Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria.

BACKGROUND: Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults. METHODS: Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases. RESULTS: We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death. CONCLUSIONS: Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.

The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke.

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms. Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011. Results: We recruited 64 HIV-infected and 107 HIV-uninfected patients. Those with HIV were significantly younger (P < .001) and less likely to have established vascular risk factors. Patients with HIV were more likely to have large artery disease (21% vs 10%; P < .001). The commonest etiology was HIV-associated vasculopathy (24 [38%]), followed by opportunistic infections (16 [25%]). Sixteen of 64 (25%) had a stroke soon after starting antiretroviral therapy (ART), suggesting an immune reconstitution-like syndrome. In this group, CD4+ T-lymphocyte count was low, despite a significantly lower HIV viral load in those recently started on treatment (P < .001). Conclusions: HIV-associated vasculopathy and opportunistic infections are common causes of HIV-related ischemic stroke. Furthermore, subtypes of HIV-associated vasculopathy may manifest as a result of an immune reconstitution-like syndrome after starting ART. A better understanding of this mechanism may point toward new treatments.

A dataset of direct observations of sea ice drift and waves in ice.

Variability in sea ice conditions, combined with strong couplings to the atmosphere and the ocean, lead to a broad range of complex sea ice dynamics. More in-situ measurements are needed to better identify the phenomena and mechanisms that govern sea ice growth, drift, and breakup. To this end, we have gathered a dataset of in-situ observations of sea ice drift and waves in ice. A total of 15 deployments were performed over a period of 5 years in both the Arctic and Antarctic, involving 72 instruments. These provide both GPS drift tracks, and measurements of waves in ice. The data can, in turn, be used for tuning sea ice drift models, investigating waves damping by sea ice, and helping calibrate other sea ice measurement techniques, such as satellite based observations.

Predicting aspiration after hemispheric stroke from timing measures of oropharyngeal bolus flow and laryngeal closure.

Deglutitive aspiration is common after stroke, affecting up to 50% of patients and predisposing them to pneumonia, yet it is virtually impossible to predict those patients at greatest risk. The aim of this study was to develop a robust predictive model for aspiration after stroke. Swallowing was assessed by digital videofluoroscopy (VF) in 90 patients following hemispheric stroke. Lesion characteristics were determined by computerized tomography (CT) brain scan using the Alberta Stroke Programme Early CT Score (ASPECTS). Aspiration severity was measured using a validated penetration-aspiration scale. The probability of aspiration was then determined from measures of swallowing pathophysiology and lesion location by discriminant analysis. Aspiration was observed in 47 (52%) patients, yet despite disrupted swallowing physiology, intrasubject aspiration scores were variable. The best discriminant model combined pharyngeal transit time, swallow response time, and laryngeal closure duration to predict 73.11% of those aspirating (sensitivity = 66.54, specificity = 80.22, p > 0.001). The addition of lesion location did not add anything further to the predictive model. We conclude that the pathophysiology of poststroke aspiration is multifactorial but in most cases can be predicted by three key swallowing measurements. These measurements, if translatable into clinical bedside evaluation, may assist with the development of novel measurement and intervention techniques to detect and treat poststroke aspiration.

Immune reconstitution associated with progressive multifocal leukoencephalopathy in human immunodeficiency virus: a case discussion and review of the literature.

OBJECTIVES: To report the neuropathological findings of a patient with immune reconstitution syndrome associated with progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV) and to review the literature. METHODS: A 38-year-old man was presented with a rapidly evolving brainstem syndrome. Serology for HIV was positive with an initial CD4 count of 130 cells/mL3. Magnetic resonance imaging showed widespread high signal changes within the brainstem bilaterally, the cerebellum, inferior cerebellar peduncle, and the frontal lobe on the right. Opportunistic infections were excluded from blood and cerebrospinal fluid samples. Despite treatment with antiretrovirals, he continued to deteriorate neurologically, and a repeat magnetic resonance imaging scan showed progression of his lesions. Cortical wedge frontal lobe brain biopsy showed features characteristic of PML, but was associated with an exaggerated inflammatory response. Polymerase chain reaction analysis of the specimen demonstrated the presence of JC virus (JCV) DNA, confirming the pathologic impression of PML. RESULTS: The patient made a rapid (within 24 hours) improvement with pulsed methylprednisolone and has maintained a clinical response 7 months later. These features clinically, radiologically, and histopathologically suggest an added component in the form of immune reconstitution syndrome to PML. CONCLUSION: This report highlights the need to carefully evaluate the clinical syndrome in patients with HIV-associated leukoencephalopathy. It also substantiates the role of corticosteroids in carefully considered cases of HIV with leukoencephalopathy secondary to immune reconstitution.

An overview of the management of pseudoaneurysm of the maxillary artery: a report of a case following mandibular subcondylar osteotomy.

BACKGROUND: Aneurysms, pseudoaneurysms, and arteriovenous malformations of the maxillary artery are rare. This is why this case report and current opinions regarding therapy are presented. PATIENT: A 41 year old woman presented in 1991 with recurrent pain and swelling in the right infra-auricular region of 3 years duration which was unresponsive to antibiotics. She had undergone subcondylar osteotomies elsewhere 5 years previously. Imaging revealed a rounded radiolucency of the upper posterior border of the right mandibular ramus with calcification posterior to the radiolucency. The lesion was surgically treated by packing, diathermy and ligation of the external carotid artery and has now resolved completely. Methods for the management of pseudoaneurysms, arteriovenous fistulae and haemorrhage from the maxillary artery include angiography both for initial diagnosis of pseudoaneurysm, arteriovenous malformation and haemorrhage and, if suitable their treatment with endovascular occlusants. The advantages and drawbacks of surgery versus endarterial occlusion are rehearsed. CONCLUSION: Although endovascular intervention has become the first line approach, particulate embolization is more commonly used as a pre-operative technique. Lesions like one described here can of course be managed by surgery alone if sophistizated facilities and skill were not available.

Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain.

The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in >90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum-infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM. IMPORTANCE The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by Plasmodium falciparum-infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions.

Arterial ischemic stroke in HIV: Defining and classifying etiology for research studies.

HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke.

Psychiatric aspects of thalamic stimulation for neuropathic pain.

Twenty-four patients with neuropathic pain underwent thalamic stimulation after conventional surgical and medical treatments had failed. Psychiatric interviews and psychometric testing were carried out before and after surgery to screen candidates and to assess therapeutic response. Eighteen patients obtained either complete or partial pain relief by regular stimulation. Because of technical problems surgery was unsuccessful in 6 patients. Predictions of outcome by the psychiatrist based on the patient's premorbid personality traits, alcohol and narcotic abuse, psychopathology at interview, and psychosocial stressors showed no correlation with these surgical results. When surgery failed, therapeutic intervention was needed for severe disappointment and suicidal behaviour. In follow-up studies 2 of the 6 patients with continuing pain have died by suicide. When surgery succeeded, patients returned to a near normal and satisfactory way of life. Thalamic stimulation offers a promising alternative treatment for intractable neuropathic pain.

Evaluating oral stimulation as a treatment for dysphagia after stroke.

Deglutitive aspiration is common after stroke and can have devastating consequences. While the application of oral sensory stimulation as a treatment for dysphagia remains controversial, data from our laboratory have suggested that it may increase corticobulbar excitability, which in previous work was correlated with swallowing recovery after stroke. Our study assessed the effects of oral stimulation at the faucial pillar on measures of swallowing and aspiration in patients with dysphagic stroke. Swallowing was assessed before and 60 min after 0.2-Hz electrical or sham stimulation in 16 stroke patients (12 male, mean age = 73 +/- 12 years). Swallowing measures included laryngeal closure (initiation and duration) and pharyngeal transit time, taken from digitally acquired videofluoroscopy. Aspiration severity was assessed using a validated penetration-aspiration scale. Preintervention, the initiation of laryngeal closure, was delayed in both groups, occurring 0.66 +/- 0.17 s after the bolus arrived at the hypopharynx. The larynx was closed for 0.79 +/- 0.07 s and pharyngeal transit time was 0.94 +/- 0.06 s. Baseline swallowing measures and aspiration severity were similar between groups (stimulation: 24.9 +/- 3.01; sham: 24.9 +/- 3.3, p = 0.2). Compared with baseline, no change was observed in the speed of laryngeal elevation, pharyngeal transit time, or aspiration severity within subjects or between groups for either active or sham stimulation. Our study found no evidence for functional change in swallow physiology after faucial pillar stimulation in dysphagic stroke. Therefore, with the parameters used in this study, oral stimulation does not offer an effective treatment for poststroke patients.

Reliability of a semi-automated technique of cerebral infarct volume measurement with CT.

BACKGROUND: A reliable method of infarct volume measurement is needed if infarct volume is to be used as an outcome measure in clinical stroke trials. We investigated the reproducibility of a semi-automated method of computed tomography (CT) infarct volume measurement amongst three stroke research fellows with no formal neuroradiology training and two consultant neuroradiologists. METHODS: CT brain scans for volumetric analysis were performed at 5 to 7 days in 34 patients with acute ischaemic stroke, of which 28 scans showed visible recent infarction. Five observers independently traced the infarct boundary on digitised images with a cursor. Volumetric analysis incorporated pixel thresholding with preset Hounsfield thresholds. One of the observers repeated the analyses on 21 of the scans in order to assess intraobserver variation. RESULTS: Median infarct volume was 35.7 cm3 (range 0.2-318 cm3). The closest limits of observed agreement (mean +/- 1.96 SD) between pairs of observers were between a research fellow and neuroradiologist (-29 to 21 cm3). The widest limits of agreement were between a different research fellow and the same neuroradiologist (-39.1 to 41.4 cm3). The limits of agreement between infarct volumes measured on two separate occasions by one of the research fellows were -7 to 8 cm3. CONCLUSIONS: Intraobserver reliability of CT infarct volume measurements performed by a stroke research fellow was superior to interobserver reliability between any pair of observers. The wide limits of agreement between different observers using manual tracing may not be acceptable in multicentre trials of acute ischaemic stroke treatment, but volume measurement by a single observer appears to be more reliable.