Michael Nocker

Prognostic value at 5 years of microvascular obstruction after acute myocardial infarction assessed by cardiovascular magnetic resonance

BackgroundEarly and late microvascular obstruction (MVO) assessed by cardiovascular magnetic resonance (CMR) are prognostic markers for short-term clinical endpoints after acute ST-elevation myocardial infarction (STEMI). However, there is a lack of studies with long-term follow-up periods (>24 months).MethodsSTEMI patients reperfused by primary angioplasty (n = 129) underwent MRI at a median of 2 days after the index event. Early MVO was determined on dynamic Gd first-pass images directly after the administration of 0.1 mmol/kg bodyweight Gd-based contrast agent. Furthermore, ejection fraction (EF, %), left ventricular myocardial mass (LVMM) and total infarct size (% of LVMM) were determined with CMR. Clinical follow-up was conducted after a median of 52 months. The primary endpoint was defined as a composite of death, myocardial re-infarction, stroke, repeat revascularization, recurrence of ischemic symptoms, atrial fibrillation, congestive heart failure and hospitalization.ResultsFollow-up was completed by 107 patients. 63 pre-defined events occurred during follow-up. Initially, 74 patients showed early MVO. Patients with early MVO had larger infarcts (mean: 24.9 g vs. 15.5 g, p = 0.002) and a lower EF (mean: 39% vs. 46%, p = 0.006). The primary endpoint occurred in 66.2% of patients with MVO and in 42.4% of patients without MVO (p < 0.05). The presence of early MVO was associated with a reduced event-free survival (log-rank p < 0.05). Early MVO was identified as the strongest independent predictor for the occurrence of the primary endpoint in the multivariable Cox regression analysis adjusting for age, ejection fraction and infarct size (hazard ratio: 2.79, 95%-CI 1.25-6.25, p = 0.012).ConclusionEarly MVO, as assessed by first-pass CMR, is an independent long-term prognosticator for morbidity after AMI.

Probable RBD and association with neurodegenerative disease markers: A population‐based study

The prevalence of rapid eye movement sleep behavior disorder (RBD) and its association with markers of neurodegeneration in the general population are poorly defined.

Dopamine transporter SPECT: How to remove subjectivity?†

Clinical criteria enable accurate and reliable diagnosis of parkinsonian syndromes when cardinal clinical features are fully developed. Single photon emission computed tomography (SPECT) investigating the striatal dopamine transporter (DAT) status have been suggested to increase the diagnostic accuracy in uncertain parkinsonian syndromes such as isolated tremor symptoms not fulfilling essential tremor criteria, as well as drug‐induced, vascular and psychogenetic parkinsonism. Several approaches for the analysis of the striatal DAT distribution have been tested for their ability to analyze and quantify SPECT images. Visual assessment of DAT binding and semiquantitative analysis using region of interests have been recommended by Nuclear Medicine Associations to be incorporated in the routine work‐up of DAT‐SPECT. Besides these observer dependent approaches, fully automated image‐analysis techniques have been validated in the clinical setting. Their potential as tools to improve the diagnostic accuracy in patients presenting with parkinsonian features is reviewed here.

Quantification of regional functional improvement of infarcted myocardium after primary PTCA by contrast-enhanced magnetic resonance imaging.

To assess with cardiac magnetic resonance imaging (CMR) the relationship between treatment delay and improvement of regional left ventricular function after primary percutaneous transluminal coronary angioplasty (p‐PTCA) for acute myocardial infarction (AMI).

Prodromal Parkinson's disease as defined per MDS research criteria in the general elderly community.

Recently, the International Parkinson and Movement Disorder Society has defined research criteria for prodromal Parkinsons disease (PD), but to date their predictive value has not yet been tested in population‐based cohorts.

Diagnostic potential of automated subcortical volume segmentation in atypical parkinsonism

Objective: To determine whether automated and observer-independent volumetric MRI analysis is able to discriminate among patients with Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) in early to moderately advanced stages of disease. Methods: T1-weighted volumetric MRI from patients with clinically probable PD (n = 40), MSA (n = 40), and PSP (n = 30) and a mean disease duration of 2.8 ± 1.7 y were examined using automated volume measures of 22 subcortical regions. The clinical follow-up period was 2.5 ± 1.2 years. The data were split into a training (n = 72) and a test set (n = 38). The training set was used to build a C4.5 decision tree model in order to classify patients as MSA, PSP, or PD. The classification algorithm was examined by the test set using the final clinical diagnosis at last follow-up as diagnostic gold standard. Results: The midbrain and putaminal volume as well as the cerebellar gray matter compartment were identified as the most significant brain regions to construct a prediction model. The diagnostic accuracy for PD vs MSA or PSP was 97.4%. In contrast, diagnostic accuracy based on validated clinical consensus criteria at the time of MRI acquisition was 62.9%. Conclusions: Volume segmentation of subcortical brain areas differentiates PD from MSA and PSP and improves diagnostic accuracy in patients presenting with early to moderately advanced stage parkinsonism. Classification of evidence: This study provides Class III evidence that automated MRI analysis accurately discriminates among early-stage PD, MSA, and PSP.

Episodic ataxia type 2: phenotype characteristics of a novel CACNA1A mutation and review of the literature

Episodic ataxia type 2 (EA2) is an autosomal dominant inherited neurological disorder that is characterized by paroxysmal episodes of ataxia. The causative gene for EA2 is CACNA1A which codes for the alpha 1A subunit of the voltage-gated P/Q-type calcium channel (Cav2.1). We detected a novel point mutation in the CACNA1A gene in a large Austrian family. All ten affected family members harbored a heterozygous c.3089+2T>C nucleotide exchange in intron 19. In silico modeling demonstrated a loss of the splice site of exon 19 by the mutation, which most likely results in exon skipping without frameshifting or use of an alternative splice site. Clinically, the family exhibited frequent ataxic episodes accompanied by headache in some individuals, which showed a good treatment response to acetazolamide or aminopyridine. Interictal phenotype variability was high ranging from an unremarkable clinical examination to a progressive cerebellar syndrome. Detailed cognitive testing with standardized neuropsychological tests revealed specific deficits in various domains including memory, executive functions and visual abilities. Moreover, a striking coincidence of socio-phobic behavior and anxiety disorders was detected within this family, which interfered with activities of daily living and has to be taken in consideration in EA2 patient management. We here characterize the phenotype of this novel CACNA1A mutation, review the respective literature and discuss implications on diagnosis and patient management.

Nonmotor Symptoms in Subjects Without Evidence of Dopaminergic Deficits: NMS IN Swedds

A subgroup of patients initially diagnosed with Parkinsons disease (PD) turn out to have normal dopamine transporter single‐photon emission computed tomography imaging and have been labeled as subjects without evidence of dopaminergic deficit (SWEDDs). In this study, we sought to further characterize these patients and have analyzed the frequency of nonmotor symptoms (NMS) in SWEDDs, PD patients, and healthy controls.

Substantia nigra hyperechogenicity as a marker for Parkinson's disease: a population-based study.

Background: The clinical diagnosis of Parkinsons disease (PD) is currently anchored in its cardinal motor symptoms. According to hospital-based studies, an enlarged echogenicity in the area of the substantia nigra (SN) assessed with transcranial sonography (TCS) may represent a useful biomarker in the diagnosis of PD. Objective: To evaluate SN hyperechogenicity as a marker for PD in the Bruneck Study cohort, which is representative of the general elderly community. Methods: The diagnostic accuracy of TCS in distinguishing clinically diagnosed PD from nonparkinsonian subjects was assessed in 574 subjects from this cohort. Results: There was a good diagnostic accuracy of TCS in distinguishing PD subjects from nonparkinsonian subjects with an area under the curve value of 0.82. At a receiver-operating characteristic curve analysis-based cutoff value for SN hyperechogenicity of 0.18 cm2, TCS had a sensitivity of 88.2% (95% confidence interval, CI, 64.4-98.0), a specificity of 77.0% (95% CI 72.8-80.6), a positive predictive value of 12.7% (95% CI 7.8-20.0) and a negative predictive value of 99.4% (95% CI 97.8-100.0) for subjects with clinically definite PD at baseline. When analyzing the same population after 5 years with regard to the presence of known and newly diagnosed PD cases, baseline TCS yielded very similar diagnostic accuracy values. Conclusion: SN hyperechogenicity may represent a useful biomarker for PD not only in a hospital-based setting but also in the general community.

White and gray matter abnormalities in narcolepsy with cataplexy.

STUDY OBJECTIVES The authors applied diffusion-tensor imaging including measurements of mean diffusivity (MD), which is a parameter of brain tissue integrity, fractional anisotropy (FA), which is a parameter of neuronal fiber integrity, and voxel-based morphometry, which is a measure of gray and white matter volume, to detect brain tissue changes in patients with narcolepsy-cataplexy. DESIGN N/A. PATIENTS Patients with narcolepsy-cataplexy (n = 16) and age-matched healthy control subjects (n = 12) were studied. INTERVENTIONS Whole cerebral MD, FA measures, and the volumes of the gray and white matter compartments were analyzed using statistical parametric mapping. MEASUREMENT AND RESULTS Significant MD increases and concomitant FA decreases were localized in the fronto-orbital cortex (P < 0.001) and the anterior cingulate (FA, P < 0.001; MD, P = 0.03) in narcolepsy-cataplexy. Additional MD increases without FA changes were detected in the ventral tegmental area, the dorsal raphe nuclei (P < 0.001), and the hypothalamus (P < 0.01). FA signal decreases were observed in the white matter tracts of the inferior frontal and inferior temporal cortices of narcolepsy-cataplexy patients (P < 0.001). Brain volume loss was evident in focal areas of the inferior and superior temporal cortices (P < 0.001) and the cingulate (P = 0.038). CONCLUSIONS Areas of increased diffusivity in the hypothalamus appear consistent with hypocretinergic cell loss reported in narcolepsy-cataplexy. Signal abnormalities in the ventral tegmental area and the dorsal raphe nuclei correspond to major synaptic targets of hypocretin neurons that were associated with the regulation of the sleep-wake cycle. Brain tissue alterations identified in the frontal cortex and cingulate are crucial in the maintenance of attention and reward-dependent decision making, both known to be impaired in narcolepsy-cataplexy.