Convolutional Neural Network for Fully Automated Cerebellar Volumetry in Children in Comparison to Manual Segmentation and Developmental Trajectory of Cerebellar Volumes.

The purpose of this study was to develop a fully automated and reliable volumetry of the cerebellum of children during infancy and childhood using deep learning algorithms in comparison to manual segmentation. In addition, the clinical usefulness of measuring the cerebellar volume is shown. One hundred patients (0 to 16.3 years old) without infratentorial signal abnormalities on conventional MRI were retrospectively selected from our pool of pediatric MRI examinations. Based on a routinely acquired 3D T1-weighted magnetization prepared rapid gradient echo (MPRAGE) sequence, the cerebella were manually segmented using ITK-SNAP. The data set of all 100 cases was divided into four splits (four-fold cross-validation) to train the network (NN) to delineate the boundaries of the cerebellum. First, the accuracy of the newly created neural network was compared with the manual segmentation. Secondly, age-related volume changes were investigated. Our trained NN achieved an excellent Spearman correlation coefficient of 0.99, a Dice Coefficient of 95.0 ± 2.1%, and an intersection over union (IoU) of 90.6 ± 3.8%. Cerebellar volume increased continuously with age, showing an exponentially rapid growth within the first year of life. Using a convolutional neural network, it was possible to achieve reliable, fully automated cerebellar volume measurements in childhood and infancy, even when based on a relatively small cohort. In this preliminary study, age-dependent cerebellar volume changes could be acquired.

Extrahepatic manifestations of progressive familial intrahepatic cholestasis syndromes: Presentation of a case series and literature review.

BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) is a collective term for a heterogenous group of rare, inherited cholestasis syndromes. The number of genes underlying the clinical PFIC phenotype is still increasing. While progressive liver disease and its sequelae such as portal hypertension, pruritus and hepatocellular carcinoma determine transplant-free survival, extrahepatic manifestations may cause relevant morbidity. METHODS: We performed a literature search for extrahepatic manifestations of PFIC associated with pathogenic gene variants in ATP8B1, ABCB11, ABCB4, TJP2, NR1H4 and MYO5B. To illustrate the extrahepatic symptoms described in the literature, PFIC cases from our centres were revisited. RESULTS: Extrahepatic symptoms are common in PFIC subtypes, where the affected gene is expressed at high levels in other tissues. While most liver-associated complications resolve after successful orthotopic liver transplantation (OLT), some extrahepatic symptoms show no response or even worsen after OLT. CONCLUSION: The spectrum of extrahepatic manifestations in PFIC highlights essential, non-redundant roles of the affected genes in other organs. Extrahepatic features contribute towards low health-related quality of life (HRQOL) and morbidity in PFIC. While OLT is often the only remaining, curative treatment, potential extrahepatic manifestations need to be carefully monitored and addressed.

Radiologic detectability of the cochlear implant electrode fixation clip using cone beam computed tomography.

INTRODUCTION: With the aim of preventing migration of cochlear implantation electrodes in the postoperative course, an electrode fixation clip has been developed. It is characterized by two clips of double U-geometry. The bone fixation clip will be clamped on the bony incus bridge, and the electrode fixation clip is clamped to the electrode lead. Although made of titanium, the detectability in radiologic imaging appears limited. MATERIALS AND METHODS: Six patients, who received a cochlear implant between August 2014 and March 2015, were retrospectively analyzed for the detectability of the Med-El Electrode Fixation Clip in postoperative cone beam CT scans. For these patients, we randomly extracted appropriate control group patients without implanted clips (matched pairs). One instructed neuro-radiologist blindly evaluated postoperative radiographs on a visual, descriptive basis of both groups with the main outcome measure of clip detectability. RESULTS: In total, images of 12 patients were evaluated. In five of the six (83%) study group patients, the clip was detected radiologically correct. One patient (17%) was appointed as false negative. All patients (100%) without a clip were correctly identified. DISCUSSION: The electrode fixation clip can be identified, despite its small size, using cone beam CT. Sensitivity and specificity are high. This aspect assumes importance especially in postoperative monitoring, e.g. in cases of revision surgery. Thus, this study contributes to the overall safety in cochlear implant surgery.

Eculizumab in Typical Hemolytic Uremic Syndrome (HUS) With Neurological Involvement.

In typical hemolytic uremic syndrome (HUS) approximately 25% of patients show central nervous system (CNS) involvement often leading to serious long-term disabilities. We used the C5-complement inhibitor Eculizumab as rescue therapy. From 2011 to 2014, 11 children (median age 22 months, range 11-175) with enterohemorrhagic Escherichia coli-positive HUS requiring dialysis who had seizures (11/11) and/or were in a stupor or coma (10/11) were treated with Eculizumab. Two patients enrolled on the Safety and Efficacy Study of Eculizumab in Shiga-Toxin Producing E coli Hemolytic-Uremic Syndrome (STEC-HUS) each received 6 doses of Eculizumab, 3 patients 2 doses, and 6 patients 1 dose. Laboratory diagnostics of blood samples and magnetic resonance imaging (MRI) were performed as per center practice. Data were analyzed retrospectively. Cranial MRI was abnormal in 8 of 10 patients with findings in the basal ganglia and/or white matter. A 2-year-old boy with severe cardiac involvement and status epilepticus needed repeated cardio-pulmonary resuscitation and extracorporeal membrane oxygenation. He died 8 days after start of Eculizumab treatment. Two patients with hemorrhagic colitis and repeated seizures required artificial ventilation for 6 and 16 days, respectively. At the time of discharge, 1 patient showed severe neurological impairment and 1 mild neurological impairment. The 8 surviving patients experienced no further seizures after the first dose of Eculizumab. Three patients showed mild neurological impairment at discharge, whilst the remaining 5 showed no impairment. The platelets normalized 4 days (median) after the first dose of Eculizumab (range 0-20 days). The mean duration of dialysis after the first dose of Eculizumab was 14.1 ± 6.1 days. In children with typical HUS and CNS involvement early use of Eculizumab appears to improve neurological outcome. In severe HUS cases which progress rapidly with multiple organ involvement, late treatment with Eculizumab seems to show less benefit. We speculate that prophylactic Eculizumab therapy before development of neurological symptoms could be advantageous.

Temporal pattern of cytotoxic edema in the perihematomal region after intracerebral hemorrhage: a serial magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Knowledge about cytotoxic edema (CE) in intracerebral hemorrhage is still limited. We aimed to analyze its presence, temporal pattern, and prognostic meaning. METHODS: Twenty-one patients with primary intracerebral hemorrhage underwent magnetic resonance imaging at days 1, 3, and 7 after symptom onset. CE was identified using diffusion-weighted imaging. Hematoma and perihematomal edema volumes were measured on fluid-attenuated inversion recovery images. National Institutes of Health Stroke Scale score was assessed at admission and with each magnetic resonance imaging. Clinical outcome was assessed by modified Rankin scale at 90 days. RESULTS: CE appeared in half of the patients within the first 24 hours. The apparent diffusion coefficient values decreased until day 3 and were significantly reversed from days 3 through 7 (P<0.01). Patients with CE showed significantly faster perihematomal edema growth from day 0 to 1 (P=0.036) than those without. Larger 3-day perihematomal edema volume (P=0.02) and presence of CE on day 3 (P=0.07) were associated with poor clinical outcome. CONCLUSIONS: CE is associated with stroke severity, perihematomal edema volume, and poor outcome. It is considered to indicate ongoing neuronal injury and, thus, might emerge as new treatment target.

Meningeal carcinomatosis from penile squamous cell carcinoma.

We report herein a clinical case of a patient with meningeal carcinomatosis from penile squamous cell carcinoma. A 68-year-old man presented with mental changes, headaches, and unstable gait. Examinations revealed brain metastases and infiltration of the leptomeninges and subarachnoid space by carcinoma cells. Only 11 months earlier the patient had been diagnosed with penile squamous cell carcinoma of poor differentiation and had underwent subtotal penectomy and adjuvant chemotherapy and radiation. Infiltration of the central nervous system with penile cancer is extremely rare, and only five cases with brain metastases have been described to date. This is the first report of a patient with penile cancer spread to the leptomeninges.

Reduced intercarotid artery distance in acromegaly: pathophysiologic considerations and implications for transsphenoidal surgery.

BACKGROUND: The objective of this study is to evaluate the significance of reduced intercarotid artery distance in the C5 segment in acromegalic patients and the implications for transsphenoidal surgery. METHODS: The skull base with the carotid canal was examined with a helical CT scan in 45 patients with acromegaly and 45 age group-matched controls. The distances between the inner walls (IWs) of the carotid sulcus (CS), the outer walls (OWs) of the CS, and the diameter of the ICA at the C5 segment were assessed. Preoperative IGF-1 and growth hormone levels and concomitant diseases were evaluated and correlated with the biometric findings. Statistical analysis was performed with JMP (JMP version 7.0.2, SAS, Cary, USA). RESULTS: The mean distance between the IW was 1.64 +/- 0.40 cm in the acromegalic patients and 1.90 +/- 0.26 cm in the control group (P = .0005). The distance between the OW measured 3.01 +/- 0.39 and 2.97 +/- 0.33 cm in the acromegalics and in the control group, respectively (P = .6230). The difference in the diameter of the ICA was statistically significant (P < .0001) between patients and control group. Within the patient group, the distance between the IW of both ICA was significantly smaller in the subgroup with arterial hypertension (P = .0256). CONCLUSION: Narrowing of the inner borders of the CS between the right and left side is a statistically significant parameter in acromegaly. Attention should be given to an altered vascular course of the ICAs when planning and performing transsphenoidal microsurgery in acromegalic patients. A preoperative skull base CT may furnish important anatomical information and further reduce the risk of vascular injury.

Mature cerebellar teratoma in adulthood.

Extragonadal teratomas in adulthood are exceptionally rare and usually not located within the cerebellum. We here report on a 66-year-old male patient clinically presenting with chronic occipital headache and episodes of severe vertigo. Neuroradiological investigations revealed a hemorrhagic tumor mass in the cerebellar vermis which was surgically removed and histologically diagnosed as mature teratoma. Hence, the presented case is extraordinary with regard to age, late clinical onset of symptoms and cerebellar location. Late clinical manifestation of the tumor in this case is probably due to an acute late-onset hemorrhage within the tumor.

Intra-individual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for contrast-enhanced magnetic resonance angiography of the supraaortic vessels at 3 Tesla.

OBJECTIVE: To compare gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine (Gd-DTPA) for contrast-enhanced magnetic resonance (MR) angiography of the supraaortic vessels at 3 Tesla. MATERIALS AND METHODS: Twelve healthy volunteers each underwent two contrast-enhanced magnetic resonance angiography examinations, one with Gd-BOPTA and one with Gd-DTPA each at a dose of 0.1 mmol/kg bodyweight. The 2 examinations were performed in randomized order and were separated by at least 72 hours. Imaging was performed in the coronal plane at 3T (Magnetom TIM Trio Siemens) using a 12-channel neurovascular array coil. The MR sequence parameters were identical for all examinations. Maximum intensity projection reconstructions were evaluated separately and in matched-pairs by a single independent blinded reviewer in terms of qualitative (5-point scales for technical quality and vessel delineation) and quantitative (relative contrast-to-noise ratio) contrast enhancement across 19 arteries/arterial segments comprising the internal carotid arteries; anterior, middle, and posterior cerebral arteries; vertebral arteries; and basilar artery. Findings were compared using the Wilcoxon signed rank test. RESULTS: The mean technical quality across all examinations was significantly (P = 0.031) greater after Gd-BOPTA. The overall median score for vessel delineation was also significantly higher for Gd-BOPTA than for Gd-DTPA (4.3 vs. 3.7; P = 0.005). Matched-pairs assessment revealed significant (P

Clinical and molecular characterisation of a Parkinson family with a novel PINK1 mutation.

Homozygous mutations in the PINK1 gene have been shown to cause early-onset parkinsonism. Here, we describe a novel homozygous mutation (Q126P), identified in two affected German sisters with a clinical phenotype typical for PINK1-associated parkinsonism. We analysed lactate, pyruvate, carnitine and acylcarnitine blood levels, lactate levels under exercise and in the cerebrospinal fluid, activity of respiratory chain complexes I-IV in muscle biopsies and proteasomal activity in immortalized lymphoblasts, but found no evidence for mitochondrial or proteasomal dysfunction. MR spectroscopy revealed raised myoinositol levels in the basal ganglia of both patients, reflecting possible astroglial proliferation.

Hemodynamic reserve and high-intensity transient signals in moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) as a rare obstructive cerebrovascular disease is assumed to present with ischemic symptoms due to hemodynamic compromise. However, alternative mechanisms, such as cerebral embolism in low-flow territories, may also contribute to clinical symptoms. The incidence of high-intensity transient signals (HITS) and the degree of hemodynamic compromise were studied in symptomatic patients with MMD. METHODS: Twenty-four patients (17 female, 7 male; mean age 33 +/- 13 years) with clinical symptoms attributable to cerebral ischemia and the angiographic features of MMD (21 definite form, 3 probable MMD; 22 patients 'late stage' MMD, 2 patients 'early stage' MMD) in 45 affected hemispheres were enrolled in the present study. Patients underwent parallel estimation of hemodynamic compromise by means of functional blood flow (rCBF) studies using SPECT, PET or xenon-CT and HITS detection by TCD. RESULTS: Hemodynamic compromise was observed in 37/40 (92%) hemispheres studied. During TCD monitoring, HITS were detected in 3 patients (12.5%), with a total frequency of 3 (6.6%) in the 45 hemispheres investigated. All patients with HITS showed hemodynamic compromise in functional rCBF studies. In these patients, HITS were recorded ipsilateral to the symptomatic hemisphere. HITS occurred in late stage MMD patients only once, while both cases with early stage MMD demonstrated multiple HITS. CONCLUSIONS: The incidence of HITS in patients with MMD appears to be lower compared to patients with atherosclerotic or atherothrombotic arterial obstructions. In addition, ischemia-related symptoms in 'late stage' MMD seem to be caused by hemodynamic compromise in the majority of these patients.

Arterio-embolic ischemic stroke in children with moyamoya disease.

INTRODUCTION: Moyamoya (MM) disease is a rare steno-occlusive cerebrovascular disease known to occur in children and adults. The most serious complications in children are developmental delay and mental retardation due to recurrent hemodynamic stroke. CASES: We report two pediatric patients without coagulopathy who suffered from severe arterio-embolic ischemic complications despite antiplatelet medication. DISCUSSION: These observations underline the potential impact of cerebral thromboembolism on the pathophysiology of the stroke and thus on the treatment of children with MM disease.

Moyamoya-like vasculopathy (moyamoya syndrome) in children.

INTRODUCTION: A large variety of inherited or acquired childhood disorders and conditions may present in conjunction with progressive bilateral stenosis and/or occlusion of the terminal segments of the internal carotid artery. In addition, the development of pathological collateral vessels can be observed in the vicinity of the steno-occlusive changes in these patients. This condition is known as moyamoya-like (MML) vasculopathy. The natural history, the angiographic appearance, and the pathology of MML vasculopathy probably differ from those of definite moyamoya disease. Adequate cerebral vascular imaging should be considered in all pediatric patients with inherited or acquired systemic disorders and symptoms attributable to cerebral ischemia. CASES AND DISCUSSION: We present four pediatric cases of MML vasculopathy, and outline the etiology, the current classification, and the therapeutic approaches for this heterogeneous disease entity.

A rapid noninvasive method to visualize ruptured aneurysms in the emergency room: three-dimensional power Doppler imaging.

OBJECT: Three-dimensional (3D) power Doppler ultrasonography imaging provides a rapid, noninvasive visualization of ruptured intracranial aneurysms, including their relationship to other vascular structures. METHODS: The authors used transcranial 3D power Doppler imaging in the emergency room to examine patients with acute subarachnoid hemorrhage. In all patients, the ruptured aneurysm was rapidly located with 3D power Doppler imaging. Conventional x-ray angiography confirmed both the ultrasonography-based diagnosis and the location of aneurysmal bleeding. CONCLUSIONS: These preliminary results indicate that 3D power Doppler imaging is a rapid, noninvasive screening method for the visualization of ruptured aneurysms.