Diffusion-Weighted MR Imaging in a Prospective Cohort of Children with Cerebral Malaria Offers Insights into Pathophysiology and Prognosis.

BACKGROUND AND PURPOSE: Validation of diffusion-weighted images obtained on 0.35T MR imaging in Malawi has facilitated meaningful review of previously unreported findings in cerebral malaria. Malawian children with acute cerebral malaria demonstrated restricted diffusion on brain MR imaging, including an unusual pattern of restriction isolated to the subcortical white matter. We describe the patterns of diffusion restriction in cerebral malaria and further evaluate risk factors for and outcomes associated with an isolated subcortical white matter diffusion restriction. MATERIALS AND METHODS: Between 2009 and 2014, comatose Malawian children admitted to the hospital with cerebral malaria underwent admission brain MR imaging. Imaging data were compiled via NeuroInterp, a RedCap data base. Clinical information obtained included coma score, serum studies, and coma duration. Electroencephalograms were obtained between 2009 and 2011. Outcomes captured included death, neurologic sequelae, or full recovery. RESULTS: One hundred ninety-four/269 (72.1%) children with cerebral malaria demonstrated at least 1 area of diffusion restriction. The most common pattern was bilateral subcortical white matter involvement (41.6%), followed by corpus callosum (37.5%), deep gray matter (36.8%), cortical gray matter (17.8%), and posterior fossa (8.9%) involvement. Sixty-one (22.7%) demonstrated isolated subcortical white matter diffusion restriction. These children had lower whole-blood lactate levels (OR, 0.9; 95% CI, 0.85-0.98), were less likely to require anticonvulsants (OR, 0.6; 95% CI, 0.30-0.98), had higher average electroencephalogram voltage (OR, 1.01; 95% CI, 1.00-1.02), were less likely to die (OR, 0.09; 95% CI, 0.01-0.67), and were more likely to recover without neurologic sequelae (OR, 3.7; 95% CI, 1.5-9.1). CONCLUSIONS: Restricted diffusion is common in pediatric cerebral malaria. Isolated subcortical white matter diffusion restriction is a unique imaging pattern associated with less severe disease and a good prognosis for full recovery. The underlying pathophysiology may be related to selective white matter vulnerability.

Brain imaging in normal kids: a community-based MRI study in Malawian children.

OBJECTIVE: To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults. METHODS: We identified a representative, community-based sample of children aged 9-14 years. Children were screened for neurodevelopmental problems. Demographic data, medical history and environmental exposures were ascertained. Eligible children underwent the Neurologic Examination for Subtle Signs (NESS) and a brain MRI. Descriptive findings and analyses to identify risk factors for MRI abnormalities are detailed. RESULTS: One hundred and two of 170 households screened had age-appropriate children. Two of 102 children had neurological problems - one each with cerebral palsy and epilepsy. Ninety-six of 100 eligible children were enrolled. Mean age was 11.9 years (SD 1.5), and 43 (45%) were boys. No acute MRI abnormalities were seen. NESS abnormalities were identified in 6 of 96 children (6%). Radiographic evidence of sinusitis in 29 children (30%) was the most common MRI finding. Brain abnormalities were found in 16 (23%): mild diffuse atrophy in 4 (4%), periventricular white matter changes/gliosis in 6 (6%), multifocal punctuate subcortical white matter changes in 2 (2%), vermian atrophy in 1 (1%), empty sella in 3 (3%) and multifocal granulomas with surrounding gliosis in 1 (1%). Having an abnormal MRI was not associated with age, sex, antenatal problems, early malnutrition, febrile seizures, an abnormal neurological examination or housing quality (all P values >0.05). No predictors of radiographic sinusitis were identified. CONCLUSION: Incidental brain MRI abnormalities are common in normal Malawian children. The incidental atrophy and white matter abnormalities seen in this African population have not been reported among incidental findings from US populations, suggesting Malawi-specific exposures may be the cause.

Acute brain MRI findings in 120 Malawian children with cerebral malaria: new insights into an ancient disease.

BACKGROUND AND PURPOSE: There have been few neuroimaging studies of pediatric CM, a common often fatal tropical condition. We undertook a prospective study of pediatric CM to better characterize the MRI features of this syndrome, comparing findings in children meeting a stringent definition of CM with those in a control group who were infected with malaria but who were likely to have a nonmalarial cause of coma. MATERIALS AND METHODS: Consecutive children admitted with traditionally defined CM (parasitemia, coma, and no other coma etiology evident) were eligible for this study. The presence or absence of malaria retinopathy was determined. MRI findings in children with ret+ CM (patients) were compared with those with ret- CM (controls). Two radiologists blinded to retinopathy status jointly developed a scoring procedure for image interpretation and provided independent reviews. MRI findings were compared between patients with and without retinopathy, to assess the specificity of changes for patients with very strictly defined CM. RESULTS: Of 152 children with clinically defined CM, 120 were ret+, and 32 were ret-. Abnormalities much more common in the patients with ret+ CM were markedly increased brain volume; abnormal T2 signal intensity; and DWI abnormalities in the cortical, deep gray, and white matter structures. Focal abnormalities rarely respected arterial vascular distributions. Most of the findings in the more clinically heterogeneous ret- group were normal, and none of the abnormalities noted were more prevalent in controls. CONCLUSIONS: Distinctive MRI findings present in patients meeting a stringent definition of CM may offer insights into disease pathogenesis and treatment.

[Progressive paraplegia in a somnolent child]. / Progredienter Querschnitt bei einem somnolenten Kind.

A somnolent small girl with septic symptoms and a progressive paraplegia was initially treated as having meningitis with complications. Subsequently it was discovered through magnetic resonance imaging (MRI) that she was suffering from spinal epidural empyema due to a staphylococcal superinfection on the basis of tuberculous vertebral osteomyelitis. Lacking surgical facilities therapy was carried out by the anesthesia department using multilevel epidural punctures and drainage. This article discusses the agreement of MRI findings with the interventional findings and the clinical features and shows the leading diagnostic role of MRI throughout the clinical course.

Magnetic resonance imaging in Malawi: contributions to clinical care, medical education and biomedical research.

Advanced medical imaging technologies are generally unavailable in low income, tropical settings despite the reality that neurologic disorders are disproportionately common in such environments. Through a series of donations as well as extramural research funding support, an MRI facility opened in Blantyre, Malawi in July 2008. Resulting opportunities for studying common tropical disorders, such as malaria and schistosomiasis, in vivo are promising. The subsequent improvements in local patient care were expected and exceptional and include major revisions in basic care protocols that may eventually impact care protocols at facilities in the region that do not have recourse to MRI. In addition, advanced neuroimaging technology has energized the medical education system, possibly slowing the brain drain. Advanced technologies, though potentially associated with significant fiscal opportunity costs, may bring unexpected and extensive benefits to the healthcare and medical education systems involved.

An experience of emergency ultrasonography in children in a sub-Saharan setting.

Emergency ultrasonography is an appealing imaging modality in paediatric emergencies, given its non-invasive nature and potential as an adjunct to physical examination in a setting where rapid decisions need to be made. This review of a case series describes the applications, versatility, and limitations of emergency physician led ultrasonography in a paediatric resuscitation room in a sub-Saharan African setting.

Differential diagnosis of stroke in a setting of high HIV prevalence in Blantyre, Malawi.

BACKGROUND AND PURPOSE: The differential diagnosis of stroke in Africa in areas with high HIV prevalence includes brain infections. We studied causes of stroke in Blantyre, Malawi, where HIV prevalence among medical inpatients is 70%. METHODS: In a descriptive study of 8-month duration, all patients presenting at Queen Elizabeth Central Hospital, Blantyre, with central neurological deficit of acute onset (<24 hours) had baseline investigations, including full blood count, blood glucose, serology for toxoplasmosis, syphilis, and HIV, ECG, echocardiogram, ultrasound of the carotid arteries, and computerized tomography scan of the brain. A lumbar puncture was performed unless contraindicated. RESULTS: Ninety-eight consecutive patients (49 males) were studied. In those who were HIV positive (48%), the mean age was 37.5 years; ischemic stroke was the commonest diagnosis (n=25; 58%), followed by infection (n=11; 23%; including tuberculous [n=4] and cryptococcal [n=2] meningitis; toxoplasmic encephalitis [n=1]; neurocysticercosis [n=1]; brain abscess [n=1]; and progressive multifocal leucoencephalopathy [n=2]). No clinical or laboratory parameters could be identified as predictors for infection, but 3 of 5 patients with fever on admission had tuberculous meningitis. In HIV-negative patients (mean age 58.6 years), 55% had ischemic stroke and 31% had intracerebral hemorrhage; no brain infection was diagnosed. Presence of vascular disease correlated with age but not with HIV status. CONCLUSIONS: Ischemic stroke was found in half of patients irrespective of HIV status. In those who are HIV positive, brain infection should be considered for which the presence of fever and examination of cerebrospinal fluid seem most useful in diagnosis.

Differential diagnosis of stroke in a setting of high HIV prevalence in Blantyre, Malawi.

BACKGROUND AND PURPOSE: The differential diagnosis of stroke in Africa in areas with high HIV prevalence includes brain infections. We studied causes of stroke in Blantyre, Malawi, where HIV prevalence among medical in-patients is 70%. METHODS: In a descriptive study of 8 month duration, all patients presenting at Queen Elizabeth Central Hospital, Blantyre with central neurological deficit of acute onset (< 24 hours) had baseline investigations, including full blood count, blood glucose; serology for toxoplasmosis, syphilis and HIV; ECG, echocardiogram, ultrasound of the carotid arteries and computerized tomography scan of the brain. A lumbar puncture was performed unless contraindicated. RESULTS: Ninety-eight consecutive patients (49 males) were studied. In those who were HIV positive (48%) the mean age was 37.5 years; ischemic stroke was the commonest diagnosis (n = 25, 58%) followed by infection (n=11, 23%; including tuberculous [n=4] and cryptococcal [n=2] meningitis; toxoplasmic encephalitis [n=1]; neurocysticercosis [n=1]; brain abscess [n=1]; and progressive multifocal leucoencephalopathy [n=2]). No clinical or laboratory parameters could be identified as predictors for infection, but 3 of 5 patients with fever on admission had tuberculous meningitis. In HIV negative patients (mean age 58.6 years) 55% had ischemic stroke and 31% had intracerebral hemorrhage; no brain infection was diagnosed. Presence of vascular disease correlated with age but not with HIV status. CONCLUSIONS: Ischemic stroke was found in half of patients irrespective of HIV status. In those who are HIV positive, brain infection should be considered for which the presence of fever and examination of CSF seem most useful in diagnosis.

Clinical indicators of mycobacteraemia in adults admitted to hospital in Blantyre.

The aims of the study were to measure the prevalence and outcome of mycobacteraemia in febrile hospitalised adults; to determine what proportion could be identified using routine methods; to assess clinical indicators of mycobacteraemia and the usefulness of a diagnostic trial of anti-TB treatment. We prospectively examined adults with fever or a history of fever admitted to adult medical wards of QECH, Blantyre. All had blood cultured for bacteria and mycobacteria, chest x-ray and sputum smears. M. tuberculosis was the commonest blood isolate, affecting 57 of 344 patients (17%). In 44 (77%) patients with mycobacteraemia, TB was identified using routine investigations; in only 6 (11%) it was not suspected. Strong clinical indicators of mycobacteraemia were anaemia, HIV seropositivity, cough, chronic fever, and a clinical diagnosis of AIDS on the day of admission. Of nine patients selected for a therapeutic trial of TB treatment, six had mycobacteraemia, of whom five died during the trial. Mortality on short course chemotherapy on the TB ward after one month, was similar whether patients had mycobacteramia (21%) or not (32%). TB can be identified with routine methods in most patients with mycobacteraemia. If treated, mycobacteraemia has as good an early outcome as TB without mycobacteraemia. Strengthening of basic facilities is likely to improve detection and treatment of mycobacterial disease.

Clinical indicators of mycobacteraemia in adults admitted to hospital in Blantyre, Malawi.

SETTING: Adult medical wards of a central hospital in Blantyre, Malawi. OBJECTIVE: To measure the prevalence and outcome of mycobacteraemia in febrile hospitalised adults, and to determine what proportion could be identified using routine methods; to assess clinical indicators of mycobacteraemia, and the usefulness of a diagnostic trial of anti-tuberculosis treatment. DESIGN: We prospectively examined adults admitted with fever or a history of fever. All had blood cultured for bacteria and mycobacteria, chest X-ray and sputum smears. FINDINGS: Mycobacterium tuberculosis was the commonest cause of blood stream infection (BSI), affecting 57 of 344 patients (17%). In 44 (77%) patients with mycobacteraemia, TB was identified using routine investigations; it was not suspected in six (11%). Strong clinical indicators of mycobacteraemia were anaemia, HIV seropositivity, cough, chronic fever and a clinical diagnosis of AIDS on the day of admission. Of nine patients selected for a therapeutic trial of tuberculosis (TB) treatment, six had mycobacteraemia, of whom five died during the trial. Mortality on short-course chemotherapy, on the TB ward after 1 month was similar whether patients had mycobacteremia (21%) or not (32%). CONCLUSION: TB can be identified with routine methods in most patients with mycobacteraemia. If treated, mycobacteraemia has as good an early outcome as TB without mycobacteraemia. Strengthening of basic facilities is likely to improve detection and treatment of mycobacterial disease.

Bloody diarrhoea of adults in Malawi: clinical features, infectious agents, and antimicrobial sensitivities.

In a prospective study, 132 hospital out-patients presenting with bloody diarrhoea ('cases') were evaluated in Malawi, Central Africa; 73 out-patient tuberculosis suspects acted as controls. Most (100/132, 76%) subjects reported an illness lasting < or = 5 d with > 5 bowel actions in the preceding 12 h; 39/132 (30%) reported use of systemic antimicrobial drugs in the preceding week; 57% (74/130) had a body mass index < 20; 4% (5/131) were febrile; and 18/130 (13%) had one or more sign(s) of dehydration. The 73 controls reported no diarrhoea and more systemic antimicrobial drug use (P = 0.0003), but were otherwise comparable to the subjects. All stool samples from controls and 38/124 (31%) from cases were macroscopically normal. Only 32% (40/124) of the cases had blood visible in the stool. Parasitic gut infections were found in 42/124 (34%) cases compared with 1/60 (2%) controls (P < 0.0001). The commonest parasite was Schistosoma mansoni. Bacterial cultures were positive in 32/124 (26%) of the subjects. Shigella dysenteriae (Sd) 1 accounted for 53% (17/32) of these. All bacterial isolates were sensitive in vitro to nalidixic acid and ciprofloxacin, while only 18% were sensitive to cotrimoxazole. Sd 1 with significant antimicrobial resistance continues to cause seasonal epidemics of dysentery in Malawi. During these, approximately two-thirds of patients presenting with bloody diarrhoea have no blood visible in the stool. Nalidixic acid remains the drug of choice but its use should be restricted to patients at greatest risk of complicated shigellosis.