Central Nervous System Impairment Research Articles

Global developmental delay, osteopenia and ectodermal defect: A new syndrome

Global developmental delay is a serious social problem. It is often unrecognized and the phenotypes are inadequately studied. To investigate the phenotypes of children with aspecific central nervous system (CNS) impairment (poor speech, maladaptive behavioral symptoms such as temper tantrums, aggressiveness, poor concentration and attention, impulsiveness, and mental retardation). Setting. Tertiary care hospital. Patients: Three children (two male siblings, and one unrelated girl). Methods: We used the results from clinical neurological evaluations; imaging and electrodiagnostic studies; metabolic and genetic tests; skin biopsies and bone mineral densitometry. All three children suffered from (A) global developmental delay, (B) osteopenia, and (C) identical skin defects. The skin ultrastructural abnormalities were [1] abnormal keratin differentiation, consisting of hyperkeratosis and granular layer thickening; [2] sweat gland abnormalities, consisting of focal, cytoplasmic clear changes in eccrine secretory cells; and [3] melanocyte abnormalities, with both morphological changes (reduced number and size without evident dendritic processes), and functional changes (defects in the migration of melanosomes in the keratinocytes). These patients present a previously unrecognized syndrome. We retain useful to report this new association, to be recognized, in the next future, as a specific key-sign of a well-defined genetic defect.

Congenital cytomegalovirus infection following first trimester maternal infection: Symptoms at birth and outcome

Background The relationship between gestational age at time of maternal cytomegalovirus (CMV) infection and outcome of fetal infection is not well defined because the timing of maternal infection is usually not known. Objective To determine whether congenital cytomegalovirus (CMV) infection following primary maternal infection during the first trimester of pregnancy is more likely to lead to central nervous system (CNS) sequelae than fetal infection due to maternal infection later in pregnancy. Study design Using serum collected during pregnancy from mothers of newborns with congenital CMV infection, maternal infection was categorized as first trimester (<13 weeks) or later based on dates and results of IgG and IgM assays for CMV antibody. Outcome of congenital CMV infection was assessed by longitudinal fotlow-up of the infected cohort. Results Sensorineural hearing loss was found in 8/34 (24%) of children in the first trimester group, compared with 1/40 (2.5%) in the later infection group ( P = 0.01, relative risk, 9.6). Considering any CNS sequela (hearing loss, mental retardation, cerebral palsy, seizures, chorioretinitis) 11/34 (32%) first trimester cases were affected compared with 6/40 (15%) in the later infection group ( P = 0.07, relative risk 2.2). None of the later group had more than one sequela, compared with 4 (12%) of the first trimester group ( P = 0.04). Conclusions Children with congenital CMV infection following first trimester maternal infection are more likely to have CNS sequelae, especially sensorineural hearing loss, than are those whose mothers were infected later in pregnancy. However, some degree of CNS impairment can follow even late gestational infection.

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 …

Experimental Diabetes Attenuates Cerebral Cortical−Evoked Forelimb Motor Responses

Poorly controlled diabetes leads to debilitating peripheral complications, including retinopathy, nephropathy, and neuropathy. Chronic diabetes also impairs the central nervous system (CNS), leading to measurable deficits in cognition, somatosensory, and motor function. The cause of diabetes-associated CNS impairment is unknown. In this study, sustained hyperglycemia resulting from insulin deficiency was shown to contribute to CNS motor dysfunction. Experimental diabetes was induced in rats by streptozotocin (STZ) injection. CNS motor function was assessed by intracortical microstimulation of the sensorimotor cortex. Experimental diabetes significantly (P < 0.01; n = 14) attenuated the number of motor cortical sites eliciting forelimb movements. The net area of the motor cortex representing the forelimb in diabetic rats was significantly reduced (4.0 +/- 0.5 [control] vs. 2.4 +/- 0.4 [STZ] mm(2); P < 0.05). Experimental diabetes attenuated the activation of some, but not all, forelimb motor cortical neurons. Insulin treatment of diabetic rats prevented the attenuation of cortical-evoked forelimb responses. Peripheral nerve-evoked responses were unaffected by this short period of diabetes, suggesting the absence of peripheral nerve dysfunction. This study showed that metabolic imbalance resulting from insulin deficiency elicits a marked attenuation of cortical-evoked motor function. Uncontrolled hyperglycemia, deficiencies of central insulin, or both may contribute to corticospinal motor dysfunction.

Effects of fexofenadine and hydroxyzine on brake reaction time during car-driving with cellular phone use

Antihistamines are a mainstay treatment for allergic rhinitis; however, many older agents cause adverse events, including sedation and central nervous system (CNS) impairment. Research has shown sedating effects of antihistamines on driving; currently, no known study has examined whether cellular phone usage while driving further compounds impairment in individuals administered antihistamines. The aim of this study was to examine this endpoint. In a randomized, double-blind, placebo-controlled, three-way crossover study, healthy volunteers received fexofenadine HCl 120 mg, hydroxyzine HCl 30 mg and placebo. Brake reaction time (BRT) was used to examine driving performance across four conditions: driving only; driving while completing simple calculations; complex calculations; and conversing on a cellular phone. Subjective sedation assessments were also conducted. Brake reaction time with and without cellular phone usage in fexofenadine-treated subjects did not differ significantly from placebo in any condition. In contrast, hydroxyzine-treated subjects were significantly more sedated and had slower BRTs, suggesting slower hazard recognition and brake application, compared with the fexofenadine and placebo groups in all conditions. Importantly, cellular phone operation was an additive factor, increasing BRTs in hydroxyzine-treated volunteers. Fexofenadine did not impair CNS function in subjects involved in a divided attention task of driving and cellular phone operation.

“One More for My Baby”: Foetal Alcohol Syndrome and its Implications for Social Workers

Foetal alcohol syndrome has been described as the commonest preventable cause of mental retardation in the Western world. It refers to a pattern of malformations, growth retardation and central nervous system impairments found in children of mothers who drink large amounts of alcohol while they are pregnant. This paper describes the nature of foetal alcohol syndrome and the related condition of foetal alcohol effect, presents findings from a study of young children in the care of social services in Northern Ireland and discusses the implications for Social Workers working with affected children and families.

Gender related effects of heroin abuse on the simple reaction time task

Accumulated studies have demonstrated that there are serious negative consequences of drug abuse, especially the impairment of central nervous system (CNS) function. The simple reaction time (SRT) is the simplest model of measuring the function of the CNS. The purpose of the present study is to examine whether the SRT is affected by heroin abuse and whether such drug effect, if exists, is gender related. We found significant slowing of the SRT in both male and female heroin dependent patients at 1–3 months from withdrawal. However, the SRT slowing remitted after 3 months of abstinence in heroin dependent males but not in females. Our results suggested that the SRT is slowed by heroin abuse and such slowing is gender related.

Drug-induced aseptic meningitis in suspected central nervous system infections

This study presents eight patients with drug-induced aseptic meningitis (DIAM) admitted to our centre with an initial suspicion of central nervous system (CNS) infection. In all patients clinical findings, cerebrospinal fluid (CSF) examination, a cause-effect relationship according to the Naranjo adverse drug reactions probability scale and other diagnostic criteria required for DIAM recognition, were fulfilled. Nonsteroidal anti-inflammatory drugs were the most frequent cause of DIAM. In two cases, there was previous antimicrobial use. The time between use of the causative drug and onset of the symptoms ranged from 2 to 7 days. Clinical symptoms and CSF findings in patients with DIAM are indistinguishable from the early stage of infections of the CNS. Detailed anamnesis is essential, particularly related to medication use immediately prior to the appearance of symptoms of CNS impairment. In conclusion, the differential diagnosis of CNS infections should include DIAM.

Genetic Polymorphisms inCX3CR1Predict HIV‐1 Disease Progression in Children Independently of CD4+Lymphocyte Count and HIV‐1 RNA Load

The impact of CX3CR1 polymorphisms on human immunodeficiency virus type 1 (HIV-1) pathogenesis is controversial, with conflicting reports of their role in disease progression in HIV-1-infected adults. A cohort of 1055 HIV-1-infected children were genotyped for 2 CX3CR1 polymorphisms, V/I249 and T/M280, and their impact on HIV-1-related disease progression, including central nervous system (CNS) impairment, was evaluated. Children with the CX3CR1 I/I249 genotype experienced more-rapid disease progression (I/I249 vs. V/V249: relative hazard [RH], 2.19 [95% confidence interval {CI}, 1.30-3.68], P=.003; I/I249 vs. V/I249: RH, 1.77 [95% CI, 1.00-3.14], P=.05) and a trend toward more CNS impairment (I/I249 vs. V/V249: RH, 2.19 [95% CI, 1.00-4.78], P=.049; I/I249 vs. V/I249: RH, 2.02 [95% CI, 0.85-4.83], P=.11). Children with the V249-T280 haplotype experienced significantly less disease progression (RH, 0.42 [95% CI, 0.24-0.73]; P=.002) and CNS impairment (RH, 0.39 [95% CI, 0.39-0.22]; P=.001). Of note, these effects remained significant after CD4+ lymphocyte count and plasma HIV-1 RNA load at baseline were adjusted for and in a longitudinal, multivariate analysis. CX3CR1 genotypes and haplotypes impact HIV-1 disease progression independently of CD4+ lymphocyte count and plasma HIV-1 RNA load, suggesting that the fundamental role of CX3CR1 in the alteration of disease progression might be the recruitment of immunomodulatory cells responsible for the control of HIV-1.

Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis

A 35-year-old male with an 11-year history of intestinal pseudo-obstruction associated with an idiopathic inflammatory insult of the myenteric plexus and the presence of circulating anti-Hu antibodies developed a neurological syndrome characterized by bilateral hearing loss, deteriorating balance, an unsteady gait and difficulty in estimating distances. A similar neurological syndrome has previously been described in older patients among the paraneoplasic syndromes associated with small-cell lung carcinoma and the presence of circulating anti-Hu antibodies, but never in the rare cancer-free patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction. The patient underwent a steroid treatment. No further episodes of functional intestinal obstruction were observed and, after an initial improvement, the neurological symptoms stabilized, leaving a permanent reduction in hearing function and an unsteady gait. The case shows that an idiopathic inflammatory insult of the myenteric plexus may precede (and perhaps lead to) central nervous system impairment in patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction.

Pediatric Allergic Rhinitis: Factors Affecting Treatment Choice

Allergic rhinitis is the mostprevalent chronic allergic disease in children. Although it is not life-threatening, it can have a significantly detrimental effect on a childs quality of life, and it may exacerbate a number of common comorbidities, including asthma and sinusitis. The Allergic Rhinitis and its Impact on Asthma guidelines, an evidence-based algorithm for the treatment of allergic rhinitis, advocate the use of antihistamines for the treatment of the broad spectrum of the disease. However, first-generation antihistamines are associated with a number of adverse events, including central nervous system impairment and anticholinergic and cardiovascular effects. Moreover, these agents have not been rigorously tested in the pediatric population. Nevertheless, first-generation antihistamines remain the most frequently prescribed agents in this class of drugs. This is despite the fact that the second-generation antihistamines are largely free of the undesirable side effects associated with their predecessors and the fact that they have been shown to be effective in relieving allergic rhinitis symptoms in children in a number of large-scale clinical trials. Therefore, when selecting an antihistamine for a child, it would be prudent to consider the full range of antihistamines and to base the selection of a particular drug on its efficacy, onset and duration of action, and safety profile.

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.

Physiological and pathological aspects of GSH metabolism

The antioxidant glutathione is found in low levels in diseases in which increasing evidence implicate oxidative stress in the development of the disease, for example retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, patent ductus arteriosus and asthma. Glutathione is metabolized in the gamma-glutamyl cycle, which involves six different enzymes. The synthesis of glutathione is a two-step process in which the first step is catalysed by gamma-glutamylcysteine synthetase and the second step by glutathione synthetase. Glutathione synthetase deficiency is an autosomal recessive disease and the most common inborn error of the gamma-glutamyl cycle. Approximately 25% of patients with hereditary glutathione synthetase deficiency die during childhood. Patients present with a clinical picture ranging from compensated haemolytic anaemia to a complex disorder with additional symptoms like 5-oxoprolinuria, metabolic acidosis and central nervous system impairment. Even though the correlation between phenotype and genotype in these patients is complex, an indication of the phenotype can be based on the type of mutation involved. Also, there is a correlation between the glutathione synthetase activity and the level of glutathione in cultured fibroblasts. Inborn errors have also been described in three additional steps of the y-glutamyl cycle, namely gamma-glutamyl-transpeptidase, 5-oxoprolinase and gamma-glutamylcysteine synthetase. The range of disorders in patients with inborn errors in the metabolism of glutathione illustrates the intricate metabolism of glutathione and its involvement in numerous essential processes in the cell. By studying these patients, further insight into the functions and metabolism of glutathione can be achieved.

Prenatal methylazoxymethanol exposure alters evoked responses in fetal rats

Although there is considerable interest in identifying methods to detect central nervous system impairment early in development, few behavioral assessment tools are available for detecting CNS deficits in the fetus. In the present study, methylazoxymethanol [MAM; Midwest Research Institute, (MRI)] was used to induce deficits in CNS development in fetal rats to assess effects on coordinated fetal behavior. Fetuses were exposed by administering MAM to pregnant rats on E17 of gestation via intraperitoneal injection and then were prepared for behavioral testing 3 days later on E20. After externalization from the uterus into a warm saline bath, fetal subjects received either an intraoral infusion of lemon extract to evoke a facial wiping response or were presented with an artificial nipple to evoke an oral grasping response. Interlimb coordination and paw–face contact during facial wiping were disrupted in MAM-exposed fetuses. Similarly, MAM exposure diminished the ability of fetuses to grasp or maintain oral contact with the artificial nipple. Although clear disruptions of movement coordination were seen in the MAM-treated subjects, there were no significant differences from saline controls in weight or anatomical measures. Together, these findings suggest that behavioral assessments of fetal motor coordination may be useful in identifying neural insult during prenatal development.

Coping styles among families of children with HIV infection

The primary aim of this study was to examine coping strategies among families of HIV-infected children and how they relate to medical, central nervous system (CNS) and family environment factors. Caregivers of HIV-positive children (N=52) completed a family coping measure (F-COPES) and provided information regarding family environment. Data regarding medical and CNS status were obtained from patient records. Results indicated that families’ passive coping and spiritual support were among the coping techniques used most often, and social support was used least often. Medical variables were unrelated to any coping styles. Families of children with CNS impairment endorsed more passive coping techniques than families of children with no apparent deficits. A trend was found for non-biological caregivers to seek out more community resources and support than biological caregivers. Findings suggest the need to target families least likely to utilize resources, and to teach them to effectively seek out and benefit from social and community supports.

Until the Crisis Is Over

Until the Crisis Is Over

Lack of protective effects of interleukin-4 -589-C/T polymorphism against HIV-1-related disease progression and central nervous system impairment, in children.

The interleukin (IL)-4 -589-C/T polymorphism has been reported to protect against human immunodeficiency virus type 1 (HIV-1)-related disease progression in white adults. In the present study, the effect of the IL-4 -589 polymorphism on HIV-1-related disease progression was evaluated in a seroprevalent cohort of 1043 children. The IL-4 -589-T allele was more prevalent in Hispanic and in black, non-Hispanic children, compared with white, non-Hispanic children. We found that the IL-4 -589-C/T polymorphism does not affect the risk of HIV-1-related disease progression or central nervous system impairment in children, and this did not differ by race/ethnicity. Our findings suggest that the IL-4 -589-C/T polymorphism is not an important determinant of HIV-1 disease progression in children.

Multiple cerebral abscesses as a complication of Mycobacterium fortuitum infection

Mycobacterium fortuitum is a rapidly growing, nontuberculous mycobacteria that has rarely been associated with central nervous system impairment. We describe the case of a patient who developed multiple cerebral abscesses revealing Mycobacterium fortuitum infection. Brain biopsy specimens showed suppurative, noncaseating, granulomatous inflammation consisting of epithelioid histiocytes and multinucleated giant cells. All clinical signs and CT scan cerebral lesions disappeared after institution of appropriate antimycobacterial therapy.

Hydrocarbon poisoning in children: a 5-year retrospective study.

To investigate the demographics, incidence, and symptoms and signs of hydrocarbon poisoning in admitted children from the Negev Desert area of Israel. The medical records of all children admitted for hydrocarbon poisoning from 1995 to 1999 were reviewed retrospectively. Of the 274 admitted children, 61% were boys and 39% were girls, with ages ranging from 6 months to 18 years (median, 1.58 years). Ninety-four percent of the patients were Moslem Arab Bedouins, and 6% were Jews. The largest group of patients (106) was admitted during the summer months (P < .003). Also, more patients were admitted in spring (63) and autumn (67) than in winter (38) (P < .013). Thirty-two percent of the cases were seen in the Pediatrics Ambulatory Unit and then discharged, while 68% were hospitalized. The most commonly observed symptoms were tachypnea (73.7%), fever (63.5%), vomiting (51.1%), and cough (38.0%). About one third of the patients showed signs of central nervous system (CNS) impairment, including drowsiness, restlessness, stupor, and convulsions. These symptoms were significantly correlated with pneumonia, hypoxemia, and fever (P < .001). Of 274 patients, 43% (118 children) had pneumonia--usually interstitial pneumonitis (90%). Vomiting was significantly correlated with pneumonia (P < .05). 1) There is a higher risk of hydrocarbon poisoning during the hot months of the year; 2) the respiratory system is the main target organ affected; 3) pneumonia is in most cases interstitial and bilateral; 4) vomiting after hydrocarbon ingestion is related to the rate of development of pneumonia; 5) symptoms of CNS impairment were correlated with hypoxemia, pneumonia, and fever; and 6) CNS toxicity may occur without hypoxemia, concurrent pulmonary pathology, or other pathology.

Anesthetic considerations in the child with myelomeningocele

Summary It is encouraging that the prevalence of myelomeningocele is declining. Owing to advances in medicine and surgery, these patients are living longer and more productive lives. It is inevitable, however, that to achieve full productivity, these patients will undergo many surgical procedures. Anesthesiologists must be knowledgeable about the central nervous system and respiratory impairment that is a prominent feature of this anomaly in order to intelligently provide care.