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To the Editor: We read with interest the recent publication by Godeoroy and colleagues.1 The authors show that the Montreal Cognitive assessment (MoCA) with a cut-off of 27 (which is the cut-off used in memory clinics to detect mild cognitive impairment) detects more poststroke patients with cognitive impairment (82%) than does the Mini-Mental State Examination (MMSE; 45%). Godefroy et al1 show that the MoCA with a cut-off of 27 has a sensitivity of 1.00, but low specificity of 0.13. However, using a cut-off of 23 gives a sensitivity of 0.84, specificity of 0.81, positive predictive value of 0.91, and negative predictive value of 0.71. It is surprising that the final message from the authors is that the MMSE using a cut-off

The pathophysiology of stretch syncope is demonstrated through the clinical, electrophysiological, and hemodynamic findings in three patients. Fifty-seven attacks were captured by video/EEG monitoring. Simultaneous EEG, transcranial (middle cerebral artery) doppler, and continuous arterial pressure measurements were obtained for at least one typical attack of each patient. They all experienced a compulsion to precipitate their attacks. Episodes started with a stereotyped phase of stretching associated with neck torsion and breath holding, followed by a variable degree of loss of consciousness and asymmetric, recurrent facial and upper limb jerks in the more prolonged episodes. Significant sinus tachycardia coincided with the phase of stretching and was followed within 9-16 seconds by rhythmic generalized slow wave abnormalities on the EEG in attacks with impairment of consciousness. Transcranial doppler studies showed a dramatic drop in cerebral perfusion in the middle cerebral arteries during the episodes. The combination of the stereotyped semiology of the attacks, the pseudofocal myoclonic jerking, and the rhythmic generalized slow wave EEG abnormalities with the tachycardia make differential diagnosis from epilepsy challenging.

To evaluate the technical feasibility of an integrated ultrafast head magnetic resonance (MR) protocol using a sensitivity encoding (SENSE) technique for depicting parenchymal ischaemia and vascular compromise in patients with suspected recent stroke.23 patients were evaluated with the ultrafast MR protocol using T2, T1, fluid attenuated inversion recovery (FLAIR), 3D time of flight magnetic resonance angiography (MRA), and diffusion weighted imaging (DWI) sequences. These were compared with routine conventional MR sequences.One patient could not tolerate conventional imaging, although imaging using the three minute head SENSE protocol was diagnostic. Both conventional and ultrafast protocols were of similar diagnostic yield in the remaining patients. There were no significant differences in clinical diagnostic quality for the T1, T2, FLAIR, and DWI sequences. One MRA examination was of better quality when SENSE was used, owing to reduced motion artefacts and shorter imaging time.It is possible to undertake a comprehensive MR examination in stroke patients in approximately three to five minutes. Ultrafast imaging may become a useful triage tool before thrombolytic therapy. It may be of particular benefit in patients unable to tolerate longer sequences. Further work is necessary to confirm these findings in hyperacute stroke.

This report discusses a biopsy proven case of cerebral amyloid angiopathy, with additional prominent vascular inflammatory features, characterized by a rapidly progressive dementia and leukoencephalopathy, where the clinical and radiological abnormalities resolved rapidly with minimal therapeutic intervention. We propose the term cerebral amyloid inflammatory vasculopathy (CAIV) to describe this condition.

Chemokines have a pivotal role in the selective mediation and amplification of inflammation. The CNS vascular endothelial cells, which form part of the blood-brain barrier (BBB) and blood-retinal barrier (BRB), are ideally situated to present chemokines to circulating lymphocytes leading to their recruitment. Monocyte-chemoattractant protein-1 (MCP-1), also known as CCL2, a potent chemoattractant of T cells and monocytes, has been implicated in inflammatory and angio-proliferative brain and retinal disease. In this study, MCP-1 expression by CNS endothelial cells was investigated in vitro. Rat brain (GP8/3.9) and retinal (JG2/1) vascular endothelial cell lines expressed MCP-1 constitutively in vitro as assessed by immunocytochemistry and enzyme linked immunosorbant assay (ELISA). Upregulation of secreted MCP-1 was observed following activation with the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IFN-gamma, and was reduced following dexamethasone treatment. Functional chemotactic activity of brain and retinal endothelial cell supernatants was demonstrated in an in vitro chemotaxis assay, which was inhibited by anti-MCP-1 antibodies. These findings suggest that endothelial cell-derived MCP-1 plays a key role in leukocyte recruitment across the blood-brain and blood-retinal barriers in vivo.

The 2009 Dementia strategy promoted a ‘memory clinic in every town’. We investigated the patient mix seen in a neurology-led memory clinic. Retrospective review (2004, 2006, 2012) attendees to memory clinic. Prospective review memory clinic from October 2012–Dec 2013. Survey to neurologists in Specialist Interest Group in Cognition (ABN). Survey of local GPs. Results Percentage of attendees with benign memory complaints increased from 30% & 32% in 2004 and 2006 to 55% in 2012. Oct 2012–Dec 2013 >50% attendees do not have dementia or MCI. 9 responders: A mean of 27% of attendees of neurology-led memory clinics in the UK have ‘benign memory complaints’. The following terms were used: ▸ Attentional amnestic disorder, ▸ Attentional cognitive complaints, ▸ Worried well, ▸ Subjective memory complaints, ▸ Subjective memory impairment, ▸ Normal cognitive ageing, ▸ Hypocondrial, ▸ ‘Stress related.’ 4. GPs used; ‘worried well’, ‘benign senescent forgetfulness’, ‘Possible dementia’, ‘mild neurocognitive disorder’ and ‘late life forgetfulness’ & treated with antidepressants but also referred to psychology or memory clinic. People attending memory clinic frequently do not have dementia and currently there is no consensus for diagnostic label or treatment.

Chemokines are a rapidly expanding family of small, secreted, 8-12 kDa, heparin-binding chemotactic cytokines, which are important in the pathogenesis of immune-mediated inflammation in the central nervous system (CNS) (Karpus et al., 1994). Chemokines mediate the activation and directional migration of inflammatory cells, including neutrophils, monocytes, T-lymphocytes, basophils, and eosinophils, to sites of injury and inflammation (Baggiolini, 1998). To date, they are divided into at least four families depending on the presence and position of a conserved motif of four cysteine residues. The majority of known chemokines are members of the CXC (α-chemokine) or CC (β-chemokine) families. Two further classes of chemokines, C and CX3C, have recently been reported, of which lymphotactin and neurotactin, respectively, are the only known members (Taub, 1996; Baggiolini, 1998). α-chemokines primarily chemoattract neutrophils, whereas β-chemokines are associated with chronic inflammation and are primarily involved in the recruitment of monocytes and T-lymphocytes to sites of inflammation. The β-chemokines include macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemoattractant protein (MCP)-l, MCP-2, MCP-3, and RANTES (regulated upon activation, normal T-cell expressed and secreted) (Vaddi et al., 1996).

Clarification of the pathophysiological mechanisms of intra-arterial thromboembolism may lead to novel treatments for cerebrovascular disease. There is increasing evidence for the role of von Willebrand factor (VWF) cleaving protease (ADAMTS-13) in modulating the thrombotic cascade in high flow arterial settings. VWF multimers are rich in ultra large forms (ULVWF) which can rapidly bind its primary platelet receptor resulting in spontaneous aggregation of platelets. Under normal conditions, these ULVWF are regulated by rapid proteolysis converting them to smaller, less active forms. The protease responsible for cleavage of ULVWF is ADAMTS-13. We measured the ADAMTS-13 antigen and ADAMTS-13 activity levels in the plasma of consecutive patients with transient ischaemic attack (TIA), compared with nonstroke controls, in a hospital based TIA clinic. This was compared with VWF levels. Samples were analysed in the acute phase and at 3 months postevent. In our pilot study patients with partial anterior circulation type TIAs had significantly reduced ADAMTS-13 activity compared to controls (p=0.0394). No significant differences were seen between high- and low-risk ABCD2 scored patients. We did not observe any significant changes in VWF levels in our study sample. Our pilot study suggests a potential role for altered ADAMTS-13 activity in the pathophysiology of TIA.

Hormone Therapy and the Brain: a Clinical Perspective on the Role of Oestrogen. By v w henderson. (Pp 112, £28.00). Published by Parthenon Publishing Group, Carnforth, 2000. ISBN 1–85070–078–8. The role of sex steroids in neurological disease is a topic of importance in our aging population and very worthy of discussion. This book is set out in chapters focusing on different individual subspecialties, including dementia, vascular disease, and epilepsy, with an initial backdrop …

Matrix metalloproteinases (MMPs) have been implicated in the early breakdown of the blood-brain barrier in neuroinflammatory disease. Although expression of these enzymes by resident glial cells and recruited immune cells has been described, altered expression of MMPs by the CNS vascular endothelial cells may also contribute to barrier disruption. In the present study, the in vitro expression of MMP-2 and -9 as well as tissue inhibitor of metalloproteinase (TIMP)-2 by rat CNS microvascular endothelial cells has been determined and compared with that by endothelial cell lines derived from rat aorta and high endothelial venules. Primary cultures of rat brain microvascular endothelial cells as well as the rat brain (GP8/3.9) and rat retinal endothelial (JG2/1) cell lines constitutively expressed MMP-2, -9 and TIMP-2. In vitro activation of CNS endothelium with the pro-inflammatory cytokines, tumour necrosis factor-alpha and interleukin-1beta, resulted in selective upregulation of MMP-9 activity, whereas no significant changes were seen in MMP-2 or TIMP-2 levels at 24 h. The addition of dexamethasone partially inhibited the cytokine-induced upregulation of MMP-9. Treatment of GP8/3.9 brain endothelial cells with active MMP-9 caused subtle but distinct alterations in the expression of the junctional protein, ZO-1. Quantitative differences found between CNS and non-CNS endothelial cells in the expression of both MMP-2 and -9, and in the expression of TIMP-2 demonstrate that CNS vascular endothelium is functionally distinct from non-CNS endothelium. These results suggest that cytokine-induced upregulation of MMP-9 expression by the CNS vascular endothelium may play a role in the pathogenesis of blood-brain and blood-retinal barrier breakdown in vivo.