Patterns Of Cerebral Injury Research Articles

Single fetal demise in monochorionic pregnancies: incidence and patterns of cerebral injury.

To evaluate the incidence, type and severity of cerebral injury in the surviving monochorionic (MC) cotwin after single fetal demise in twin pregnancies. All MC pregnancies with single fetal demise that were evaluated at the Leiden University Medical Center between 2002 and 2013 were included. Perinatal characteristics, neonatal outcome and the presence of cerebral injury, observed on neuroimaging, were recorded for all cotwin survivors. A total of 49 MC pregnancies with single fetal demise, including one MC triplet, were included in the study (n = 50 cotwins). Median gestational age at occurrence of single fetal demise was 25 weeks and median interval between single fetal demise and live birth was 61 days, with a median gestational age at birth of 36 weeks. Severe cerebral injury was diagnosed in 13 (26%) of the 50 cotwins and was detected antenatally in 4/50 (8%) and postnatally in 9/50 (18%) cases. Cerebral injury was mostly due to hypoxic-ischemic injury resulting in cystic periventricular leukomalacia, middle cerebral artery infarction or injury to basal ganglia, thalamus and/or cortex. Risk factors associated with severe cerebral injury were advanced gestational age at the occurrence of single fetal demise (odds ratio (OR), 1.14 (95% CI, 1.01-1.29) for each week of gestation; P = 0.03), twin-twin transfusion syndrome developing prior to single fetal demise (OR, 5.0 (95% CI, 1.30-19.13); P = 0.02) and a lower gestational age at birth (OR, 0.83 (95% CI, 0.69-0.99) for each week of gestation; P = 0.04). Single fetal demise in MC pregnancies is associated with severe cerebral injury occurring in 1 in 4 surviving cotwins. Routine antenatal and postnatal neuroimaging, followed by standardized long-term follow-up, is mandatory.

Advances in Vascular Cognitive Impairment

Advances in Vascular Cognitive Impairment

Dementia More Likely in Diabetics With Severe Hypoglycemia

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessDementia More Likely in Diabetics With Severe HypoglycemiaJun YanJun YanSearch for more papers by this authorPublished Online:5 Jun 2009https://doi.org/10.1176/pn.44.11.0020Severe hypoglycemic events are a significant risk factor for developing dementia in older patients with type 2 diabetes, according to an epidemiological study from Kaiser Permanente published in the April 15 Journal of the American Medical Association.For patients with type 2 diabetes, having had at least one episode of hypoglycemia severe enough for hospitalization or an emergency department visit was associated with a 50 percent increase in the risk of being diagnosed with dementia in the next few years.The risk of dementia appeared to rise with the number of severe hypoglycemic events documented in the past. Using patients with no hypoglycemic events as reference, the risk of dementia was 25 percent higher for patients who had had one hypoglycemic episode, 80 percent higher for those with two episodes, and 94 percent for those with three or more episodes. All the risk ratios were statistically significant after adjusting for age and other potential confounding factors.Rachel Whitmer, Ph.D., an investigator at the Division of Research at Kaiser Permanente Northern California (KPNC), and colleagues collected medical data on 16,667 type 2 diabetic patients in the KPNC Diabetes Registry who were aged 55 or older in January 2003 and had not been diagnosed with dementia, mild cognitive impairment, or general memory complaints at the time. The risk of getting dementia was analyzed for potential correlation with records of hypoglycemia-related hospitalizations and emergency department visits from 1980 and 2002. Approximately 1 in 10 of the diabetic patients was later diagnosed for dementia of any type, including Alzheimer's disease and vascular dementia, in the follow-up years from 2003 through January 2007.The increased risk of developing dementia was also significantly predicted by emergency department admissions related to hypoglycemia. Patients who had had two or more emergency department admissions before 2003 had more than double the risk of being diagnosed with dementia after 2003.There has been evidence to suggest a link between diabetes and the development of dementia, but scientists are only beginning to explore the mechanisms of the connections between neurological disorders and metabolic abnormalities, including but not limited to diabetes, dyslipidemia, and obesity. The authors of the JAMA study speculated that, because severe hypoglycemia episodes can impair nutrient delivery to the brain and increase the amount of neurotoxic glutamate, some patients experiencing hypoglycemia might have subclinical but permanent neurological damage that subsequently exacerbated the risk of developing dementia.A neuropathology study on brain tissue and autopsies published in the March Archives of Neurology suggested that dementia patients with and without diabetes may have two patterns of cerebral injury that lead to dementia. Joshua Sonnen, M.D., and colleagues at the University of Washington and Oregon Health and Sciences University found that the cerebral cortex of dementia patients without diabetes had more amyloid-beta peptide deposits and higher levels of F2-iso-prostanes, which are a molecular marker for neural injury caused by free radicals. In contrast, the brains of patients with diabetes and dementia showed more microvascular infarcts and elevated levels of interleukin-6, a chemical related to inflammation.An abstract of “Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus” is posted at<jama.ama-assn.org/cgi/content/abstract/301/15/1565>.▪ ISSUES NewArchived

Different Patterns of Cerebral Injury in Dementia With or Without Diabetes

Diabetes mellitus (DM) increases the risk of dementia in the elderly. However, its underlying mechanisms, its connection with Alzheimer disease and vascular cognitive impairment, and effects of therapy remain unclear. To test the hypothesis that DM promotes specific neuropathologic processes that contribute to dementia and that these processes may be suppressed by antidiabetic therapy. A comprehensive neuropathologic assessment of all cases from a community-based study of incident dementia (Adult Changes in Thought Study) that underwent autopsies (n = 259) and had information on DM status (n = 196). Biochemical analysis was conducted on a subset of these cases with rapidly frozen brain tissue (n = 57). Autopsy cases were divided into 4 groups: no DM/no dementia (DM-/dementia-), DM/no dementia (DM+/dementia-), no DM/dementia (DM-/dementia+), and DM/dementia (DM+/dementia+). Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnosis of dementia was assigned through a consensus of experts following biennial cognitive and physical evaluations. Diabetes was diagnosed based on information obtained from participants' extensive medical records. In cases without dementia (n = 125), neuropathologic and biochemical end points did not differ significantly by DM status. However, we observed 2 patterns of injury in patients with dementia (n = 71) by their DM status. Individuals without DM but with dementia (DM-/dementia+) had a greater amyloid-beta peptide load and increased levels of F(2)-isoprostanes in the cerebral cortex, while DM+/dementia+ patients had more microvascular infarcts and an increased cortical IL-6 (interleukin 6) concentration. The number of microvascular infarcts was greater in deep cerebral structures in patients with dementia whose diabetes was treated, whereas amyloid plaque load tended to be greater for untreated diabetic patients with dementia. These novel characterizations of 2 different patterns of cerebral injury in patients with dementia depending on DM status may have etiologic and therapeutic implications. Published online January 12, 2009 (doi:10.1001/archneurol.2008.579).

Patterns of Cerebral Injury and Neurodevelopmental Outcomes After Symptomatic Neonatal Hypoglycemia

Symptomatic neonatal hypoglycemia may be associated with later neurodevelopmental impairment. Brain injury patterns identified on early MRI scans and their relationships to the nature of the hypoglycemic insult and neurodevelopmental outcomes are poorly defined. We studied 35 term infants with early brain MRI scans after symptomatic neonatal hypoglycemia (median glucose level: 1 mmol/L) without evidence of hypoxic-ischemic encephalopathy. Perinatal data were compared with equivalent data from 229 term, neurologically normal infants (control subjects), to identify risk factors for hypoglycemia. Neurodevelopmental outcomes were assessed at a minimum of 18 months. White matter abnormalities occurred in 94% of infants with hypoglycemia, being severe in 43%, with a predominantly posterior pattern in 29% of cases. Cortical abnormalities occurred in 51% of infants; 30% had white matter hemorrhage, 40% basal ganglia/thalamic lesions, and 11% an abnormal posterior limb of the internal capsule. Three infants had middle cerebral artery territory infarctions. Twenty-three infants (65%) demonstrated impairments at 18 months, which were related to the severity of white matter injury and involvement of the posterior limb of the internal capsule. Fourteen infants demonstrated growth restriction, 1 had macrosomia, and 2 had mothers with diabetes mellitus. Pregnancy-induced hypertension, a family history of seizures, emergency cesarean section, and the need for resuscitation were more common among case subjects than control subjects. Patterns of injury associated with symptomatic neonatal hypoglycemia were more varied than described previously. White matter injury was not confined to the posterior regions; hemorrhage, middle cerebral artery infarction, and basal ganglia/thalamic abnormalities were seen, and cortical involvement was common. Early MRI findings were more instructive than the severity or duration of hypoglycemia for predicting neurodevelopmental outcomes.

Patterns of Cerebral Injury in a Primate Model of Preterm Birth and Neonatal Intensive Care

Very preterm birth is associated with significant neurodevelopmental morbidity, with 10% to 15% of these infants later developing cerebral palsy and up to 50% experiencing learning disabilities. The nature of the cerebral lesion predisposing these infants to such impairments is not fully understood but is likely related to both cerebral injury and alterations in cerebral development associated with neonatal intensive care. To study the impact of both preterm birth and neonatal intensive care on the immature brain, we are studying a preterm primate model delivered at 125 days of a 184-day gestational period and cared for in a neonatal intensive care unit for 2 to 4 weeks in a fashion highly similar to that for human preterm infants. The most common neuropathology in this model is white-matter damage manifested by reactive astrogliosis or activated microglia and enlarged ventricular size. Subarachnoid, germinal matrix, and intraventricular hemorrhages are also common. These preliminary results support the similarity of this model to both the alterations in cerebral developmental and the pattern of cerebral injury found in human preterm infants. We are now investigating the impact of randomized respiratory therapies on the pattern of cerebral injury. The prematurely born baboon appears to be an accurate and relevant model for the study of preterm human birth.

Investigation of Cerebral Development and Injury in the Prematurely Born Primate by Magnetic Resonance Imaging and Histopathology

We summarize the preliminary results of brain histopathology and magnetic resonance imaging applied to a premature baboon model developed for evaluation of the pathogenesis and treatment of bronchopulmonary dysplasia. Cerebral development was assessed in 10 gestational control animals at time points of 125, 140 and 160 days of gestation (dg). On the basis of histopathology, conventional MRI and diffusion MRI, 125 dg is equivalent to 26–28 weeks of human gestation, 140 dg is equivalent to 30–32 weeks, and 160 dg is equivalent to term. Preliminary data are also presented for 33 experimental cases delivered at 125 dg, nursed for 2 weeks in an intensive care facility, and sacrificed at 139–140 dg. The commonest neuropathology in this cohort is white matter damage, manifest by reactive astrogliosis or activated microglia, and enlarged ventricular size. Subarachnoid, germinal matrix and intraventricular hemorrhages are also common. These preliminary results support the similarity of this model to the human preterm infant for both cerebral development and the pattern of cerebral injury. The prematurely born baboon appears an important model for the study of preterm human birth.

The Pattern of Cerebral Injury in a Primate Model of Preterm Birth and Neonatal Intensive Care

Survivors of very premature birth face an increased risk of adverse motor, cognitive, and behavior sequelae. In order to understand the pathogenesis of these adverse outcomes, an animal model of premature birth and neonatal care in a species with a close similarity to the human infant is sought. In this histological and immunohistochemical study we have defined the pattern of cerebral injury in a premature baboon model undergoing similar neonatal intensive care to that of the human premature infant. Sixteen baboons were delivered at 125 days gestation (dg; term approximately184 dg) with 14 days neonatal intensive care and were compared with gestational control brains at 125, 140, and 160 dg. The premature baboons undergoing neonatal intensive care sustained a spectrum of neuropathologies including white matter injury, hemorrhage, and ventriculomegaly, which resemble lesions frequently observed in the human premature infant. These data suggest that the premature baboon is a model with similarities in maturation and pattern of cerebral injury to the human infant that may provide useful insights of relevance to the human preterm infant.

Patterns of cerebral injury in a series of infants with congenital diaphragmatic hernia utilizing magnetic resonance imaging

Background Congenital diaphragmatic hernia (CDH) is a condition with significant mortality and respiratory morbidity. Long-term neurodevelopmental outcome is not yet well documented. Methods The authors examined all cases of CDH at their institution over a 12-month period and performed magnetic resonance imaging (MRI) of the brain postoperatively. Results Eight of 10 patients survived to have an MR brain scan. All 8 patients had cerebral injury detected on MRI, with a predominance of white matter and deep nuclear gray matter injury. Conclusions Cerebral injury detected with MRI is common in infants with congenital diaphragmatic hernia. The long-term significance of these MRI abnormalities is unknown, although the need for good long-term neurodevelopmental follow-up of infants with CDH is highlighted.

Patterns of cerebral injury and clinical presentation in the vascular disruptive syndrome of monozygotic twins

The prenatal histories, clinical courses, and neuroradiographic studies of 8 infants who had survived the in utero demise of a homozygous co-twin were reviewed. Three distinct modes of clinical presentation were found: (1) severe neonatal encephalopathy with seizures; (2) a more benign neonatal course with onset of seizures and profound developmental disabilities within the first 6 months of age; (3) late infantile presentation with seizures. Only the third group had milder outcomes. Neuroradiographic studies demonstrated two pathologic patterns: varying degrees of periventricular white matter infarction with migrational abnormalities observed with earlier demise of the co-twin, and multicystic encephalomalacia observed when the demise occurred at or near term. Pathophysiology is uncertain and most likely multifactorial. Exsanguination injury to the survivor can occur acutely following co-twin demise, so urgent delivery may be appropriate at or near term.