Hyperacute neurology at a regional neurosciences centre: a 1-year experience of an innovative service model.

St George's Hospital hyperacute neurology service (HANS) is a comprehensive, consultant-delivered service set in a teaching hospital regional neuroscience centre. The service addresses deficiencies in acute neurological care previously highlighted by the Royal College of Physicians and the Association of British Neurologists. HANS adopts a disease-agnostic approach to acute neurology, prioritising the emergency department (ED) management of both stroke and stroke mimics alike alongside proactive daily support to the acute medical unit and acute medical take. Rapid access clinics provide a means to assess ambulatory patients, providing an outlet to reduce the burden of referral from primary care to acute medicine. This paper reports the results from the first year of the service. Admission was avoided in 25% of the cases reviewed in the ED. Compared to historic data, there was a significant improvement in the length of stay for non-stroke disorders while the occupancy of stroke beds by non-stroke cases reduced by 50%. The configuration of this service is replicable in other neuroscience centres and provides a framework to reduce the barriers facing patients who present with acute neurological symptoms.

Acute neurology: a suggested approach.

Acute neurological problems are common, accounting for 10-20% of medical admissions. In the coming years, there will be increased neurology involvement in the acute care of these patients complementing traditional outpatient-based services. Models of acute neurology are reliant on close collaboration between the emergency department, acute medicine and neurology and should integrate with existing hyperacute stroke pathways. In this article the authors briefly describe the two models of acute neurology set up recently in our neuroscience group and suggest a clinical approach that may help non-neurologists involved in acute care settings. The authors emphasise some of the lessons learnt in delivering the service, particularly the importance of focusing on the acute problem and tailoring the examination and investigations to tackling it in the context of the patient's functional level and personal circumstances. Early neurology intervention can reduce admission and hospital length of stay.

Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study.

The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer's disease (AD), and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT) is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment (MCI) due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from MCI to dementia. Fifteen patients with MCI underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test "B" (TMT-B). At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen's d = 2.52). The predictive accuracies of the comparator measures were as follows: CSF tau/ß-amyloid1-42 ratio 92% (d = 1.81), RAVLT 64% (d = 0.41), TMT-B 78% (d = 1.56), and hippocampal volume 77% (d = 0.65). CSF tau levels were strongly negatively correlated with 4MT scores (r = -0.71). This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, non-invasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents, which may be more efficacious when given earlier in the disease course. By applying a test based on studies of hippocampal function in rodents to patient populations, this work represents the first step in the development of translatable biomarkers of hippocampal involvement in early AD for use in both animal models and human subjects.

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease.

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images. Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer's disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI). The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus. 4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of ≤8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55). In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series.

BACKGROUND: Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. OBJECTIVES: The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. METHOD: PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen's kappa. RESULTS: Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0-0.25 for PCA to 0.29-0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. CONCLUSION: The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice.

Diagnostic differentiation of mild cognitive impairment due to Alzheimer's disease using a hippocampus-dependent test of spatial memory.

The hippocampus is one of the earliest brain regions affected in Alzheimer's disease (AD) and tests of hippocampal function have the potential to detect AD in its earliest stages. Given that the hippocampus is critically involved in allocentric spatial memory, this study applied a short test of spatial memory, the 4 Mountains Test (4MT), to determine whether test performance can differentiate mild cognitive impairment (MCI) patients with and without CSF biomarker evidence of underlying AD and whether the test can distinguish patients with MCI and mild AD dementia when applied in different cultural settings. Healthy controls (HC), patients with MCI, and mild AD dementia were recruited from study sites in UK and Italy. Study numbers were: HC (UK 20, Italy 10), MCI (UK 21, Italy 14), and AD (UK 11, Italy 9). Nineteen UK MCI patients were grouped into CSF biomarker-positive (MCI+, n = 10) and biomarker-negative (MCI-, n = 9) subgroups. Behavioral data were correlated with hippocampal volume and cortical thickness of the precuneus and posterior cingulate gyrus. Spatial memory was impaired in both UK and Italy MCI and AD patients. Test performance additionally differentiated between MCI+ and MCI- subgroups (P = 0.001). A 4MT score of ≤8/15 was associated with 100% sensitivity and 90% specificity for detection of early AD (MCI+ and mild AD dementia) in the UK population, and with 100% sensitivity and 50% specificity for detection of MCI and AD in the Italy sample. 4MT performance correlated with hippocampal volume in the UK population and cortical thickness of the precuneus in both study populations. In conclusion, performance on a hippocampus-sensitive test of spatial memory differentiates MCI due to AD with high diagnostic sensitivity and specificity. The observation that similar diagnostic sensitivity was obtained in two separate study populations, allied to the scalability and usability of the test in community memory clinics, supports future application of the 4MT in the diagnosis of pre-dementia due to AD.

Fifty Percent Prevalence of Extracampine Hallucinations in Parkinson's Disease Patients.

Extracampine hallucinations (EH), the sense of a presence or fleeting movement in the absence of an associated visual percept, have been reported in Parkinson's disease (PD) patients but their prevalence, characteristics, and temporal relationship to visual hallucinations (VH) remain unclear. Given that, VH are predictive of cognitive impairment in PD, improved understanding of EH may have significant prognostic implications. The objective of this study is to evaluate the prevalence and characteristics of EH in a large unselected population with PD and to assess the temporal relationship between EH, VH, and memory decline. Cross-sectional data were collected from 414 PD patients using a questionnaire circulated via an online patient community. Data were obtained regarding the occurrence, timing, and characteristics of VH and EH and symptoms of PD, disease duration, disease severity, and medication history. About 50.4% of respondents reported EH and 15.5% reported VH. EH were typically experienced alongside, rather than behind, the individual (p < 0.001) without clear lateralization (p = 0.438) and were more likely to be of unfamiliar presences (p < 0.001). The occurrence of EH was associated with Hoehn and Yahr score (p = 0.002) but not disease duration (p = 0.158). EH onset was associated with VH onset (p = 0.046) and occurred after the onset of anosmia (p < 0.001), cognitive decline (p = 0.002), and sleep disturbance (p = 0.002). The reported prevalence of EH in PD patients was threefold greater than that of VH, with similar timings of onset, suggesting that EH are under-recognized and under-reported. Further work is needed to determine whether EH are predictive of cognitive decline.

Autoimmune limbic encephalitis presenting as relapsing psychosis.

A 34-year-old woman with a history of relapsing psychosis presented with a 15-month history of impassivity and social withdrawal associated with cognitive impairment. The subsequent recurrence of psychomotor agitation, auditory hallucinations and delusional thinking resulted in an emergency admission under psychiatric services. Initial investigations, including MRI of the brain and cerebrospinal fluid studies were unremarkable and she was treated for a primary psychiatric disorder. The diagnosis of autoimmune limbic encephalitis was established after further investigations revealed the presence of antibodies to the NR1 subunit of the N-Methyl-d-aspartate receptor (NMDAR). Immunotherapy resulted in rapid resolution of psychosis and marked improvement in cognitive and social function. This case underlines the importance of considering anti-NMDAR encephalitis within the differential diagnosis of psychosis associated with cognitive impairment even in those with an apparent previous psychiatric history and response to antipsychotics.

Sheehan syndrome associated with raised intracranial pressure.

UNLABELLED: Intracranial hypertension (IH) has been associated with hypocortisolism caused by either primary adrenocortical insufficiency or corticosteroid withdrawal. METHOD: The authors describe a case of IH in association with Sheehan syndrome (SS) in a postpartum 29-year-old woman. RESULTS: The clinical manifestations of IH resolved with corticosteroid replacement. CONCLUSIONS: This case supports a causal role of hypocortisolism in IH. The authors are unaware of previous reports of hypocortisolism caused by SS leading to IH.