Long-term cognitive recovery following isolated bilateral infarction of the fornix presenting with amnesia.

Introduction: Isolated infarction of the fornix is a relatively rare stroke syndrome frequently associated with amnesia. The long-term cognitive outcome in cases of acute fornix infarction is poorly understood. This is largely due to the limited number of case studies that have documented cognitive outcomes beyond the acute recovery phase on quantifiable neuropsychological measures. We describe a patient who developed acute amnesia and was subsequently diagnosed on cerebral MRI with bilateral infarction in the anterior columns of the fornix. Method: Comprehensive neuropsychological review was undertaken prospectively at baseline, early and late phases of recovery. Results: At 9 months post-stroke, there was some reduction in the severity of memory dysfunction, but a significant anterograde amnesia persisted. Conclusion: This is one of the very few cases in the literature where neuropsychological function has been comprehensively and serially examined over the first year post-isolated bilateral fornix infarction. It is concluded that amnesia can persist well beyond 6 months in these cases, with associated functional impairment in daily life.

Smartphone-delivered approach bias modification for reducing harmful drinking amongst middle-older age adults: Secondary analyses of a single-arm pilot study.

INTRODUCTION: Novel, scalable, low-cost interventions are needed to reduce harmful drinking amongst middle-older adults. Approach bias modification (ApBM) is a promising form of cognitive training for preventing/reducing alcohol use that can be delivered via smartphone. This study explored the acceptability and preliminary effectiveness of smartphone delivered and personalised ApBM amongst Australians ≥55 years, an age cohort at risk of alcohol-related harms. METHODS: Secondary analyses in a middle-older adult subsample (≥55 years, n = 289) of an open-label pilot study using a retrospective, repeated measures design. We explored acceptability (adherence, user mobile acceptability ratings, free-text responses) and preliminary effectiveness (changes in drinking quantity and frequency, craving, dependence and proportion drinking within government-recommended guidelines) of two sessions/week over 4 weeks of evidence-based ApBM training, adapted to include personalisation and smartphone delivery amongst Australians ≥55 years. RESULTS: Although minor adaptations to training were suggested, the intervention was acceptable amongst survey completers, with 72% training adherence. Relative to baseline, there was a significant increase in the proportion of drinking within recommended single-session and weekly guidelines post-training (from 25% to 41% and 6% to 28%, respectively, p < 0.001), with past-week standard drinks significantly decreasing by 18% (p < 0.001) and significant reductions in drinking days, mean craving and dependence scores (p < 0.001). DISCUSSION AND CONCLUSIONS: Findings suggest smartphone ApBM is acceptable amongst middle-to-older aged Australians and may support this 'at risk' cohort to remain within government-recommended alcohol consumption guidelines to optimise healthy aging, although, in the context of a single-arm study, preliminary results should be interpreted cautiously.

Mood and Cognitive Trajectories Over the First Year after Mild Ischemic Stroke.

OBJECTIVES: Cognitive and mood dysfunction are major contributors to post-stroke disability. The longer-term trajectories of mood and cognition post-stroke remain unclear, as do which cognitive domains decline, improve, or remain stable after stroke, and in which patients. We aimed to characterize the cognitive trajectories of mild ischemic stroke survivors over one year compared to stroke-free controls, and to investigate whether symptoms of anxiety and depression were associated with cognitive function. MATERIALS AND METHODS: All participants were tested with a neuropsychological test battery at 3-months and 12-months post-stroke, assessing attention/processing speed, memory, visuospatial function, executive function, and language. Anxiety and depression symptomatology were also assessed at both timepoints. RESULTS: Stroke participants (N=126, mean age 68.44 years ±11.83, 87 males, median [Q1, Q3] admission NIHSS=2 [1, 4]) performed worse on cognitive tests and endorsed significantly higher depression and anxiety symptomatology than controls (N=40, mean age=68.82 years ±6.33, 25 males) at both timepoints. Mood scores were not correlated with cognitive performance. Stroke participants' scores trended higher across cognitive domains from 3- to 12-months but statistically significant improvement was only observed on executive function tasks. CONCLUSION: Stroke participants performed significantly worse than controls on all cognitive domains following mild ischemic stroke. Stroke participants only exhibited statistically significant improvement on executive function tasks between 3- and 12- months. Whilst anxiety and depression symptoms were higher in stroke participants, this was not correlated with cognitive performance. Further studies are needed to understand factors underlying cognitive recovery and decline after stroke.

Neurodegeneration Over 3 Years Following Ischaemic Stroke: Findings From the Cognition and Neocortical Volume After Stroke Study.

Background: Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippocampal volume (HV) loss over 3 years than controls. We examined whether stroke survivors who were cognitively impaired (CI) at 3 months following their stroke had greater brain volume loss than cognitively normal (CN) stroke participants over the next 3 years. Methods: Cognition And Neocortical Volume After Stroke (CANVAS) study is a multi-centre cohort study of first-ever or recurrent adult ischaemic stroke participants compared to age- and sex-matched community controls. Participants were followed with MRI and cognitive assessments over 3 years and were free of a history of cognitive impairment or decline at inclusion. Our primary outcome measure was TBV change between 3 months and 3 years; secondary outcomes were TBV and HV change comparing CI and CN participants. We investigated associations between group status and brain volume change using a baseline-volume adjusted linear regression model with robust standard error. Results: Ninety-three stroke (26 women, 66.7 ± 12 years) and 39 control participants (15 women, 68.7 ± 7 years) were available at 3 years. TBV loss in stroke patients was greater than controls: stroke mean (M) = 20.3 cm3 ± SD 14.8 cm3; controls M = 14.2 cm3 ± SD 13.2 cm3; [adjusted mean difference 7.88 95%CI (2.84, 12.91) p-value = 0.002]. TBV decline was greater in those stroke participants who were cognitively impaired (M = 30.7 cm3; SD = 14.2 cm3) at 3 months (M = 19.6 cm3; SD = 13.8 cm3); [adjusted mean difference 10.42; 95%CI (3.04, 17.80), p-value = 0.006]. No statistically significant differences in HV change were observed. Conclusions: Ischaemic stroke survivors exhibit greater neurodegeneration compared to stroke-free controls. Brain atrophy is greater in stroke participants who were cognitively impaired early after their stroke. Early cognitive impairment was associated greater subsequent atrophy, reflecting the combined impacts of stroke and vascular brain burden. Atrophy rates could serve as a useful biomarker for trials testing interventions to reduce post-stroke secondary neurodegeneration. Clinical Trail Registration: http://www.clinicaltrials.gov, identifier: NCT02205424.

Randomized controlled trial comparing magnetic marker localization (MaMaLoc) with wire-guided localization in the treatment of early-stage breast cancer.

Wire-guided localization (WGL) is the standard of care in the surgical treatment of nonpalpable breast tumors. In this study, we compare the use of a new magnetic marker localization (MaMaLoc) technique to WGL in the treatment of early-stage breast cancer patients. Open-label, single-center, randomized controlled trial comparing MaMaLoc (intervention) to WGL (control) in women with early-stage breast cancer. Primary outcome was surgical usability measured using the System Usability Scale (SUS, 0-100 score). Secondary outcomes were patient reported, clinical, and pathological outcomes such as retrieval rate, operative time, resected specimen weight, margin status, and reoperation rate. Thirty-two patients were analyzed in the MaMaLoc group and 35 in the WGL group. Patient and tumor characteristics were comparable between groups. No in situ complications occurred. Retrieval rate was 100% in both groups. Surgical usability was higher for MaMaLoc: 70.2 ± 8.9 vs. 58.1 ± 9.1, p < 0.001. Patients reported higher overall satisfaction with MaMaLoc (median score 5/5) versus WGL (score 4/5), p < 0.001. The use of magnetic marker localization (MaMaLoc) for early-stage breast cancer is effective and has higher surgical usability than standard WGL.

Real world implementation of a group-based memory rehabilitation program into stroke services: A knowledge translation evaluation.

BACKGROUND: Support for memory difficulties remains a significant unmet need for survivors of stroke. Memory skills group training of compensatory strategies can be effective for improving everyday memory function. However, access to these services remains limited. OBJECTIVES: We aimed to evaluate the fidelity, acceptability, and effectiveness of implementing an evidence-based memory group in real-world clinical settings, to establish a potentially scalable implementation model. METHODS: The program was facilitated at one acute and one community-based rehabilitation health service. Three clinical neuropsychologists received comprehensive training in facilitating the program. Implementation followed the Knowledge to Action framework, and implementation outcome measures included fidelity monitoring of adherence and competence, as well as clinician and participant reports of acceptability. The clinical effectiveness outcome was attainment of memory-specific goals using Goal Attainment Scaling at post-intervention and six-week follow-up. RESULTS: The training process resulted in full adherence to the program content and demonstration of all essential clinical competencies. The program was acceptable and enjoyable for the clinicians and participants (n= 19, 63% male, 73% ischemic stroke). Participants demonstrated high levels of goal attainment (>80% at follow-up), comparable in magnitude to previous controlled trials. CONCLUSIONS: The stroke memory skills program has the potential to be implemented successfully in real-world clinical settings using the Knowledge to Action framework, incorporating comprehensive clinician training.

Antegrade removal of a knotted ureteric stent: Case report and review of literature.

Ureteral stents are routinely used in urological practice for many indications including obstruction of ureter, ureteral stricture, prior to treatment with extracorporeal shock wave lithotripsy, and to promote healing following ureteral injury. Complications reported with ureteric stents include stent migration, stent rupture, encrustation, ureteral perforation, erosion, and fistulation. Knotting of an indwelling ureteral stent is a very rare complication, with fewer than 30 cases reported in the literature. Techniques for managing this complication include using a holmium laser to cut the knot, percutaneous antegrade removal, and gentle traction. We describe the case of a knotted stent and its removal along with a comprehensive literature review.

APOE ɛ4 Carriers Show Delayed Recovery of Verbal Memory and Smaller Entorhinal Volume in the First Year After Ischemic Stroke.

BACKGROUND: The apolipoprotein E (APOE) gene ɛ4 allele is a risk factor for Alzheimer's disease and cardiovascular disease. However, its relationship with cognition and brain volume after stroke is not clear. OBJECTIVE: We compared cognition and medial temporal lobe volumes in APOEɛ4 carriers and non-carriers in the first year after ischemic stroke. METHODS: We sampled 20 APOEɛ4 carriers and 20 non-carriers from a larger cohort of 135 ischemic stroke participants in the longitudinal CANVAS study. Participants were matched on a range of demographic and stroke characteristics. We used linear mixed-effect models to compare cognitive domain z-scores (attention, processing speed, executive function, verbal and visual memory, language, visuospatial function) and regional medial temporal lobe volumes (hippocampal, entorhinal cortex) between groups at each time-point (3, 12-months post-stroke), and within groups across time-points. APOE gene single nucleotide polymorphisms (SNPs; rs7412, rs429358) were genotyped on venous blood. RESULTS: APOEɛ4 carriers and non-carriers did not differ on any demographic, clinical, or stroke variable. Carriers performed worse than non-carriers in verbal memory at 3 months post-stroke (p = 0.046), but were better in executive function at 12 months (p = 0.035). Carriers demonstrated a significant improvement in verbal memory (p = 0.012) and executive function (p = 0.015) between time-points. Non-carriers demonstrated a significant improvement in visual memory (p = 0.0005). Carriers had smaller bilateral entorhinal cortex volumes (p < 0.05), and larger right sided and contralesional hippocampal volumes, at both time-points (p < 0.05). CONCLUSION: APOE ɛ4 is associated with delayed recovery of verbal memory function and reduced entorhinal cortex volumes in the first year after ischemic stroke.

Charting cognitive and volumetric trajectories after stroke: protocol for the Cognition And Neocortical Volume After Stroke (CANVAS) study.

RATIONALE: Globally, stroke and dementia are leading causes of disability and mortality. More than one third of stroke patients will develop dementia, but mechanisms are unclear. AIMS: The study aims to establish whether brain volume change is associated with poststroke dementia, and to elucidate potential causal mechanisms, including genetic markers, amyloid deposition and vascular risk factors. An understanding of whether - and in whom - stroke is neurodegenerative is critical for the strategic use of potential disease-modifying therapies. HYPOTHESES: That stroke patients will exhibit greater brain volume loss than comparable cohorts of stroke-free controls; and that those who develop dementia will exhibit greater brain volume loss than those who do not. DESIGN: Advanced brain imaging techniques are used to longitudinally measure brain volume and cortical thickness in 135 stroke patients. Concurrent neuropsychological testing will correlate clinical profile with these measures. PRIMARY OUTCOMES: Primary imaging end-point is brain volume change between three-months and three-years poststroke; primary clinical outcome is the presence of dementia at three-years. SECONDARY OUTCOMES: We will examine the correlations with the following variables: dementia subtype; physical activity levels; behavioral dysfunction as measured by patient and caregiver-reported scales; structural and functional brain connectivity disruption; apolipoprotein E; and specific neuropsychological test scores. DISCUSSION: Magnetic resonance imaging markers of structural brain aging and performance on neuropsychological tests are powerful predictors of dementia. We need to understand the trajectory of regional brain volume change and cognitive decline in patients after stroke. This will allow future risk stratification for prognostic counseling, service planning, and early therapeutic intervention.

Neurocognitive recovery in SMART syndrome: a case report.

INTRODUCTION: Stroke-like migraine attacks after radiation therapy, or SMART syndrome, is characterised by migraine-like headache with or without aura, transient neurological dysfunction, including seizures, and gyriform enhancement on magnetic resonance imaging (MRI) which resolves over a period of weeks. Detailed neuropsychological characterisation in SMART syndrome is lacking and there are no published data on the course and pattern of neurocognitive recovery. RESULTS: The acute clinical presentation was one of unstable, fluctuating neurocognitive disturbances, complicated by seizure activity, followed by a longer term lag in the recovery of focal neuropsychological deficits which, we believe, was due to the more slowly resolving cerebral effects of SMART. CONCLUSIONS: To our knowledge, this is the first case of SMART syndrome in which neuropsychological functioning has been comprehensively and serially examined. This case is also unique due to the development of complex partial seizures. We suggest that epileptiform activity during clinical seizures should not be regarded as inconsistent with a diagnosis of SMART, provided that the seizures do not explain the onset of the other clinical and radiological features.

The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies.

UNLABELLED: Neuroimaging is increasingly used to supplement the clinical diagnosis of dementia with Lewy bodies (DLB) by showing reduced occipital metabolism and perfusion and reduced striatal dopaminergic innervation. We aimed to optimize the interpretation of (18)F-FDG PET images for differentiating DLB from Alzheimer disease (AD) and to compare the results with dopamine transporter imaging using (123)I-beta-carbomethoxy-3ss-(4-iodophenyl)tropane ((123)I-beta-CIT) SPECT. METHODS: Fourteen subjects with a clinical diagnosis of DLB and 10 with AD underwent both (18)F-FDG PET and (123)I-beta-CIT SPECT. Four DLB and 1 AD diagnoses were subsequently confirmed at autopsy. Diagnostic accuracy was calculated for visual interpretation by 3 readers of standard 3-plane and stereotactic surface projection (18)F-FDG PET images, receiver-operating-characteristic analysis of regional (18)F-FDG uptake, and a cutoff value for the striatal-to-occipital binding ratio of beta-CIT defined by receiver-operating-characteristic analysis. RESULTS: Visual interpretation of 3-plane (18)F-FDG PET images had a sensitivity of 83% and specificity of 93% for DLB, slightly higher than the results with the stereotactic surface projection images. Regionally, hypometabolism in the lateral occipital cortex had the highest sensitivity (88%), but relative preservation of the mid or posterior cingulate gyrus (cingulate island sign) had the highest specificity (100%). Region-of-interest analysis revealed that occipital hypometabolism and relative preservation of the posterior cingulate both had a sensitivity of 77% and specificity of 80%. beta-CIT achieved 100% accuracy and greater effect size than did (18)F-FDG PET (Cohen d = 4.1 vs. 1.9). CONCLUSION: Both (18)F-FDG PET and (123)I-beta-CIT SPECT appear useful for the diagnosis of DLB, although the latter provides more robust results. The cingulate island sign may enhance the specificity of (18)F-FDG PET.

Management of vagal paraganglioma: is operative resection really the best option?

BACKGROUND: Vagal paragangliomas cannot be resected without sacrifice of the vagal nerve. The risk of bilateral vocal cord palsy has been reason to postpone treatment of this benign and slow growing neoplasm in hereditary cases. Postponement could be considered for solitary cases as well. METHODS: An institute-based review of 48 patients with vagal paragangliomas over the past 30 years was performed. RESULTS: Forty-eight patients with 58 vagal paragangliomas were studied. All but 4 patients had multiple paragangliomas and should be considered hereditary cases. The 10 patients that underwent an operation lost the vagal nerve; 60% of them had additional cranial nerve palsy postoperatively. In the group of patients who were followed for an average period of 8.5 years, 3 patients (8%) developed cranial nerve palsy. CONCLUSIONS: Aggressive treatment of vagal paragangliomas leads to unnecessary early loss of vagal nerve function. A period of clinical and radiologic follow-up preceding an operation may lead to prolonged preservation of voice and swallowing functions in these patients, without grave consequences for other lower cranial nerves.

Associated autoimmune diseases in patients with the Lambert-Eaton myasthenic syndrome and their families.

In view of the clustering of autoimmune diseases (AIDs), we studied the frequency and nature of additional AIDs in patients with the Lambert-Eaton myasthenic syndrome (LEMS) and their family members, in both small cell lung carcinoma (SCLC) related and non-tumour (NT) related cases. Additional AIDs in patients with LEMS were assessed by interviewing the patient and studying the medical record. Family histories up to second-degree family members were established by interviewing patients, controls and family members. Forty-four patients with LEMS were assessed, of whom eighteen (41%) had SCLC. In the NT group seven patients (27%) had an additional AID, in the SCLC group two (11 %) (p=0.20). Thyroid disorder (five patients) and insulin dependent diabetes mellitus (two patients) were the most common AIDs. AIDs were significantly more frequent in families of patients with NT-LEMS (64%) than in control families (27%) (p=0.002), which was not found in SCLC-LEMS (36%, p=0.53). Affected family members were linked to the NT-LEMS patient through the maternal line in all cases. In conclusion, AIDs were more frequently found in LEMS patients without a tumour and their families, which could not be shown for SCLC-LEMS. This suggests that NT-LEMS shares immunogenetic factors with other AIDs. In families of NT-LEMS, a remarkable preponderance of maternal inheritance was seen, as has been reported previously in myasthenia gravis.