Severe Central Nervous System Impairment Research Articles

Continuous Glucose Monitoring in Enterally Fed Children with Severe Central Nervous System Impairment.

This prospective, observational study included nineteen patients (median (25-75 pc) age: 12.75 (6.17-15.55) years) with permanent CNS damage (Gross Motor Function Classification System V) receiving long-term tube enteral feeding, recruited from two paediatric university nutritional treatment centres. Patients with acute conditions and diagnosed diabetes were excluded. The nutritional status and nutritional support were analysed in all the inpatients in accordance with a uniform protocol. Using the CGM system (Medtronic iPro2), glycaemic curves were analysed, and in addition, HbA1C levels were determined in fourteen patients. CGM results were analysed using GlyCulator2.0. Statistical analysis was performed using the Statistica version 11 software (StatSoft Inc. Tulsa, OK, USA). More than half (11/19; 58%) of the patients were undernourished (BMI < 3 pc for age and gender), with the stature age being significantly lower than calendar age (5 (4.5-9) vs. 12.75 (6.17-15.55) years; p = 0.0010). The actual caloric intake was 50 (37.7-68.8) kcal/kg (median; 25-75 pc). In patients fed using the bolus method, the number of calories consumed per day was statistically significantly higher than in children subjected to a continuous feeding supply (56.00 (41.00-75.00) vs. 33.40 (26.70-50.00) kcal/kg BW (body weight; p = 0.0159). Decreases in blood glucose levels below the alarm level (<70 mg/dL) were recorded in fifteen patients (78.9%), including two patients with episodes of clinically significant hypoglycaemia (<54 mg/dL). The minimum and maximum glycaemic values recorded in any individual CGM records were 67 mg/dL (median) (minimum: 41 mg/dL; maximum: 77 mg/dL) and 146 (minimum: 114 mg/dL; maximum: 180 g/dL), respectively, for the entire recording. The maximum percentage of glycaemic concentrations > 140 mg/dL (TAR 140) recorded overnight in children with BMI ≥ 3 amounted to 1.6% vs. 0% in undernourished patients (TAR 140: 0.0 (0.00-1.6%) vs. 0% (0.00-0.0%; p = 0.0375); the percentage of glycaemic concentrations <70 mg/dL in the entire recording was comparable (0.77% (0.13-2.2%) vs. 1.8% (0.5-14.4%) vs. p = 0.2629). There was a positive correlation between the mean daily glucose recorded using the CGM method and patients' BMI z-scores (R = 0.48, p = 0.0397). No statistically significant relationship was demonstrated between the occurrence of alarm hypoglycaemia events in the CGM records and undernutrition expressed by BMI z-scores (OR = 1.50 (95%CI: 0.16-13.75), the type of diet (for commercially manufactured OR = 0.36 (95%CI: 0.04-3.52), and the modality of diet delivery (for bolus feeding OR = 2.75 (95%CI: 0.28-26.61). In children with chronic OU damage, enteral feeding is associated with a risk of hypoglycaemia, but further studies involving a larger number of patients are needed, and CGM might be a useful tool to estimate the metabolic adequacy of enteral nutritional support in terms of glucose control.

Carbamazepine poisoning: A narrow escape

Carbamazepine is an anticonvulsant medication used in the treatment of focal epilepsy, neuropathic pain, and manic-depressive illness. Acute ingestion above the therapeutic range can lead to a range of manifestations ranging from the excessive somnolence to severe life-threatening multi-organ involvement. Here, we present one case of a 1 year-6 month-old girl who was brought to our hospital with a history of accidental ingestion of carbamazepine above therapeutic dose with features of the severe central nervous system impairment. After a stormy course in the pediatric intensive care unit, the child developed neurological sequele but improved after rehabilitation therapy.

Arsenic Neurotoxicity in Humans.

Arsenic (As) contamination affects hundreds of millions of people globally. Although the number of patients with chronic As exposure is large, the symptoms and long-term clinical courses of the patients remain unclear. In addition to reviewing the literature on As contamination and toxicity, we provide useful clinical information on medical care for As-exposed patients. Further, As metabolite pathways, toxicity, speculated toxicity mechanisms, and clinical neurological symptoms are documented. Several mechanisms that seem to play key roles in As-induced neurotoxicity, including oxidative stress, apoptosis, thiamine deficiency, and decreased acetyl cholinesterase activity, are described. The observed neurotoxicity predominantly affects peripheral nerves in sensory fibers, with a lesser effect on motor fibers. A sural nerve biopsy showed the axonal degeneration of peripheral nerves mainly in small myelinated and unmyelinated fibers. Exposure to high concentrations of As causes severe central nervous system impairment in infants, but no or minimal impairment in adults. The exposure dose–response relationship was observed in various organs including neurological systems. The symptoms caused by heavy metal pollution (including As) are often nonspecific. Therefore, in order to recognize patients experiencing health problems caused by As, a multifaceted approach is needed, including not only clinicians, but also specialists from multiple fields.

Anticipating Death in Children and Adults with Childhood Onset Severe Central Nervous System Impairment: A Case Series Review (FR480)

•Discuss problems due to severe central nervous system impairment that can remain intractable to treatment options.•Define tipping points that can prompt anticipatory discussions, including suggested recommendations that best meet goals.•Utilize language strategies that prepare families when prognosis is not possible. Little is written about trajectories and features that precede death in those with childhood onset severe central nervous system (CNS) impairment. This session will cover this topic through a review of deaths at a long-term care facility for children and young adults with severe neurological impairment and associated complex medical care needs. Of the more than 30 deaths, the majority (70%) were anticipated and guided by goals of care. Circumstances that prompted discussions included: problems that can be attributed to the CNS and remained intractable to various interventions, including seizures, recurrent intestinal pseudo-obstruction (hypothalamus and medulla), pain (thalamus), agitation (loss of CNS inhibition), and edema (medulla); increasing symptom burden; and gradual changes in alertness and ability to participate in activities. Details that preceded unexpected deaths will also be reviewed, including several with acute ileus who died following transfer to a hospital. Details will include: the length of time from the redirection of care plans until death, symptom management at the end-of-life, results of tests, prolonged survival following discontinuation of mechanical ventilation, changes in medical nutrition and hydration, and differences in planned vs unexpected deaths. Outcomes in those who survived using the same noninvasive management strategies will be included given the lack of prognostic ability, a time when parents were prepared for their child’s potential death, and how parents responded before and after this experience. This is an important session given the lack of prognostic information, placing such individuals at significant risk for invasive testing and interventions, including surgery, at the end of life. Consideration of testable and “fixable” problems versus problems that can be due to the CNS without confirmatory tests will be discussed. This information will be used to outline “tipping points” that can prompt anticipatory discussions with parents and guardians, with suggested language offered.

Effect of Ginkgo Biloba Leaves Extract on Some Formaldehyde Induced Toxicity in hippocampus of Adult Male Albino Rats

Formaldehyde (FA) heavily impacts the everyday consumer products. It is widely used in the construction, textile, furniture, medical, chemical, and pharmaceutical industries. Exposure to FA poses a significant threat to public health. It can cause severe central nervous system impairment. Extract from the leaves of Ginkgo biloba exerts a novel spectrum of biological, pharmacological and therapeutic properties against oxidative stress, so it was of special concern to investigate the role of Ginkgo biloba leaves extract (GBE) on the neurotoxic effects of FA on hippocampus of adult male albino rats. Thirty adult male albino rats were used in the present study. They were divided into 5 equal groups: Group I negative control, Group II received distilled water by intraperitoneal (i.p.) injection. Group III received GBE (300 mg/kg/day) orally. Group IV received FA (0.2 mg/kg/day i.p. and Group V received 0.2 mg/kg FA + 300 mg/kg GBE. After the end of the study ( 4weeks), all rats were sacrificed and brain were dissected out and hippocampus subjected to estimation of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) catalase (CAT) and malondialdehyde (MDA) levels. Histological examination of the hippocampus and immunohistochemical staining for Glial fibrillary acidic protein (GFAP) were also done. The results of this study revealed that, the levels of SOD, CAT and GSH-Px were significantly decreased, while MDA level in hippocampus tissue were significantly increased in rats treated with FA compared to those of the controls. Microscopic examination of neurons of the hippocampus in this group revealed picnotic nuclei, vacuolar degeneration and neuronal loss. Immunostaining showed areas with significantly increased GFAP immunopositivity. Concomitant administration of GBE with FA resulted in a significant increase in antioxidant enzymes activity (SOD, GSH-Px and CAT), decreased MDA, and improvement of histopathological changes induced by FA. Also a significant reduction in expression of GFAP was observed. It was concluded that short term administration of FA induced neurotoxicity on the hippocampus of adult male albino rats, with oxidant stress and lipid peroxidation which may be a molecular mechanism involved in FA induced neurotoxicity. Furthermore, these effects were decreased by the concomitant use of GBE. It is recommended to use GBE for amelioration of toxic manifestations of formaldehyde in exposed population.

Immunoquantification of β-Glucosidase: Diagnosis and Prediction of Severity in Gaucher Disease

Gaucher disease is an inborn error of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme β-glucosidase (1)(2). Acid β-glucosidase is responsible for the cleavage of the β-glucosidic bond of its primary substrate glucosylceramide, an intermediate in the catabolism of globoside and gangliosides. Gaucher disease is the most prevalent lysosomal storage disorder with an estimated frequency of 1 in 57 000 births in Australia(3). The disease has been broadly classified into 3 clinical subtypes, but a broad spectrum of phenotypes exists within each group(1). Type 1, the most common, is a chronic nonneuronopathic form of the disease associated with various degrees of anemia, thrombocytopenia, hepatosplenomegaly, and bone disease. Clinical onset may occur at any age, but usually occurs after childhood and in some instances does not manifest until later adulthood. Type 2 is an acute neuronopathic form of the disease, characterized by early onset, severe central nervous system impairment, and death, usually by the second year of life. Type 3 is a subacute neuronopathic form, usually with a more chronic course and later onset than type 2. More than 187 mutations in the β-glucosidase gene have been associated with Gaucher disease (4), although there are rare instances of mutations in the prosaposin gene producing a Gaucher phenotype(5). Defined correlations between genotype and phenotype are not overly apparent, and there is broad phenotypic expression among all genotypes. A notable exception is the association of homozygosity for the L444P mutation with neuronopathic disease; similarly, the presence of the N370S allele precludes neuronopathic disease(6)(7). Patients with the nonneuronopathic form of the disease are treated with enzyme replacement therapy (8)(9), which may also slow the progression of neuronopathic disease(10). Early and accurate diagnosis for Gaucher disease, as well as the prediction …

Vitamin E against oxidative damage caused by formaldehyde in frontal cortex and hippocampus: Biochemical and histological studies

Formaldehyde (FA) can cause severe central nervous system impairment. But, there are only a few studies about biochemical and histopathological changes of frontal cortex and hippocampal tissue caused by FA toxicity. The aim of our study was to investigate these changes occurring after chronic formaldehyde toxicity in frontal cortex and hippocampal tissues, and protective effect of Vitamin E (vit E) against oxidative damage. Eighteen rats were divided into three groups: (1) control, (2) treated with FA (FAt), and (3) treated with FA and vit E (FAt + vit E) groups. After the treatment, the animals were sacrificed and frontal cortex and hippocampal tissues were removed for biochemical and histopathological investigation. FA significantly increased tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD) and catalase (CAT) enzyme activities in frontal cortex and hippocampal tissue compared to control. Vit E treatment decreased MDA and PC levels and prevented inhibition of SOD and CAT enzymes in the tissues. In the FAt group, the neurons of both tissues became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in FAt + vit E group was protected well, but not as neurons of the control group. The number of neurons in frontal cortex and hippocampal tissue of FAt group was significantly less than both control and FAt + vit E groups. It was concluded that vit E treatment might be beneficial in preventing FA-induced oxidative frontal cortex and hippocampal tissue damage, therefore, shows potential for clinical use.

Estimation of energy requirements in persons with severe central nervous system impairment

We measured resting metabolic rate (RMR) in 12 persons (aged 10 to 30 years) with severe impairment of the central nervous system requiring gastrostomy feedings, and compared our findings with the RMR predicted from standardized equations. The RMR was 70.6% ± 15.7% of that predicted from the Mayo Clinic nomogram, 63.7% ± 18% of that predicted from the Food and Agriculture Organization/World Health Organization/United Nations University equation, and 75.4% ± 17.3% of that predicted from the Robertson and Reid equation. Energy intake was 756 ± 225 kcal/day and RMR was 708 ± 231 kcal/day; RMR adjusted for changes in body energy stores was 729 ± 231 kcal/day. No significant differences were found between energy intake and RMR, or between energy intake and the sum of RMR and changes in body energy stores. These findings demonstrate that standardized equations overestimate energy needs of individuals with severe CNS impairment. Measures of energy intake adjusted for weight changes represent a valid method to determine energy requirements in a group of individuals with severe CNS impairment. Length was found to be significantly correlated with RMR ( r = 0.79; p <0.01). When the regression equation was tested on another group of subjects from the same residential facility, the equation predicted energy needs reasonably well for those individuals with similar energy intakes but not for all patients with CNS disorders. (J P EDIATR 1995;126:828-32)

Alcohol Abuse, Violence, and Neurological Impairment

The relationship between the frequency and severity of violence and three parameters of alcohol abuse (acuteness, chronicity, and age of onset) was examined retrospectively in a sample of forensic psychiatric patients. Subjects were further compared with respect to electroencephalographic characteristics. Acuteness and chronicity of alcohol abuse were found to be related to severity but not to frequency of violence. Acute alcohol abusers appeared to suffer from more severe central nervous system impairment than did nonabusers. Age of onset of alcohol abuse was found to have little impact on the variables examined. Results are discussed in the framework of empirically derived typologies of psychopathology.