To assess the time course of brain atrophy and the difference across clinical subtypes in multiple sclerosis (MS).
The percent brain volume change (PBVC) was computed on existing longitudinal (2 time ...points) T1-weighted MRI from untreated (trial and nontrial) patients with MS. Patients (n = 963) were classified as clinically isolated syndromes suggestive of MS (CIS, 16%), relapsing-remitting (RR, 60%), secondary progressive (SP, 15%), and primary progressive (9%) MS. The median length of follow-up was 14 months (range 12-68).
There was marked heterogeneity of the annualized PBVC (PBVC/y) across MS subtypes (p = 0.003), with higher PBVC/y in SP than in CIS (p = 0.003). However, this heterogeneity disappeared when data were corrected for the baseline normalized brain volume. When the MS population was divided into trial and nontrial subjects, the heterogeneity of PBVC/y across MS subtypes was present only in the second group, due to the higher PBVC/y values found in trial data in CIS (p = 0.01) and RR (p < 0.001). The estimation of the sample sizes required for demonstrating a reduction of brain atrophy in patients in a placebo-controlled trial showed that this was larger in patients with early MS than in those with the progressive forms of the disease.
This first large study in untreated patients with multiple sclerosis (MS) with different disease subtypes shows that brain atrophy proceeds relentlessly throughout the course of MS, with a rate that seems largely independent of the MS subtype, when adjusting for baseline brain volume.
The diagnosis of rare diseases (RDs) is often challenging due to their rarity, variability and the high number of individual RDs, resulting in a delay in diagnosis with adverse effects for patients ...and healthcare systems. The development of computer assisted diagnostic decision support systems could help to improve these problems by supporting differential diagnosis and by prompting physicians to initiate the right diagnostic tests. Towards this end, we developed, trained and tested a machine learning model implemented as part of the software called Pain2D to classify four rare diseases (EDS, GBS, FSHD and PROMM), as well as a control group of unspecific chronic pain, from pen-and-paper pain drawings filled in by patients.
Pain drawings (PDs) were collected from patients suffering from one of the four RDs, or from unspecific chronic pain. The latter PDs were used as an outgroup in order to test how Pain2D handles more common pain causes. A total of 262 (59 EDS, 29 GBS, 35 FSHD, 89 PROMM, 50 unspecific chronic pain) PDs were collected and used to generate disease specific pain profiles. PDs were then classified by Pain2D in a leave-one-out-cross-validation approach.
Pain2D was able to classify the four rare diseases with an accuracy of 61-77% with its binary classifier. EDS, GBS and FSHD were classified correctly by the Pain2D k-disease classifier with sensitivities between 63 and 86% and specificities between 81 and 89%. For PROMM, the k-disease classifier achieved a sensitivity of 51% and specificity of 90%.
Pain2D is a scalable, open-source tool that could potentially be trained for all diseases presenting with pain.
Migrainous infarction is considered a rare complication of migraine. Although several studies reported silent brain lesions on neuroimaging in patients with migraine with aura, knowledge about lesion ...patterns in acute migrainous infarction is scarce. We investigated clinical and MRI characteristics in a series of patients with migraine-associated acute cerebral ischemia.
Seventeen patients among 8,137 stroke patients over an 11-year period were included. All had undergone a dedicated stroke workup including diffusion-weighted imaging (DWI) and a detailed assessment of clinical features and of vascular risk factors.
The majority of patients presented with prolonged aura symptoms (visual aura 82.3%, sensory dysfunction 41.2%, and aphasia 5.9%; median NIH Stroke Scale score 2). Presentation at hospital was significantly delayed after symptom onset (mean 33 hours). A total of 70.6% had acute ischemic lesions in the posterior circulation; the middle cerebral artery territory was affected in 29.4%. Small lesions were present in 64.7%; multiple lesions were found in 41.2%. No overlapping ischemic lesions of different vascular territories were found. The prevalence of a patent foramen ovale was high (64.7%).
This study supports previous observations that migrainous infarction mostly occurs in the posterior circulation, and in younger women with a history of migraine with aura. Acute ischemic lesions were often multiple and located in distinct arterial territories. As there were no overlapping ischemic lesions, hemodynamic compromise during the development of migraine is unlikely the cause of infarction. Differentiation between migrainous infarction and prolonged migraine aura is difficult and associated with delayed admission of patients.
Background and purpose
Diagnostic uncertainty is common in the emergency evaluation of neurological conditions such as acute confusional states, particularly for non‐neurologists. We aimed to ...investigate the clinical recognition process of transient global amnesia (TGA) before arrival at the hospital and in the emergency department (ED).
Methods
In this retrospective observational study, medical records of 365 patients with TGA were analysed concerning mode of arrival, symptoms and suspected diagnosis made by pre‐hospital medical care providers and the ED neurologist.
Results
More than half of the 248 patients who were evaluated before arrival at the hospital (N = 157, 63.3%) received a diagnosis of suspected stroke, whereas TGA was considered in only 16 patients (6.5%), with recognition of acute amnesia in 150 patients (60.5%) and disturbed orientation in 86 patients (34.7%). Repetitive questions by the patient were noted in 28 patients (11.3%). In contrast, in 355 patients (97.3%), TGA was considered the primary diagnosis by the ED neurologist. Diagnosis in the ED was achieved by documenting ongoing impairment of episodic verbal memory (100.0%), repetitive questions as a prominent ancillary finding (95.5%) and the lack of focal neurological symptoms (100.0%) or by carefully obtaining collateral history suggestive of anterograde memory disturbance (89.9%) and/or repetitive questions (85.7%).
Conclusion
Recognizing TGA crucially depends on identifying isolated anterograde episodic long‐term memory disturbance or its observable effects such as repetitive questions and actions.
The human hippocampus can be affected in a large variety of very different neurological diseases, of which acute ischemic stroke, transient global amnesia, epilepsy, and limbic encephalitis are the ...most common. Less frequent etiologies include various infections and encephalopathy of different origins. Clinical presentation notably comprises confusional state, altered vigilance, memory deficits of various extent and seizures. While in hypoxic or hypoglycemic encephalopathy, clinical presentation and surrounding circumstances provide some clues to reach the correct diagnosis, in the above-listed more common disorders, signs and symptoms might overlap, making the differential diagnosis difficult. This review presents recent studies using the diffusion-weighted imaging (DWI) technique in diseases involving the hippocampus.
References for the review were identified through searches of PubMed from 1965 to January 2011. Only papers published in English were reviewed. Full articles were obtained and references were checked for additional material where appropriate.
All pathologies affecting the hippocampus are associated with distinct lesion patterns on magnetic resonance imaging, and especially DWI has the ability to demonstrate even minute and transient hippocampal lesions. In acute ischemic stroke in the posterior cerebral artery territory, involvement of the hippocampal formation occurs in four distinct patterns on DWI that can be easily differentiated and correspond to the known vascular anatomy of the hippocampus. In the subacute phase after transient global amnesia (TGA), dot-like hyperintense lesions are regularly found in the lateral aspect of the hippocampus on DWI. The DWI lesions described after prolonged seizures or status epilepticus include unilateral or bilateral hippocampal, thalamic, and cortical lesions of various extent, not restricted to vascular territories. In limbic encephalitis, DWI lesions are only infrequently found and usually affect the hippocampus, uncus and amygdala. Furthermore, in some rare cases DWI lesions of different etiology may coexist.
In patients with diseases affecting the hippocampus, DWI appears to be useful in differentiating between underlying pathologies and may facilitate a definite diagnosis conducive to an optimal treatment. With a careful clinical examination, experience with the interpretation of DWI findings and knowledge of associated phenomena, it is indeed possible to differentiate between ischemic, ictal, metabolic, and TGA-associated findings.
The first Fe(III) qsal-X complex exhibiting abrupt complete spin crossover at 228 K with a hysteresis of 8 K, Fe(qsal-I)2OTf is reported. Structural studies of the MeOH solvate in the LS and HS state ...and at the spin transition are described.
The reaction of Fe(NCS)3 prepared in situ in MeOH with Hqsal-X (Hqsal-X = 5-X-N-quinolylsalicylaldimine) in CH2Cl2 yields the FeIII complexes, Fe(qsal-X)2NCS·solvent (X = F 1; X = Cl, 2, Br, 3 ...solvent = MeOH; X = I, solvent = 0.25CH2Cl2·0.5MeOH 4) in moderate to good yields. IR spectroscopy confirms that NCS− acts as a counteranion only and that the qsal-X ligand is bound to the FeIII centre. SQUID magnetometric studies reveal stepped hysteretic spin crossover in 1 and 2, which is abrupt in both steps in latter compound. Mössbauer spectroscopic studies of 1 and 2 support these conclusions. The bromo derivative, 3, undergoes half spin crossover up to 340 K while 4 is low spin at all temperatures measured. The spin transition temperature, T1/2 is found to increase on moving from F to Br. UV-Vis and NMR spectroscopic studies indicate that 1–4 have spin states intermediate between HS and LS in solution. Structural studies show that 1, 2 and 3 crystallize in triclinic P while 4 is in monoclinic P21/c. Crystallographic studies of 1 at 100, 200 and 270 K show that spin crossover proceeds from a LS–LS state through a LS–HS intermediate to a HS–HS state (LS = low spin, S = 1/2, HS = high spin, S = 5/2). Similar results are found for 3 although this time a LS–IS state exists at 123 K while a LS–HS state is found at 295 K (IS = intermediate spin state where partial spin crossover has occurred). Both 2 and 4 are found to have LS FeIII centres although the latter contains two crystallographically independent FeIII centres in the asymmetric unit. The crystal packing in 1–4 consists of extensive π–π interactions through the planar qsal-X ligands and CH∙∙∙X (X = O, halogen) and/or X∙∙∙π (X = halogen) interactions which result in pseudo 3D supramolecular networks. This results in high cooperativity in 1 and 2 and is probably responsible for the hysteretic stepped spin crossover in these compounds.
Multiple sclerosis is a disease continuum with an initial relapsing remitting course (RRMS) and secondary progression (SPMS) at later stages. Most of the hitherto approved treatments do not ...adequately control for the phase of secondary progression. Thus, early detection of SPMS conversion is a key issue to initiate SPMS-tailored treatment. In this context, assessment of cognitive functions and magnetic resonance imaging (MRI) both play an important role in the longitudinal follow-up of MS patients.
To elucidate the importance of cognitive testing and MRI for prediction and detection of SPMS conversion as well as to discuss strategies for disease monitoring and for optimizing treatment in standard clinical care, particularly in outpatient settings.
Review article based on a nonsystematic literature review.
Standardized cognitive testing can support early diagnosis of SPMS and facilitate disease monitoring. Annual application of sensitive screening tests, such as the Symbol Digit Modalities Test (SDMT) and Brief Visual Memory Test-Revised (BVMT‑R) or the entire Brief International Cognitive Assessment for MS (BICAMS) test battery are recommended in this context. The MRI evidence of persistent inflammatory activity within 3 years of diagnosis as well as evidence of cortical lesions are predictive for SPMS conversion. Standardized MRI monitoring for markers of progression can substantiate clinical and neurocognitive signs of SPMS conversion.
Multidisciplinary patient care involving careful clinical examination, neuropsychological testing and MRI monitoring is of great significance for the prediction of SPMS conversion and diagnostics. This enables early treatment adaptation, since pharmacological interventions in SPMS differ from those in RRMS. Continuous clinical, neuropsychological and MRI vigilance enable stringent monitoring of treatment outcomes with respect to neuroinflammatory and neurodegenerative activity as well as treatment-related complications.
PURPOSE: To demonstrate possible retinal damage caused by indocyanine green dye for staining of the internal limiting membrane in surgery for idiopathic macular hole.
METHODS: Consecutive ...interventional case series. We report on the ultrastructural findings of the internal limiting membrane in 10 eyes of 10 patients.
RESULTS: All specimens revealed not only the internal limiting membrane, but also some small amounts of retinal elements, such as the plasma membrane of Müller cells and other undetermined structures. This indicates a cleavage plane not exactly at the inner undulating aspect of the internal limiting membrane but within the innermost retinal layers.
CONCLUSION: Dilutions of indocyanine green as recommended in the literature may alter the structure of the retina to some degree. Possible factors responsible for this inadvertent action may include (1) concentration, (2) osmolarity pH, (3) time of tissue contact, and (4) mechanical factors from more forceful traction during peeling. Although functional consequences of these findings remain unclear as yet, factors that may induce damage to the innermost retina should be elucidated.
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