MDS clinical diagnostic criteria for Parkinson's disease

This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances. © 2015 International Parkinson and Movement Disorder Society     

Flat panel detector angiographic CT for stent-assisted coil embolization of broad-based cerebral aneurysms

BACKGROUND AND PURPOSE: The purpose of this work was to evaluate angiographic CT (ACT) in the combined application of a self-expanding neurovascular stent and detachable platinum coils in the management of broad-based and fusiform intracranial aneurysms. MATERIALS AND METHODS: Eleven patients harboring wide-necked intracranial aneurysms were treated with a flexible self-expanding neurovascular stent and subsequent aneurysm embolization with platinum microcoils. ACT was performed after the interventional procedure to analyze stent position and the relationship of coils to the stent. Postprocessing included multiplanar reconstructions (MPRs) and maximum intensity projections (MIPs). ACT volume datasets were postprocessed for soft tissue visualization. RESULTS: Accurate stent placement with subsequent coil occlusion of the aneurysms was feasible in all of the patients. Similar to nonsubtracted digital subtraction angiography (DSA) images, radiopaque platinum stent markers showed excellent visibility in ACT as well. The stent struts themselves, hardly visible in nonsubtracted DSA, were visible in MPRs and MIPs of ACT in all of the patients. In aneurysms larger than 10 mm in diameter, accurate stent assessment at the level of the coils was limited due to beam hardening artifacts. Postprocedural ACT in all of the patients did not reveal any evidence of procedure-related intracranial hemorrhage. CONCLUSION: ACT provides cross-sectional, 3D visualization of endovascular stents otherwise hardly visible with plain fluoroscopy. ACT enables us to accurately determine stent position, which may be helpful in complex stent-assisted aneurysm coiling procedures. However, in aneurysms larger than 10 mm in diameter, beam hardening artifacts caused by the endoaneurysmal coil package impair visibility of the stent. Further data are necessary to evaluate the usefulness of ACT in stent-assisted aneurysm coiling.     

Neuroendocrine Changes in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage

Background

Neuroendocrine changes have been reported after ischemic stroke, subarachnoid hemorrhage, and brain trauma. As there are no corresponding data in patients with intracerebral hemorrhage (ICH) we analyzed various neuroendocrine parameters to investigate possible alterations in hormone profiles of patients with ICH.

Methods

Twenty patients with ICH were prospectively enrolled in the study. Patients were a priori parted into two groups: Ten non-ventilated patients treated on the stroke-unit (hemorrhage volumes <20 ml, “small ICH”), and 10 ventilated patients treated on the neurocritical care unit (hematoma volumes >20 ml with possible additional ventricular involvement (“large ICH”). Neuroendocrine parameters were compared between both groups referring to reference values. The following parameters were obtained over a period of 9 days in 20 patients with spontaneous supratentorial ICH: thyrotropin, free thiiodothyronine and thyroxine, human growth hormone, insulin-like growth factor 1, luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, adrenocorticotropic hormone, and cortisol.

Results

Small ICH patients were in a median 71 (54–88) years old and had a mean ICH volume of 9.5 ± 6.5 ml, whereas large ICH patients were 65 (47–80) years old and showed a mean volume of 56 ± 30.2 ml. None of the patients revealed pathological alterations for thyrotropin, free thiiodothyronine, thyroxine, human growth hormone, insulin-like growth factor 1, and testosterone. There was only a mild decrease of adrenocorticotropic hormone and cortisol on day 3 in large ICH patients. Small ICH patients showed pathologically elevated levels of luteinizing and follicle-stimulating hormone throughout the observation period. Large ICH patients showed a marked increase of prolactin that developed during the course.

Conclusions

Overall, neuroendocrine changes in ICH patients are not as profound as reported for ischemic stroke or subarachnoid hemorrhage. The clinical significance of increased LH and FSH levels in small ICH is unclear, whereas elevation of prolactin in large ICH was anticipated. Future randomized controlled trials should also focus on neuroendocrine parameters to clarify the impact of possible hormonal alterations on functional outcome.     

Radiopacity of intracerebral hemorrhage correlates with perihemorrhagic edema

Background: Experimental evidence indicates that iron plays a key role in edema formation after intracerebral hemorrhage (ICH). We investigated the relationship between ICH radiopacity on CT as a marker of hematoma iron content and perihemorrhagic edema (PHE) after ICH. Methods: We retrospectively investigated patients with spontaneous lobar and ganglionic supratentorial ICH who received follow‐up CT scans during the first 7 days after symptom onset (d1, d2–4, d5–7). Measurements of ICH and edema volumes were taken using a semiautomatic threshold‐based volumetric algorithm. Radiopacity of the blood clot was determined using the mean Hounsfield unit (HU) count of the ICH. Results: A total of 117 patients aged 71.92 ± 11.55 years with spontaneous ICH (34.63 ± 32.44 ml) were included in the analysis. Mean ICH radiopacity was 59.7 ± 3.4 HU. We found significantly larger relative PHE at d2–4 (1.7 ± 0.9 vs. 1.3 ± 0.8; P = 0.032) and d5–7 (2.0 ± 1.3 vs. 1.3 ± 0.9; P = 0.007) and larger peak relative PHE (2.3 ± 1.6 vs. 1.6 ± 1.1; P = 0.006) in patients with ICH radiopacity >60 HU (n = 59), as compared to patients with ICH radiopacity <60 HU (n = 58). Conclusions: Higher ICH radiopacity, reflecting higher in vivo hematoma iron content, is associated with more PHE after ICH.     

Expression and purification of functional recombinant epitopes for the platelet antigens, PlA1 and PlA2

The platelet antigens, PlA1 and PlA2, are responsible for most cases of posttransfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAIT) in the caucasian population and are determined by two allelic forms of the platelet glycoprotein GPIIIa gene. To study the interaction between these antigens and their respective antibodies, we inserted the sequence that encodes the signal peptide and the N- terminal 66 amino acids of the PlA1 form of GPIIIa into the expression vector pGEX1. To express the PlA2 antigen, nucleotide 196 of the PlA1 coding sequence was mutated to the PlA2 allelic form. When transformed and induced in Escherichia coli, the two constructs produce glutathione S-transferase (GST)/N-terminal GPIIIa fusion proteins, one containing leucine at position 33 (PlA1), the other proline (PlA2). These proteins are easily purified in milligram quantities using glutathione-Sepharose and react specifically with their respective antibodies by immunoblot and enzyme-linked immunosorbent assay. Antigenicity of the PlA1 fusion protein in reduced glutathione increases with time; moreover, the addition of oxidized glutathione accelerates this process, presumably because of formation of the native disulfide bonds. Neutralization assays indicate that the PlA1 fusion protein competes for all of the anti-PlA1 antibody in the serum of patients with PTP and NAIT that is capable of interacting with the surface of intact platelets. This study shows that the GST/N-terminal GPIIIa fusion proteins contain conformational epitopes that mimic those involved in alloimmunization, and that regions other than the amino terminal 66 amino acids of GPIIIa are not likely to contain or be required for the development of functional PlA1 epitopes. Furthermore, these recombinant proteins can be used for the affinity-purification of clinical anti-PlA1 antibodies and specific antibody identification by western blotting, making them useful in the diagnosis of patients alloimmunized to PlA1 alloantigens.     

(1)H-MRS profile in MRI positive- versus MRI negative patients with temporal lobe epilepsy.

INTRODUCTION: The objective of this study was to quantitate and compare ipsilateral total N-acetyl aspartate (tNAA), creatine (Cr), choline (Cho), myo-inositol (m-Ins) and glutamate plus glutamine (Glx) levels in the hippocampi of patients with temporal lobe epilepsy (TLE) with and without magnetic resonance imaging (MRI) evidence for mesial temporal sclerosis (MRI positive/negative). PATIENTS AND METHODS: Twenty-three age matched healthy controls and 26 consecutive patients with unilateral TLE, based on intensive 24h video-EEG, were investigated with proton magnetic resonance spectroscopy ((1)H-MRS) (17 with unilateral hippocampal sclerosis (HS) in MRI-MRI positive; 9 MRI negative). For statistical analysis one-way analysis of variance (ANOVA) with post hoc multiple comparisons and Bonferroni correction was applied. The significance level was based on p<0.05. RESULTS: The mean tNAA level ipsilateral to the seizure focus was significantly decreased in MRI negative, respectively MRI positive patients in comparison to healthy controls (p<0.001). The lowest tNAA level was noticed in the MRI positive group (p<0.001). Statistical analysis highlighted a clear "tNAA cut-off" (95% confidence interval) between MRI positive- and MRI negative patients and healthy controls. Mean level of Glx and m-Ins was not significantly elevated or reduced. However, in individual cases a significant elevation was noticed for Glx in MRI negative patients, respectively for m-Ins in MRI positive patients. CONCLUSION: MRI negative TLE patients have a different MRS profile than MRI positive patients (HS) with marginal but significant decrease of tNAA. Our results reveal a clear "tNAA cut-off" between the groups. The value of m-Ins and Glx in focus detection in TLE patients remains controversy.     

Brain diffusion during hyperventilation: diffusion-weighted MR-monitoring in patients with temporal lobe epilepsy and in healthy volunteers

Hyperventilation (HV) can be used to provoke epileptiform activity and occasionally seizures in generalised and in focal epilepsies. Based on the hypothesis that HV might alter brain diffusion in the epileptogenic areas of patients with temporal lobe epilepsy (TLE), we examined these alterations using quantitative diffusion MR imaging (DI) in four patients with TLE and unilateral hippocampal sclerosis (TLE-HS) and six patients with TLE without hippocampal sclerosis (TLE-pure), and in 10 healthy volunteers. Brain diffusion was measured at baseline and immediately after 4 min of HV. In all patients with TLE HV was repeated two times, 4 min each, followed by subsequent DI. The apparent diffusion coefficient (ADC) was quantified in predefined regions of interest. In controls, the ADC did not differ between baseline and HV and between right and left side. Compared to controls TLE-HS patients showed significantly higher ADC at baseline in the hippocampus of the ictogenic side (111+/-13 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.029). During HV ADC decreased significantly in the ictogenic hippocampus compared to controls (-17.3+/-7.1 vs. -3.34+/-8.7, P=0.004). In TLE-pure patients ADC of the ictogenic hippocampus was higher than in normals (99.3+/-14.2 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.031) but there was no significant decrease during HV. Serial HV did not further enhance this decrease. No significant HV-induced changes were seen in other brain areas. In conclusion, our results show that HV can induce dynamic changes of brain diffusion in patients with sclerotic hippocampi but not in non-sclerotic hippocampi. These findings may be utilized for lateralisation of the epileptogenic hippocampus during presurgical evaluation of TLE.     

Endovascular treatment of unruptured intracranial aneurysms

BACKGROUND AND PURPOSE: Intracranial aneurysms are common, with an overall frequency ranging from 0.8% to 10%. Because prognosis after subarachnoid hemorrhage is still very poor, treatment of unruptured aneurysms, either neurosurgically or endovascularly, has been advocated. However, risk of rupture and subsequent subarachnoid hemorrhage needs to be considered against the risks of elective treatment. We analyzed the technical feasibility, safety, and efficacy of endovascular treatment of a consecutive series of unruptured cerebral aneurysms. METHODS: From July 1997 through December 2000, a total of 76 patients with 82 unruptured cerebral aneurysms were treated at our institution. Endovascular treatment was administered to 39 consecutive patients with a total of 42 unruptured cerebral aneurysms. Thirty-six aneurysms were treated with an endovascular technique; in six patients, the parent artery was occluded to eliminate aneurysmal perfusion. Aneurysms were located either in the anterior (n = 31) or posterior (n = 11) circulation. Eight patients had experienced previous subarachnoid hemorrhage from other aneurysms and were treated electively after complete rehabilitation. Ten patients had neurologic symptoms; in 21 patients, the aneurysm was an incidental finding. Eighteen aneurysms were small (0-5 mm), 11 were medium (6-10 mm), nine were large (11-25 mm), and four were giant (> 25 mm). Occlusion rate was categorized as complete (100%), subtotal (95-99%), and incomplete (< 95%) obliteration. RESULTS: Endovascular treatment was technically feasible for 38 of 42 aneurysms. Complete (100%) or nearly complete (95-99%) occlusion was achieved in 34 of 38 aneurysms. In four aneurysms of the internal carotid artery, only incomplete (< 95%) occlusion was achieved. All patients except one with mild neurologic deficits according to the Glasgow Outcome Scale and one with mild memory dysfunction but no focal neurologic deficit achieved good recovery, resulting in a morbidity rate of 4.8% and a mortality rate of 0%. CONCLUSION: Endovascular embolization of unruptured cerebral aneurysms is an effective therapeutic alternative to neurosurgical clipping and is associated with low morbidity and mortality rates. For the management of unruptured aneurysms, endovascular treatment should be considered.