Concomitant granule cell neuronopathy in patients with natalizumab-associated PML

Granule cell neuronopathy (GCN) is a rare JC virus infection of the cerebellar granule cell neurons in immunocompromised patients. On brain imaging, GCN is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions. The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort. MRI scans from before, at the time of, and during follow-up after diagnosis of PML in 44 natalizumab-treated MS patients, and a control group of 25 natalizumab-treated non-PML MS patients were retrospectively reviewed for imaging findings suggestive of GCN. To assess and quantify the degree of cerebellar atrophy, we used a 4 grade rating scale. Three patients in the PML group showed imaging findings suggestive of GCN and none in the control group. In two of these PML patients, cerebellar atrophy progressed from grade 0 at the time of diagnosis of isolated supratentorial PML to grade 1 and 2 after 2.5 and 3 months, respectively, in the absence of infratentorial white mater lesions. The third patient had grade 1 cerebellar atrophy before diagnosis of infra- and supratentorial PML, and showed progression of cerebellar atrophy to grade 2 in the 3 months following PML diagnosis. None of the other eight patients with infratentorial PML lesions developed cerebellar atrophy suggestive of GCN. Three cases with imaging findings suggestive of GCN were detected among 44 natalizumab-associated PML patients. GCN may, therefore, be more common than previously considered in natalizumab-associated PML patients

Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4

Introduction Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis (RMS) since 2017. A full treatment course comprises two treatment cycles given 1 year apart, followed by two treatment-free years. The management of cladribine-treated patients beyond year 4 needs to be addressed as patients have now passed the initial 4 years since European Medical Agency approval. Areas covered A panel of neurologists and a neuroradiologist experienced in MS treatment/monitoring evaluated clinical trial data and real-world evidence and proposed recommendations for the management of cladribine-treated patients beyond year 4. Expert opinion Continuous monitoring of disease activity during the treatment-free period is important. Subsequent management depends on the presence or absence of inflammatory disease activity, determined in the absence of consistent guidelines via practice-driven neurological decision criteria. Persisting or newly occurring inflammatory disease activity is an indication for further treatment, i.e. either re-initiation of cladribine or switching to another highly effective disease-modifying therapy. The decision to retreat or switch should be based on clinical and radiological evaluation considering disease course, treatment history, and safety aspects. In the absence of disease activity, either retreatment can be offered, or the treatment-free period can be extended under structured monitoring

Beeldvormende diagnostiek bij dementie: inventarisatie van de praktijk binnen de Nederlandse geheugenklinieken

Doel Evaluatie van de toepassing van MRI en CT bij dementiediagnostiek binnen Nederlandse geheugenklinieken, met analyse van de keuze voor elke modaliteit. Opzet Een digitale enquête werd gemaild aan alle specialisten verbonden aan een Nederlandse geheugenkliniek (n = 235). Resultaten Respons was 64% (151): 85% geriaters, 13% neurologen en 2% anders, verdeeld over 69 klinieken. Voor beeldvorming kiest 40% wisselend CT of MRI, 37% kiest MRI, 19% CT, 4% CT én MRI. Keuzefactoren hierbij zijn: contra-indicaties voor MRI, lichamelijke beperkingen, leeftijd, vasculaire of oncologische voorgeschiedenis en wachttijd. Met alleen CT mist 87% informatie: vasculaire schade/witte stofafwijkingen, (hippocampus)atrofie en specifieke pathologie (o.a. metastasen, amyloïd-angiopathie). Aanvullend noemt men bij MRI een betere eigen beoordelingsvaardigheid. Bij slechts 50% bevat het CT-protocol coronale reconstructies, daarnaast lijken deze inconsequent te worden bijgeleverd. Beelden worden in 5% met scoringsschalen beschreven, 75% zegt dat er geen uniforme beoordeling plaatsvindt. Conclusie Bij de diagnostiek van dementie heeft men, conform de richtlijnen, een duidelijke voorkeur voor MRI-onderzoek. Dit is echter gebaseerd op verouderde literatuur en men is relatief onbekend met de huidige multislice CT-technieken. Deze CT biedt in geheugenklinieken mogelijk een goed alternatief voor MRI, maar wordt daarvoor nog onvoldoende met multiplanaire reconstructies geleverd. Verder behoeft verslaglegging door radiologen verbetering door uniformer scoringsschalen te gebruiken

Visual ratings of atrophy in MCI: prediction of conversion and relationship with CSF biomarkers.

Medial temporal lobe atrophy (MTA) and cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) pathology may aid the early detection of AD in mild cognitive impairment (MCI). However, the relationship between structural and pathological markers is not well understood. Furthermore, while posterior atrophy (PA) is well recognized in AD, its value in predicting conversion from late-onset amnestic MCI to AD is unclear. In this study we used visual ratings of MTA and PA to assess their value in predicting conversion to AD in 394 MCI patients. The relationship of atrophy patterns with CSF Aβ1-42, tau, and p-tau(181) was further investigated in 114 controls, 192 MCI, and 99 AD patients. There was a strong association of MTA ratings with conversion to AD (p < 0.001), with a weaker association for PA ratings (p = 0.047). Specific associations between visual ratings and CSF biomarkers were found; MTA was associated with lower levels of Aβ1-42 in MCI, while PA was associated with elevated levels of tau in MCI and AD, which may reflect widespread neuronal loss including posterior regions. These findings suggest both that posterior atrophy may predict conversion to AD in late-onset MCI, and that there may be differential relationships between CSF biomarkers and regional atrophy patterns

Improved in vivo detection of cortical lesions in multiple sclerosis using double inversion recovery MR imaging at 3 Tesla

Objective: To investigate the impact of a higher magnetic field strength of 3 Tesla (T) on the detection rate of cortical lesions in multiple sclerosis (MS) patients, in particular using a dedicated double inversion recovery (DIR) pulse sequence. Methods: Thirty-four patients with clinically isolated syndromes or definite MS were included. All patients underwent magnetic resonance imaging (MRI) at 1.5 T and 3 T, including T2-weighted turbo spin echo (TSE), fluid-attenuated inversion recovery (FLAIR) and DIR sequences. All images were analysed for focal lesions categorised according to their anatomical location. Results: The total number of detected lesions was higher at 3 T across all pulse sequences. We observed significantly higher numbers of lesions involving the cortex at 3 T using a DIR sequence. DIR at 3 T showed 192% more pure intracortical (p<0.001) and 30% more mixed grey matter-white matter lesions (p=0.008). No significant increase in cortical lesions could be detected on the FLAIR and T2-weighted images. Using the T2-weighted and FLAIR sequences, significantly more lesions could be detected at 3 T in the infratentorial, periventricular and juxtacortical white matter. Conclusion: DIR brain MR imaging at 3 T substantially improves the sensitivity of the detection of cortical lesions compared with the standard magnetic field strength of 1.5 T. © European Society of Radiology 2009

Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans

We evaluated the use of a mock scanner training protocol as an alternative for sedation and for preparing young children for (functional) magnetic resonance imaging (MRI). Children with severe mental retardation or developmental disorders were excluded. A group of 90 children (median age 6.5 years, range 3.65–14.5 years) participated in this study. Children were referred to the actual MRI investigation only when they passed the training. We assessed the pass rate of the mock scanner training sessions. In addition, the quality of both structural and functional MRI (fMRI) scans was rated on a semi-quantitative scale. The overall pass rate of the mock scanner training sessions was 85/90. Structural scans of diagnostic quality were obtained in 81/90 children, and fMRI scans with sufficient quality for further analysis were obtained in 30/43 of the children. Even in children under 7 years of age, who are generally sedated, the success rate of structural scans with diagnostic quality was 53/60. FMRI scans with sufficient quality were obtained in 23/36 of the children in this younger age group. The association between age and proportion of children with fMRI scans of sufficient quality was not statistically significant. We conclude that a mock MRI scanner training protocol can be useful to prepare children for a diagnostic MRI scan. It may reduce the need for sedation in young children undergoing MRI. Our protocol is also effective in preparing young children to participate in fMRI investigations

Impact of the McDonald Criteria 2017 on Early Diagnosis of Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis is a chronic immune mediated demyelinating disease leading to neurological disabilities that need to be diagnosed and treated early. Guidelines on multiple sclerosis diagnosis and monitoring experienced comprehensive changes over the last decades. The first McDonald criteria published in 2001 emphasized the importance of MR imaging but also recognized the role of cerebrospinal fluid diagnostics. The demonstration of an intrathecal immunoglobulin G synthesis is a well-established additional component and has a long tradition in the diagnosis of relapsing-remitting multiple sclerosis. However, the role of cerebrospinal fluid for diagnostic purposes was rather diminished in each revision of the McDonald criteria. In the latest revision of the McDonald criteria of 2017, the detection of an intrathecal immunoglobulin G synthesis as oligoclonal bands experienced a revival. Patients with the first clinical event suggesting multiple sclerosis who fulfill the criteria for dissemination in space can be diagnosed with relapsing-remitting multiple sclerosis when oligoclonal bands in cerebrospinal fluid are detected. The diagnostic sensitivity of these novel criteria with a focus on dissemination in time and oligoclonal bands as a substitute for dissemination in time was published in different cohorts in the last year and is of special interest in this review. Recently published data show that by applying the 2017 McDonald criteria, multiple sclerosis can be diagnosed more frequently at the time of first clinical event as compared to the 2010 McDonald criteria. The main effect was due to the implementation of oligoclonal bands as a substitute for dissemination in time. However, careful differential diagnosis is essential in patients with atypical clinical manifestations to avoid misdiagnoses