Distinctive diffusion-weighted imaging features in late-onset genetic leukoencephalopathies.

Genetic leukoencephalopathies are inherited disorders characterized by progressive white matter involvement. Although most are paediatric conditions, late-onset adult leukoencephalopathies are being increasingly recognized. Adult leukoencephalopathies may present as neurodegenerative diseases with cognitive decline and motor symptoms. Similar to their paediatric counterparts, different adult leukoencephalopathies often have distinctive MRI appearances. In particular, DWI has been recently shown to demonstrate specific patterns of persistent diffusion restriction in several adult-onset leukoencephalopathies. As such, DWI may provide important clues to the diagnosis of adult-onset leukoencephalopathy. The purpose of this review is to discuss characteristic DWI features in some late-onset leukoencephalopathies.

Clinical vascular imaging in the brain at 7T.

Stroke and related cerebrovascular diseases are a major cause of mortality and disability. Even at standard-field-strengths (1.5T), MRI is by far the most sensitive imaging technique to detect acute brain infarctions and to characterize incidental cerebrovascular lesions, such as white matter hyperintensities, lacunes and microbleeds. Arterial time-of-flight (TOF) MR angiography (MRA) can depict luminal narrowing or occlusion of the major brain feeding arteries, and this without the need for contrast administration. Compared to 1.5T MRA, the use of high-field strength (3T) and even more so ultra-high-field strengths (7T), enables the visualization of the lumen of much smaller intracranial vessels, while adding a contrast agent to TOF MRA at 7T may enable the visualization of even more distal arteries in addition to veins and venules. Moreover, with 3T and 7T, the arterial vessel walls beyond the circle of Willis become visible with high-resolution vessel wall imaging. In addition, with 7T MRI, the brain parenchyma can now be visualized on a submillimeter scale. As a result, high-resolution imaging studies of the brain and its blood supply at 7T have generated new concepts of different cerebrovascular diseases. In the current article, we will discuss emerging clinical applications and future directions of vascular imaging in the brain at 7T MRI.

Current concepts in radiologic assessment of pediatric brain tumors during treatment, part 1.

Pediatric brain tumors differ from those in adults by location, phenotype and genotype. In addition, they show dissimilar imaging characteristics before and after treatment. While adult brain tumor treatment effects are primarily assessed on MRI by measuring the contrast-enhancing components in addition to abnormalities on T2-weighted and fluid-attenuated inversion recovery images, these methods cannot be simply extrapolated to pediatric central nervous system tumors. A number of researchers have attempted to solve the problem of tumor assessment during treatment in pediatric neuro-oncology; specifically, the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group was recently established to deal with the distinct challenges in evaluating treatment-related changes on imaging, but no established criteria are available. In this article we review the current methods to evaluate brain tumor therapy and the numerous challenges that remain. In part 1, we examine the role of T2-weighted imaging and fluid-attenuated inversion recovery sequences, contrast enhancement, volumetrics and diffusion imaging techniques. We pay particular attention to several specific pediatric brain tumors, such as optic pathway glioma, diffuse midline glioma and medulloblastoma. Finally, we review the best means to assess leptomeningeal seeding.

Do Lacunar Infarcts Have Different Aetiologies? Risk Factor Profiles of Lacunar Infarcts in Deep White Matter and Basal Ganglia: The Second Manifestations of ARTerial Disease-Magnetic Resonance Study.

BACKGROUND: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up. RESULTS: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter. CONCLUSIONS: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities.

MRI of Cerebellar Infarction.

BACKGROUND: MRI is the imaging modality of choice for diagnosing brain infarction. Because of few or atypical clinical symptoms and a relatively low sensitivity of CT scans, many cerebellar infarctions may be detected only with MRI. With adequate recognition of cerebellar infarction on MRI and prompt initiation or optimisation of preventive therapeutic measures, more dramatic strokes may be avoided in selected cases. SUMMARY: We first briefly review the clinical presentation of cerebellar infarctions, followed by a short refresher on cerebellar anatomy and pathophysiological mechanisms of cerebellar infarcts. Then, we review the arterial cerebellar perfusion territories recently made visible with territorial arterial spin labeling (ASL), followed by a discussion and illustration of the MRI appearance of cerebellar infarcts in different stages. Similar to large cerebellar infarcts, recent studies investigating volumetric MRI datasets have now shown that small cerebellar infarcts occur in typical spatial patterns, knowledge of which may help in the diagnosis of even the smallest of cerebellar infarcts on MRI. Key Messages: MRI is the modality of choice for diagnosing cerebellar infarction. The posterior inferior cerebellar artery (PICA)-territories can be visualised with super-selective territorial ASL MRI. The PICA supplies at least the medial part of the posterior cerebellar surface. Anterior inferior cerebellar artery-infarcts can be mistaken for lateral PICA-infarcts. Small infarcts typically affect the cortex and often present as incidental cavities. Subacute cerebellar infarcts may be missed on imaging due to a phenomenon called "fogging."

Misinterpretation of ischaemic infarct location in relationship to the cerebrovascular territories.

PURPOSE: Cerebral perfusion territories are known to vary widely among individuals. This may lead to misinterpretation of the symptomatic artery in patients with ischaemic stroke to a wrong assumption of the underlying aetiology being thromboembolic or hypoperfusion. The aim of the present study was to investigate such potential misinterpretation with territorial arterial spin labelling (T-ASL) by correlating infarct location with imaging of the perfusion territory of the carotid arteries or basilar artery. MATERIALS AND METHODS: 223 patients with subacute stroke underwent MRI including structural imaging scans to determine infarct location, time-of-flight MR angiography (MRA) to determine the morphology of the circle of Willis and T-ASL to identify the perfusion territories of the internal carotid arteries, and basilar artery. Infarct location and the perfusion territory of its feeding artery were classified with standard MRI and MRA according to a perfusion atlas, and were compared to the classification made according to T-ASL. RESULTS: A total of 149 infarctions were detected in 87 of 223 patients. 15 out of 149 (10%) infarcts were erroneously attributed to a single perfusion territory; these infarcts were partly located in the originally determined perfusion territory but proved to be localised in the border zone with the adjacent perfusion territory instead. 12 out of 149 (8%) infarcts were misclassified with standard assessments and were not located in the original perfusion territory. CONCLUSIONS: T-ASL with territorial perfusion imaging may provide important additional information for classifying the symptomatic brain-feeding artery when compared to expert evaluation with MRI and MRA.

Cerebellar cortical infarct cavities and vertebral artery disease.

INTRODUCTION: Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. METHODS: We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. RESULTS: Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. CONCLUSION: Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI.

Cerebellar Cortical Infarct Cavities: Correlation With Risk Factors and MRI Markers of Cerebrovascular Disease.

BACKGROUND AND PURPOSE: Small cerebellar infarct cavities have been recently found on magnetic resonance imaging (MRI) to preferentially involve the cerebellar cortex, but epidemiological studies are lacking. We aimed to determine the prevalence and risk factor profiles of cerebellar cortical infarct cavities (≤1.5 cm) as well as their association with MRI markers of cerebrovascular disease and functioning. METHODS: We analyzed the 1.5 Tesla MRI of 636 patients (mean age, 62±9 years; 81% men) from the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study. Logistic regression analyses were performed to estimate the associations of age, sex, vascular risk factors, MRI markers of cerebrovascular disease, and functioning with cerebellar cortical cavities, adjusted for age and sex. RESULTS: Cerebellar cortical infarct cavities occurred on MRI in 10% of patients and were significantly associated with age, intima-media thickness (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7), high levels of homocysteinemia (OR, 1.8; 95% CI, 1.0-3.3), cortical infarcts (OR, 2.9; 95% CI, 1.6-5.4), gray matter lacunes of presumed vascular origin (OR, 3.0; 95% CI, 1.6-5.8), brain stem infarcts (OR, 5.1; 95% CI, 1.9-13.6), and decreased brain parenchymal fraction (OR, 0.84; 95% CI, 0.74-0.94), but not with white matter hyperintensities (OR, 1.2; 95% CI, 0.8-1.8) or white matter lacunes of presumed vascular origin (OR, 1.1; 95% CI, 0.5-2.5). They were also associated with worse physical functioning (OR, 0.96; 95% CI, 0.94 to -0.99) [corrected] but not with mental functioning. CONCLUSIONS: Cerebellar cortical infarct cavities are far more common than previously assumed based on symptomatic case series and are associated with markers of atherothromboembolic cerebrovascular disease.

Ischaemic cavities in the cerebellum: an ex vivo 7-tesla MRI study with pathological correlation.

BACKGROUND: Small cerebellar cavities (≤15 mm) are often observed coincidentally in ageing subjects and have also been associated with migraine. Although generally assumed to be of ischaemic origin, descriptive imaging studies are sparse and imaging findings have not been correlated with histopathology. We aimed to investigate whether small ischaemic cavities in the cerebellum show characteristic infarct patterns that might be helpful for diagnostic imaging. METHODS: We examined 40 whole postmortem cerebella with 7-tesla MRI ex vivo for the presence of small ischaemic cavities. The scan protocol included a T2-, T2*- and fluid-attenuated inversion recovery-weighted sequence for all specimens. We investigated to which degree small ischaemic cavities affect the cortical, juxtacortical and/or deep subcortical regions of the cerebellum. In a subset of the cavities identified, we correlated the imaging data with histopathological findings. This was performed by cutting the particular cerebellar specimen into 5-mm-thick slices. Serial sections were performed if cavities remained unidentified macroscopically. RESULTS: Twenty-two cavities were seen on ex vivo MRI in 8 out of 40 examined cerebella. Twenty out of 22 cerebellar cavities were located in the cortex, and only 2 in the deep white matter, with no cavities located in the juxtacortical white matter. None of the 20 cerebellar cortical cavities showed extension into the juxtacortical white matter on MRI, although in 1 cortical cavity some surrounding gliosis was seen to extend into the juxtacortical white matter. Nine out of 22 cavities were sampled for pathological correlation, including 7 cerebellar cortical cavities and both cavities or lacunes in the deep white matter. Three out of 7 cortical and both the deep cavities were histopathologically verified as cavities of ischaemic origin, while the remaining cortical cavities could not be retrieved upon histopathologic examination. Some microscopic gliosis was seen to extend into the juxtacortical white matter of all confirmed cortical cavities. CONCLUSION: Knowledge of typical infarct patterns may facilitate the detection and characterisation of cerebellar ischaemic cavities in vivo. Cerebellar cortical cavities appeared to be much more common than deep cavities and presented on imaging as a full-thickness defect in the cerebellar cortex without extension in the adjacent white matter.

In vivo visualization of the PICA perfusion territory with super-selective pseudo-continuous arterial spin labeling MRI.

In this work a method is described to discern the perfusion territories in the cerebellum that are exclusively supplied by either or both vertebral arteries. In normal vascular anatomy the posterior inferior cerebellar artery (PICA) is supplied exclusively by its ipsilateral vertebral artery. The perfusion territories of the vertebral arteries were determined in 14 healthy subjects by means of a super-selective pseudo-continuous ASL sequence on a 3T MRI scanner. Data is presented to show the feasibility of determining the PICA perfusion territory. In 10 subjects it was possible to accurately determine both PICA perfusion territories. In two subjects it was possible to determine the perfusion territory of one PICA. Examples in which it was not possible to accurately determine the PICA territory are also given. Additionally, the high variability of the extent of the PICA territory is illustrated using a statistical map. The posterior surface of the cerebellum is entirely supplied by the PICA in six subjects. The most posterior part of the superior surface is supplied by the PICA in eight subjects, and the inferior half of the anterior surface in six subjects. The inferior part of the vermis is supplied by the PICA in all subjects. Two subjects were found with interhemispheric blood flow to both tonsils from one PICA without contribution from the contralateral PICA. With the method as presented, clinicians may in the future accurately classify cerebellar infarcts according to affected perfusion territories, which might be helpful in the decision whether a stenosis should be considered symptomatic.

Very small cerebellar infarcts: integration of recent insights into a functional topographic classification.

BACKGROUND: Very small cerebellar infarcts (diameter <2 cm) are a frequent finding on MRI. With an increasing scientific interest in cerebral microinfarcts, very small infarcts in the cerebellum deserve more of our attention as well. The goal of the present article was to review infarct terminology and mechanisms, as well as to critically appraise the current classification system for very small cerebellar infarcts. METHODS: A search strategy was designed to identify all relevant studies on very small cerebellar infarcts in the English language. This search was restricted to papers published up to February 21, 2013. Studies were initially identified from the MEDLINE/PubMed database using the search terms 'small cerebellar infarct', 'lacunar infarct', 'microinfarct', 'end zone infarct', 'border zone infarct', 'watershed infarct', 'territorial infarct', and 'nonterritorial infarct'. Furthermore, a similar search strategy was directed to identify all relevant articles on (descriptive and functional) neuroanatomy and neuroimaging of the cerebellum. RESULTS: Very small cerebellar infarcts have been referred to as lacunar infarcts, as junctional, border zone or watershed infarcts, as nonterritorial infarcts, as very small territorial or end zone infarcts, or simply as (very) small cerebellar infarcts. Since the original clinicoradiological study on these small infarcts, the classification into border zones remains in common use. This classification is based upon the assumption that these infarcts occur secondary to low flow in between arterial perfusion territories, where flow is believed to be the lowest. Later studies, however, have suggested occlusion of small (end-) arteries as a prerequisite for the pathogenesis of even small cerebellar infarcts, with low flow merely as a potential contributor. Therefore, it is likely that infarcts may as well occur in a nonborder zone distribution. Moreover, the classification into border zones may be considered unreliable since the location of border zones is highly variable among individuals and is not known in a particular patient. Recently, a functional topographic organization has been found in the cerebellum with evidence for a motor-nonmotor dichotomy between the anterior and posterior lobe. Since the cerebellar lobes can be easily and reliably distinguished with both CT and MRI, we recommend the classification of very small cerebellar infarcts according to topographic location. CONCLUSION: There are several fundamental concerns with the current classification of very small cerebellar infarcts according to border zones, which we would like to overcome by recommending a new classification system based on topography. This will allow for a reliable and reproducible way of classifying very small cerebellar infarcts and is expected to improve clinicoradiological correlation.

Anything but Little: a Pictorial Review on Anatomy and Pathology of the Cerebellum.

Despite its small size the cerebellum is an anatomically complex and functionally important part of the brain. Traditionally the cerebellum is viewed as a motor control structure entirely devoted to motor control and learning, but recent functional magnetic resonance imaging (fMRI) studies demonstrated significant involvement of the cerebellum in higher order cognitive functions. The anatomical complexity of the cerebellum is reflected by the several nomenclature systems that exist for the description of cerebellar anatomy. The cerebellum can be affected by a variety of pathological processes, including congenital, infectious and inflammatory, neoplastic, vascular, degenerative and toxic metabolic diseases. The purpose of this pictorial review is to (1) provide a general overview of cerebellar anatomy and function, (2) demonstrate normal cerebellar anatomy on imaging studies, and (3) illustrate both common as well as rare pathological conditions affecting the cerebellum.

Acute interstitial nephritis manifesting as a persistent nephogram.

We report a case of a 61-year-old woman who presented to the emergency department with high inflammatory parameters and acute renal failure. Marked enlarged kidneys with persistent nephrogram were found on contrast-enhanced computed tomography . Renal biopsy showed acute interstitial nephritis. Acute interstitial nephritis must be included in the differential diagnosis in patients presenting with a persistent nephrogram.

First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients.

Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, significantly prolonged survival compared to standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published yet regarding the effect of EV on brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old white male patient, who had been heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. After three cycles, the first evaluation showed a partial remission by RECIST v1.1, with a near complete response on the brain metastasis and disappearance of neurological symptoms. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and avelumab in maintenance. The patient achieved a complete response and received therapy for five months. Nevertheless, therapy was discontinued at the patient's request. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old white male patient also received EV after previous progression on cisplatin-gemcitabine and atezolizumab maintenance, followed by palliative whole-brain radiotherapy and two cycles of vinflunine. After three cycles of EV, there was a significant reduction in the brain metastases. The patient is currently still receiving EV. These are the first reports on the efficacy of EV in patients with urothelial carcinoma and active brain metastases.

Spinal Non-Hodgkin Lymphoma Mimicking Epidural Hematoma.

A patient, recently diagnosed with non-Hodgkin lymphoma, presented with acute tetraplegia after surgical cervical lymph node biopsy. MRI of the cervical spine demonstrated an epidural space-occupying lesion with compressive myelopathy. While epidural hematoma was the tentative diagnosis, intra-operatively non-Hodgkin lymphoma was found. Several factors may have accounted for the inaccurate interpretation of the MRI: the acute clinical presentation appearing shortly after surgery, the non-specific signal intensities of (hyper-) acute hematomas, the lack of contrast-enhanced images, and the absence of the FDG-avid spinal mass in the PET/CT-report. Without radiological features of invasiveness and contrast-enhanced images, careful interpretation is mandatory for space-occupying epidural lesions. Teaching Point: Caution is needed when interpreting an epidural space-occupying lesion in the absence of contrast-enhanced images.

Neuroradiological findings in three cases of pontocerebellar hypoplasia type 9 due to AMPD2 mutation: typical MRI appearances and pearls for differential diagnosis.

Pontocerebellar hypoplasia type 9 (PCH9) is a rare autosomal recessive neurodegenerative disorder with prenatal onset caused by mutations in adenosine monophosphate deaminase 2 (AMPD2). PCH9 patients demonstrate severe neurodevelopmental delay with early onset and typical magnetic resonance imaging (MRI) findings consisting in: pontine hypoplasia or atrophy with dragonfly cerebellar atrophy appearance on coronal images, reduction in size of the pons and middle cerebellar peduncles, abnormal midbrain describing a figure of "8" on axial images, diffuse loss of cerebral white matter with striking periventricular leukomalacia (PVL), and absence or extreme thinning of the corpus callosum. A review of the literature on PCH9 shows that the MRI phenotype observed in the series herein presented is similar to the eleven cases of PCH9 previously reported. Finally, the main radiological elements which differentiate this diagnosis from other PCH subtypes are described.