需要由训练有素的技术人员使用昂贵的高科技设备来评估这些生物标记物。上述问题限制了这些诊断标准的临床应用,资源匮乏的地方受限更甚,因为那里负责诊断和治疗AD患者的临床医生获得的培训有限,并且还缺少设备来确定上述生物标记物。     

Neurochemical Monitoring of Therapeutic Effects in Large Human MCA Infarction

Background and purpose  Cerebral microdialysis is an invasive monitoring tool allowing analysis of various substances derived from the extracellular space in brain tissue such as glutamate, glycerol, lactate, and pyruvate. In order to assess the potential effects of hemicraniectomy, hypothermia and conservative therapy on these substances, we used neurochemical monitoring with microdialysis in large human stroke patients. Methods  This is an open, prospective observational study in 24 patients with large MCA infarction undergoing either hypothermia (33°C), hemicraniectomy, or maximum conservative therapy. Microdialysis probe placement was aimed at the peri-infarct tissue within 24 h after stroke onset. Glutamate, glycerol, pyruvate, and lactate were analyzed every 60 min. Measurements of two consecutive days were pooled for statistical analysis. Results  Average glutamate concentrations in patients treated with hemicraniectomy (5.3 ± 0.5 μmol/l, P < 0.0001; n = 6) and hypothermia (14.5 ± 3.6 μmol/l, P < 0.0001; n = 14) were significantly lower than in conservatively treated patients (68.3 ± 5.2 μmol/l; n = 4). Glycerol concentration was significantly lower in patients treated by hypothermia (111 ± 17 μmol/l; P < 0.0001) and hemicraniectomy (138 ± 8 μmol/l; P < 0.0001) as compared to conservatively treated patients with 612 ± 27 μmol/l. The lactate–pyruvate ratio was significantly lower both in the hypothermia (16.2 ± 3.3) and hemicraniectomy groups (31.3 ± 1.5) than in the conservative treatment group (56 ± 2.9). Conclusion  Microdialysis allows bed-side monitoring of neuroprotective effects of stroke rescue therapies such as hypothermia and hemicraniectomy. Rescue of peri-infarct tissue and/or prevention of secondary ischemic injury could be associated with a lower mortality in invasively treated patients.     

Magnetic resonance imaging assessment of cardiac dysfunction in δ-sarcoglycan null mice

Delta-sarcoglycan (δ-sarcoglycan) null, Scgd^−/−, mice develop cardiac and skeletal muscle histopathological alterations similar to those in humans with limb-girdle muscular dystrophy. The objective of this study was to assess the feasibility of using MRI to investigate cardiac dysfunction in Scgd^−/− mice. Cardiac MRI of 8 month old Scgd^−/− and wild type (WT) mice was performed. Compared to WT, Scgd^−/− mice had significantly lower LV ejection fraction (44 ± 5% vs. 66 ± 4%, p = 0.014), lower RV ejection fraction (25 ± 2% vs. 51 ± 3%, p < 0.001) lower myocardial circumferential strain, (15.0 ± 0.3% vs. 16.9 ± 0.3%, p = 0.007) and RV dilatation (54 ± 3 μL vs. 40 ± 3 μL, p = 0.007). The regional circumferential strain also demonstrated significant temporal dyssynchrony between opposing regions of the Scgd^−/− LV. Our results demonstrate severe cardiac dysfunction in Scgd^−/− mice at 8 months. The study identifies a set of non-invasive markers that could be used to study efficacy of novel therapeutic agents in dystrophic mice.     

Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials

Limited options are available for clozapine-resistant schizophrenia and intolerable side effects of clozapine. We conducted a systematic review of randomized-controlled trials (RCTs) to determine the efficacy and safety of aripiprazole augmentation of clozapine for schizophrenia. Electronic databases searched included PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. This review synthesized the data of four short-term (8–24 weeks), placebo-controlled trials (N = 347). The overall relative risk (RR, 95% confidence interval) of discontinuation rates was not significantly different between groups (RR = 1.41, 95% CI = 0.78 to 2.56). The pooled standardized mean differences (SMDs, 95% CIs) (Z-test; number of study; I²-index) suggested trends of aripiprazole augmentation benefits on overall psychotic [−0.40 (−0.87 to 0.07) (n = 3; Z = 1.68, p = 0.09; I² = 68%)], positive [−1.05 (−2.39 to 0.29) (n = 3; Z = 1.54, p = 0.12; I² = 94%)], and negative [−0.36 (−0.77 to 0.05) (n = 3; Z = 1.74, p = 0.08; I² = 54%)] symptoms. Despite of no benefit on three cardiometabolic indices (i.e., fasting plasma glucose, triglyceride, and high-density lipoprotein), aripiprazole augmentation was superior for weight change with a mean difference (95% CI) of −1.36 kg (−2.35 to −0.36) (n = 3; Z = 2.67, p = 0.008; I² = 39%) and LDL-cholesterol with a mean difference of −11.06 mg/dL (−18.25 to −3.87) (n = 3; Z = 3.02, p = 0.003; I² = 31%). Aripiprazole augmentation was not correlated with headache and insomnia but significantly associated with agitation/akathesia (RR = 7.59, 95% CI = 1.43 to 40.18) (n = 3; Z = 2.38, p = 0.02; I² = 0%) and anxiety (RR = 2.70, 95% CI = 1.02 to 7.15) (n = 1; Z = 2.00, p = 0.05). The limited short-term data suggested that aripiprazole augmentation of clozapine can minimize the cardiometabolic risk, causes agitation/akathesia, and may be effective in attenuating psychotic symptoms.     

Psychoeducation and cognitive-behavioral therapy for patients with refractory bipolar disorder: A 5-year controlled clinical trial

ObjectiveThe aim of this research, which represents an additional and longer follow-up to a previous trial, was to evaluate a 5-year follow-up study of a combined treatment (pharmacological + psychoeducational and cognitive-behavioral therapy) as compared with a standard pharmacological treatment in patients with refractory bipolar disorder.MethodForty patients were randomly assigned to either an Experimental group–under combined treatment — or a Control group — under pharmacological treatment. Data were analyzed by analysis of variance (ANOVA), with repeated measures at different evaluation time points.ResultsBetween-group differences were significant at all evaluation time points after treatment. Experimental group had less hospitalization events than Control group in the 12-month evaluation (P = 0.015). The Experimental group showed lower depression and anxiety in the 6-month (P = 0.006; P = 0.019), 12-month (P = 0.001; P < 0.001) and 5-year (P < 0.001, P < 0.001) evaluation time points. Significant differences emerged in mania and misadjustment already in the post-treatment evaluation (P = 0.009; P < 0.001) and were sustained throughout the study (6-month: P = 0.006, P < 0.001; 12-month: P < 0.001, P < 0.001; 5-year: P = 0.004, P < 0.001). After 5-year follow-up, 88.9% of patients in the Control group and 20% of patients in the Experimental group showed persistent affective symptoms and/or difficulties in social-occupational functioning.ConclusionsA combined therapy is long-term effective for patients with refractory bipolar disorder. Suggestions for future research are commented.     

Causal associations of intelligence with schizophrenia and bipolar disorder: A Mendelian randomization analysis

BackgroundIntelligence is inversely associated with schizophrenia (SCZ) and bipolar disorder (BD); it remains unclear whether low intelligence is a cause or consequence. We investigated causal associations of intelligence with SCZ or BD risk and a shared risk between SCZ and BD and SCZ-specific risk.MethodsTo estimate putative causal associations, we performed multi-single nucleotide polymorphism (SNP) Mendelian randomization (MR) using generalized summary-data-based MR (GSMR). Summary-level datasets from five GWASs (intelligence, SCZ vs. control [CON], BD vs. CON, SCZ + BD vs. CON, and SCZ vs. BD; sample sizes of up to 269,867) were utilized.ResultsA strong bidirectional association between risks for SCZ and BD was observed (odds ratio; OR_SCZ → BD = 1.47, p = 2.89 × 10⁻⁴¹, OR_BD → SCZ = 1.44, p = 1.85 × 10⁻⁵²). Low intelligence was bidirectionally associated with a high risk for SCZ, with a stronger effect of intelligence on SCZ risk (OR_{lower intelligence → SCZ} = 1.62, p = 3.23 × 10⁻¹⁴) than the reverse (OR_{SCZ → lower intelligence} = 1.06, p = 3.70 × 10⁻²³). Furthermore, low intelligence affected a shared risk between SCZ and BD (OR _{lower intelligence → SCZ + BD} = 1.23, p = 3.41 × 10⁻⁵) and SCZ-specific risk (OR_{lower intelligence → SCZvsBD} = 1.64, p = 9.72 × 10⁻¹⁰); the shared risk (OR_{SCZ + BD → lower intelligence} = 1.04, p = 3.09 × 10⁻¹⁴) but not SCZ-specific risk (OR_{SCZvsBD → lower intelligence} = 1.00, p = 0.88) weakly affected low intelligence. Conversely, there was no significant causal association between intelligence and BD risk (p > 0.05).ConclusionsThese findings support observational studies showing that patients with SCZ display impairment in premorbid intelligence and intelligence decline. Moreover, a shared factor between SCZ and BD might contribute to impairment in premorbid intelligence and intelligence decline but SCZ-specific factors might be affected by impairment in premorbid intelligence. We suggest that patients with these genetic factors should be categorized as having a cognitive disorder SCZ or BD subtype.     

Ambient temperature affects thrombotic potential at rest and following exercise

Introduction

During exercise, ischemic risk increases, possibly due to changes in coagulation and fibrinolytic activity. Previous research suggests ambient temperature affects resting thrombotic potential, but the effect of heat and cold on hemostasis during exercise is unknown. The purpose of this study was to assess changes in coagulation and fibrinolysis during maximal exercise in hot and cold temperatures, and to compare those responses to exercise under temperate conditions.

Materials & Methods

Fifteen healthy men completed maximal exercise tests in hot (30 °C), temperate (20 °C) and cold (5° - 8 °C) temperatures. Blood samples were obtained before and immediately after exercise and analyzed for concentrations of thrombin-antithrombin III (TAT), active tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). Results were analyzed by ANOVA.

Results

A main effect of time was observed for TAT (temperate = 1.71 ± 0.82 - 2.61 ± 0.43 ng/ml, hot = 1.81 ± 0.73 - 2.62 ± 0.67 ng/ml, cold = 2.33 ± 0.65 - 2.89 ± 0.81 ng/ml, PRE to POST, respectively) and tPA activity (temperate = 0.72 ± 0.44 - 2.71 ± 0.55 IU/ml, hot = 0.72 ± 0.38 - 2.64 ± 0.61 IU/ml, cold = 0.86 ± 0.45 - 2.65 ± 0.77 IU/ml, PRE to POST, respectively). A trend was observed for the PAI-1 response to exercise (temperate = 14.5 ± 23.7 - 12.3 ± 20.2 IU/ml, hot = 15.1 ± 26.5 - 10.0 ± 15.1 IU/ml, cold = 10.5 ± 10.4 - 7.9 ± 9.7 IU/ml, PRE to POST, respectively, p = 0.08). TAT concentrations were significantly higher in cold compared to temperate and hot conditions.

Conclusion

Coagulation potential is elevated during exposure to cold temperatures. These data suggest that risk of an ischemic event may be elevated in the cold.     

Multicentre analysis of 178,992 type 2 diabetes patients revealed better metabolic control despite higher rates of hypertension,stroke, dementia and repeated inpatient care in patients with comorbid Parkinson's disease

BackgroundEspecially in older people, physicians are faced with the coexistence of type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). Therefore, this research aimed to compare diabetes endpoints between T2DM with and without PD.MethodsBased on the standardized, multicenter, prospective DPV database, 178,992 T2DM patients (≥40 years) were analyzed. 1579 were diagnosed with PD and/or received specific treatment. Hierarchical multivariable regression models were used for group comparisons; adjusted estimates based on observed marginal frequencies were calculated.ResultsPD patients were significantly older (77.9 vs. 70.0 years; p < 0.0001) and had a longer diabetes duration (10.3 vs. 8.4 years; p < 0.0001). In young PD patients (<50 years), percentage of females was significantly higher compared to age-matched T2DM patients without PD or people of the German population (66.7 vs. 38.1 vs. 49.0%; p < 0.0001, p < 0.02).After demographic adjustment, T2DM patients with PD showed a significantly lower HbA1c (58.0 vs. 60.3 mmol/mol; p < 0.0001), OAD/GLP-1 treatment (41.9 vs. 45.9%; p < 0.01) and frequency of dyslipidemia (62.0 vs. 64.5%; p < 0.05). In contrast, rates of insulin therapy (57.8 vs. 54.8%; p < 0.05), hypertension (73.3 vs. 68.6%; p < 0.001), antihypertensive medication (60.4 vs. 56.1%; p < 0.01), stroke (12.0 vs. 7.3%; p < 0.0001), dementia (9.2 vs. 2.6%; p < 0.0001) and repeated inpatient care (15.7 vs. 12.0%; p < 0.0001) were significantly higher and duration of hospital stay (6.2 vs. 4.7 days; p < 0.0001) was significantly longer in T2DM with PD.ConclusionClear demographic and clinical differences were observed between T2DM with and without PD. In PD patients, metabolic control is better, potentially due to more intensive medical care.     

Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BP_ND). Here, we used blockade of the TSPO radioligand [¹¹C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (V_ND), and hence estimate the BP_ND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [¹¹C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V_ND was estimated via the occupancy plot. Values of BP_ND for all subjects were calculated using this V_ND estimate. Total volume of distribution (V_T) of MABs (2.94±0.31) was lower than V_T of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a V_ND estimate of 1.98 (1.69, 2.26). Based on these V_ND estimates, BP_ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [¹¹C]PBR28 V_ND and hence BP_ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V_ND for TSPO targeting radioligands.