COVID-19 Severity and Stroke: Correlation of Imaging and Laboratory Markers.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) appears to be an independent risk factor for stroke. We hypothesize that patients who develop stroke while hospitalized for severe COVID-19 will have higher inflammatory markers and distinct stroke imaging patterns compared with patients positive for COVID-19 with out-of-hospital stroke onset and milder or no COVID-19 symptoms. MATERIALS AND METHODS: This is a retrospective case series of patients positive for COVID-19 on polymerase chain reaction testing with imaging-confirmed stroke treated within a large health care network in New York City and Long Island between March 14 and April 26, 2020. Clinical and laboratory data collected retrospectively included complete blood counts and creatinine, alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. All CT and MR imaging studies were independently reviewed by 2 neuroradiologists who recorded stroke subtype and patterns of infarction and intracranial hemorrhage. RESULTS: Compared with patients with COVID-19 with outside-of-hospital stroke onset and milder or no COVID-19 symptoms (n = 45, 52.3%), patients with stroke already hospitalized for severe COVID-19 (n = 41, 47.7%) had significantly more frequent infarctions (95.1% versus 73.3%, P = .006), with multivascular distributions (56.4% versus 33.3%, P = .022) and associated hemorrhage (31.7% versus 4.4%, P = .001). Patients with stroke admitted with more severe COVID-19 had significantly higher C-reactive protein and ferritin levels, elevated D-dimer levels, and more frequent lymphopenia and renal and hepatic injury (all, P < .003). CONCLUSIONS: Patients with stroke hospitalized with severe COVID-19 are characterized by higher inflammatory, coagulopathy, and tissue-damage biomarkers, supporting proposed pathogenic mechanisms of hyperinflammation activating a prothrombotic state. Cautious balancing of thrombosis and the risk of hemorrhagic transformation is warranted when considering anticoagulation.

Neurovascular Complications in COVID-19 Infection: Case Series.

We present a series of 10 hospitalized patients with confirmed coronavirus 2019 infections who developed severe neurovascular complications and discuss the possible reasons for these findings and their relationship to the novel Severe Acute Respiratory Syndrome coronavirus 2 infection.

Differences between anterior and posterior circulation stroke in TOAST.

BACKGROUND AND PURPOSE: Clinicians have tended to view anterior circulation (AC) and posterior circulation (PC) strokes as separate entities, with different underlying pathogenesis, natural histories, and potential responsiveness to interventions such as anticoagulation. We sought to explore differences between AC and PC stroke in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). METHODS: For patients enrolled in TOAST, prospective clinical information was collected including outcome at 3 months. Data on vascular distribution were obtained from the clinical impression of the investigators. Group comparisons for categorical data were performed using Fisher's exact test. Independent sample t tests and analysis of covariance were used for all continuous data. RESULTS: The analysis included 1,039 patients with AC stroke and 180 patients with PC stroke. There were fewer women in the PC than in the AC groups, but otherwise there were no differences in demographics, risk factors or stroke subtypes between the two groups. Headache (AC 8.7%, PC 15%, p = 0.013) and vomiting (AC 3.5%, PC 17.8%, p < 0.001) were more common among PC patients. Mean baseline National Institutes of Health Stroke Scale (NIHSS) score was lower (less severe) among PC (6.1) than AC patients (9.5; p < 0.001). On univariate analysis, favorable outcome at 3 months was more common for PC patients in both the placebo group (PC 82%, AC 71%, p = 0.04) and heparinoid group (PC 87%, AC 73%, p = 0.005). However, multivariate analysis, controlling for gender, history of previous stroke and baseline NIHSS score, showed no difference in outcome between PC and AC stroke. For favorable outcome, there was no interaction between vascular distribution and treatment category, suggesting that the effect of heparinoid did not differ between PC and AC strokes. CONCLUSION: Patients with PC stroke seem to have a better long-term outcome than do AC patients, but this difference is no longer apparent when controlling for important prognostic variables. PC patients did not show any particular benefit from anticoagulation, and the efficacy of heparinoid did not vary between AC and PC stroke. While AC and PC patients do differ in some respects, it may be inappropriate to single out PC patients for anticoagulant treatment.

Infratentorial and supratentorial leukoencephalopathy associated with vitamin B12 deficiency.

BACKGROUND: Striking cerebral white matter abnormalities involving supratentorial regions seen on magnetic resonance imaging (MRI) scans have been described in patients with vitamin B12 deficiency. Severe involvement of infratentorial structures with partial reversibility has not been previously documented. OBSERVATION: A 54-year-old man experienced severe weight loss, associated with dementia and focal deficits. Laboratory analysis showed a severe vitamin B12 deficiency and elevated serum homocysteine. MRI scans showed a severe and diffuse white matter abnormal signal involving both the supra- and infratentorial compartments. Vitamin B12 supplementation resulted in a mild improvement in cognitive deficits and a marked resolution of imaging abnormalities. CONCLUSION: Leukoencephalopathy and dementia should raise the suspicion of a vitamin B12 deficiency because vitamin B12 supplementation may result in at least partial clinical improvement.

Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group.

BACKGROUND: In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Trial found that patients who were treated with tissue plasminogen activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. METHODS: In the NINDS Trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a "favorable outcome," defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. RESULTS: Using an intention-to-treat analysis for the combined results of the two parts of the trial at 6 months and 12 months, we found that the global statistic favored the t-PA group (odds ratio for a favorable outcome at 6 months, 1.7; 95 percent confidence interval, 1.3 to 2.3; odds ratio at 12 months, 95 percent confidence interval, 1.7; 1.2 to 2.3). The patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at 12 months than were the placebo-treated patients (absolute increase in the proportion with a favorable outcome, 11 to 13 percentage points). There was no significant difference in mortality at 12 months between the t-PA group and the placebo group (24 percent vs. 28 percent, P=0.29). There was no interaction between the type of stroke identified at base line and treatment with respect to the long-term response. The rate of recurrent stroke at 12 months was similar in the two groups. CONCLUSIONS: During 12 months of follow-up, the patients with acute ischemic stroke who were treated with t-PA within three hours after the onset of symptoms were more likely to have minimal or no disability, than the patients given placebo. These results indicate a sustained benefit of t-PA for such patients.

Adult-onset MELAS presenting as herpes encephalitis.

OBJECTIVE: To report an unusual presentation of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) manifested in late life with a clinical picture of herpes simplex encephalitis. DESIGN: Case report. SETTING: Clinical neurology department in a tertiary care hospital. CASE DESCRIPTION: A 55-year-old woman developed aphasia and delirium during ophthalmic herpes zoster infection treated with oral prednisone and ophthalmic steroids, which was followed by progressive cognitive decline without acute neurologic events for 5 years. At age 60, the patient presented with new onset of seizures, hemiparesis, and hemianopsia. Subsequently she developed cortical blindness, multiple traumatic soft tissue injuries from falls, acute psychosis, and severe dementia with periods of agitation. She died in a nursing home in March 1997, 6 years after initial presentation. RESULTS: Magnetic resonance imaging scan of the brain showed hyperintensity on T2-weighted images involving temporal, parietal, and occipital lobes bilaterally as well as mild atrophy of brainstem and cerebellum. Single photon emission computed tomographic imaging showed hypoperfusion of temporal, parietal, and occipital lobes. Results of video electroencephalographic monitoring showed periodic lateralizing epileptiform discharges in temporal and occipital areas. The serum lactate level was normal in May 1996 and elevated in October 1996. The creatine kinase level was elevated with a 100% MM fraction in August 1991 and normal in March 1996. Results of repeated cerebrospinal fluid analyses indicated elevated protein levels. Analysis of DNA was diagnostic of MELAS by mitochondrial DNA point mutation at position 3243. The results of autopsy showed moderate cerebral, cerebellar, and brainstem atrophy with signs of infarction in temporal and parietal lobes bilaterally. CONCLUSIONS: The clinical presentation as well as age at onset of MELAS are highly variable. Onset of mitochondrial disorders can be provoked by febrile illness when there is mismatch between energy requirements and availability. In the differential diagnosis of herpes encephalitides, MELAS syndrome should be considered.

Basilar artery migraine and reversible imaging abnormalities.

We report a case of a basilar artery migraine in a 17-year-old boy with transient CT and MR abnormalities after each of two migraine episodes. A repeat MR study 6 months after the last event showed complete resolution of the lesion. Transient abnormalities on brain images similar to those shown in our case have been reported in patients with migraine and other neurologic conditions and are most likely related to cerebral vasogenic edema.

Posterior cerebral artery infarction associated with carotid dissection.

UNLABELLED: Posterior circulation stroke may rarely be associated with occlusive disease in the anterior circulation, such as in the context of a direct (fetal) origin of the posterior cerebral artery (PCA) from the internal carotid artery (ICA), or in the presence of a persistent trigeminal artery. Carotid dissection is an increasingly recognized cause of anterior circulation ischemia. It is possible that in the setting of certain cerebral hemodynamics, embolism from carotid dissection could cause PCA infarction via a patent posterior communicating artery. CASE DESCRIPTION: We report the MR and MR angiography findings of cerebral dynamics whereby a patient presents with posterior circulation symptoms from anterior circulation pathology: left ICA dissection with subsequent left PCA territory infarction. CONCLUSIONS: Cerebral hemodynamics may allow PCA infarction from carotid disease even in the absence of a fetal PCA origin. This report also broadens the spectrum of stroke associated with carotid dissection.

Hashimot's encephalopathy-response to intravenous immunoglobulin.

BACKGROUND: Hashimoto's encephalopathy is an unusual brain disorder consisting of focal and diffuse cerebral dysfunction that may present in a stroke-like fashion. Treatment has consisted of steroids and immunosuppression. Treatment with a potentially less toxic modality such as intravenous immunoglobulin (IVIG), if found to be effective, might offer an alternative approach to these patients. CASE DESCRIPTION: We present an 82-year-old woman who developed headache, changes in mental status, and multifocal neurological deficits. Investigation revealed significantly elevated titers of antithyroid antibodies. Treatment with prednisone and methotrexate was unsuccessful. Treatment with monthly courses of IVIG resulted in marked clinical improvement. CONCLUSION: Hashimoto's encephalopathy may be more common than is generally recognized. A trial of IVIG should be considered for patients with this devastating condition.

Recurrent intracerebral hemorrhage from sarcoid angiitis.

BACKGROUND: Sarcoid affecting the central nervous system may cause granulomatous angiitis. Nevertheless, neurosarcoid manifesting as intracerebral hemorrhage has been infrequently reported. CASE DESCRIPTION: A 48-year-old woman with systemic sarcoid developed recurrent intracerebral hemorrhages culminating in death despite treatment with corticosteroids. Pathological examination of the brain revealed inflammatory changes of blood vessels including multinucleated giant cells. CONCLUSION: Sarcoid cerebral angiitis may result in intracerebral hemorrhage. This emphasizes one potentially devastating neurological outcome of this disorder.

Stroke associated with cardiac surgery. Determinants, timing, and stroke subtypes.

OBJECTIVE: To determine the nature of strokes complicating cardiac surgery. DESIGN: A medical record review was undertaken of all patients who underwent cardiac surgery (either coronary bypass, valvular surgery, or both) between January 1990 and July 1995. Univariate and multivariate analyses were done using odds ratios (ORs) and logistic regression. RESULTS: A total of 2211 patients underwent cardiac surgery. A total of 44 patients (2%) had postoperative strokes. They were compared with 104 surgical controls. Univariate analysis revealed that the patients with stroke were significantly older and had significantly higher rates of transient ischemic attack, congestive heart failure, and peripheral vascular disease by history. A multivariate logistic regression revealed the significant variables associated with stroke were congestive heart failure (OR, 6.8) and transient ischemic attack (OR, 1.2). Analyses of surgical variables revealed that bypass pump time of more than 120 minutes (OR, 1.40) was the only significant predictor. The majority of strokes (61%) had occurred by postoperative day 2, but 39% occurred between postoperative days 3 to 9. Hemispheric syndromes occurred in 70%, brain stem and cerebellar syndromes in 14%, and lacunar syndromes in 16%. Computed tomographic scans revealed that 29 patients had new infarcts, of which 20 (69%) were territorial, 5 (17%) were small deep, and 4 (14%) were border zone. Hemorrhagic infarction was found in 2 cases (5%). One patient (2.5%) had a cardiorespiratory arrest while undergoing computed tomography. Discharge disposition was good in 88% of patients with stroke (12% with poor outcomes) vs 97% of controls with good outcomes (3% with poor outcomes) (P = .04). CONCLUSIONS: Strokes may be delayed following cardiac surgery perhaps because of ongoing risk of embolism or a hypercoagulable state. A surprisingly high proportion of patients have lacunar syndromes or small-deep infarcts shown on computed tomography. Early computed tomographic imaging may be useful to exclude hemorrhage if anticoagulation is considered, but is not without risk in these potentially unstable patients. Greater understanding of risk factors for stroke, timing, and subtypes may ultimately allow identification of patients at particularly high risk for perioperative stroke.

Utility of repeat brain imaging in stroke.

PURPOSE: To determine the utility of repeat brain imaging in patients with stroke. METHODS: We reviewed the medical records of 98 consecutive patients in whom stroke was diagnosed between January 1 and December 31, 1991. We noted the number of brain scans performed, the indications cited, and whether repeat imaging changed the therapeutic decisions or final diagnosis. RESULTS: Ninety-eight patients underwent 221 procedures, with 123 repeat imaging studies (98 CT scans and 25 MR images). Sixteen patients had only one scan; 51 had two, and 31 had three or more. Indications for repeat imaging were explicitly documented in 62 (50%) of 123 repeated scans and inferred in another 41 (33%). In 20 (16%), no definite indication could be determined. Indications included lack of acute abnormal imaging findings on the initial scan (n = 48, 39%); compliance with stroke research protocol (n = 11, 9%). In none of the 82 patients did the repeated scan change the diagnosis; therapy was changed in only two (2%) of 82 patients (aspirin was discontinued). CONCLUSIONS: Repeat imaging in patients rarely results in changes in the initial diagnosis or the therapeutic plan; indications for repeat imaging are frequently not clearly stated; in certain groups of patients with stroke, repeat imaging may not be useful.

Conditions that mimic stroke in the emergency department. Implications for acute stroke trials.

OBJECTIVE: To determine if any clinical variables allow early discrimination between stroke and other conditions presenting with a strokelike picture. BACKGROUND: New therapeutic modalities for the treatment of acute ischemic stroke are under active investigation. Many of these treatments have potential adverse effects. It is well known that noncerebrovascular conditions can present with a clinical picture mimicking stroke, so early accurate differentiation of such "mimics" from true stroke is essential. METHODS: Consecutive patients who presented to the emergency department with an initial diagnosis of stroke between January 1990 and January 1992 were evaluated. Chart review allowed these patients to be classified into two final diagnostic groups: stroke mimic and true stroke. Logistic regression was used to estimate the effects of predictor variables measured at initial evaluation on the final diagnosis. RESULTS: There were 411 patients initially diagnosed as having stroke. Of these, 78 patients (19%) were eventually found to have mimics, the majority comprising postictal states, systemic infections, tumors, and toxic-metabolic disturbances. Univariate analysis showed that decreased level of consciousness and normal eye movements increased the odds of mimic, while abnormal visual fields, diastolic blood pressure greater than 90 mm Hg, atrial fibrillation on electrocardiogram, and history of angina decreased the odds of mimic. Multivariate analysis showed that decreased consciousness increased, while history of angina decreased, the odds of mimic. Sensitivity of this model for predicting mimics was only 21% while specificity was 96%. CONCLUSION: For the neurologist faced with an immediate decision as to whether to randomize a patient with probable stroke to an acute treatment protocol, these findings have some usefulness but mandate further research into conditions that mimic stroke in the emergency department.

Seizures and 'disappearing' brain lesions.

BACKGROUND--Patients with seizures may have abnormal brain imaging. Lesions demonstrated on computerized tomography or magnetic resonance imaging often suggest the underlying cause of the seizures, and may prompt an invasive investigation for diagnosis and treatment. In an increasingly recognized subset of patients however, the imaged lesions spontaneously resolve. While poorly understood, these 'disappearing' lesions may in fact be the consequence of seizures, rather than the cause. Two patients with 'disappearing' lesions are presented: the first patient had a proven cause, the second a probable one. Case 1. A patient with new onset seizures had an abnormal MRI. An angiogram confirmed thrombosis of the straight sinus. On follow-up, she was doing well; repeat imaging was normal with resolution of the lesion. Case 2. A patient with a long seizure history had been well controlled on medications, and had no change in frequency of her seizures. She was found to have a left homonymous hemianopsia. MRI revealed a right parieto-occipital lesion. The patient refused further work-up and was lost to follow-up. She returned almost a year later; repeat imaging was normal. CONCLUSION--Patients with seizures and abnormal imaging suggestive of structural lesions may occasionally have lesions that resolve spontaneously. While some diagnoses remain elusive, an important consideration to exclude in these patients is venous thrombosis.

When is isolated vertigo a harbinger of stroke?

Isolated vertigo is usually a distressing though benign clinical entity. Recently, however, it has been recognized that in a subset of patients isolated vertigo may be a harbinger of vertebrobasilar stroke. Recognition of this "at risk" subgroup may be difficult. Brainstem auditory evoked potentials (BAEPs) are usually normal in patients with vertigo from labyrinthine disease. We describe a patient with isolated vertigo, in whom BAEPs were abnormal, and who subsequently developed an anterior inferior cerebellar artery territory infarct. BAEP testing might lead to early recognition of those patients at risk for catastrophic stroke, and prompt appropriate investigation and treatment to prevent this outcome.

Outcome after carotid endarterectomy for asymptomatic carotid stenosis.

OBJECTIVE: To compare the long-term outcome in patients with asymptomatic carotid stenosis (ACS) among those treated with carotid endarterectomy (CE) or medical therapy. BACKGROUND: Until randomized trials are completed, treatment of ACS will depend on identification of subgroups likely to benefit from CE. METHODS: A retrospective cohort study was done on 215 patients with ACS: 107 underwent CE, and 108 were treated medically (MED). A neurologist reviewed medical records and performed a telephone interview to detect outcome (stroke and death). Mean follow-up was 3.8 years; only 4% were lost to follow-up. RESULTS: Among CE patients, there was a 4.7% risk of postoperative ipsilateral stroke within 30 days. Four of five postoperative strokes occurred among patients with prior contralateral symptoms. There was no significant difference between CE and MED in the cumulative life-table 5-year risk of ipsilateral stroke, any stroke, or survival free of any stroke. Among diabetics, however, there were no ipsilateral strokes at 5 years after CE compared to 20% in MED (p = 0.03). Excluding postoperative complications, the 5-year risk of ipsilateral stroke was reduced among CE patients who "ever smoked" (CE 1%, MED 8%, p = 0.03) and the 5-year risk of any stroke was reduced among CE patients who had no prior myocardial infarction (CE 6%, MED 16%, p = 0.02). Among those with prior contralateral carotid territory symptoms, the 5-year risk of any stroke was worse in the MED patients (CE 5% MED 32%, p = 0.004). Among CE patients, a Cox proportional hazards model determined that the independent predictors of worse long-term outcome were: a history of myocardial infarction; admission systolic blood pressure greater than 160 mm Hg; and age greater than 65. CONCLUSION: The approach to patients with ACS will await completion of large, randomized clinical trials, now in progress. Even if these studies are negative, there may remain specific subgroups of patients who show clear benefit from carotid endarterectomy.

Central retinal artery occlusion from carotid dissection diagnosed by cervical computed tomography.

BACKGROUND: Carotid dissection may lead to many different types of neurological deficits, both transient and permanent. CASE DESCRIPTION: We present a patient with an isolated central retinal artery occlusion who was found to have an ipsilateral carotid dissection by neck computed tomographic scan, later confirmed by angiography. CONCLUSIONS: This is the first reported case of carotid dissection causing central retinal artery occlusion without any other neurological deficits. It demonstrates the diagnostic usefulness of computed tomographic imaging in such cases.