Introduction: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. Methods: In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. Conclusion: Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective.

OBJECTIVE Sturge-Weber syndrome (SWS) is often accompanied by seizures and neurocognitive deterioration, although previous studies have suggested that early functional brain reorganization may diminish the cognitive sequelae in some children with unilateral SWS. The ‘rules’ governing these plasticity mechanisms are poorly understood. In this study we evaluated longitudinal changes of cognitive functioning (IQ) and assessed the performance of clinical, EEG, and MRI variables for predicting IQ in children with SWS. METHODS Thirty-three young children (mean age: 3.3 years at baseline) with unilateral SWS underwent MRI, scalp EEG and neuro-psychology evaluation twice, with a median follow-up of two years. None of the children had epilepsy surgery. Longitudinal IQ changes were calculated. Seizure variables, interictal EEG abnormalities, as well as extent and location of MRI brain involvement were correlated with IQ assessed at follow-up. RESULTS Global IQ showed a highly variable course with both increases and decreases over time. Lower IQ at baseline was associated with interval IQ increase. In univariate analyses, lower outcome IQ was associated with baseline EEG abnormalities (p<0.001), young age at seizure onset (p=0.001), high seizure frequency (p=0.02), and early frontal lobe involvement on MRI (p=0.01). In multivariate analysis EEG abnormalities at baseline remained a robust, independent predictor of outcome IQ. CONCLUSIONS The early trajectory of cognitive changes in children with unilateral SWS is highly variable; children with improving IQ likely undergo effective unimpeded functional reorganization. Early onset, frequent seizures and interictal epileptiform abnormalities on EEG likely interfere with this process resulting in poor cognitive functions. Future studies assessing interventions should target this high-risk subgroup to optimize cognitive outcome in SWS.

Sleep problems are one of the most common non-motor symptoms of Parkinson's disease (PD). The Parkinson's disease Sleep Scale 2 nd version (PDSS-2) was published in 2011 showing satisfactory clinimetric results. We performed an independent testing of the scale adding further information on its clinimetric properties.In this nationwide study 537 PD patients were enrolled. Besides PDSS-2, we assessed Patient's Global Impression-Severity (PGI) scale on sleep disturbances, Non-motor Symptoms Scale and MDS-UPDRS.Following the Classical Theory of Tests we performed descriptive data analysis, factor analysis, reliability, validity and precision measurements. Subsequently, we evaluated cut-off value for detecting clinically meaningful sleep problems based on receiver operating characteristics analysis.Based on the PGI scale, 161 patients (30.0%) did not reported any sleep problems. Factor analysis revealed almost the same factor structure described by the original PDSS-2 validation study. Cronbach's alpha was 0.863 and all item had good item-total correlation. PDSS-2 demonstrated high convergent validity with Non-Motor Symptoms Scale and Clinical Global Impression-Severity and non-motor part of MDS-UPDRS, and divergent validity with age, gender, education-level, disease-duration and Hoehn-Yahr Stages.Presence of sleep problems was identified by scores >10.5 points on PDSS-2 (sensitivity: 85.3%, specificity: 60.8%, diagnostic accuracy: 78.1%); whereas scores >19.5 points indicated marked sleep-related problems (specificity: 68.5%, sensitivity: 78.0%, diagnostic accuracy: 74.3%).Independent and cross-cultural validation of patient reported outcomes is essential to confirm or reject the findings obtained by the developers of the scale. Our results demonstrate that fundamental clinimetric properties of the PDSS-2 are satisfactory.

Background. Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. Methods. Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[ 11 C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined. Results. A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = −0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98-31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients. Conclusions. Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival. Key Points1. Regions with high tryptophan uptake in peritumoral brain show high cellularity on diffusion MRI.2. Nonresection of such regions predicts the site of posttreatment tumor progression.3. High tryptophan uptake in contrast-enhancing tumor regions is prognostic for longer survival. 265John et al. Multimodal imaging-defined glioblastoma subregions Neuro-OncologyDespite aggressive multimodal treatment with surgery and chemoradiation therapy, glioblastomas continue to have extremely poor prognosis, with a median overall survival of 15 months. 1,2 Clinical prognostic factors for glioblastoma include age, performance status, tumor radiologic features, and extent of initial tumor resection. 3,4 Among molecular features, high Ki-67 nuclear labeling index carries unfavorable prognosis, 5 whereas isocitrate dehydrogenase 1 (IDH1) mutation is associated with prolonged survival. 6,7 O 6methylguanine-DNA methyltransferase (MGMT) promoter methylation is associated with a favorable response to the alkylating chemotherapeutic agent temozolomide. 8,9 In clinical practice, conventi...