Functional Outcomes in Conservatively vs Surgically Treated Cerebellar Infarcts.

Importance: According to the current American Heart Association/American Stroke Association guidelines, decompressive surgery is indicated in patients with cerebellar infarcts that demonstrate severe cerebellar swelling. However, there is no universal definition of swelling and/or infarct volume(s) available to support a decision for surgery. Objective: To evaluate functional outcomes in surgically compared with conservatively managed patients with cerebellar infarcts. Design, Setting, and Participants: In this retrospective multicenter cohort study, patients with cerebellar infarcts treated at 5 tertiary referral hospitals or stroke centers within Germany between 2008 and 2021 were included. Data were analyzed from November 2020 to November 2023. Exposures: Surgical treatment (ie, posterior fossa decompression plus standard of care) vs conservative management (ie, medical standard of care). Main Outcomes and Measures: The primary outcome examined was functional status evaluated by the modified Rankin Scale (mRS) at discharge and 1-year follow-up. Secondary outcomes included the predicted probabilities for favorable outcome (mRS score of 0 to 3) stratified by infarct volumes or Glasgow Coma Scale score at admission and treatment modality. Analyses included propensity score matching, with adjustments for age, sex, Glasgow Coma Scale score at admission, brainstem involvement, and infarct volume. Results: Of 531 included patients with cerebellar infarcts, 301 (57%) were male, and the mean (SD) age was 68 (14.4) years. After propensity score matching, a total of 71 patients received surgical treatment and 71 patients conservative treatment. There was no significant difference in favorable outcomes (ie, mRS score of 0 to 3) at discharge for those treated surgically vs conservatively (47 [66%] vs 45 [65%]; odds ratio, 1.1; 95% CI, 0.5-2.2; P > .99) or at follow-up (35 [73%] vs 33 [61%]; odds ratio, 1.8; 95% CI, 0.7-4.2; P > .99). In patients with cerebellar infarct volumes of 35 mL or greater, surgical treatment was associated with a significant improvement in favorable outcomes at 1-year follow-up (38 [61%] vs 3 [25%]; odds ratio, 4.8; 95% CI, 1.2-19.3; P = .03), while conservative treatment was associated with favorable outcomes at 1-year follow-up in patients with infarct volumes of less than 25 mL (2 [34%] vs 218 [74%]; odds ratio, 0.2; 95% CI, 0-1.0; P = .047). Conclusions and Relevance: Overall, surgery was not associated with improved outcomes compared with conservative management in patients with cerebellar infarcts. However, when stratifying based on infarct volume, surgical treatment appeared to be beneficial in patients with larger infarct volumes, while conservative management appeared favorable in patients with smaller infarct volumes.

Necrosectomy Versus Stand-Alone Suboccipital Decompressive Craniectomy for the Management of Space-Occupying Cerebellar Infarctions-A Retrospective Multicenter Study.

BACKGROUND AND OBJECTIVES: Space-occupying cerebellar stroke (SOCS) when coupled with neurological deterioration represents a neurosurgical emergency. Although current evidence supports surgical intervention in such patients with SOCS and rapid neurological deterioration, the optimal surgical methods/techniques to be applied remain a matter of debate. METHODS: We conducted a retrospective, multicenter study of patients undergoing surgery for SOCS. Patients were stratified according to the type of surgery as (1) suboccipital decompressive craniectomy (SDC) or (2) suboccipital craniotomy with concurrent necrosectomy. The primary end point examined was functional outcome using the modified Rankin Scale (mRS) at discharge and at 3 months (mRS 0-3 defined as favorable and mRS 4-6 as unfavorable outcome). Secondary end points included the analysis of in-house postoperative complications, mortality, and length of hospitalization. RESULTS: Ninety-two patients were included in the final analysis: 49 underwent necrosectomy and 43 underwent SDC. Those with necrosectomy displayed significantly higher rate of favorable outcome at discharge as compared with those who underwent SDC alone: 65.3% vs 27.9%, respectively ( P < .001, odds ratios 4.9, 95% CI 2.0-11.8). This difference was also observed at 3 months: 65.3% vs 41.7% ( P = .030, odds ratios 2.7, 95% CI 1.1-6.7). No significant differences were observed in mortality and/or postoperative complications, such as hemorrhagic transformation, infection, and/or the development of cerebrospinal fluid leaks/fistulas. CONCLUSION: In the setting of SOCS, patients treated with necrosectomy displayed better functional outcomes than those patients who underwent SDC alone. Ultimately, prospective, randomized studies will be needed to confirm this finding.

Uncoupling protein 2 deficiency of non-cancerous tissues inhibits the progression of pancreatic cancer in mice.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. METHODS: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient (Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type (WT) PDAC cells (cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. RESULTS: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ mRNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. CONCLUSIONS: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.

Protein Biomarkers in Blood Reflect the Interrelationships Between Stroke Outcome, Inflammation, Coagulation, Adhesion, Senescence and Cancer.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle/environmental factors also play a role. Of all these, only the latter can be influenced after the event. Recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. Here we aim to provide an up-to-date protein biomarker signature that allows a maximum of mechanistic understanding, to predict health deterioration following stroke. We thus surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥ 3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune­inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

Reduced midbrain raphe echogenicity in patients with fibromyalgia syndrome.

OBJECTIVES: The pathogenesis of fibromyalgia syndrome (FMS) is unclear. Transcranial ultrasonography revealed anechoic alteration of midbrain raphe in depression and anxiety disorders, suggesting affection of the central serotonergic system. Here, we assessed midbrain raphe echogenicity in FMS. METHODS: Sixty-six patients underwent transcranial sonography, of whom 53 were patients with FMS (27 women, 26 men), 13 patients with major depression and physical pain (all women), and 14 healthy controls (11 women, 3 men). Raphe echogenicity was graded visually as normal or hypoechogenic, and quantified by digitized image analysis, each by investigators blinded to the clinical diagnosis. RESULTS: Quantitative midbrain raphe echogenicity was lower in patients with FMS compared to healthy controls (p<0.05), but not different from that of patients with depression and accompanying physical pain. Pain and FMS symptom burden did not correlate with midbrain raphe echogenicity as well as the presence and severity of depressive symptoms. CONCLUSION: We found reduced echogenicity of the midbrain raphe area in patients with FMS and in patients with depression and physical pain, independent of the presence or severity of pain, FMS, and depressive symptoms. Further exploration of this sonographic finding is necessary before this objective technique may enter diagnostic algorithms in FMS and depression.

Cerebral venous sinus thrombosis after adenovirus-vectored COVID-19 vaccination: review of the neurological-neuroradiological procedure.

Cerebral venous and sinus thrombosis (CVST) after adenovirus-vectored COVID-19 ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) is a rare complication, occurring mainly in individuals under 60 years of age and more frequently in women. It manifests 4-24 days after vaccination. In most cases, antibodies against platelet factor-4/polyanion complexes play a pathogenic role, leading to thrombosis with thrombocytopenia syndrome (TTS) and sometimes a severe clinical or even fatal course. The leading symptom is headache, which usually increases in intensity over a few days. Seizures, visual disturbances, focal neurological symptoms, and signs of increased intracranial pressure are also possible. These symptoms may be combined with clinical signs of disseminated intravascular coagulation such as petechiae or gastrointestinal bleeding. If TTS-CVST is suspected, checking D-dimers, platelet count, and screening for heparin-induced thrombocytopenia (HIT-2) are diagnostically and therapeutically guiding. The imaging method of choice for diagnosis or exclusion of CVST is magnetic resonance imaging (MRI) combined with contrast-enhanced venous MR angiography (MRA). On T2*-weighted or susceptibility weighted MR sequences, the thrombus causes susceptibility artefacts (blooming), that allow for the detection even of isolated cortical vein thromboses. The diagnosis of TTS-CVST can usually be made reliably in synopsis with the clinical and laboratory findings. A close collaboration between neurologists and neuroradiologists is mandatory. TTS-CVST requires specific regimens of anticoagulation and immunomodulation therapy if thrombocytopenia and/or pathogenic antibodies to PF4/polyanion complexes are present. In this review article, the diagnostic and therapeutic steps in cases of suspected TTS associated CSVT are presented.

A novel ex vivo model for critical illness neuromyopathy using freshly resected human colon smooth muscle.

Patients suffering from critical illness are at risk to develop critical illness neuromyopathy (CINM). The underlying pathophysiology is complex and controversial. A central question is whether soluble serum factors are involved in the pathogenesis of CINM. In this study, smooth muscle preparations obtained from the colon of patients undergoing elective surgery were used to investigate the effects of serum from critically ill patients. At the time of blood draw, CINM was assessed by clinical rating and electrophysiology. Muscle strips were incubated with serum of healthy controls or patients in organ baths and isometric force was measured. Fifteen samples from healthy controls and 98 from patients were studied. Ratios of responses to electric field stimulation (EFS) before and after incubation were 118% for serum from controls and 51% and 62% with serum from critically ill patients obtained at day 3 and 10 of critical illness, respectively (p = 0.003, One-Way-ANOVA). Responses to carbachol and high-K+ were equal between these groups. Ratios of post/pre-EFS responses correlated with less severe CINM. These results support the existence of pathogenic, i.e. neurotoxic factors in the serum of critically ill patients. Using human colon smooth muscle as a bioassay may facilitate their future molecular identification.

Serious Complications After Epidural Catheter Placement: Two Case Reports.

Thoracic epidural analgesia (TEA) is a standard procedure in multimodal analgesia applied in major thoracic and abdominal surgeries. Two cases are presented with serious complications related to TEA. In both cases, earlier reaction of the treating physicians to patient-reported sensory symptoms could have prevented the complicated course. The first case was a 73-year-old patient with bronchial carcinoma who underwent right lower lobe resection. In this case, dabigatran 150 mg/d (indication: permanent atrial fibrillation) had been discontinued 72 hours before surgery, and enoxaparin 80 mg (every 12 hours) had been started 11 hours after surgery. An epidural hematoma developed postoperatively. Magnetic resonance imaging (MRI) was performed only after paraplegia had developed the next day. Unfortunately, delayed hematoma evacuation could not prevent persistent paraplegia in this case, which was complicated by hospital-acquired pneumonia with sepsis and acute renal failure. The second case was a 39-year-old patient with ulcerative colitis and an initially undetected malposition of the epidural catheter. Immediately after test bolus injection, the patient reported paresthesia and overall discomfort, which however could not be safely attributed to either the test dose or the already started general anesthesia. The patient could only be extubated after stopping the epidural infusion. Accidental re-start of epidural infusion led to coma, conjugate eye deviation, and respiratory arrest, necessitating re-intubation. Computed tomography (CT) ruled out intracerebral pathology and showed a catheter position centrally in the spinal canal. Fortunately, no neurological deficits were detected after catheter removal.

[Cerebral venous sinus thrombosis after COVID-19 vaccination : Neurological and radiological management]. / Hirnvenen- und Sinusthrombose nach COVID-19-Schutzimpfung : Neurologisch-radiologisches Prozedere.

BACKGROUND: Vaccine-induced cerebral venous and sinus thrombosis (VI-CVST) is a rare complication in recipients of the adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccine ChAdOx1 nCov-19 (Vaxzevria®; AstraZeneca). OBJECTIVES: Development of a diagnostic and therapeutic standard. MATERIALS AND METHODS: Analysis of clinical and basic research findings, expert opinions, and experience with our own cases. RESULTS: VI-CVST usually manifests on day 4-24 after vaccination, mostly in individuals aged < 60 years, and women. In the majority there is an immune pathogenesis caused by antibodies against platelet factor 4/polyanion complexes, leading to thrombotic thrombocytopenia which can result in severe, sometimes fatal, course. The cardinal symptom is headache worsening within days which, however, also can be of variable intensity. Other possible symptoms are seizures, visual disturbance, focal neurological deficits and signs of increased intracranial pressure. If VI-CVST is suspected, the determination of plasma D­dimer level, platelet count, and screening for heparin-induced thrombocytopenia (HIT-2) are essential for treatment decision-making. Magnetic resonance imaging (MRI) with venous MR-angiography is the neuroimaging modality of choice to confirm or exclude VI-CVST. On T2* susceptibility-weighted MRI, the clot in the sinuses or veins produces marked susceptibility artifacts ("blooming"), which also enables the detection of isolated cortical venous thromboses. MRI/MR-angiography or computed tomography (CT)/CT-angiography usually allow-in combination with clinical and laboratory findings-reliable diagnosis of VI-CVST. CONCLUSIONS: The clinical suspicion of VI-CVST calls for urgent laboratory and neuroimaging workup. In the presence of thrombocytopenia and/or pathogenic antibodies, specific medications for anticoagulation and immunomodulation are recommended.

Adenovirus-Vectored COVID-19 Vaccine-Induced Immune Thrombosis of Carotid Artery: A Case Report.

OBJECTIVE: Venous thromboses and thrombocytopenia after vaccination with the adenovirus-vectored COVID-19 vaccine ChAdOx1 nCov-19 (AstraZeneca) have been linked to serum antibodies against platelet factor 4 (PF4)-polyanion complexes. We here report vaccine-induced isolated carotid arterial thrombosis. METHODS: Imaging and laboratory findings, treatment decisions and outcome of this case are presented. RESULTS: Eight days after having received the first dose of ChAdOx1 nCov-19 vaccine, a 31-year-old man was admitted to our stroke unit with acute headache, aphasia, and hemiparesis. D-dimers were slightly elevated, but platelet count and fibrinogen level were normal. MRI-confirmed mainstem occlusion of middle cerebral artery resolved within 1 hour after start of IV thrombolysis. A wall-adherent, non-occluding thrombus in the ipsilateral carotid bulb was identified as the source of embolism. Cardiac or paradoxical (venous) embolism was excluded. Screening for presence of heparin-induced thrombocytopenia-related antibodies was positive, and highly elevated serum IgG antibodies against PF4-polyanion complexes were subsequently proven. Treatment with aspirin and subcutaneous danaparoid, followed by phenprocoumon, led to thrombus shrinkage and dissolution within 19 days, and favorable clinical outcome. DISCUSSION: Vaccine history is important in patients not only with venous but also with arterial thromboembolic events. Vaccine-induced immune thrombosis of brain-supplying arteries may well be handled.

Evaluation of Choroidal Melanoma Vascularization by Color Doppler Flow Imaging: An Option for Follow-Up Tumor Control Assessment after CyberKnife®?

Background and Objectives: Thus far, tumor control for choroidal melanoma after teletherapeutic radiation is clinically difficult. In contrast to brachytherapy, the tumor height does not necessarily have to shrink as a result of teletherapy. Therefore, the objective of this study was to evaluate tumor vascularization determined by color Doppler flow imaging (CDFI) as a possible approach for monitoring the therapy response after teletherapy of choroidal melanoma. Materials and Methods: A single-center retrospective pilot study of 24 patients was conducted, all of whom had been diagnosed with choroidal neoplasm, treated and followed up. Besides tumor vascularization, the following parameters were collected: age, gender, tumor entity, location, radiation dose, knowledge of relapse, tumor height, radiation-related complications, occurrence of metastases, visual acuity in logMAR. Results: The level of choroidal melanoma vascularization markedly decreased in all included subjects after treatment with the CyberKnife® technology. Initially, the level of vascularization was 2.1 (SD: 0.76 for n = 10); post-therapeutically, it averaged 0.14 (SD: 0.4). Regarding the tumor apex, CDFI sonography also demonstrated a significant tumor regression (mean value pre-therapeutically: 8.35 mm-SD: 3.92 for n = 10; mean value post-therapeutically: 4.86 mm-SD: 3.21). The level of choroidal melanoma vascularization declined in the patient collective treated with ruthenium-106 brachytherapy. The pre-therapeutic level of vascularization of 2 (SD: 0 for n = 2) decreased significantly to a level of 0 (mean: 0-SD: 0). The tumor height determined by CDFI did not allow any valid statement regarding local tumor control. In contrast to these findings, the patient population of the control group without any radiation therapy did not show any alterations in vascularization. Conclusions: Our data suggest that the determination of the tumor vascularization level using CDFI might be a useful and supplementary course parameter in the follow-up care of choroidal melanoma to monitor the success of treatment. This especially applies to robot-assisted radiotherapy using CyberKnife®. Further studies are necessary to validate the first results of this assessment.

Towards biomarkers for outcomes after pancreatic ductal adenocarcinoma and ischaemic stroke, with focus on (co)-morbidity and ageing/cellular senescence (SASKit): protocol for a prospective cohort study.

INTRODUCTION: Ageing-related processes such as cellular senescence are believed to underlie the accumulation of diseases in time, causing (co)morbidity, including cancer, thromboembolism and stroke. Interfering with these processes may delay, stop or reverse morbidity. The aim of this study is to investigate the link between (co)morbidity and ageing by exploring biomarkers and molecular mechanisms of disease-triggered deterioration in patients with pancreatic ductal adenocarcinoma (PDAC) and (thromboembolic) ischaemic stroke (IS). METHODS AND ANALYSIS: We will recruit 50 patients with PDAC, 50 patients with (thromboembolic) IS and 50 controls at Rostock University Medical Center, Germany. We will gather routine blood data, clinical performance measurements and patient-reported outcomes at up to seven points in time, alongside in-depth transcriptomics and proteomics at two of the early time points. Aiming for clinically relevant biomarkers, the primary outcome is a composite of probable sarcopenia, clinical performance (described by ECOG Performance Status for patients with PDAC and the Modified Rankin Scale for patients with stroke) and quality of life. Further outcomes cover other aspects of morbidity such as cognitive decline and of comorbidity such as vascular or cancerous events. The data analysis is comprehensive in that it includes biostatistics and machine learning, both following standard role models and additional explorative approaches. Prognostic and predictive biomarkers for interventions addressing senescence may become available if the biomarkers that we find are specifically related to ageing/cellular senescence. Similarly, diagnostic biomarkers will be explored. Our findings will require validation in independent studies, and our dataset shall be useful to validate the findings of other studies. In some of the explorative analyses, we shall include insights from systems biology modelling as well as insights from preclinical animal models. We anticipate that our detailed study protocol and data analysis plan may also guide other biomarker exploration trials. ETHICS AND DISSEMINATION: The study was approved by the local ethics committee (Ethikkommission an der Medizinischen Fakultät der Universität Rostock, A2019-0174), registered at the German Clinical Trials Register (DRKS00021184), and results will be published following standard guidelines.

Muscular Ultrasound, Syndecan-1 and Procalcitonin Serum Levels to Assess Intensive Care Unit-Acquired Weakness.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is associated with poorer outcome of critically ill patients. Microcirculatory changes and altered vascular permeability of skeletal muscles might contribute to the pathogenesis of ICU-AW. Muscular ultrasound (MUS) displays increased muscle echogenicity, although its pathogenesis is uncertain. OBJECTIVE: We investigated the combined measurement of serum and ultrasound markers to assess ICU-AW and clinical patient outcome. METHODS: Fifteen patients and five healthy controls were longitudinally assessed for signs of ICU-AW at study days 3 and 10 using a muscle strength sum score. The definition of ICU-AW was based on decreased muscle strength assessed by the muscular research council-sum score. Ultrasound echogenicity of extremity muscles was assessed using a standardized protocol. Serum markers of inflammation and endothelial damage were measured. The 3-month outcome was assessed on the modified Rankin scale. RESULTS: ICU-AW was present in eight patients, and seven patients and the control subjects did not develop ICU-AW. The global muscle echogenicity score (GME) differed significantly between controls and patients (mean GME, 1.1 ± 0.06 vs. 2.3 ± 0.41; p = 0.001). Mean GME values significantly decreased in patients without ICU-AW from assessment 1 (2.30 ± 0.48) to assessment 2 (2.06 ± 0.45; p = 0.027), which was not observed in patients with ICU-AW. Serum levels of syndecan-1 at day 3 significantly correlated with higher GME values at day 10 (r = 0.63, p = 0.012). Furthermore, the patients' GME significantly correlated with mRS at day 100 (r = 0.67, p = 0.013). CONCLUSION: The combined use of muscular ultrasound and inflammatory biomarkers might be helpful to diagnose ICU-AW and to predict long-term outcome in critical illness.

Defining spasticity: a new approach considering current movement disorders terminology and botulinum toxin therapy.

Spasticity is a symptom occurring in many neurological conditions including stroke, multiple sclerosis, hypoxic brain damage, traumatic brain injury, tumours and heredodegenerative diseases. It affects large numbers of patients and may cause major disability. So far, spasticity has merely been described as part of the upper motor neurone syndrome or defined in a narrowed neurophysiological sense. This consensus organised by IAB-Interdisciplinary Working Group Movement Disorders wants to provide a brief and practical new definition of spasticity-for the first time-based on its various forms of muscle hyperactivity as described in the current movement disorders terminology. We propose the following new definition system: Spasticity describes involuntary muscle hyperactivity in the presence of central paresis. The involuntary muscle hyperactivity can consist of various forms of muscle hyperactivity: spasticity sensu strictu describes involuntary muscle hyperactivity triggered by rapid passive joint movements, rigidity involuntary muscle hyperactivity triggered by slow passive joint movements, dystonia spontaneous involuntary muscle hyperactivity and spasms complex involuntary movements usually triggered by sensory or acoustic stimuli. Spasticity can be described by a documentation system grouped along clinical picture (axis 1), aetiology (axis 2), localisation (axis 3) and additional central nervous system deficits (axis 4). Our new definition allows distinction of spasticity components accessible to BT therapy and those inaccessible. The documentation sheet presented provides essential information for planning of BT therapy.

Frequency and profile of Parkinson's disease prodromi in patients with malignant melanoma.

OBJECTIVE: The results of register studies suggest an association between Parkinson's disease (PD) and melanoma. We studied the frequency and profile of early markers of PD in patients with malignant melanoma. METHODS: 100 participants were enrolled in a prospective observational study, of whom 65 had a history of high-risk cutaneous (n=53) or uveal (n=12) melanoma (31 women; age, 61.2±14.9 years) and another 35 served as control participants (19 women; 54.6±20.5 years). Participants underwent assessments of motor function (Unified PD Rating Scale; keyboard tapping test), olfactory function, colour vision, depressive symptoms, the Non-Motor Symptoms Questionnaire, and transcranial brain sonography. Raters were blinded to the diagnosis and clinical data of study participants. RESULTS: Patients with melanoma showed increased frequency of substantia nigra hyperechogenicity and prodromal motor and non-motor features of PD, especially asymmetric motor slowing and apathy. Hyposmia and colour vision disturbance were, however, infrequent. Larger echogenicity of substantia nigra correlated with lower serum iron in patients with melanoma, similar to previously reported findings in PD, and independently from the earlier findings, with lighter skin pigmentation. Substantia nigra hyperechogenicity, combined with motor asymmetry or hyposmia, was present at baseline in all participants with mild or definite parkinsonism diagnosed after 1 year. Parkinsonism was specifically related to melanoma location at the sun-exposed skin of the head or neck. CONCLUSIONS: History of melanoma was associated with increased prevalence of prodromal markers of PD. Their predictive value needs to be established in long-term investigations. The similarity of serum iron characteristics found in patients with melanoma and PD deserves further research.

Anatomic and pathological characterization of choroidal melanoma using multimodal imaging: what is practical, what is needed?

Choroidal melanoma is the most frequently occurring intraocular tumor in adults. The aim of this work is to assess the potential of state-of-the art in-vivo and ex-vivo imaging modalities for the characterization of choroidal melanoma. Multimodal imaging of a choroidal melanoma was performed in a 53-year-old male patient. In-vivo ophthalmoscopy, ultrasound microscopy, duplex ultrasound, and 7.0 T MRI were performed. Ex-vivo examination of the enucleated eye included 7.0 and 9.4 T magnetic resonance microscopy as well as histopathology with hematoxylin and eosin staining. Imaging of choroidal melanoma with ultrahigh field MRI and duplex sonography provides detailed morphologic and functional information of the eye. High-spatial-resolution MRI at 9.4 T shows details of the internal texture of melanoma and other structures of the eye with an in-plane spatial resolution of 32 µm. Ultrahigh field in-vivo MRI at 7.0 T and ex-vivo MRI at 7.0 and 9.4 T correlate well with histologic evaluation. In-vivo ultrahigh field MRI is an emerging technique for the characterization and staging of ocular tumors. The combination of in-vivo ultrahigh-field MRI and duplex sonography has the potential to complement or even substitute complex and invasive biopsies.

Relevance of sonography for botulinum toxin treatment of cervical dystonia: an expert statement.

Botulinum neurotoxin A (BoNT A) is the first-line treatment for cervical dystonia. However, although BoNT A has a favorable safety profile and is effective in the majority of patients, in some cases the treatment outcome is disappointing or side effects occur when higher doses are used. It is likely that in such cases either the target muscles were not injected accurately or unintended weakness of non-target muscles occurred. It has been demonstrated in clinical trials for spastic movement disorders that sonography-guided BoNT A injections could improve treatment outcome. As the published evidence for a benefit of sonography-guided BoNT injection in patients with cervical dystonia is scarce, it is the aim of this review to discuss the relevance of sonography in this indication and provide a statement from clinical experts for its use. The clear advantage of sonography-guided injections is non-invasive, real-time visualization of the targeted muscle, thus improving the precision of injections and potentially the treatment outcomes as well as avoiding adverse effects. Other imaging techniques are of limited value due to high costs, radiation exposure or non-availability in clinical routine. In the hands of a trained injector, sonography is a quick and non-invasive imaging technique. Novel treatment concepts of cervical dystonia considering the differential contributions of distinct cranial and cervical muscles can reliably be implemented only by use of imaging-guided injection protocols.

Lenticular nucleus hyperechogenicity in Wilson's disease reflects local copper, but not iron accumulation.

In patients with Wilson's disease (WD) transcranial brain sonography typically reveals areas of increased echogenicity (hyperechogenicity) of the lenticular nucleus (LN). Correlation with T2-hypointensity on magnetic resonance images suggested that LN hyperechogenicity in WD is caused by trace metal accumulation. Accumulation of both, copper and iron, in the brain of WD patients has been reported. The present study was designed to elucidate whether LN hyperechogenicity in WD reflects accumulation of copper or iron. Post-mortem brains of 15 WD patients and one non-WD subject were studied with ultrasonography in an investigator-blinded fashion. LN hyperechogenicity was measured planimetrically by manual tracing as well as using digitized image analysis. The putaminal copper content was determined in samples of 11 WD brains and the non-WD brains using inductively coupled plasma mass spectrometry, and iron content was assessed using flame atomic absorption spectroscopy. LN was normal on ultrasonography only in the non-WD brain, but abnormal (hyperechogenic) in all WD brains. Digitized image analysis measures of LN hyperechogenicity and, by trend, manual measures correlated with putaminal copper content (Pearson test; digitized: r = 0.77, p = 0.04; manual: r = 0.57, p = 0.051) but not with iron content (each, p > 0.18). LN hyperechogenicity measures were unrelated to age at death of patients, age at onset of WD, WD duration, age of brain specimen, serum copper or serum ceruloplasmin (each, p > 0.1). We conclude that LN hyperechogenicity in WD reflects copper, but not iron accumulation. Further studies are warranted to elucidate the use of transcranial brain sonography for monitoring therapeutic effects of chelating agents in WD patients.

Ultrahigh field magnetic resonance and colour Doppler real-time fusion imaging of the orbit--a hybrid tool for assessment of choroidal melanoma.

OBJECTIVES: A combination of magnetic resonance images with real-time high-resolution ultrasound known as fusion imaging may improve ophthalmologic examination. This study was undertaken to evaluate the feasibility of orbital high-field magnetic resonance and real-time colour Doppler ultrasound image fusion and navigation. METHODS: This case study, performed between April and June 2013, included one healthy man (age, 47 years) and two patients (one woman, 57 years; one man, 67 years) with choroidal melanomas. All cases underwent 7.0-T magnetic resonance imaging using a custom-made ocular imaging surface coil. The Digital Imaging and Communications in Medicine volume data set was then loaded into the ultrasound system for manual registration of the live ultrasound image and fusion imaging examination. RESULTS: Data registration, matching and then volume navigation were feasible in all cases. Fusion imaging provided real-time imaging capabilities and high tissue contrast of choroidal tumour and optic nerve. It also allowed adding a real-time colour Doppler signal on magnetic resonance images for assessment of vasculature of tumour and retrobulbar structures. CONCLUSIONS: The combination of orbital high-field magnetic resonance and colour Doppler ultrasound image fusion and navigation is feasible. Multimodal fusion imaging promises to foster assessment and monitoring of choroidal melanoma and optic nerve disorders. KEY POINTS: • Orbital magnetic resonance and colour Doppler ultrasound real-time fusion imaging is feasible • Fusion imaging combines the spatial and temporal resolution advantages of each modality • Magnetic resonance and ultrasound fusion imaging improves assessment of choroidal melanoma vascularisation.