Permanent Neurological Sequelae Despite Haemodialysis for Lithium Intoxication

Three patients with lithium toxicity are reported, two of whom were exposed to toxic lithium levels for a prolonged period: both survived with permanent damage to basal ganglia and cerebellar connexions despite effective lowering of lithium levels by haemodialysis. Data obtained during dialysis treatment show prolonged haemodialysis to be the treatment of choice. If facilities for haemodialysis are not available or the patient presents with toxic lithium levels and minimal symptoms peritoneal dialysis will effectively lower serum lithium levels, but more slowly than haemodialysis.     

Psychological Sequelae of Accidental Injury: A Medico-Legal Quagmire

Litigation for personal injury following accidental trauma is an expensive and confused process involving three protagonists: patient, doctor and lawyer. Although post-traumatic conditions can be elaborately classified, the intrinsic validity of such classifications is often questionable. Current methods of evaluating psychological sequelae of accidental injury are inaccurate and unsatisfactory, partly because of the protagonists'' conceptual, motivational and semantic differences. In addition, there is no really satisfactory method of (a) determining and quantifying minor but significant degrees of brain damage, (b) distinguishing these from “post-traumatic neurosis”, or (c) determining the relationship between the trauma and subsequent disturbance of function. Increasingly “expert” advice is solicited but owing to the nature of the data and conditions of examination, such advice does little to clarify the underlying problems. Furthermore, doctors are often unable to communicate effectively to the judiciary just how the trauma has affected the patient. Even though certain suggestions for improvement are advanced, the need for comprehensive, longitudinal research is inescapable.     

West Nile Virus Retinopathy and Associations with Long Term Neurological and Neurocognitive Sequelae

West Nile virus (WNV) has emerged as an important vector-borne pathogen in North America, with more than 3 million estimated to have been infected. Retinopathy from WNV infection has been previously reported in acute cases, though those prior reports did not evaluate the risk of retinopathy based on clinical severity of neurologic disease. The purpose of this cross-sectional study was to perform comprehensive ophthalmological and neurological examinations on 111 patients with a history of West Nile virus infection and describe the ocular manifestations. Out of 111 patients, 27 (24%) had evidence for West Nile virus associated retinopathy (WNVR); this observation was higher (49%) in those patients who initially presented with encephalitis. Individuals with WNVR had more frequent involvement of the macula and peripheral involvement compared to those patients without WNVR (p<0.05). WNVR was also associated with a greater likelihood of abnormal reflexes on neurological exam, poorer learning, greater dependence in activities of daily living, and lower quality of life (p<0.05). WNVR was seen more frequently in elderly patients (age > 60 years), and was associated with higher rates of diabetes mellitus and a history of encephalitis (p<0.05). A multivariable logistic regression revealed that only a history of encephalitis was independently associated with WNVR [Adjusted Odds Ratio = 4.9 (1.8–13.2); p = 0.001]. Our study found that WNVR occurs in one fourth of patients with a history of WNV infection and is more frequently observed in those with apparent severe neurological sequelae (e.g., encephalitis). The clinical relevance of WNVR was supported by its associations with dependence in activities of daily living and lower quality of life. This unique evaluation of WNV patients included fundoscopic examinations and their associations with neurologic impairment. Our findings can be used during ophthalmological consultation for the evaluation, treatment and rehabilitation phases of care for WNV patients.     

Burden of Invasive Group B Streptococcus Disease and Early Neurological Sequelae in South African Infants

Introduction

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0–6 days of life, EOD) and late-onset (7–89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women.

Methods

A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age.

Results

We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24–9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94–386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44–49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17–10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44–120.95) greater in cases (13.2%) than controls (0.4%).

Discussion

The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting.     

Prenatal Treatment for Serious Neurological Sequelae of Congenital Toxoplasmosis: An Observational Prospective Cohort Study

Background

The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known.

Methods and Findings

Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07–0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2–15) after maternal seroconversion at 10 weeks, and 18 (9–75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21–2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%–38.1%).

Conclusion

The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection. Please see later in the article for the Editors'' Summary     

Effect of Noncompetitive Blockade of N-Methyl-d-Aspartate Receptors on the Neurochemical Sequelae of Experimental Brain Injury

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia, and improves neurological outcome after experimental spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate receptor blocker MK-801 on neurochemical sequelae following experimental fluid-percussion brain injury in the rat. Fifteen minutes after fluid-percussion brain injury (2.8 atmospheres), animals received either MK-801 (1 mg/kg, i.v.) or saline. MK-801 treatment significantly attenuated the development of focal brain edema at the site of injury 48 h after brain injury, significantly reduced the increase in tissue sodium, and prevented the localized decline in total tissue magnesium that was observed in injured tissue of saline-treated animals. Using phosphorus nuclear magnetic resonance spectroscopy, we also observed that MK-801 treatment improved brain metabolic status and promoted a significant recovery of intracellular free magnesium concentrations that fell precipitously after brain injury. These results suggest that excitatory amino acid neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive N-methyl-D-aspartate receptor antagonists may effectively attenuate some of the potentially deleterious neurochemical sequelae of brain injury.     

Lack of Pupil Reflex and Loss of Consciousness Predict 30-Day Neurological Sequelae in Patients with Carbon Monoxide Poisoning

Background

Predicting the neurological sequelae of carbon monoxide poisoning (COP) has not been well studied. We investigated the independent predictors of neurological sequelae in patients with COP and combined these predictors to predict the prognosis.

Methods

This study was conducted at four hospitals in Shandong Province, China. Data were retrospectively collected from 258 patients with COP between November 1990 and October 2011. Thirty-day neurological sequelae were the primary endpoints.

Results

A lack of pupil reflex and a loss of consciousness appear to be independent predictors for neurological sequelae in patients with COP. The presence of either one had a sensitivity of 77.0% (95% confidence interval [CI]: 69.3–83.2), a specificity of 47.1% (95% CI: 38.3–56.0), positive predictive value (PPV) of 62.9% (95% CI: 55.2–70.1), and a negative predictive value (NPV) of 63.6% (95% CI: 52.6–73.4). With both predictors present, the sensitivity was 11.5% (95% CI: 6.9 to 18.3), the specificity was 99.2 (95% CI: 94.7–100.0), the PPV was 94.1% (95% CI: 69.2–99.7), and the NPV was 49.0% (95% CI: 42.5–55.5).

Conclusions

The risk for neurological sequelae apparently increased with the number of independent predictors. In patients with both predictors, the risk for neurological sequelae was 94.1%. Almost all (99.2%) patients with neither predictor had no neurological sequelae. This finding may help physicians make decisions about and dispositions for patients with COP. For patients with a higher risk, earlier treatment and more appropriate utilization of health care services, including hyperbaric oxygen, should be considered.     

Neurorestorative Targets of Dietary Long-Chain Omega-3 Fatty Acids in Neurological Injury

Long-chain omega-3 polyunsaturated fatty acids (LC-O3PUFAs) exhibit therapeutic potential for the treatment and prevention of the neurological deficits associated with spinal cord injury (SCI). However, the mechanisms implicated in these protective responses remain unclear. The objective of the present functional metabolomics study was to identify and define the dominant metabolic pathways targeted by dietary LC-O3PUFAs. Sprague-Dawley rats were fed rodent purified chows containing menhaden fish oil-derived LC-O3PUFAs for 8 weeks before being subjected to sham or spinal cord contusion surgeries. We show, through untargeted metabolomics, that dietary LC-O3PUFAs regulate important biochemical signatures associated with amino acid metabolism and free radical scavenging in both the injured and sham-operated spinal cord. Of particular significance, the spinal cord metabolome of animals fed with LC-O3PUFAs exhibited reduced glucose levels (?48 %) and polar uncharged/hydrophobic amino acids (less than ?20 %) while showing significant increases in the levels of antioxidant/anti-inflammatory amino acids and peptides metabolites, including β-alanine (+24 %), carnosine (+33 %), homocarnosine (+27 %), kynurenine (+88 %), when compared to animals receiving control diets (p?N-acetylglutamate (+43 %) and acetyl CoA levels (+27 %), respectively. Interestingly, this dietary intervention resulted in a global correction of the pro-oxidant metabolic profile that characterized the SCI-mediated sensorimotor dysfunction. In summary, the significant benefits of metabolic homeostasis and increased antioxidant defenses unlock important neurorestorative pathways of dietary LC-O3PUFAs against SCI.     

Hemorrhage Control of Liver Injury by Short Electrical Pulses

Trauma is a leading cause of death among young individuals globally and uncontrolled hemorrhage is the leading cause of preventable death. Controlling hemorrhage from a solid organ is often very challenging in military as well as civilian setting. Recent studies demonstrated reversible vasoconstriction and irreversible thrombosis following application of microseconds-long electrical pulses. The current paper describes for the first time reduction in bleeding from the injured liver in rat and rabbit model in-vivo. We applied short (25 and 50 µs) electrical pulses of 1250 V/cm to rats and rabbit liver following induction of standardized penetrating injury and measured the amount of bleeding into the abdominal cavity one hour post injury. We found a 60 and 36 percent reduction in blood volume in rats treated by 25 µs and 50 µs, respectively (P<0.001). Similar results were found for the rabbit model. Finite element simulation revealed that the effect was likely non-thermal. Histological evaluation found local cellular injury with intravascular thrombosis. Further research should be done to fully explore the mechanism of action and the potential use of short electric pulses for hemorrhage control.     

莫诺苷对大鼠局灶性脑缺血再灌注损伤神经功能的影响

目的观察中药山茱萸的有效成分莫诺苷对大鼠局灶性脑缺血再灌注后神经功能的影响。方法Wistar雄性大鼠随机分为假手术组、模型组、莫诺苷小剂量组（30 mg/kg）、莫诺苷中剂量组（90 mg/kg）、莫诺苷大剂量组（270 mg/kg）、维生素E（VE）（35 mg/kg）,采用线栓法制作大鼠局灶性脑缺血再灌注模型,缺血30 min后再灌注3 d,应用Zea Longa法、爬网格、平行木、吊绳、Ludmila Belayev 12分评分法,观察莫诺苷对神经功能缺损的改善作用。结果与模型组比较,莫诺苷给药组（小、中、大剂量）Zea Longa法评分均差异极显著（P〈0.01）;与模型组比较,莫诺苷给药组（小、中、大剂量）吊绳法评分均差异极显著（P〈0.01）;Ludmila Belayev 12分评分法评分与模型组比较,莫诺苷大剂量组差异极显著（P〈0.001）,中剂量组差异极显著（P〈0.01）。结论莫诺苷对局灶性脑缺血再灌注模型大鼠有改善行为学评分的作用。     

The Ocular Sequelae of Third Cranial Nerve Palsy

The ocular sequelae in nineteen patients who had suffered from a complete paralysis of the third cranial nerve were analyzed. In eleven of these patients, the paralysis was associated with an aneurysm of the internal carotid artery system. None of the cases in this group showed complete recovery of the third nerve function; however, six recovered sufficiently to permit binocular single vision in most fields of gaze. Two cases of aberrant regeneration of the third nerve were diagnosed.Trauma accounted for four cases of third nerve paralysis. One of these recovered completely and one showed features of aberrant regeneration. Of the cases of oculomotor paralysis associated with herpes zoster ophthalmicus, encephalitis, or an obscure etiology (two cases), all recovered completely.     

Clofibrate and Fat Embolism: A Double-Blind Trial of the Effects of Clofibrate on Sequelae to Injury

In a double-blind prospective trial clofibrate was found not to influence significantly the clinical and laboratory indices thought to reflect the state of fat embolism in patients with fractures.     

The Sequelae of Acute Purulent Meningitis in Childhood

Of a series of 122 children suffering from acute purulent meningitis at the Children''s Hospital, Winnipeg, in the years 1952-56, 12 (9.8%) succumbed, all deaths occurring in those 12 months of age or less. Fortyone of the survivors were re-studied 2.5 to 7.5 years after their acute illness to assess the nature and incidence of sequelae, the relationship of sequelae to the severity of the acute illness, and the correlation between the various methods of identifying sequelae. Five children exhibited psychiatric evidence of organic brain damage; seven, neurological abnormality; 11, electroencephalographic abnormality. Three had defective intelligence and nine psychological test evidence of organic brain damage. Children with sequelae tended to have several abnormal test results, the total number with neuropsychiatric and/or psychological sequelae being 11 (26%). There was a positive correlation between the severity of the acute illness and the presence of neuropsychiatric sequelae; also between neuropsychiatric sequelae, defective intelligence and psychological evidence of brain damage. No correlation existed between the electroencephalographic abnormality and neuropsychiatric defect.