Anthony Pereira

Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis.

BackgroundIschemic leukoaraiosis (ILA) refers to diffuse T2-weighted white matter hyperintensity in the context of a previous clinical lacunar stroke. Reduced cerebral blood flow (CBF) in white matter has been demonstrated, but it is not known whether hypoperfusion is confined to lesions or extends into normal-appearing white matter. Demonstrating changes in normal-appearing white matter would provide clues to the importance of hypoperfusion in pathogenesis and would be an obvious target for therapies aimed at restoring white matter blood flow. MethodsTwenty-one patients with ILA, and 16 age-matched control subjects, underwent exogenous contrast-based quantitative perfusion MRI. CBF was determined both within and outside areas of T2-weighted hyperintensity in both periventricular white matter and the centrum semiovale. ResultsCBF of normal-appearing white matter was reduced in periventricular regions (for patients with ILA, 17.9 ± 5.6 mL/100 g/min; for controls, 21.6 ± 5.1 mL/100 g/min;p = 0.046). CBF in gray matter and normal-appearing white matter of the centrum semiovale did not differ significantly between groups. In normal-appearing white matter in patients, CBF was higher in the centrum semiovale than periventricular white matter, with a similar trend in control subjects. ConclusionsHypoperfusion may be an early feature in the development of periventricular lesions in ILA and may play a direct pathogenic role. Serial studies are now needed to determine whether these changes herald the appearance of new lesions and represent ‘at risk’ white matter, and to determine whether pharmacological agents can restore perfusion of normal-appearing white matter.

Restenosis After Carotid Angioplasty, Stenting, or Endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS)

Background and Purpose— Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) patients with carotid stenosis were randomized between endovascular treatment and endarterectomy. The rates of residual severe stenosis and restenosis and their contribution to recurrent symptoms was unclear. Methods— Endovascular patients were treated by balloon angioplasty alone (88%) or stenting (22%). Patches were used in 63% of endarterectomy patients. Carotid stenosis was categorized as mild (0% to 49%), moderate (50% to 69%), severe (70% to 99%), or occluded, using standardized Doppler ultrasound criteria at the examination closest to 1 month (n=283) and 1 year (n=347) after treatment. Recurrent cerebrovascular symptoms during follow-up were analyzed. Results— More patients had ≥70% stenosis of the ipsilateral carotid artery 1 year after endovascular treatment than after endarterectomy (18.5% versus 5.2%, P=0.0001). Residual severe stenosis was present in 6.5% of patients at 1 month after endovascular treatment. Between 1 month and 1 year, restenosis to ≥70% stenosis occurred in 10.5% of the endovascular group. After endarterectomy, 1.7% had residual severe stenosis at 1 month, and 2.5% developed severe restenosis. The results were significantly better after stenting compared with angioplasty alone at 1 month (P<0.001) but not at 1 year. Recurrent ipsilateral symptoms were more common in endovascular patients with severe stenosis (5/32 [15.6%]) compared with lesser degrees of stenosis at 1 year (11/141 [7.8%], P=0.02), but most were transient ischemic attacks and none were disabling or fatal strokes. There were no recurrent symptoms in the 9 endarterectomy patients with ≥70% stenosis at 1 year. Conclusions— Carotid stenosis 1 year after endovascular treatment is partly explained by poor initial anatomical results and partly by restenosis. The majority of patients were treated by angioplasty without stenting. Further randomized studies are required to determine whether newer carotid stenting techniques are associated with a lower risk of restenosis. The low rate of recurrent stroke in both endovascular and endarterectomy patients suggests that treatment of restenosis should be limited to patients with recurrent symptoms, but long term follow up data are required.

Delivering regional thrombolysis via a hub-and-spoke model:

Summary Objectives Audits in the United Kingdom and other countries show that only a small proportion of eligible stroke patients receive thrombolysis. Providing 24-hour thrombolysis cover presents major challenges in both infrastructure and staffing. One model for improving access is to provide out-of-hours cover in a regional centre but this may present problems including greater delays to hospital admissions. Design Evaluation of the introduction of a ‘hub-and-spoke’ model of thrombolysis to increase access to thrombolysis for patients in south west London. One-year data are presented. Setting A network in south-west London comprised of a hub hospital and three district ‘spoke’ hospitals. Participants All suspected stroke admissions to a regional stroke centre. Main outcome measures Thrombolysis rates for acute stroke. Results Increased out-of-hours thrombolysis rates were achieved with only a small increase in stroke admissions (approximately 10%) in the hub hospital. Thrombolysis rates increased from 1.2 per 100 stroke admissions for the local daytime service to 6 per 100 admissions for the regional service. Most patients thrombolysed were not local to the hub hospital. Only 1 in 4 patients considered for thrombolysis was thrombolysed, in line with previous data. Ten percent of all thrombolysis calls were not stroke but represented stroke mimics. Median length of stay was 6 days (target was 3 days). Fifty percent of the thrombolysed patients from spoke hospitals were discharged directly home. Conclusions In an urban area, a hub-and-spoke thrombolysis model increased access to thrombolysis without resulting in a marked increase in overall stroke admission numbers for the hub hospital. Proactive plans to repatriate patients back to district hospitals are required, and repatriation protocols have to prioritize regional patients over other targets in spoke hospitals to facilitate capacity in the hub hospital.

Magnetic resonance markers of ischaemia: their correlation with vasodilatory reserve in patients with carotid artery stenosis and occlusion

OBJECTIVES Better methods of identifying patients with asymptomatic carotid artery stenosis who are at high risk of stroke are required. It has been suggested that proton magnetic resonance spectroscopy (MRS) may allow the identification of ongoing ischaemia in this patient group by the detection of a potentially reversible reduction of N-acetyl aspartate (NAA), a presumed marker of neuronal integrity, and the presence of lactate, a marker of anaerobic metabolism. Previous studies have reported metabolite ratios rather than absolute concentrations. This study was performed to determine if NAA was reduced ipsilateral to carotid stenosis or occlusion, and if its concentration was related to carbon dioxide reactivity, a marker of cerebrovascular reserve. METHODS Twenty one patients with unilateral carotid stenosis (>70%) or occlusion were studied. Single voxel proton MRS was performed in the ipsilateral and contralateral hemispheres, with the voxel positioned in the arterial borderzone region between the middle and anterior cerebral artery territories. Absolute quantification of metabolite concentrations was performed. Cerebrovascular reactivity to 6% carbon dioxide was determined in both middle cerebral artery territories using transcranial Doppler ultrasonography. RESULTS Mean (SD) cerebrovascular reactivity was significantly lower in the stenosed compared with the contralateral hemisphere (13.3 (7.7)v 19.2 (8.2)%/kPa, p=0.002). There were no significant differences in the absolute concentrations of NAA, choline, or creatine between the ipsilateral and contralateral hemispheres (for example, NAA 10.1 (1.1) v 10.5 (1.1) mmol/l, p=0.1). No lactate peak was seen in any spectra. For each metabolite measured, there was no correlation between the absolute concentration and cerebrovascular reactivity for either hemisphere. CONCLUSIONS In patients with carotid stenosis and occlusion we found no evidence that chronic hypoperfusion is associated with a reduction in NAA or the presence of lactate. Magnetic resonance spectroscopy is unlikely to help in the selection of patients with asymptomatic carotid stenosis for endarterectomy.

Aspirin or heparin in acute stroke

Acute stroke treatment using aspirin and/or heparin was studied in the International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST) which randomised over 40,000 patients altogether. Combining the results demonstrated that aspirin (150-300 mg) given within 48 h of the onset of stroke produced a small but significant improvement in outcome (death or dependency) 4 weeks to 6 months after stroke of about 1 patient per 100 treated. There was a significant reduction in recurrent ischaemic stroke of similar degree, which was not associated with significant increase in cerebral haemorrhage. Therefore, aspirin should be used as early secondary prevention against recurrent stroke, after excluding cerebral haemorrhage by scanning the patient. Heparin does not improve clinical outcome after stroke even in patients in atrial fibrillation. It decreased recurrent ischaemic stroke significantly in IST, but at the cost of a significant increase in cerebral haemorrhage. Low molecular weight heparins and heparinoids have not proved any more beneficial. Therefore, heparin does not appear to be a useful routine therapy in acute stroke. The use of heparin should, therefore, be limited to patients at high risk of deep vein thrombosis or early recurrence.

Novel Genetic, Clinical, and Pathomechanistic Insights into TFG‐Associated Hereditary Spastic Paraplegia

Hereditary spastic paraplegias (HSPs) are genetically and clinically heterogeneous axonopathies primarily affecting upper motor neurons and, in complex forms, additional neurons. Here, we report two families with distinct recessive mutations in TFG, previously suggested to cause HSP based on findings in a single small family with complex HSP. The first carried a homozygous c.317G>A (p.R106H) variant and presented with pure HSP. The second carried the same homozygous c.316C>T (p.R106C) variant previously reported and displayed a similarly complex phenotype including optic atrophy. Haplotyping and bisulfate sequencing revealed evidence for a c.316C>T founder allele, as well as for a c.316_317 mutation hotspot. Expression of mutant TFG proteins in cultured neurons revealed mitochondrial fragmentation, the extent of which correlated with clinical severity. Our findings confirm the causal nature of bi‐allelic TFG mutations for HSP, broaden the clinical and mutational spectra, and suggest mitochondrial impairment to represent a pathomechanistic link to other neurodegenerative conditions.

Brief Report: Novel Genetic, Clinical and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia.

Hereditary spastic paraplegias (HSPs) are genetically and clinically heterogeneous axonopathies primarily affecting upper motor neurons and, in complex forms, additional neurons. Here, we report two families with distinct recessive mutations in TFG, previously suggested to cause HSP based on findings in a single small family with complex HSP. The first carried a homozygous c.317G>A (p.R106H) variant and presented with pure HSP. The second carried the same homozygous c.316C>T (p.R106C) variant previously reported and displayed a similarly complex phenotype including optic atrophy. Haplotyping and bisulfate sequencing revealed evidence for a c.316C>T founder allele, as well as for a c.316_317 mutation hotspot. Expression of mutant TFG proteins in cultured neurons revealed mitochondrial fragmentation, the extent of which correlated with clinical severity. Our findings confirm the causal nature of bi‐allelic TFG mutations for HSP, broaden the clinical and mutational spectra, and suggest mitochondrial impairment to represent a pathomechanistic link to other neurodegenerative conditions.

Localization of bilateral auditory hallucinations and correlation to imaging in posterior circulation stroke.

Hearing disturbances are not commonly reported in stroke or transient ischemic attack. We describe a case of a 60-year-old man with fluctuating brainstem ischemia with basilar artery thrombosis where the patient has consistently described hearing “white noise,” bilaterally becoming progressively louder over 10 minutes that prevented him from hearing surrounding noise including the radio. These episodes were transient and preceded episodes of hemiparesis or reduced conscious level. We correlate this to the sequential imaging findings from the patient. We discuss how this case provides in vivo evidence for localization of auditory hallucinations in the context of the auditory pathways and their blood supply, and review 25 previous cases of auditory hallucinations and possible mechanisms.

Acute neurology simulation training

Acute neurology is the neurological care that a patient receives in an emergency or urgent care situation. This can be adapted successfully to training in a simulation where learners are immersed in realistic scenarios in a safe, controlled and reproducible environment. In addition to teaching important technical skills that improve knowledge of the diagnosis and management of acute neurology, the simulation laboratory provides a valuable setting to improve human factors and non-technical skills, such as teamwork and leadership. Simulations are best conducted in a multiprofessional group with scenarios that allow different team members (nurses, physician associates, core medical and specialist trainees) to participate in their actual role. These training sessions require clear learning objectives, and involve designing the scenarios, running the session and ending with a structured debriefing to consolidate learning. The ultimate aim is to improve the team’s effectiveness to deliver safe acute neurological care in the emergency department and on the wards.

Acute neurology: a suggested approach

ABSTRACT 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 patients functional level and personal circumstances. Early neurology intervention can reduce admission and hospital length of stay.