Edward H.C. Wong

Acute Encephalopathy Associated with Influenza A Infection in Adults

We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios >3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis.

Significance of good collateral compensation in symptomatic intracranial atherosclerosis.

Background: Collateral circulation stabilizes cerebral blood flow in patients with acute occlusion, but its prognostic role is less studied in intracranial atherosclerosis and appears different in moderate to severe stenosis. We aimed to study the associations between antegrade flow across stenosis, collateral flow via leptomeningeal anastomosis, and the neurological outcome and recurrence risk in patients with symptomatic intracranial stenosis. Methods: We examined a cohort of consecutive patients admitted for stroke or transient ischemic attack (TIA) with symptomatic intracranial stenosis confirmed by digital subtraction angiography in a single-center retrospective study. Angiograms were graded systematically in a blinded fashion for antegrade and collateral flow, using Thrombolysis in Cerebral Infarction (TICI) and American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading, respectively, and integrated to a simple composite circulation score. Demographic and clinical variables, modified Rankin Scale (mRS) scores at 3 months, recurrent stroke or TIA in 12 months were collected. Uni- and multivariate analyses were performed to identify independent predictors of good outcome (mRS 0–2) and recurrence in a logistic regression model. Results: Among 69 patients with pure intracranial atherosclerosis ≥50%, compromised antegrade flow (TICI 0–2a) was observed in 26 (36%) patients and was associated with more severe arterial stenosis (mean 86 vs. 74%, p = 0.001). Poor collateral compensation resulting in a poor composite circulation score was observed in 8 (12%) patients. Patients with a good circulation score (n = 61, 88%) had preserved flow, which was associated with more favorable outcome (OR 7.50, 95% CI 1.11–50.7, p = 0.04) and less recurrent TIA or stroke (OR 0.18, 95% CI 0.04–0.96, p = 0.04). Prognosis was not significantly associated with antegrade or collateral grade per se. Conclusion: Good collateral compensations are more important in patients with symptomatic intracranial stenosis and compromised antegrade flow, and are associated with favorable outcome and less recurrence risk. The feasibility of composite flow assessment should be explored in future studies to identify high-risk intracranial stenosis with compromised hemodynamics.

Long‐term prognosis of Chinese patients with a lacunar infarct associated with small vessel disease: a five‐year longitudinal study

Rationale Lacunar infarct associated with small vessel disease is a common stroke subtype in China and has a favorable short-term prognosis. Data on its long-term prognosis among Chinese patients are lacking. Aims We aimed to study its long-term prognosis and predictors for poor outcomes. Design We followed up to 75 consecutive Chinese stroke patients who had a lacunar infarct for a period of 5 years. Clinical outcomes with respect to mortality and recurrent stroke were noted. We evaluated baseline clinical and imaging predictors for such outcomes using the Cox regression analysis. Study Outcomes Sixteen (21·3%) patients died and 12 (16%) patients had recurrent stroke during follow-up. Twenty-one (28%) patients had combined events of either death and/or recurrent stroke. Univariate Cox regression analysis showed that age, literacy, National Institute of Health Stroke Scale, incident stroke/transient ischemic attack, and white matter lesion volume predicted survival, while, age, National Institute of Health Stroke Scale, systolic blood pressure, hyperhomocysteinemia, silent lacunes, microbleeds, and white matter lesion volume predicted recurrent stroke. Multivariate Cox regression analysis showed that National Institute of Health Stroke Scale (HR 1·25, 95% CI 1·05–1·48) and white matter lesion volume (HR 1·46, 95% CI 1·11–1·92) predicted combined events of mortality and/or recurrent stroke after age adjustment. Conclusion Approximately one in four patients either died and/or had recurrent stroke within 5 years after a lacunar infarct. Age, stroke severity, and volume of white matter lesion predict a poor long-term prognosis.

A Man with Labile Blood Pressure

Ronald Ma and colleagues discuss the differential diagnosis and management of a patient who presented with recurrent episodes of chest discomfort, palpitations, and labile blood pressure.

Persistent Benign Oligemia Causes CT Perfusion Mismatch in Patients with Intracranial Large Artery Occlusive Disease during Subacute Stroke

CT perfusion (CTP) imaging provides quantitative parameters of cerebral perfusion using cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). It is increasingly being used in selecting patients for thrombolytic therapy [1,2]. Penumbra is usually characterized as the mismatch area with increased or normal CBV and prolonged MTT [3]. MTT ratio (symptomatic ipsilateral MTT compared with the contralateral side), with a threshold more than 145%, affords the most accurate delineation of the tissue at risk of infarction [4]. The recently published study [5] described the concept of benign oligemia at acute phase of stroke and distinguished it from penumbra. Intracranial large artery occlusive disease (ICAD) accounts for about one quarter to one-third of all stroke patients in Asians [6,7]. Little is known about the clinical significance of the mismatch shown on CTP in patients with ICAD during subacute stroke. Will the mismatch area be persistent? Is it a real penumbra? In the present study, consecutive stroke patients who were referred for CTP in the Prince of Wales Hospital, Hong Kong, in 2009 were screened. Inclusion criteria were as follows: (1) baseline CT angiography (CTA), CTP, and/or additional vascular imaging magnetic resonance angiography (MRA), (2) ICAD was diagnosed when CTA and MRA showed stenosis or occlusion of intracranial large artery, (3) with infarction in corresponding middle cerebral artery (MCA) territory in acute (within 1 day) and subacute group (more than 1 day) of ischemic stroke, and (4) more than 20% mismatch on CTP. Exclusion criteria were as follows: (1) bilateral intracranial occlusive stenosis, (2) unsatisfactory quality of CTP studies, (3) with document source of embolism from cardiac or extracranial artery, and (4) unclear clinical data. CT perfusion was performed on a multidetector scanner (GE Healthcare, Tokyo, Japan), as a 60-second cine series, beginning 5 seconds after a 50-mL injection of IOP300. Source images were transferred to a workstation and were evaluated with CT Perfusion 3 software (GE Healthcare). To obtain arterial input and venous output, we placed 3to 5-pixel squared regions in unaffected large artery (such as anterior cerebral artery) and vein (such as superior sagittal sinus) respectively. Bilateral MCA territories were circled as region of interest. Any area of old infarct was excluded. SPSS 12.0 (SPSS Inc, Chicago, IL, USA) was performed for statistical analyses. In all analyses, nonparametric Mann– Whitney U-test was used for comparison of continuous variables, and chi-squared test was used for categorical variables. Values were considered significantly different with P < 0.05. Thirty-four stroke patients with ICAD and infarction in relevant MCA territory were screened. Four patients were excluded due to poor quality image or incomplete data, and ten patients were excluded due to less than 20% mismatch. Finally, fourteen patients were enrolled in subacute group and six in acute group. An example of mismatch area was shown in Figure 1. Table 1 demonstrated the characteristics of recruited patients and the value of CTP-related parameters. Due to small sample size, the patients in acute group were older and severer than those in subacute group. The median time between CTP and onset of symptom

Angiographic Features, Collaterals, and Infarct Topography of Symptomatic Occlusive Radiation Vasculopathy A Case-Referent Study

Background and Purpose— Occlusive radiation vasculopathy (ORV) predisposes head-and-neck cancer survivors to ischemic strokes. Methods— We analyzed the digital subtraction angiography acquired in 96 patients who had first-ever transient ischemic attack or ischemic strokes attributed to ORV. Another age-matched 115 patients who had no radiotherapy but symptomatic high-grade (>70%) carotid stenoses were enrolled as referent subjects. Digital subtraction angiography was performed within 2 months from stroke onset and delineated carotid and vertebrobasilar circulations from aortic arch up to intracranial branches. Two reviewers blinded to group assignment recorded all vascular lesions, collateral status, and infarct pattern. Results— ORV patients had less atherosclerotic risk factors at presentation. In referent patients, high-grade stenoses were mostly focal at the proximal internal carotid artery. In contrast, high-grade ORV lesions diffusely involved the common carotid artery and internal carotid artery and were more frequently bilateral (54% versus 22%), tandem (23% versus 10%), associated with complete occlusion in one or both carotid arteries (30% versus 9%), vertebral artery (VA) steno-occlusions (28% versus 16%), and external carotid artery stenosis (19% versus 5%) (all P<0.05). With comparable rates of vascular anomaly, ORV patients showed more established collateral circulations through leptomeningeal arteries, anterior communicating artery, posterior communicating artery, suboccipital/costocervical artery, and retrograde flow in ophthalmic artery. In terms of infarct topography, the frequencies of cortical or subcortical watershed infarcts were similar in both groups. Conclusions— ORV angiographic features and corresponding collaterals are distinct from atherosclerotic patterns at initial stroke presentation. Clinical decompensation, despite more extensive collateralization, may precipitate stroke in ORV.

Stroke Caused by Small Vessel Occlusion in a Patient Taking Etoricoxib and Thalidomide

We report a 33‐year‐old man with seronegative arthritis who had an acute infarct at the left lentiform nucleus while taking etoricoxib and thalidomide regularly. Extensive investigations did not find any evidence of large artery atherosclerosis, vasculitis, cardioembolic source or anti‐phospholipid antibodies. While it is possible that a short smoking history, hyperlipidemia, and the use of thalidomide could have contributed to the thrombosis of a small penetrator vessel, we postulated that the prolonged use of etoricoxib is another possible contributing factor.

Intravenous alteplase for Chinese patients with stroke and borderline eligibility.

Lack of efficacy and safety data among Chinese patients with stroke have contributed to the slow development of stroke thrombolysis as standard-of-care for these patients. We examined a retrospective cohort of 57 patients who received intravenous alteplase for acute ischemic stroke to identify predictors of outcome, including age, stroke severity, onset-to-treatment time, and early ischemic changes on brain CT scan. Overall, the mean National Institute of Health Stroke Scale (NIHSS) score was 15.7 and the mean onset-to-treatment time was 142 minutes. Twenty-nine (51%) patients had a favorable outcome with modified Rankin Scale (mRS) score of ≤2 at three months. Ten (17.5%) patients were deceased at three months. Four (7%) patients developed symptomatic intracranial hemorrhage (sICH). For patients aged >80 years (n=18), five (28%) achieved favorable outcome, six (33%) were deceased at three months and three (17%) had sICH. Prognosis was worst for patients with NIHSS score >25 (n=5); one (20%) was dependent (mRS 4) and the other four (80%) were deceased. Multivariate analysis found that the Alberta Stroke Program Early CT Score (ASPECTS) was associated with favorable outcome (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-3.0), and mortality (OR 0.5, 95% CI 0.3-0.9). Our findings showed advanced age and severe stroke were associated with less favorable outcome in Chinese patients receiving intravenous alteplase, ASPECTS can be used reliably to identify patients at risk of poor outcomes. Further studies are warranted.

A young man who kept falling over

In January, 2005, an 18-year-old student was referred to us, by a private neurologist, for investigation of a movement disorder. 4 months previously, the patient had begun to have episodic, involuntary, single “jerks” of the trunk and limbs; after each jerk, he had to support himself with his hands, to avoid falling. Since the jerks began, his academic performance had deteriorated. His medical and family histories were unremarkable. We observed sudden, stereotyped, involuntary movements, consisting of truncal myoclonus and limb extension, accompanied by tongue protrusion and momentary speech arrest. Each episode lasted 1 s, and was succeeded by a loss of muscle tone of about 0∙5 s, which caused the patient to fall. Blood tests showed no abnormalities: notably, concentrations of caeruloplasmin, creatine kinase, thyroid hormones, and autoantibodies were normal. MRI of the brain showed nothing of note. Cerebrospinal fl uid (CSF) concentrations of protein and glucose were normal; microscopy and culture of CSF gave negative results. Video-electroencephalography (EEG) showed periodic discharges of generalised, large-amplitude, slow-wave complexes, coinciding with myoclonus (fi gure). Measles antibody titres, measured by complement fi xation assay, were high in CSF and serum, at 1:64 and 1:320 respectively. We identifi ed a positive IgG oligoclonal band, consistent with infl ammation, in the CSF. The parents revealed that the patient had had measles in 1988, before scheduled immunisation at 12 months. We diagnosed subacute sclerosing panencephalitis (SSPE). We prescribed inosine pranobex to treat the infection, and clonazepam and levetiracetam to counteract myoclonus. However, 3 months later, the CSF measles antibody titre had not decreased, and myoclonus persisted. Intraventricular inter feron was declined by the patient and his parents, because they felt that the risks of implanting an Ommaya reservoir outweighed the likely benefi ts. A trial of subcutaneous interferon β was initiated, but stopped owing to intolerable adverse eff ects. Despite continuing treatment with inosine pranobex, clonazepam, and levetiracetam, the patient’s condition continued to deteriorate. When last seen, in December, 2005, he was heavily dependent on his parents, and had frequent, violent myoclonus. 1 week later, he was found unconscious in bed by his parents, and was certifi ed dead on arrival at hospital. SSPE is a neurodegenerative disorder, caused by measles virus infection persisting in the CNS. The diagnostic criteria of SSPE are clinical presentation, EEG changes, positive CSF oligoclonal bands, high measles antibody titres in CSF or serum, and positive fi ndings on biopsy of the brain; biopsy is rarely needed when the clinical picture supports the diagnosis. The median incubation period is 6–8 years. Although observational studies suggest that treatment with inosine pranobex, an immunomodulating agent, combined with intra ventri cular interferon, might temporarily delay progress of the disease, such treatment does not improve prognosis, which is uniformly poor: the patient is expected to survive 1–3 years after diagnosis. The risk of developing SSPE after childhood measles is estimated to be 1 in 25 000, but only 1 in 5500 if infection occurs before the patient is 1 year old. SSPE, like other complications of measles, is rare in affl uent societies— including Hong Kong, where a measles vaccination programme began in 1967. World wide, numbers of deaths from measles fell by more than half between 2000 and 2005; the decline is attributed to vaccination. In the UK, a decreased rate of MMR vaccination, in recent years, has coincided with an increased rate of infection; it has become a challenge for health profes sionals to clarify parental beliefs about vaccine safety. Of the seven cases of SSPE reported in Hong Kong between 1988 and 2002, fi ve were attributed to a measles outbreak in 1988; our patient’s history indicates that his SSPE was also caused by this outbreak—with an incubation period of nearly 17 years.