Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study.

BACKGROUND: A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes. METHODS: For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 109 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 µg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3-6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis. FINDINGS: Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32-55) was lower than in the non-VITT group (57 years; 41-62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2-4) than non-VITT patients (two, 2-3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022). INTERPRETATION: Cerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate. FUNDING: None.

An Unusual Cause of Cranial Dural Thickening.

We describe an unusual cause of cranial dural thickening in an elderly female with a chronic meningeal inflammatory process. A 70-year-old ethnically Chinese, Singaporean female presented with a history of chronic daily headache with no other meningeal signs. Serial MRI brains showed progressive pachymeningeal and leptomeningeal enhancement in the left frontal region with underlying vasogenic oedema, similar appearances in the right frontal region to a lesser extent, and persistent inflammatory changes in her bilateral paranasal sinuses. Investigative work-up showed a chronically raised ESR with a normal CRP, negative ANCA, and a chronically raised serum IgA kappa paraprotein. Bone marrow trephine biopsy was suggestive of a low level plasma cell disorder. Olfactory cleft biopsy showed no evidence of IgG4-related disease or vasculitis and no significant plasma cell infiltrate. Histopathological examination from a meningeal biopsy revealed a diagnosis of an en-plaque meningioma (the WHO, 2016; Grade I) causing an unusual granulomatous reaction. We discuss the radiological and histological relations of this rare form of meningioma. Clinicians can consider en-plaque meningioma in the differential diagnosis of linear dural thickening and enhancement.

MOG-antibody-associated hypertrophic pachymeningitis.

BACKGROUND: The clinical spectrum of myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease is expanding. OBJECTIVE: To describe an unusual case of MOG-antibody-associated hypertrophic pachymeningitis (HP). METHODS: Case study. RESULTS: A 57-year-old female presented with a generalised seizure on a background of 3 months history of progressive cognitive decline and behavioural changes. Brain Magnetic Resonance Imaging (MRI) revealed widespread pachymeningeal enhancement and hyperintense signal in both hippocampi. Cerebrospinal Fluid (CSF) examination was normal. The patient was found positive for MOG-antibody. She clinically improved with steroids and the MRI abnormalities completely resolved. CONCLUSIONS: Clinicians might consider testing for MOG-antibody in cases with HP.

Case report: meningitis as a presenting feature of anti-NMDA receptor encephalitis.

BACKGROUND: Meningitis is a very rare atypical presenting feature of anti-NMDA receptor encephalitis. In our case report, we describe an unusual clinical presentation of anti-NMDA receptor encephalitis with a biphasic pattern of meningitis followed by encephalitis and discuss potential mechanisms underlying this presentation. We aim to widen the differential diagnosis to be considered in a patient presenting with clinical meningitis and pyrexia. CASE PRESENTATION: This is a case of a 33-year old Caucasian woman who initially presented with a lymphocytic meningitis attributed to a viral infection. She subsequently developed fluctuating consciousness, agitation, visual hallucinations, dyskinetic movements, a generalized tonic-clonic seizure, and autonomic instability. Investigations revealed a diagnosis of anti-NMDA receptor encephalitis secondary to a previously unidentified ovarian teratoma. She made an excellent recovery with immunotherapy and removal of the teratoma. CONCLUSION: Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative pathogen and there is rapid development of an encephalitic phenotype.

Seeing again: treatment of functional visual loss.

There is very little published literature on treatment strategies for functional visual loss. We present two people with long duration of functional visual loss who achieved complete recovery with a novel combination of therapeutic approaches. These included: (1) the clinician being transparent regarding positive signs such as optokinetic nystagmus, in order to persuade family members of the diagnosis, (2) regularly positively acknowledging everyday events that indicated visual ability, (3) using occipital transcranial magnetic stimulation to induce phosphenes as an artificial temporary visual experience and (4) using hypnotherapy to promote visual recovery. We discuss these individual therapeutic approaches in further detail including their background and rationale and include patients' reflection on their treatment experiences.

Antimicrobial stewardship: Improving antibiotic prescribing practice in a respiratory ward.

International efforts have mandated guidelines on antibiotic use and prescribing, therefore the focus is now on encouraging positive behavioral changes in antibiotic prescribing practice. Documentation of indication and intended duration of antibiotic use in drug charts is an evidence-based method of reducing inappropriate antibiotic prescribing. It is also a standard detailed in our local antimicrobial guidelines. We collected baseline data on compliance with documentation of indication and duration in drug charts in a respiratory ward which revealed compliance rates of 24% and 39% respectively. We introduced interventions to improve accessibility to the guideline and to increase awareness by distributing antibiotic guardian pocket cards with a three-point checklist and strategically-placed mini-posters. We also aim to increase team motivation by obtaining their feedback in multidisciplinary team meetings and by introducing certificates for their involvement in the quality improvement process. The results of the second cycle post-intervention showed an increase in compliance rates for documentation of indication and duration of 97% and 69% respectively. After a further awareness and discussion session at the multidisciplinary team meeting with the local antimicrobial management team audit nurses, a third cycle showed compliance rates of 94% and 71% for indication and duration respectively. This project has highlighted the importance of improving accessibility and of encouraging interventions that would bring about a change in personal value and subsequently in behavior and individual practice.

A systematic review and meta-analysis of (18)F-labeled amyloid imaging in Alzheimer's disease.

BACKGROUND: Amyloid imaging using fluorine 18-labeled tracers florbetapir, florbetaben, and flutemetamol has recently been reported in Alzheimer's disease (AD). METHODS: We systematically searched MEDLINE and EMBASE for relevant studies published from January 1980 to March 2014. Studies comparing imaging findings in AD and normal controls (NCs) were pooled in a meta-analysis, calculating pooled weighted sensitivity, specificity, and diagnostic odds ratio (OR) using the DerSimonian-Laird random-effects model. RESULTS: Nineteen studies, investigating 682 patients with AD, met inclusion criteria. Meta-analysis demonstrated a sensitivity of 89.6%, a specificity of 87.2%, and an OR of 91.7 for florbetapir in differentiating AD patients from NCs, and a sensitivity of 89.3%, a specificity of 87.6%, and a diagnostic OR of 69.9 for florbetaben. There were insufficient data to complete analyses for flutemetamol. CONCLUSIONS: Results suggest favorable sensitivity and specificity of amyloid imaging with fluorine 18-labeled tracers in AD. Prospective studies are required to determine optimal imaging analysis methods and resolve outstanding clinical uncertainties.

A systematic review and meta-analysis of retinal nerve fiber layer change in dementia, using optical coherence tomography.

INTRODUCTION: Retinal nerve fiber layer (RNFL) thinning, assessed by optical coherence tomography (OCT), has recently been reported in various dementias. METHODS: We conducted a systematic review and meta-analysis to investigate the diagnostic utility of RNFL thickness measurement using OCT in dementia (including Alzheimer's disease [AD] and mild cognitive impairment [MCI]) compared with healthy controls (HC). RESULTS: Seventeen studies comparing AD with HC (702 AD eyes and 790 HC eyes) were included, demonstrating a significant reduction in mean RNFL thickness in AD (weighted mean difference [WMD] 12.44, 95% confidence interval or CI [-16.64, -8.25], P <.0001). Five studies comparing MCI and HC (214 MCI eyes and 421 HC eyes) were included demonstrating a significant reduction in mean RNFL thickness in MCI (WMD -8.23, 95% CI [-14.00, -2.45], P =.005). No relevant studies were identified for other dementias. DISCUSSION: OCT measurement of RNFL thickness appears diagnostically useful in discriminating between AD, or MCI, and HC.

Systematic review of the diagnostic utility of SPECT imaging in dementia.

Single-photon emission-computed tomography (SPECT) may potentially contribute to the diagnostic work up of patients with neurodegenerative dementia. This systematic review aims to establish the diagnostic utility of 99mTc-hexamethylpropyleneamine (99mTc-HMPAO) and 99mTc-ethylcysteine dimer SPECT in distinguishing between Alzheimer's disease (AD) and frontotemporal dementia (FTD), AD and vascular dementia (VD), AD and dementia with Lewy bodies (DLB), and AD and normal controls (NC). We searched MEDLINE and Embase databases via OVID for articles from January 1985 to May 2012 and identified additional studies from reviews and references. Of 755 studies, 49 studies met the inclusion and exclusion criteria for this systematic review; AD versus FTD (n=13), AD versus VD (n=18), AD versus DLB (n=5), and AD versus NC (n=18). We compiled relevant data and graded the studies with an internal and external validity criteria checklist. We pooled the studies with a clinical diagnosis and those using 99mTc-HMPAO SPECT in a meta-analysis, calculating the pooled weighted sensitivity, specificity, likelihood ratios, and diagnostic odds ratios using DerSimonian-Laird random-effects model. The pooled weighted sensitivity and specificity of 99mTc-HMPAO-SPECT in distinguishing clinically diagnosed AD from FTD are 79.7 and 79.9%, respectively, AD from VD are 74.5 and 72.4%, AD from DLB are 70.2 and 76.2%, and AD from NC are 76.1 and 85.4%. SPECT does have diagnostic value, particularly in differentiating Alzheimer's disease from frontotemporal dementia and normal controls; however, it should not be used in isolation, rather as an adjunct, and interpreted in the context of clinical information and paraclinical test results.

The diagnostic utility of cerebrospinal fluid alpha-synuclein analysis in dementia with Lewy bodies - a systematic review and meta-analysis.

BACKGROUND: Dementia with Lewy Bodies (DLB) can be difficult to distinguish clinically from other dementias. OBJECTIVE: To investigate the diagnostic utility of CSF alpha-synuclein in differentiating between DLB and other dementias. METHODS: Electronic databases were systematically searched for studies investigating reproducible alpha synuclein quantification methods. Random effects model was used to calculate weighted mean difference (WMD) and 95% confidence intervals between DLB and other groups. RESULTS: A total of 13 studies, comprising 2728 patients were included. Mean CSF alpha-synuclein concentration was significantly lower in DLB patients compared to those with Alzheimers disease (AD) [WMD -0.24; 95% CI, -0.45, -0.03; p = 0.02]. No significant difference was found between patients with DLB compared to Parkinsons disease [WMD 0.05; 95% CI, -0.17, 0.28; p = 0.65] or other neurodegenerative conditions. CONCLUSION: CSF alpha synuclein may be of diagnostic use in differentiating between DLB and AD. We propose several recommendations to guide better design of future studies.