Neurological complications of kernicterus

OBJECTIVE AND BACKGROUND: Prevention of bilirubin encephalopathy relies on the detection of newborns who are at risk of developing serious hyperbilirubinemia. The objective of this study was to reassess the clinical syndrome of kernicterus as neurodiagnostic studies have become more readily available and can be used to evaluate these infants. METHODS: The study population was neonates born at term or near term admitted to The Hospital for Sick Children in Toronto, Ontario, Canada, between January 1990 and May 2000. During the study period, there were 9776 admissions (average number of admissions per year--888 infants). The inclusion criteria were that patients had total serum bilirubin levels of >400 micromol/L at the time of diagnosis and no evidence of hypoxic ischemic encephalopathy. Records were reviewed to establish neurodevelopment outcomes. RESULTS: Twelve neonates (nine males) were identified. Bilirubin levels at the time of diagnosis ranged from 405 to 825 micromol/L. Causes of these elevated levels included glucose-6-phosphate dehydrogenase deficiency (seven patients), dehydration (three patients), sepsis (one patient), and was undetermined in one patient. Abnormal visual evoked potentials were found in three of nine patients and abnormal brainstem auditory evoked potentials in seven of ten patients. Abnormal electroencephalograms were documented in five patients studied. Brain magnetic resonance imaging results were abnormal in three of four patients. CONCLUSIONS: Magnetic resonance imaging typically showed an increased signal in the posteromedial aspect of the globus pallidus and was, therefore, useful in the assessment of the structural changes of chronic bilirubin encephalopathy after kernicterus.     

Magnetic resonance imaging in three children with kernicterus.

The incidence of kernicterus has been greatly reduced by effective monitoring and treatment for hyperbilirubinemia. Findings on magnetic resonance imaging (MRI) in patients with kernicterus are characteristic. This study presents three cases of possible kernicterus without typical symptoms but with MRI features consistent with kernicterus. These cases suggest that kernicterus can develop, especially in preterm infants, in the presence of relatively low levels of bilirubin and the absence of obvious acute symptoms. Therefore assessing the risk of kernicterus may be difficult in the neonatal period. In addition, MRI findings at the posteromedial border of the globus pallidus in patients with athetotic cerebral palsy are strong evidence of brain damage caused by kernicterus.     

Magnetic resonance imaging of the brain in children with chronic kernicterus

Advances in perinatal monitoring and early treatment for hyperbilirubinemia in high-risk patients have greatly reduced the incidence of kernicterus. Findings on MRI in patients with kernicterus are characteristic. The most characteristic pattern of neuropathological lesions in kernicterus is symmetric and highly selective involvement of the basal ganglia. In this study, we report the MRI findings in 2 infants with clinical and laboratory evidence of kernicterus.     

Single photon emission computed tomography and serial MRI in preterm infants with kernicterus

Single photon emission computed tomography was performed in three preterm infants with athetoid cerebral palsy due to kernicterus. No clinical signs and symptoms of kernicterus, or ultrasonographic abnormalities were seen during the neonatal period in any patients. Although MRI during infancy revealed high intensity areas in bilateral globi pallidi in all of them, MRI abnormalities were mild in two of them. On later MRI, subtle high intensity areas in the globi pallidi were recognized in only one of them. Single photon emission computed tomography demonstrated hypoperfusion in the basal ganglia regions in all patients. Regions of interest analyses showed decreased blood flow in the basal ganglia related to the cortical areas. Single photon emission computed tomography will be useful for the diagnosis of kernicterus, whereas MRI abnormalities become less clear beyond infancy.     

Possible mechanisms in infants for selective basal ganglia damage from asphyxia, kernicterus, or mitochondrial encephalopathies

Magnetic resonance imaging and neuropathologic studies have demonstrated remarkably selective patterns of injury to subregions of the basal ganglia in children. Examples are kernicterus and certain mitochondrial encephalopathies, which cause selective injury to the globus pallidus, and near-total perinatal asphyxia, which causes lesions in the putamen and thalamus. To explain the differential vulnerability of nuclei within millimeters of each other, we hypothesize that their locations within the neurotransmitter-specific circuitry of the basal ganglia motor loop are important. In severe hypoxic-ischemic encephalopathy, excitatory glutamatergic pathways into the putamen and thalamus are overactive, but the globus pallidus might be protected because its activity is silenced by inhibitory neuronal activity. In contrast, the relatively high resting neuronal activity in the globus pallidus might make it more vulnerable to less intense, subacute oxidative stresses from mitochondrial toxins such as bilirubin or from genetic mitochondrial disorders. This hypothesis has implications for designing neuroprotective therapies and for treating associated chronic movement disorders.     

Cerebellar axon/myelin loss, angiogenic sprouting, and neuronal increase of vascular endothelial growth factor in a preterm infant with kernicterus

We performed histologic and immunohistochemical analysis of cerebellar sections from a preterm infant (32 weeks 5 days) dead on the 4th day of life with the diagnosis of kernicterus and compared the results with 1 age-matched nonicteric patient. Poorer Luxol fast blue-periodic acid Schiff and Bodian-Luxol fast blue stainings as well as neurofilament expression were observed in the kernicterus case, indicating loss of axon neurites and myelin fibers. Elevated claudin-5 and cluster of differentiation 34 expression associated with increased blood vessel density suggests bilirubin-induced angiogenic sprouting. Upregulation of vascular endothelial growth factor and its receptor 2 was observed in nucleus dentatus and Purkinje neurons. Although upregulation of multidrug resistance-associated protein 1 was increased in cerebellar neurons, it was not able to prevent bilirubin-induced neurotoxicity. These data add new insights into the pathophysiology of kernicterus, revealing vascular endothelial growth factor and its receptor 2, as well as angiogenic sprouting, as new players in neurologic damage by unconjugated bilirubin.     

alpha-Bungarotoxin aggregates on radioiodination with chloramine-T but not with iodogen

The presence of polymer(s) of radioiodinated bungarotoxin (Bgt) in preparations iodinated with chloramine-T or with iodogen, was investigated by chromatography on Sephadex-G50. In addition to a monomeric peak (P2), chloramine-T preparations showed a high content of polymeric forms (16-43%) eluting in the void volume (P1), present only to the extent of 1-3% in iodogen preparations. In purified [125I]Bgt prepared by the iodogen method, the content of P1 increased on treatment with chloramine-T, in the absence of radioiodine. The nonspecific binding of [125I]Bgt to DE-81 filter discs was high in the case of chloramine-T preparations and proportional to the content of P1 in each batch. Purified P1 (polymer) but not P2 (monomer) showed a concentration-dependent high degree of binding to DE-81 discs.     

奎硫平联合舒必利治疗精神分裂症对照研究

目的:比较奎硫平联合舒必利与单用舒必利治疗经奎硫平治疗无效的精神分裂症的疗效和安全性. 方法:105例患者随机分为两组,合用组52例,给予奎硫平联合舒必利治疗;单用组53例,单用舒必利治疗.疗程均8周.于治疗前及治疗2,4、8周,采用阳性与阴性症状量表(PANSS)评定临床疗效;采用治疗中出现的症状量表(TESS)评定药物的安全性. 结果:治疗2～4周,两组PANSS总分及各因子分均较治疗前显著下降(P<0.05或P<0.01);合用组有效率73.1%,单用组有效率64.2%(P>0.05). 结论:奎硫平联合舒必利与单用舒必利治疗对奎硫平无效的精神分裂症疗效相仿.     

急性脑血管病合并睡眠呼吸暂停综合征的临床研究

目的分析急性脑血管病（CVD）患者合并睡眠呼吸暂停综合征（SAS）的发生率和类型,探讨脑血管病（CVD）合并SAS事件的发病机制。方法随机抽取急性CVD患者82例,利用多导睡眠图（PSG）进行睡眠呼吸监测,观察睡眠呼吸监测指标。结果（1）82例急性CVD患者中存在SAS者61例（74．39％）,其中阻塞性睡眠呼吸暂停综合征（OSAS）40例（65．57％）,混合性睡眠呼吸暂停综合征（MSAS）14例（22．95％）,中枢性睡眠呼吸暂停综合征（CSAS）7例（11．48％）;（2）急性CVD患者中存在SAS组的呼吸暂停低通气指数、低氧时间、平均和最低血氧饱和度与不存在SAS组差别显著（P〈0．01）。结论SAS与CVD关系密切,认为SAS是CVD被忽视的危险因素,但不排除CVD诱发了SAS的可能,两者形成恶性循环,影响CVD康复。     

Psychosocial effects on carers of living with persons with dementia

A survey of members of the Alzheimer's Disease and Related Disorders Society confirmed high rates of psychological morbidity, though not of depression, and social isolation in family carers of persons with dementia. Psychological morbidity in carers was associated with having an affected person at home, the carer being a spouse, demanding problem behaviours, poor physical health in the carer, social isolation, dissatisfaction with social supports, greater use of psychotropic medication, and a deteriorated marital relationship. Carers and patients had high rates of consultations with doctors and other health professionals. There was a vulnerable group of carers who were impaired psychologically, socially and physically. The identification of risk factors to carer morbidity may lead to useful interventions.     

奥卡西平联合银杏达莫注射液对癫痫患儿的作用机制研究

目的探讨奥卡西平联合银杏达莫注射液对癫痫患儿T淋巴细胞亚群及血清碱性磷酸酶(ALP)、细胞间黏附分子1(ICAM-1)水平变化的影响。方法选取洛阳市妇女儿童医疗保健中心77例癫痫患儿,按照随机数字表法分组,对照组38例予以单一奥卡西平治疗,观察组39例给予奥卡西平+银杏达莫注射液治疗,观察2组临床治疗效果、T淋巴细胞亚群(CD3+、CD4+、CD8+)及血清ALP、ICAM-1水平变化情况,并统计2组不良反应发生情况及生活质量评分。结果观察组总有效率94.87%(37/39),高于对照组的71.05%(27/38),差异有统计学意义(P0.05)。治疗3个月后观察组CD3+及CD4+均高于对照组,CD8+低于对照组,差异有统计学意义(P0.05)。治疗3个月后2组血清ALP水平比较,差异无统计学意义(P0.05),观察组血清ICAM-1水平低于对照组,差异有统计学意义(P0.05)。观察组不良反应发生率15.38%(6/39),对照组为10.53%(4/38),差异无统计学意义(P0.05)。治疗3个月后观察组社会能力、认知功能、总体健康、生活质量、药物影响、精神健康及生活满意度评分均高于对照组,差异有统计学意义(P0.05)。结论银杏达莫注射液辅助奥卡西平治疗癫痫效果显著,安全性高,可改善患儿血清ICAM-1水平及T淋巴细胞亚群,提高其生活质量。     

Applying EMDR on children with PTSD

Objective To find out child-adjusted protocol for eye movement desensitization and reprocessing (EMDR). Methods Child-adjusted modification were made in the original adult-based protocol, and within-session measurements, when EMDR was used in a randomized controlled trial (RCT) on thirty-three 6–16-year-old children with post-traumatic stress disorder (PTSD). Results EMDR was applicable after certain modifications adjusted to the age and developmental level of the child. The average treatment effect size was largest on re-experiencing, and smallest on hyperarousal scale. The age of the child yielded no significant effects on the dependent variables in the study. Conclusions A child-adjusted protocol for EMDR is suggested after being applied in a RCT for PTSD among traumatized and psychosocially exposed children.     

Communicating with dementia patients on hospice

There are distinct differences in caringfor the "typical " hospice patient as opposed to the hospice patient who has Alzheimer's disease. The entire long-term care team, from volunteers to physicians, can benefit from hospice training in this area. This article addresses this topic in terms of what to be aware of in the disease process, understanding and responding to the caregiver's experience and needs, and, of course, patient care. Particular communication techniques are presented to facilitate interactions with the dementia patient at each of the stages of his or her disease.