Sphingolipide sind wichtige Bestandteile von Zellmembranen und wichtig für die Zellproliferation, Zelldifferenzierung, neuronale Signalverarbeitung sowie den Aufbau von Myelin. Bislang bekannte Defekte in Enzymen des Auf- und Abbauweges von Sphingolipiden führen zur sensorischen Neuropathie, Epilepsie, dem M. Fabry, M. Gaucher, M. Niemann-Pick oder der Tay-Sachs-Erkrankung. Nicht alle beteiligten Enzyme des Sphingolipidmetabolismus konnten bislang mit einer Erkrankung assoziiert werden.

PDE10A (OMIM *610652, #616921, #616922) encodes phosphodiesterase 10A, which regulates the intracellular concentration of cAMP and cGMP in medium spiny neurons (MSNs) of the corpus striatum (for review [ [1] Threlfell S. West A.R. Review: modulation of striatal neuron activity by cyclic nucleotide signaling and phosphodiesterase inhibition. Basal Ganglia. 2013; 3: 137-146 Crossref PubMed Scopus (44) Google Scholar ]). Both recessive [ [2] Diggle C.P. Sukoff Rizzo S.J. Popiolek M. Hinttala R. Schülke J.P. Kurian M.A. Carr I.M. Markham A.F. Bonthron D.T. Watson C. Sharif S.M. Reinhart V. James L.C. Vanase-Frawley M.A. Charych E. Allen M. Harms J. Schmidt C.J. Ng J. Pysden K. Strick C. Vieira P. Mankinen K. Kokkonen H. Kallioinen M. Sormunen R. Rinne J.O. Johansson J. Alakurtti K. Huilaja L. Hurskainen T. Tasanen K. Anttila E. Marques T.R. Howes O. Politis M. Fahiminiya S. Nguyen K.Q. Majewski J. Uusimaa J. Sheridan E. Brandon N.J. Biallelic mutations in PDE10A lead to loss of striatal PDE10A and a hyperkinetic movement disorder with onset in infancy. Am. J. Hum. Genet. 2016; 98: 735-743 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar ] and dominant mutations [ [3] Mencacci N.E. Kamsteeg E.J. Nakashima K. R'Bibo L. Lynch D.S. Balint B. Willemsen M.A. Adams M.E. Wiethoff S. Suzuki K. Davies C.H. Ng J. Meyer E. Veneziano L. Giunti P. Hughes D. Raymond F.L. Carecchio M. Zorzi G. Nardocci N. Barzaghi C. Garavaglia B. Salpietro V. Hardy J. Pittman A.M. Houlden H. Kurian M.A. Kimura H. Vissers L.E. Wood N.W. Bhatia K.P. De novo mutations in PDE10A cause childhood-onset chorea with bilateral striatal lesions. Am. J. Hum. Genet. 2016; 98: 763-771 Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar ] in PDE10A have recently been found to cause an infantile/childhood-onset hyperkinetic movement disorder. In comparison to patients with dominant PDE10A mutations, the eight reported patients of two families with homozygous PDE10A mutations showed no striatal lesions on MRI but a more severe clinical presentation with a generalized hyperkinetic movement disorder characterized by limb and orofacial dyskinesia within the first six months of life, and mild cognitive impairment in some patients [ [2] Diggle C.P. Sukoff Rizzo S.J. Popiolek M. Hinttala R. Schülke J.P. Kurian M.A. Carr I.M. Markham A.F. Bonthron D.T. Watson C. Sharif S.M. Reinhart V. James L.C. Vanase-Frawley M.A. Charych E. Allen M. Harms J. Schmidt C.J. Ng J. Pysden K. Strick C. Vieira P. Mankinen K. Kokkonen H. Kallioinen M. Sormunen R. Rinne J.O. Johansson J. Alakurtti K. Huilaja L. Hurskainen T. Tasanen K. Anttila E. Marques T.R. Howes O. Politis M. Fahiminiya S. Nguyen K.Q. Majewski J. Uusimaa J. Sheridan E. Brandon N.J. Biallelic mutations in PDE10A lead to loss of striatal PDE10A and a hyperkinetic movement disorder with onset in infancy. Am. J. Hum. Genet. 2016; 98: 735-743 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar ]. Here we describe two sisters with a novel homozygous PDE10A mutation, presenting with a generalized hyperkinetic movement disorder. This is the first report showing improved clinical outcome of levodopa therapy.

PURPOSE:This study focuses on the following questions: What are the morphological features at the transdural course of radiculomedullary veins? How are these short transdural segments that may harbour pathological arteriovenous shunts connected to the internal vertebral venous plexus? Is the conception of a reflux-impeding mechanism at the transdural segment indispensable and convincing?METHODS:A total of 102 radiculospinal veins were studied microscopically at various levels of the spinal canal using serial paraffin and semi-thin sections. In addition, 26 vessels were investigated microangiographically following orthograde (12) or attempted retrograde (14) opacification of the intradural venous segment with barium sulphate. After paraplast-embedding, contact-microradiographs were taken using high-resolution spectroscopic plates.RESULTS:At their transdural course, the veins showed narrowing of their lumen accompanied by changes in the vessel wall composition and a tortuous course. Two structurally distinct arrangements of the transdural segment could be identified: A slit type was seen in 60% of the veins studied and a bulge- or nodular type was seen in 35% of the veins. In total, 5% of cases could not be assigned to either one of these types. Reflux to radicular veins from the outside of the dura mater could be produced in 2 out of 14 specimens. The extradural venous plexus, which primarily receives the radicular vein, was composed more frequently of lacunar spaces rather than plexiform blood vessel convolutions. Rare observations were fibrotic, blind ending radiculomedullary veins and continuation of a distinct venous blood vessel after crossing the dura.CONCLUSIONS:Reflux from the epidural plexus to radicular veins is not reliably stopped at the dural level and possibly physiological. Different arrangements of the transdural course of the veins appear to be at least appropriate to modulate flow. The purpose for two different types of radicular vein exit is unclear. The clinical impact of disturbed reflux-control is uncertain, which is in stark contrast to the severe consequences resulting from dural arteriovenous shunts. The functional role of the probably predominant epidural venous plexus for the spinal cord blood circulation remains poorly understood.

Purpose: To assess physiological spinal cord motion during the cardiac cycle compared with the influence of respiration based on magnetic resonance imaging (MRI) measurements.Materials and Methods: Anterior-posterior spinal cord motion within the spinal canal was assessed in 16 healthy volunteers (median age, 25 years) by cardiac-triggered and cardiac-gated gradient echo pulse sequence MRI. Image acquisition was performed during breath-holding, normal breathing, and forced breathing. Normal spinal cord motion values were computed using descriptive statistics. Breathing-dependent differences were assessed using the Wilcoxon signed-rank test and compared with the cardiac-based cord motion.Results: A normal value table was set up for the spinal cord motion of each vertebral cervico-thoracic-lumbar segment. Significant differences in cord motion were found between cardiac-based motion while breath-holding and the two breathing modalities (P < 0.01 each). Spinal cord motion was found to be highest during forced breathing, with a maximum in the lower cervical spinal segments (C5; mean, 2.1 mm +/- 1.17). Image acquisition during breath-holding revealed the lowest motion.Conclusion: MRI permits the demonstration and evaluation of cardiac and respiration-dependent spinal cord motion within the spinal canal from the cervical to lumbar segments. Breathing conditions have a considerably greater impact than cardiac activity on spinal cord motion.Key points:Cardiac-triggered and ECG-gated MRI allows for demonstration of the smallest spinal cord motions.Respiratory influences seem to have the highest impact on spine motion.In contrast, the influence of the cardiac cycle seems to be small.The smallest spinal cord motions were measured during breath-hold.

On conventional (non-contrast-enhanced) MR imaging signs of increased signal intensity in the central cord and enlarged subarachnoid flow voids are suggestive for the presence of a vascular spinal cord malformation. However, they provide no predictive information on the exact location of the malformation and thus additional imaging is warranted. At present, catheter angiography is still the standard of reference to image the arteries and veins of the spinal cord 1 and the preferred technique for diagnosing, localizing, and classifying vascular spinal lesions . Although it provides superior spatial resolution and image quality, catheter angiography has, however, several major drawbacks, as it is invasive, involves exposure to ionizing radiation, and has a small risk for major complications, including spinal cord infarction . In addition, it can often be time consuming and may require multiple catheterizations to locate the vascular spinal cord malformation. For these reasons, new imaging methods were searched and developed in order to non-invasively visualize the aberrant spinal cord vasculature. Recent advances in MR and CT angiography have strongly improved the vessel-to-background contrast by using fast acquisition in combination with contrast agent bolus injection and are now able to depict and differentiate normal from abnormal spinal cord vasculature. In this paper the relevant vascular radiological anatomy of the spinal cord is first briefly outlined. Subsequently, previously used and new spinal cord MR angiography techniques as well as CT angiography techniques will be discussed. Then the MR and CT angiography techniques will be compared for spinal cord angiography. To conclude an outlook is provided on possible future developments and applications of non-invasive spinal cord angiography.

BACKGROUND AND PURPOSE: The purpose of this work was to study the validity of MR angiography (MRA) for identification of spinal arteriovenous (AV) abnormalities. MATERIALS AND METHODS: Thirty-four consecutive patients with suspicion of spinal vascular abnormalities underwent digital subtraction angiography (DSA) after MRA. The level and side of the suspected spinal dural arteriovenous fistula (SDAVF) and the feeding arteries in spinal arteriovenous malformations (SAVMs) were determined from the MRA and compared with DSA. RESULTS: DSA revealed SDAVF in 20 abnormalities of which 19 were spinal and 1 was tentorial with spinal drainage, as well as SAVM in 11 patients. In 3 patients, MRA and DSA were both normal. For detection of spinal arteriovenous abnormalities, neither false-positive nor false-negative MRA results were obtained. The MRA-derived level of the feeding artery in SDAVF agreed with DSA in 14 of 19 cases. In 5 cases, a mismatch of 1 vertebral level (not side) was noted for the feeding artery. For the tentorial AVF, only the spinal drainage was depicted; the feeding artery was outside the MRA field of view. In intradural SAVM, the main feeding artery was identified by MRA in 10 of 11 patients. MRA could differentiate between glomerular and fistulous SAVM in 4 of 6 cases and between sacral SDAVF and filum terminale SAVM in 2 of 5 cases. CONCLUSIONS: MRA reliably detects or excludes various types of spinal AV abnormalities and localizes the (predominant) arterial feeder of most spinal AV shunts. Although classification of the subtype of SAVMs remains difficult, with MRA it greatly helps to focus subsequent DSA.

INTRODUCTION:The aim of the present investigation was to elucidate in a large consecutive patient cohort whether the level of training has an effect on the number of microemboli detected by diffusion-weighted imaging (DWI) and which additional risk factors can be identified.METHODS:A total of 107 consecutive patients in whom a diagnostic cerebral angiography had been performed were prospectively investigated with DWI; 51 angiographies were performed by experienced neuroradiologists, 56 by neuroradiologists in training.RESULTS:In 12 patients (11.1%), a total of 17 new lesions without any clinically overt neurological symptoms were identified. Of these, 12 patients, 11 (91.7%) with 16 lesions were investigated by junior neuroradiologists. In 11 of 12 patients with DWI abnormalities (91.7%), risk factors could be identified (atherosclerotic vessel wall disease, vasculitis, hypercoagulable states). Experienced neuroradiologists performed 21 of 48 angiographies (43.8%) on patients with the above-mentioned risk factors, whereas junior neuroradiologists performed 27 angiographies in this subgroup (46.2%). The rate of diffusion abnormalities in patients with risk factors was 11/48 (22.9%) - considerably higher than in patients without risk factors (1/59; 1.7%).CONCLUSION:The level of experience and the nature of the underlying disease are predictors of the occurrence of cerebral ischemic events following neuroangiography. Alternative diagnostic modalities should be employed in patients who are investigated for diseases with the highest risk of angiographic complications (i.e., vasculitis, and arteriosclerotic vessel wall disease). If diagnostic angiography remains necessary in these patients, the highest level of practitioner training is necessary to ensure good patient outcome.

BACKGROUND AND PURPOSE: Imaging of the anterior superficial spinal cord arteries by MR angiography is hindered by their small calibers and the similarity in configuration with the anterior superficial spinal cord veins. To validate the location and spatial configuration of the great anterior radiculomedullary artery, (ie, the Adamkiewicz artery [AKA]), contrast-enhanced MR angiography (CE-MRA) was compared with digital subtraction angiography (DSA).METHODS: Fifteen patients with suspected spinal cord vascular pathology underwent both spinal CE-MRA and selective spinal DSA. Two phase CE-MRA was performed with the use of a centric k-space filling scheme synchronized to the contrast bolus arrival. The level and side of the AKA origin were scored on the DSA and CE-MRA images and compared regarding image quality in terms of vessel conspicuity, contrast, continuity, sharpness, and background homogeneity on a relative 5-point scale.RESULTS: Localization and spatial configuration of the AKA by CE-MRA was in agreement with DSA findings in 14 of 15 cases. One mismatch of 1 vertebral level (not side) appeared as a result of the tangled vascular pathology. Comparison of image quality revealed that DSA is superior to CE-MRA concerning vessel continuity, sharpness, and background homogeneity (P <.001). Overall vessel conspicuity and contrast were judged to be similar.CONCLUSION: CE-MRA can visualize and localize the level of the AKA correctly. Image quality of CE-MRA is sufficient for detection of the AKA but is inferior to DSA.

We report on a 54-year-old man with megadolicho basilar artery presenting with acute signs of raised intracranial pressure due to a compromise of cerebrospinal fluid (CSF) flow at the level of the foramina of Monro by the basilar apex extending more than 3 cm cranially to the dorsum sellae. The diagnosis was confirmed on computed tomographic angiography and emergent CSF drainage relieved symptoms immediately.

BACKGROUND AND PURPOSEIn the anterior circulation, the hyperdense middle cerebral artery (MCA) sign is a well-established marker for early ischemia. Similarly, the hyperdense basilar artery sign or the MCA "dot" sign may be a diagnostic clue for basilar artery or distal MCA branch thrombosis. The purpose of this study was to define the hyperdense posterior cerebral artery (PCA) sign and determine its incidence, diagnostic value, and reliability as a marker for ischemia in the territory of the PCA.METHODSCranial computed tomographies (CCTs) of 48 patients with proven acute ischemia (<12 hours) in the PCA territory were compared by 3 independent and blinded readers to the CCTs of 86 age-matched patients without PCA infarction. Using follow-up imaging, the correlation of the hyperdense PCA (HPCA) with infarct size, thalamic infarction, and bleeding were investigated.RESULTSAn HPCA was found in 35.4% of all patients with PCA infarction, typically within the ambient cistern, with a specificity of 95.4%. The thalamus was affected significantly more often (P=0.009) and the size of the infarct was significantly more often large than medium (P=0.018) or small (P<0.001) when an HPCA was present. Hemorrhagic transformation tended to occur more often when the HPCA was present.CONCLUSIONSAn HPCA was detected in more than one third of all patients with PCA ischemia, suiting the incidence of the hyperdense MCA. Based on our results, this sign may not only be helpful in the early diagnosis of PCA infarction but might also act as a prognostic marker in acute PCA territory ischemic stroke.

The authors report on a 69-year-old man presenting with progressive leg weakness and gait ataxia over two years. A central intramedullary cord lesion ranging from T8-12 on MR imaging was misdiagnosed as a low-grade glioma and a biopsy was attempted followed by temporary clinical deterioration. Selective spinal angiography revealed a spinal dural arteriovenous (AV) fistula on the left L3 nerve root sheath despite the absence of pathological vessels on MR imaging. The fistula was successfully treated by microsurgical interruption of the arterialized intradural vein. The present case should remind us to include selective spinal angiography in our diagnostic work-up in patients predisposed for spinal dural AV fistula by male sex, advanced age and clinical presentation of slowly progressive sensorimotor symptoms with myelopathy on MR imaging, even in the absence of any pathological vascular structures.

Among spinal cord vascular malformations, dural arteriovenous fistulas (DAVFs) must be distinguished from intradural malformations. The concurrence of both is extremely rare. The authors report the case of a 35-year-old man who suffered from progressive myelopathy and who harbored both a DAVF and an intradural perimedullary fistula. During surgery, both fistulas were identified, confirmed, and subsequently obliterated. The fistulas were located at two levels directly adjacent to each other. Although the incidence of concurrent spinal DAVFs is presumed to be approximately 2%, the combination of a dural and an intradural fistula is exceedingly rare; only two other cases have been reported in the literature. One can speculate whether the alteration in venous drainage caused by the (presumably congenital) perimedullary fistula could possibly promote the production of a second dural fistula due to elevated pressure with concomitant venous stagnation and subsequent thrombosis. The authors conclude that despite the rarity of dual pathological entities, the clinician should be aware of the possibility of the concurrence of more than one spinal fistula in the same patient.

In small arteriovenous malformations (AVM) with large hematomas, surgery remains the main therapeutic option. However, intraoperative identification of the AVM, feeders, and draining veins could be difficult in the environment of substantial intracerebral blood. In those selected cases, we use navigated computed tomographic angiography (CTA) for the microneurosurgical management. It is our objective to report our initial experiences. Prior to operation a conventional CTA with superficial skin fiducials placed on a patient's head was acquired for diagnostic and neuronavigation purposes. Image data were transferred to a neuronavigation device with integrated volume rendering capacities which allows a three-dimensional reconstruction of the vascular tree and the AVM to be created. In all patients the AVM was removed successfully after having been localized with CTA-based neuronavigation. Navigated CTA is helpful for the operative management of small AVMs with large hematomas. The technique allows feeding arteries to be distinguished from draining veins thereby allowing the nidus of the AVM to be identified despite the presence of substantial intracerebral blood. CTA can be easily implemented into commercial neuronavigation systems.

Spinal dural arteriovenous fistula (SDAVF) is the most common spinal vascular malformation. It mainly affects men after the fifth decade and is usually an acquired lesion with an unknown etiology. We report on a patient with the unusual finding of two separate SDAVFs at the level of L1 on the right and L2 on the left side. Initial selective spinal digital subtraction angiography (DSA) was terminated with demonstration of a SDAVF at the level of L1 but incomplete demonstration of all segmental arteries. Due to a recurrent deterioration of the patient's neurological status, and persistent pathological vessels seen on MRI, a second spinal DSA was performed 6 years later, demonstrating the second fistula at the level of L2 on the left side with a separate venous drainage pattern. A retrospective analysis of the angiographic films suggested that both fistulas had already been present 6 years previously. This conclusion is justified because of a transient and faint opacification of the left L2 fistula demonstrated on the films after injection of the right L2 segmental artery. We conclude that in the case of incomplete angiography and persistent clinical and MR findings not only reopening of the treated SDAVF has to be taken into account but also the existence of a second fistula. Since this is the first case of a double fistula in our series of 129 SDAVFs, and given the few reported cases of double SDAVFs, we do not think that completion of selective spinal DSA has to be postulated routinely after a fistula has been found. However, repeat angiography should be performed in patients who continue to deteriorate, fail to improve with persisting MRI pathologies, or demonstrate delayed deterioration after a period of improvement.

We assessed the diagnostic accuracy of multislice CT in detection of intracranial aneurysms in patients presenting with subarachnoid or intracranial haemorrhage. Multislice CT and multiplanar digital subtraction angiography (DSA) images were obtained in 50 consecutive patients presenting with subarachnoid (SAH) and/or intracranial haemorrhage and reviewed by three neuroradiologists for the number, size and site of any aneurysms. The CT data were assessed using multiplanar reformats (MPR), maximum-intensity projections (MIP), surface-shaded display (SSD) and volume-rendering (VRT). In conventional angiography 51 aneurysms were detected in 41 patients. CT angiography (CTA) showed up to 48 aneurysms in 39 patients, depending on the observer. The overall sensitivity of multislice CT was 83.3% for small (<4 mm), 90.6% for medium-size (5–12 mm) and 100% for large (>13 mm) aneurysms. The sensitivity of multislice CTA to medium-size and large intracranial aneurysm is within the upper part of the range reported for helical single-slice CT. However, as small aneurysms may not be found, DSA remains the standard technique for investigation of SAH.

We report on a patient with fibromuscular dysplasia who presented with a right-sided giant calcified cavernous internal carotid artery (ICA) aneurysm and two additional supraophthalmic ICA aneurysms. Endovascular closure of the right ICA using detachable balloons was performed with collateralisation of the right hemisphere via the right-sided posterior communicating and the anterior communicating arteries. Repeat angiography after 6 months demonstrated spontaneous complete regression of the two supraophthalmic aneurysms, although the parent vessel was still perfused. In comparison to the former angiography, the flow within the parent vessel was reversed due to the proximal ICA balloon occlusion. MRI demonstrated that the aneurysms were not obliterated by thrombosis alone, but showed a real regression in size. This case report demonstrates that changes in cerebral hemodynamics potentially lead to plastic changes in the vessel architecture in adults and that aneurysms can be flow-related, even if not associated with high flow fistulas or arteriovenous malformations, especially in cases with an arterial wall disease.

Zielsetzung: Methoden: Resultate: Schlussfolgerung: Objective: Methods: Results: Conclusion: