Previous work (Mayes et al., Hippocampus 12:325-340, 2002) found that patient YR, who suffered a selective bilateral lesion to the hippocampus in 1986, showed relatively preserved verbal and visual item recognition memory in the face of clearly impaired verbal and visual recall. In this study, we found that YR's Yes/No as well as forced-choice recognition of both intra-item associations and associations between items of the same kind was as well preserved as her item recognition memory. In contrast, YR was clearly impaired, and more so than she was on the above kinds of recognition, at recognition of associations between different kinds of information. Thus, her recognition memory for associations between objects and their locations, words and their temporal positions, abstract visual items or words and their temporal order, animal pictures and names of professions, faces and voices, faces and spoken names, words and definitions, and pictures and sounds, was clearly impaired. Several of the different information associative recognition tests at which YR was impaired could be compared with related item or inter-item association recognition tests of similar difficulty that she performed relatively normally around the same time. It is suggested that YR's familiarity memory for items, intra-item associations, and associations between items of the same kind was mediated by her intact medial temporal lobe cortices and was preserved, whereas her hippocampally mediated recall/recollection of these kinds of information was impaired. It is also suggested that the components of associations between different kinds of information are represented in distinct neocortical regions and that initially they only converge for memory processing within the hippocampus. No familiarity memory may exist in normal subjects for such associations, and, if so, YR's often chance recognition occurred because of her severe recall/recollection deficit. Conflicting data and views are discussed, and the way in which recall as well as item and associative recognition need to be systematically explored in patients with apparently selective hippocampal lesions, in order to resolve existing conflicts, is outlined.

SummaryBackgroundIntensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.MethodsWe did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001).InterpretationAmong patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice.FundingNational Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

Objectives: The sympathetic skin response (SSR) is a technique to assess the sympathetic cholinergic pathways, and it can be used to study the central sympathetic pathways in spinal cord injury (SCI). This study investigated the capacity of the isolated spinal cord to generate an SSR, and determined the relation between SSR, levels of spinal cord lesion, and supraspinal connections. Methods: Palmar and plantar SSR to peripheral nerve electrical stimulation (median or supraorbital nerve above the lesion, and peroneal nerve below the lesion) were recorded in 29 patients with SCI at various neurological levels and in 10 healthy control subjects. Results: In complete SCI at any neurological level, SSR was absent below the lesion. Palmar SSR to median nerve stimuli was absent in complete SCI with level of lesion above T6. Plantar SSR was absent in all patients with complete SCI at the cervical and thoracic level. In incomplete SCI, the occurrence of SSR was dependent on the preservation of supraspinal connections. For all stimulated nerves, there was no difference between recording from ipsilateral and contralateral limbs. Conclusions: No evidence was found to support the hypothesis that the spinal cord isolated from the brain stem could generate an SSR. The results indicate that supraspinal connections are necessary for the SSR, together with integrity of central sympathetic pathways of the upper thoracic segments for palmar SSR, and possibly all thoracic segments for plantar SSR.

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