Progressive Brain Atrophy in Multiple System Atrophy: A Longitudinal, Multicenter, Magnetic Resonance Imaging Study.

OBJECTIVE: To determine the rates of brain atrophy progression in vivo in patients with multiple system atrophy (MSA). BACKGROUND: Surrogate biomarkers of disease progression are a major unmet need in MSA. Small-scale longitudinal studies in patients with MSA using magnetic resonance imaging (MRI) to assess progression of brain atrophy have produced inconsistent results. In recent years, novel MRI post-processing methods have been developed enabling reliable quantification of brain atrophy in an automated fashion. METHODS: Serial 3D-T1-weighted MRI assessments (baseline and after 1 year of follow-up) of 43 patients with MSA were analyzed and compared to a cohort of early-stage Parkinson's disease (PD) patients and healthy controls (HC). FreeSurfer's longitudinal analysis stream was used to determine the brain atrophy rates in an observer-independent fashion. RESULTS: Mean ages at baseline were 64.4 ± 8.3, 60.0 ± 7.5, and 59.8 ± 9.2 years in MSA, PD patients and HC, respectively. A mean disease duration at baseline of 4.1 ± 2.5 years in MSA patients and 2.3 ± 1.4 years in PD patients was observed. Brain regions chiefly affected by MSA pathology showed progressive atrophy with annual rates of atrophy for the cerebellar cortex, cerebellar white matter, pons, and putamen of -4.24 ± 6.8%, -8.22 ± 8.8%, -4.67 ± 4.9%, and - 4.25 ± 4.9%, respectively. Similar to HC, atrophy rates in PD patients were minimal with values of -0.41% ± 1.8%, -1.47% ± 4.1%, -0.04% ± 1.8%, and -1.54% ± 2.2% for cerebellar cortex, cerebellar white matter, pons, and putamen, respectively. CONCLUSIONS: Patients with MSA show significant brain volume loss over 12 months, and cerebellar, pontine, and putaminal volumes were the most sensitive to change in mid-stage disease. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dorsolateral Nigral Hyperintensity on 1.5 T Versus 3 T Susceptibility-Weighted Magnetic Resonance Imaging in Neurodegenerative Parkinsonism.

Background: An absent dorsolateral nigral hyperintensity (DNH) is a common finding in patients with neurodegenerative parkinsonism at high or ultra-high field susceptibility-weighted magnetic resonance imaging (SWI). Objective: Despite increasing use of high field magnetic resonance imaging (MRI) in specialized centers, these scanners are still frequently unavailable in primary care or outpatient facilities and underdeveloped or emerging countries. Therefore, the aim of the present study was to evaluate the diagnostic utility of DNH assessment at 1.5 versus 3 T MRI to distinguish patients with neurodegenerative parkinsonism, including Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), from healthy controls (HC). Methods: Absence of DNH was assessed on visual inspection of anonymized 1.5 T and 3.0 T SWI scans in a case-control study including 86 patients with neurodegenerative parkinsonism and 33 healthy controls (HC). All study participants were consecutively recruited to undergo 1.5 and 3 T MRI. Results: Overall correct classification was 81.7% (95% CI, 72.6-88.4%) for 1.5 T and 95.7% (95% CI, 89.1-98.7%) for 3 T MRI in discriminating neurodegenerative parkinsonism from controls. However, while DNH was bilaterally present in all but one of the HC at 3 T MRI, it was rated as abnormal (at least unilateral absence) in 15 of 22 HC at 1.5 T MRI, resulting in a specificity of 31.8%. Conclusions: The results of the present study demonstrate an insufficient specificity of visual assessment of DNH at 1.5 T MRI for the diagnosis of neurodegenerative parkinsonism.

Cardiac exercise imaging using a 3-tesla magnetic resonance-conditional pedal ergometer: Preliminary results in healthy volunteers and patients with known or suspected coronary artery disease.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) remains underutilized as an exercise imaging modality, mostly because of the limited availability of MR-compatible exercise equipment. This study prospectively evaluates the clinical feasibility of a newly developed MR-conditional pedal ergometer for exercise CMR METHODS: Ten healthy volunteers (mean age 44 ± 16 years) and 11 patients (mean age 60 ± 9 years) with known or suspected coronary artery disease (CAD) underwent rest and post-exercise cinematic 3T CMR. Visual analysis of wall motion abnormalities (WMA) was rated by 2 experienced radiologists, and volumes and ejection fractions (EF) were determined. Image quality was assessed by a 4-point Likert scale for visibility of endocardial borders. RESULTS: Median subjective image quality of real-time cine at rest was 1 (interquartile range [IQR] 1-2) and 2 (IQR 2-2.5) for post-exercise real-time cine (p = 0.001). Exercise induced a significant increase in heart rate (62 [62-73] to 111 [104-143] bpm, p < 0.0001). Stroke volume and cardiac index increased from resting to post-exercise conditions (85 ± 21 to 101 ± 19 mL and 2.9 ± 0.7 to 6.6 ± 1.9 L/min/m2, respectively; both p < 0.0001), driven by a reduction in end-systolic volume (55 ± 20 to 42 ± 21 mL, p < 0.0001). Patients (2/11) with inducible regional WMA at high-resolution postexercise cine imaging revealed significant coronary artery stenosis in subsequently performed invasive coronary angiography. CONCLUSIONS: Exercise-CMR using our newly developed 3T MR-conditional pedal ergometer is clinically feasible. Imaging of both cardiac response and myocardial ischemia, triggered by dynamic stress, is rapidly conducted while the patient is near their peak heart rate.

Evolution of Myocardial Tissue Injury: A CMR Study Over a Decade After STEMI.

BACKGROUND: In patients with a first ST-segment elevation myocardial infarction (STEMI), the multi-annual evolution of myocardial tissue injury parameters, as assessed by cardiac magnetic resonance (CMR), has not yet been described. OBJECTIVES: This study examined myocardial tissue injury dynamics over a decade after STEMI. METHODS: Sequential CMR examinations (within the first week after STEMI, and at 4, 12, months, and 9 years thereafter) were conducted in 74 patients with STEMI treated with primary percutaneous coronary intervention. Left ventricular function, infarct size (IS), and microvascular obstruction (MVO) were assessed at all time points. T2∗, T2, and T1 mapping (n = 59) were added at 9-year scan to evaluate the presence of iron and edema within the infarct core, respectively. RESULTS: IS decreased progressively and significantly between all CMR time points (all P < 0.001), with an average reduction rate of 5.8% per year (IQR: 3.5%-8.8%) and a relative reduction of 49% (IQR: 39%-76%) over a decade. MVO was present in 61% of patients at baseline, but was not present at the follow-up examinations. At 9-year CMR, 17 of 59 (29%) patients showed iron deposition within the infarct core, whereas 82% had persistent edema. Persistent iron and edema were associated with greater IS on any occasion (all P < 0.001), as well as the presence of MVO (P < 0.001). Patients with persistent iron and edema showed a lower relative regression of IS (P = 0.005 and P = 0.032, respectively) and greater end-systolic volumes over a decade (all P < 0.012 and P > 0.023, respectively). A T1 hypointense infarct core without evidence of T2∗ iron deposition (14 of 59 [24%] patients) was attributed to lipomatous metaplasia of the infarct. CONCLUSIONS: The evolution of IS is a dynamic process that extends well beyond the first few months after STEMI. Persistence of iron and edema within the infarct core occurs up to a decade after STEMI and is associated with initial infarct severity and poor infarct healing.

Energy metabolism measured by 31P magnetic resonance spectroscopy in the healthy human brain.

BACKGROUND AND PURPOSE: Phosphorous magnetic resonance spectroscopy (31P-MRS) allows a non-invasive analysis of phosphorus-containing compounds in vivo. The present study investigated the influence of brain region, hemisphere, age, sex and brain volume on 31P-MRS metabolites in healthy adults. MATERIALS AND METHODS: Supratentorial brain 31P-MRS spectra of 125 prospectively recruited healthy volunteers (64 female, 61 male) aged 20 to 85 years (mean: 49.4 ± 16.9 years) were examined with a 3D-31P-MRS sequence at 3T, and the compounds phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. From this data, the metabolite ratios PCr/ATP, Pi/ATP and PCr/Pi were calculated for different brain regions. In addition, volumes of gray matter, white matter and cerebrospinal fluid were determined. RESULTS: For all metabolite ratios significant regional differences and in several regions sex differences were found. In some brain regions and for some metabolites hemispheric differences were detected. In addition, changes with aging were found, which differed between women and men. CONCLUSIONS: The present results indicate that 31P-MRS metabolism varies throughout the brain, with age and between sexes, and therefore have important practical implications for the design and the interpretation of future 31P-MRS studies under physiological conditions and in patients with various cerebral diseases.

Characterization and diagnostic potential of diffusion tractography in multiple system atrophy.

INTRODUCTION: Microstructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the parkinsonian and cerebellar variants of multiple system atrophy (MSA-P, MSA-C) compared to Parkinson's disease (PD). The current study applied DTI and tractography in order to 1) characterize the distribution of DTI metrics along the tracts of the MCP and from the putamen in MSA variants, and 2) evaluate the usefulness of combining these measures for the differential diagnosis of MSA-P against PD in the clinical setting. METHODS: Twenty-nine MSA patients (MSA-C, n = 10; MSA-P, n = 19), with a mean disease duration of 2.8 ± 1.7 years, 19 PD patients, and 27 healthy controls (HC) were included in the study. Automatized tractography with a masking procedure was employed to isolate the MCP tracts. DTI measures along the tracts of the MCP and within the putamen were acquired and jointly used to classify MSA vs. PD, and MSA-P vs. PD. Putamen volume was additionally tested as classification feature in post hoc analyses. RESULTS: DTI measures within the MCP and putamen showed significant alterations in MSA variants compared to HC and PD. Classification accuracy for MSA vs. PD and MSA-P vs PD using diffusion measures was 91.7% and 89.5%, respectively. When replacing the putaminal DTI measure by a normalized measure of putamen volume classification accuracy improved to 95.8% and 94.7%, respectively. CONCLUSION: Multimodal information from MCP tractography and putamen volume yields excellent diagnostic accuracy to discriminate between early-to-moderately advanced patients with MSA and PD.

Diagnostic accuracy of MR planimetry in clinically unclassifiable parkinsonism.

INTRODUCTION: Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages. METHODS: The pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up. RESULTS: Final diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0. CONCLUSIONS: Brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3rdV width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI.

Correction to: Endovascular stroke treatment's impact on malignant type of edema (ESTIMATE).

The original keywords were not sufficiently precise in describing the article content. Therefore, the key words were amended to include hemicraniectomy and malignant edema.

No effect of age, gender and total intracranial volume on brainstem MR planimetric measurements.

OBJECTIVES: MR planimetry of brainstem structures can be helpful for the discrimination of Parkinsonian syndromes. It has been suggested that ageing might influence brainstem MR measurements assessed by MR planimetry, while effects of gender and total intracranial volume (TIV) have not been assessed so far. The aim of this study was to evaluate age, gender and TIV effects on brainstem MR planimetric measures. METHODS: Brainstem MR planimetric measures of diameters (midbrain, pons, middle and superior cerebellar peduncle) and areas (pons and midbrain), the derived ratios, and the magnetic resonance Parkinsonism index (MRPI) were assessed on 1.5-T MR images in a large cohort of 97 healthy controls and analysed for the influence of age, gender and TIV with univariate and multivariate linear models. RESULTS: Neither gender nor age effects on planimetric measurements were observed in the population relevant for the differential diagnosis of neurodegenerative Parkinsonism, aged 50 to 80 years, except for single area-derived measurements, with gender effects on pontine area (p = 0.013) and age effects on midbrain area (p = 0.037). Results were similar upon inclusion of the TIV in the analyses. CONCLUSIONS: There is no need to correct for age, gender or TIV when using brainstem-derived MR planimetric measurements in the differential diagnosis of neurodegenerative Parkinsonism. KEY POINTS: • There were no gender effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for pontine area). • There were no age effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for midbrain area). • There is no need for age- or gender-specific cut-offs for the relevant age group.

Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen.

Background: Nusinersen is an antisense-oligonucleotide (ASO) approved for treatment of 5q-spinal muscular atrophy (SMA). Since the drug cannot cross the blood-brain barrier (BBB), it must be administered into the cerebrospinal fluid (CSF) space repeatedly by lumbar puncture. However, little is known whether ASOs have an impact on CSF routine parameters that may yield information on CSF flow and/or intrathecal inflammation. The objective of this study was to examine CSF routine parameters in SMA patients treated with nusinersen. Methods: Routine CSF parameters [white cell count, total protein, CSF/serum quotients of albumin (Qalb), lactate, and oligoclonal IgG bands (OCB)] of 60 SMA patients (type 1, 2, and 3, aged 7-60 years) were retrospectively analyzed. Results: White cells ranged from 0 to 4/µL in CSF; a singular case of pleocytosis (8/µL) was observed in a patient in parallel with a systemic infection. Total protein and Qalb showed a mild increase from baseline to the following lumbar punctures (except for total protein in CSF at the fourth injection of nusinersen). Lactate levels revealed a stable course. In one patient, positive OCB in CSF were transiently observed. The slight change in total CSF protein and Qalb may be caused by repeated lumbar puncture and/or intrathecal administration of the drug. Conclusion: Our data suggest that a regular examination of routine CSF parameters in patients in which intrathecal ASOs are administered is important to obtain information on possible side effects and to gain further insights into intrathecal processes.

Diagnostic Potential of Multimodal MRI Markers in Atypical Parkinsonian Disorders.

BACKGROUND: The diagnostic potential of multimodal MRI approaches to discriminate among progressive supranuclear palsy (PSP), Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD) has not been well investigated. OBJECTIVE: To identify disease-specific neurodegenerative patterns and evaluate the diagnostic accuracy of dedicated MRI, iron concentration (R2*), microstructural integrity (mean diffusivity; MD and fractional anisotropy; FA) as well as volumes were analyzed in patients with PSP, MSA-P and PD. METHODS: 3T MRI of 18 PSP and 16 MSA-P patients were compared with 16 PD patients matched for age and disease duration as well as 21 healthy controls. Statistical parametric mapping (SPM) was applied to objectively identify focal MRI changes throughout the whole-brain. Following dimensionality reduction of significant and multiple comparison-corrected SPM clusters through principal component analysis (PCA), stepwise receiver-operating characteristic curve analysis (ROC) was applied to determine the diagnostic potential of multimodal MRI parameters. RESULTS: PCA revealed two components involving multiple regions identified from SPM analysis. The first component was primarily composed of the mean MD value of the thalamus and the mean MD and FA values of the dentatorubrothalamic tract and the corpus callosum. The second component mainly consisted of mean MD and FA values of the middle cerebellar peduncle. ROC analysis showed 92% of PSP patients were differentiated correctly from MSA-P and PD and 80% of MSA-P patients could be distinguished from PD. CONCLUSION: Multimodal MRI improved the detection of disease-specific neurodegenerative patterns in PSP and MSA-P and highlights its potential to improve the diagnostic accuracy of atypical parkinsonian disorders.

Biocomposite Suture Anchors Remain Visible Two Years After Rotator Cuff Repair.

BACKGROUND: Biocomposite suture anchors containing osteoconductive materials have gained popularity in rotator cuff repairs. However, little is known about the influence of the addition of osteoconductive materials on implant resorption, bone reaction, tendon healing, and clinical outcomes scores. QUESTIONS/PURPOSES: (1) What percentage of suture anchors were not completely resorbed 2 years after implantation? (2) What are the diameters of the bone bed in relation to the implant? (3) Is tendon integrity correlated with bone tunnel diameter? (4) Is there an association between tunnel widening, periimplant fluid film grade, biodegradation grade, and retear with clinical outcomes scores, such as the Western Ontario Rotator Cuff Index (WORC) and the Oxford Shoulder Score (OSS)? METHODS: Thirty-six patients were enrolled from August 2012 to January 2014. The following inclusion criteria were applied: (1) reparable full-thickness supraspinatus tendon tears, (2) double-row suture bridge techniques applied for supraspinatus repair, (3) use of biocomposites suture anchor implants composed of poly L-lactic acid (PLLA) and ß-tricalcium phosphate (TCP) exclusively, and (4) a minimum of 2 years followup. Four patients met the exclusion criteria, and seven of 36 patients (19%) were lost to followup. Thereby, 25 patients (84 implants) were included in this retrospective study. To answer the study's questions, the following methods were applied: (1) The resorption of the implants and periimplant fluid film were assessed on MRI using a four-stage scale system, (2) bone bed diameter was measured on MRI at three different points on the longitudinal central axis of each anchor, (3) tendon integrity was evaluated on MRI according to the Sugaya classification and correlated to bone tunnel diameter, and (4) assessed tunnel diameters, periimplant fluid film grade, biodegradation grade, and tendon condition were related to clinical outcomes scores at the time of followup (2.3 ± 0.3 years). The intraobserver reliability was 0.981 (p < 0.001) and interobserver reliability was 0.895 (p < 0.001). RESULTS: At 2.3 ± 0.3 years, most analyzed suture anchors (76 of 84 [90%]) were, with varying degrees of degradation, still visible. Bone tunnels showed minor widening (0.4 ± 1.4 mm) at the base, but osseous ingrowth was detected as narrowing at the middle (0.1 ± 1.1 mm) and at the apex (1.4 ± 1.7 mm) of the implants. Patients with retears (Sugaya Grades 4-5) had narrower tunnels (3.6 ± 1.8 mm) than patients without retears (Sugaya Grades 1-3; 4.4 ± 1.6 mm; mean difference, 0.782 [95% confidence interval {CI}: 0.009-1.6]; p = 0.050). WORC and Oxford scores were not associated with the tunnel widening amount, fluid film grade, biodegradation grade, or tendon retear. CONCLUSIONS: In light of the results of the present study, surgeons should consider in their daily practice that the resorption process of these implants may be slower than assumed so far, but no association with severe implant-related complications has been found in the short term. Future studies should focus on the evaluation of the effects of osteoconductive materials on resorption, tendon healing, and clinical outcomes in the long term and on the integration process in different rotator cuff reconstruction techniques. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Abnormalities on structural MRI associate with faster disease progression in multiple system atrophy.

BACKGROUND: The rate of clinical progression in patients with multiple system atrophy (MSA) varies between individuals and predictors for disease progression remain undefined. While the MSA-rasagiline study found no difference in the rates of clinical progression for patients treated with rasagiline versus placebo, it included a large, prospective magnetic resonance imaging (MRI) substudy that can provide new information on the underlying disease progression in patients with early MSA. METHODS: This post-hoc analysis compared the rate of clinical progression in patients with MSA-specific structural changes at baseline (MRI-positive group) versus the rate of progression in patients without evidence of such changes at baseline (MRI-negative group) using a repeated measures ANCOVA. Clinical progression was assessed using the Unified MSA Rating Scale (UMSARS) and Clinical Global Impression of Improvement (CGI-I). RESULTS: Twenty-eight patients with early MSA of the parkinsonian subtype (MRI-positive n = 13; MRI-negative n = 15) who had complete baseline and follow-up UMSARS data were included in this analysis. Patients in the MRI-positive group had faster clinical progression from baseline to the end of the 48-week study compared with those in the MR-negative group as assessed by the UMSARS total (p = 0.028) and UMSARS motor (p = 0.008) scales. At week 48, MRI-positive patients also had a significantly worse health status vs. MRI-negative patients (p = 0.015). CONCLUSIONS: This is the first study to demonstrate that MSA-specific abnormalities on structural MRI might represent a variant of MSA-P that is associated with more rapid progression and an overall worse prognosis.

Intrathecal administration of nusinersen in adolescent and adult SMA type 2 and 3 patients.

Spinal muscular atrophy is a genetic motor neuron disease that leads to progressive muscular atrophy and muscle weakness. In December 2016, the Food and Drug Administration, and in June 2017, the European Medicines Agency approved the antisense oligonucleotide nusinersen for treatment of spinal muscular atrophy. Nusinersen has to be repeatedly administered intrathecally. Due to the clinical features of SMA, the application of the ASO by lumbar puncture can be challenging in symptomatic patients considering the frequently observed scoliosis, previous spine fusion surgeries, joint contractures, and respiratory insufficiency. To evaluate safety and feasibility of the intrathecal treatment in adolescent and adult SMA type 2 and 3 patients, we analyzed 93 lumbar punctures, monitored number of lumbar puncture attempts, duration of the procedure, injection site, and needle length. Oxygen saturation during the intervention, medication for sedation and local anesthesia, adverse events related to lumbar punctures, and macroscopic analysis of CSF were recorded. Moreover, we analyzed the use of CT-scans for performing lumbar punctures and its associated radiation exposure. Performing lumbar puncture for the intrathecal administration of nusinersen in adolescent and adult patients with later-onset SMA is feasible and safe, even in patients with complex spinal anatomies and respiratory insufficiency. To guarantee the quality of the procedure, we recommend establishing an experienced interdisciplinary team consisting of neurologists and/or neuropediatricians, anesthesiologists, orthopedic surgeons, and/or neuroradiologists.

Endovascular stroke treatment's impact on malignant type of edema (ESTIMATE).

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke and large vessel occlusion, the prognosis has improved tremendously since the implementation of endovascular thrombectomy (EVT). The effect of EVT on the incidence of malignant middle cerebral artery infarctions (MMI) has not been studied before. METHODS: ESTIMATE, a multicenter retrospective study, evaluates data of ischemic stroke patients with occlusion in the anterior circulation in the years of 2007-2015 comparing three treatment options (no therapy; IV-TPA; IV-TPA plus EVT or EVT only). Primary endpoint of the study was the incidence of MMI on follow-up imaging and mortality rates. Secondary endpoints were functional outcome, further clinical and imaging data. Logistic and Cox-regression models with a propensity score weighting approach were applied to evaluate differences between treatment groups. RESULTS: In 2161 patients over 9 years, EVT reduced the MMI rates significantly: patients without acute stroke treatment had increased odds for MMI of 1.57 [95% confidence interval (CI) 1.49-1.65]. In contrast, after treatment with IV-TPA, only we observed an OR of 0.88 (95% CI 0.83-0.94, p < 0.001), and after EVT an OR of 0.80 (95% CI 0.76-0.85, p < 0.001). This was more pronounced in larger pretreatment infarctions (ASPECTS < 5, p < 0.01). IV-TPA also lowers the MMI rates but not to the same extent. EVT-treated patients had increased survival rates (p < 0.05) and the best functional outcome at discharge. CONCLUSIONS: The findings of this study illustrate that occurrence of MMI and mortality rates was significantly reduced in patients treated with EVT.

Acute DWI Reductions In Patients After Single Epileptic Seizures - More Common Than Assumed.

Background: Changes of cerebral diffusivity detected by magnetic resonance imaging (MRI) have been reported in epilepsy. Diffusion weighted imaging (DWI) detects changes in the distribution of water molecules by measuring the apparent diffusion coefficient (ADC) and is mainly used in the diagnosis of ischemic stroke. DWI changes in epilepsy were reported in status epilepticus (SE) or series of seizures. It remains unclear whether this phenomenon also occurs after single seizures. Accordingly, possible pathomechanisms have only been discussed on the presumed basis of ongoing epileptic brain activity. Methods: In this retrospective study, we systematically analyzed DWI alterations related to epileptic seizures in 454 patients who received MRI scanning within the first 24 h after seizure onset. Results: DWI restrictions not classified as ischemic stroke were observed in 18 patients (4%). We found DWI restrictions in 19% of patients with SE/seizure series and in 3% of patients after single focal and 2.5% after single generalized seizures. 17 patients with DWI alterations were diagnosed with a structural epilepsy. DWI signal decreased in the majority of patients within the first days and could not be detected in follow-up imaging >3 months. In all patients except one, DWI alterations were detected in the same hemisphere as the lesion. In the case of seizure series or SE, DWI restrictions mostly presented with a typical "garland-like" pattern alongside the cortical band or on the border of a defined lesion, while in isolated seizures, the restrictions were often rather subtle and small. Discussion: We show that DWI restrictions can be observed in patients after single epileptic seizures. As the vast majority of these patients was diagnosed with an epilepsy due to structural cerebral pathology, DWI restriction may reflect a higher vulnerability in these regions. This might also explain the fact that diffusivity changes were observed after single focal seizures as well as after multiple seizures or SE. The occurence itself on one side as well as the spatial pattern of this phenomenon on the other may thus not only be related to the duration of ictal activity, but to structural pathology.

The diagnostic accuracy of the hummingbird and morning glory sign in patients with neurodegenerative parkinsonism.

INTRODUCTION: The hummingbird sign and the morning glory flower sign, reflecting midbrain pathology on MRI, have previously been shown to separate patients with progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and multiple system atrophy (MSA). The aim of the present study was to determine the diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy patterns in a large cohort of patients with neurodegenerative parkinsonism. METHODS: Retrospective analysis of midbrain atrophy patterns on T1-weighted MRI in a large cohort of patients with neurodegenerative parkinsonism and healthy controls who underwent MR imaging during their diagnostic work-up. RESULTS: 481 patients with neurodegenerative parkinsonism and 79 healthy controls were included in the present study. The presence of the hummingbird sign had a specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP, but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early, clinically unclassifiable parkinsonism. Visual assessment of these midbrain alterations showed excellent inter-rater agreement. CONCLUSION: Midbrain atrophy patterns are useful in the differential diagnosis of neurodegenerative parkinsonism but both the hummingbird sign and more so the morning glory flower sign suffer from low sensitivity, especially in early disease stages.

The reorganization of functional architecture in the early-stages of Parkinson's disease.

INTRODUCTION: The study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. METHODS: 3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ±â€¯1.2 years at baseline with a clinical follow-up of 1.5 ±â€¯0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. RESULTS: At baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. CONCLUSION: Resting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions.

MR planimetry in neurodegenerative parkinsonism yields high diagnostic accuracy for PSP.

INTRODUCTION: Several previous studies examined different brainstem-derived MR planimetric measures with regards to their diagnostic accuracy in separating patients with neurodegenerative parkinsonian disorders and reported conflicting results. The current study aimed to compare their performance in a well-characterized sample of patients with neurodegenerative parkinsonian disorders. METHODS: MR planimetric measurements were assessed in a large retrospective cohort of 55 progressive supranuclear palsy (PSP), 194 Parkinson's disease (PD) and 63 multiple system atrophy (MSA) patients. This cohort served as a training set used to build C4.5 decision tree models to discriminate PSP, PD and MSA. The models were validated in two independent test sets. The first test set comprised 84 patients with early, clinically unclassifiable parkinsonism (CUP). A prospective cohort of patients with PSP (n = 23), PD (n = 40) and MSA (n = 22) was exploited as a second test-set. RESULTS: The pons-to-midbrain diameter ratio, the midbrain diameter, the middle cerebellar peduncle width and the pons area were identified as the most predictive parameters to separate PSP, MSA and PD in C4.5 decision tree models derived from the training set. Using these decision models, AUCs in discriminating PSP, MSA and PD were 0.90, 0.57 and 0.73 in the CUP-cohort and 0.95, 0.61 and 0.87 in the prospective cohort, respectively. CONCLUSION: We were able to demonstrate that brainstem-derived MR planimetric measures yield high diagnostic accuracy for the discrimination of PSP from related disorders when decision tree algorithms are applied, even at early, clinically uncertain stages. However, their diagnostic accuracy in discriminating PD and MSA was suboptimal.

GFAP in early multiple sclerosis: A biomarker for inflammation.

OBJECTIVE: The role of Glial Fibrillic Acidic Protein (GFAP) as a potential biomarker for relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) has been controversially discussed. The aim was to characterize the added value of GFAP levels in the CSF of RRMS and CIS patients in correlation with MRI lesion load. MATERIALS & METHODS: GFAP levels in the CSF from 18 patients with RRMS, 8 patients with CIS and 35 controls were analyzed together with MRI data for acute and chronic inflammatory lesion load. RESULTS: GFAP levels of patients vs. controls were higher (p=0.005), while there was no difference between GFAP levels in RRMS and CIS. There was no correlation between the number of supra- or infratentorial gadolinium enhancing lesions and GFAP levels, while there was a correlation between GFAP levels with infratentorial chronic inflammatory lesion load (p=0.0035). Most importantly, a highly significant correlation could be observed between GFAP levels and the intensity of gadolinium-enhancement as a parameter for the acute activity of inflammatory processes (p=0.0002). CONCLUSIONS: GFAP seems to be a useful biomarker for highly active acute inflammation in patients with RRMS as well as with CIS.