Background: The diagnostic criteria for primary–progressive multiple sclerosis (PPMS) have undergone revision over the last 20 years. Cerebrospinal fluid oligoclonal bands (CSFOBs) have received less emphasis in recent revisions of the McDonald criteria. The aim of this study was to examine the sensitivity of the diagnostic criteria for PPMS with particular reference to spinal cord criteria and examine the utility of CSFOBs in a cohort of PPMS patients. Methods: All new PPMS diagnoses between 1990 and 2011 were identified. Baseline clinical details and paraclinical evaluations including MRI of the brain, spinal cord, CSF and visually evoked responses (VERs) were assessed. The proportion of patients who met the requirements for diagnosis of PPMS on the basis of Thompson’s and the McDonald Criteria (2001, 2005, 2010) were determined. Results: There were 88/95 PPMS patients who had at least two diagnostic investigations. The sensitivity of Thompson’s and the McDonald 2001 criteria was 64%; the McDonald 2010 revisions gave the highest sensitivity (77%); the McDonald 2005 criteria had intermediate sensitivity (74%). The combination of CSFOBs and MRI of the brain yielded the greatest number of patients demonstrating dissemination in space (DIS) on only two investigations. VERs did not aid diagnosis. Reducing requirements for the number of spinal cord lesions (symptomatic or not) to one increased diagnostic sensitivity to 84%. Conclusion: An alternative criterion requiring two of: i) MRI of the brain with one or more lesions in two of three regions typical for demyelination; ii) the presence of one T2-weighted spinal cord plaque (typical for demyelination); iii) CSFOBs; would increase the diagnostic sensitivity for PPMS.
To provide an overview and highlight recent updates in the field of paraneoplastic neurologic disorders.The prevalence of paraneoplastic neurologic disorders is greater than previously reported and the incidence has been rising over time, due to improved recognition in the era of antibody biomarkers. Updated diagnostic criteria that are broadly inclusive and also contain diagnostic risk for clinical presentations (high and intermediate) and diagnostic antibodies (high, intermediate, and low) have replaced the original 2004 criteria. Antibody biomarkers continue to be characterized (e.g., KLHL-11 associated with seminoma in men with brainstem encephalitis). Some paraneoplastic antibodies also provide insight into likely immunotherapy response and prognosis. The rise of immune checkpoint inhibitors as cancer therapeutics has been associated with newly observed immune-mediated adverse effects including paraneoplastic neurological disorders. The therapeutic approach to paraneoplastic neurologic disorders is centered around cancer care and trials of immune therapy. The field of paraneoplastic neurologic disorders continues to be advanced by the identification of novel antibody biomarkers which have diagnostic utility, and give insight into likely treatment responses and outcomes.
Abstract Colorectal carcinomas in ulcerative colitis patients are more commonly missed endoscopically compared to those in other symptomatic patients. They may present as flat lesions on a background of colitis, making them harder to visualise. Those presenting after negative colonoscopies are termed interval cancers, and account for up to 50% of colorectal cancers in patients with inflammatory bowel disease (IBD). Professional bodies recommend the use of chromoendoscopy for IBD surveillance to improve diagnostic yield by allowing targeted biopsies of non-polypoid lesions. We present an asymptomatic missed cancer in a patient with UC following a complete white light surveillance colonoscopy. After the sole endoscopic finding of a small, raised rectal lesion, found to be dysplastic, a CT scan incidentally demonstrated a missed ascending colon tumour. Had chromoendoscopy been used, this cancer may have been detected initially. This case report demonstrates that missed tumours remain a problem during surveillance endoscopy for IBD.
FDG PET diagnosis of primary intracranial lymphoma: radiology-pathology correlationA 61-year-old gentleman presented to the emergency department with fevers and ataxia.He had a 2-year history of haemophagocytic lymphohistiocytosis (HLH), a rare disorder associated with haematological malignancy, infection or autoimmune disease. 1 Magnetic resonance imaging (MRI) brain (Figure 1A) was performed and demonstrated symmetrical T2 high signal within the basal ganglia (arrows) and thalami (*).The differential diagnosis for this appearance is extensive, including toxic, metabolic, vascular, infective and neoplastic aetiologies.Given the background of HLH, lymphoma or infection (toxoplasmosis, viral encephalitis) were considered most likely.A pathological diagnosis was not possible and lumbar puncture was nondiagnostic, therefore 18 F-FDG brain PET (Figure 1B) was performed.This demonstrated marked FDG uptake within the basal ganglia and thalami, corresponding to the MRI findings (SUVmax (maximum standardized uptake value) of 15.4, reference 7.76 for normal brain 2 ), which is typical of primary central nervous system (CNS) lymphoma.
Abstract Cognitive difficulties are reported in up to 60% of people with MS (pwMS). There is often a discrepancy between self‐reported cognitive difficulties and performance on cognitive assessments. Some of this discrepancy can be explained by depression and fatigue. Pre‐MS cognitive abilities may be another important variable in explaining differences between self‐reported and assessed cognitive abilities. PwMS with high estimated premorbid cognitive functioning (ePCF) may notice cognitive difficulties in daily life whilst performing within the average range on cognitive assessments. We hypothesised that, taking into account depression and fatigue, ePCF would predict (1) differences between self‐reported and assessed cognitive abilities and (2) performance on cognitive assessments. We explored whether ePCF predicted (3) self‐reported cognitive difficulties. Eighty‐seven pwMS completed the Test of Premorbid Functioning (TOPF), the Brief International Cognitive Assessment for MS (BICAMS), self‐report measures of cognitive difficulty (MS Neuropsychological Questionnaire; MSNQ), fatigue (MS Fatigue Impact Scale; MFIS) and depression (Hospital Anxiety and Depression Scale; HADS). Results revealed that, taking into account covariates, ePCF predicted (1) differences between self‐reported and assessed cognitive abilities, p < .001 (model explained 29.35% of variance), and (2) performance on cognitive assessments, p < .001 (model explained 46.00% of variance), but not (3) self‐reported cognitive difficulties, p = .545 (model explained 35.10% of variance). These results provide new and unique insights into predictors of the frequently observed discrepancy between self‐reported and assessed cognitive abilities for pwMS. These findings have important implications for clinical practice, including the importance of exploring premorbid factors in self‐reported experience of cognitive difficulties.
Reported is a case of a man aged 55 years who presented with progressive spastic paraparesis. Examination demonstrated multiple cutaneous telangiectases. Subsequent development of upper limb weakness, acute urinary retention and eventual respiratory compromise resulted in the requirement for intensive care unit admission and mechanical ventilation. MRI spine revealed diffuse T2 hyperintensity in the cervical cord with enhancement and cord expansion. Immunomodulatory therapy for a presumed diagnosis of transverse myelitis yielded no response, so a vascular aetiology was suspected. Spinal angiography demonstrated an arteriovenous fistula involving the upper cervical cord. Endovascular embolisation was successfully performed and a marked clinical improvement was achieved. Cervical arteriovenous fistulas can cause progressive myelopathy, subarachnoid haemorrhage and brainstem dysfunction. Management typically comprises endovascular embolisation or surgical interruption. A clinical diagnosis of hereditary haemorrhagic telangiectasia was also made in this case, and spinal arteriovenous fistula formation has been associated with this condition.
Objective: To evaluate for longitudinal change in anti-JCV antibody index with natalizumab treatment. Background: Anti-JCV antibody index has recently been shown to differentiate PML risk in natalizumab-treated anti-JCV seropositive MS patients. Cross-sectional data has not established an association between anti-JCV antibody index and natalizumab therapy presence/duration, however an increase in index over time was demonstrated in one longitudinal study of natalizumab-treated patients. Methods: Anti-JCV antibody serostatus and index were collated from all natalizumab-treated MS patients in a university hospital since the introduction of the second-generation anti-JCV antibody assay (STRATIFY JCV Dx SelectTM) between February 2012 and July 2015. Analysis for changes in serostatus and median index were performed across sequential tests. Results: Data were available for 164 patients, with 415 results in total (272 (65.5[percnt]) seronegative, 143 (34.5[percnt]) seropositive). Of those, there were 251 pairs of sequential tests with a median inter-test interval of 6 months. An overall increase in median index of 0.013 (p=0.039) was demonstrated across all pairs. Change in serostatus was analysed for all those serially tested, with 21 (24.1[percnt]) demonstrating seroconversion and 8 of these (38.1[percnt]) subsequently seroreverting (median time to seroreversion 8 months). There were significant differences in baseline index in paired tests which demonstrated seroconversion versus those which remained negative (p=0.011), and in seroreverting pairs versus those remaining positive (p=0.004). Median index change in those with low positive (<0.9) index at baseline was significantly different to that in those with negative, medium (0.9-1.5) and high (>1.5) baseline index (p<0.0005), with a tendency for decreases in index with repeat testing in the former. There was no significant association between gender (p=0.741) or age category (p=0.25) and serostatus. Conclusions: Consistent with other recent longitudinal data, this analysis suggests that anti-JCV antibody index increases over time with natalizumab treatment.
It is accepted that a lumbar puncture (LP) and cerebrospinal fluid (CSF) biomarker analysis support the routine diagnostic work-up for the differential diagnosis of dementia due to Alzheimer's disease (AD) within certain patient cohorts1. These tests, which measure CSF protein concentrations of amyloid-β42 (Aβ42), total tau (t-tau) and phospho tau (p-tau), were recently validated, accredited and made available clinically for the first time in Ireland. A working group, comprising Irish clinical and scientific researchers, met to review a) the validation results; b) international consensus opinions, and c) research and clinical evidence as to the clinical utility of CSF biomarker analysis for AD dementia diagnosis. The outcome of this meeting was the formulation of a consensus statement paper for the benefit of health care professionals involved in the diagnosis and management of dementia to ensure appropriate use of these biomarker tests in clinical settings in Ireland.
OBJECTIVE: The causes of multiple cranial nerve palsies are widely varied and there is a broad differential. We describe a rare genetic cause of this presentation.
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