Cerebral Palsy

PURPOSE OF REVIEW: Recombinant factor VIIa (rFVIIa) and thromboelastography have acquired increasing importance in patients with severe bleeding and coagulopathy. This article reviews the current opinions regarding their use, with the purpose of clarifying the ambiguities that exist in dealing with trauma patients. RECENT FINDINGS: Recent evidence encourages the early use of rFVIIa and thromboelastography in the severe trauma patient with hemorrhagic shock, as a component of the damage control strategy. rFVIIa may decrease short-term mortality and the rate of required blood components during resuscitation, with no apparent increase in thromboembolic complications. Thromboelastometry enables better and earlier recognition of the coagulopathy accompanying such trauma patients. In patients with traumatic brain injury and coagulopathy, rFVIIa may delay or even halt the need for surgery, with no proven decrease in mortality. In those who needed urgent neurosurgical intervention, rFVIIa may rapidly correct the coagulopathy, enabling earlier and safer surgical intervention. SUMMARY: Thromboelastometry may guide the medical staff when and to whom rFVIIa could be administered. Evidence also encourages the use of rFVIIa in traumatic brain injury. More research is required to prove decreases in mortality using both thromboelastography and rFVIIa in trauma, with a focus on clear end points and goal-directed therapy.

BACKGROUND AND PURPOSE: Lacunar ischemic stroke accounts for 25% of all ischemic strokes, but the exact etiology is unknown. Numerous pathophysiologies have been proposed, including atheroma and endothelial dysfunction. Models of any of these pathological features would aid understanding of the etiology and help develop treatments for lacunar stroke. We therefore aimed to assess the relevance of all available potential animal models of lacunar stroke. METHODS: We systematically reviewed the published literature for animal models that could represent lacunar stroke using validated search strategies. We included studies that could represent an aspect of lacunar stroke as well as those aiming to model conditions with potentially similar pathology and extracted data on species, induction method, and resulting brain and vessel lesions. RESULTS: From 5670 papers, 41 studies (46 papers) met inclusion criteria representing over 10 different classes of stroke induction. Important data like infarct size and animal numbers were often missing. Many models’ infarcts were too large or affected the cortex. Emboli mostly caused cortical but not small subcortical lesions. Most models focused on creating ischemic lesions in brain tissue. Only one (spontaneous lesions in spontaneously hypertensive stroke-prone rats) also mimicked small vessel pathology. Here, the precursor to small vessel and brain damage was blood-brain barrier failure. CONCLUSIONS: Some animal models produce small subcortical infarcts, but few mimic the human small vessel pathology. Models of small vessel disease could help improve understanding of human lacunar disease, particularly to clarify factors associated with the small vessel morphological changes preceding brain damage. Much lacunar stroke may arise after blood-brain barrier disruption.

In Alzheimer’s disease (AD) mitochondrial abnormalities occur early in the pathogenic process and likely play a significant role in disease progression. Tau is a microtubule-associated protein that is abnormally processed in AD, and a connection between tau pathology and mitochondrial impairment has been proposed. However few studies have examined the relationship between pathological forms of tau and mitochondrial dysfunction. We recently demonstrated that inducible expression of tau truncated at Asp421 to mimic caspase cleavage (T4C3) was toxic to immortalized cortical neurons compared to a full-length tau isoform (T4). In this study we investigated the effects of T4C3 on mitochondrial function. Expression of T4C3 induced mitochondrial fragmentation and elevated oxidative stress levels in comparison with T4-expressing cells. Thapsigargin treatment of T4 or T4C3 cells, which causes an increase in intracellular calcium levels, resulted in a significant decrease in mitochondrial potential and loss of mitochondrial membrane integrity in T4C3 cells when compared to cells expressing T4. The mitochondrial fragmentation and mitochondrial membrane damage were ameliorated in T4C3 cells by pre-treatment with cyclosporine A or FK506, implicating the calcium dependent phosphatase calcineurin in these pathogenic events. Increased calcineurin activity has been reported in AD brain, and thus inhibition of this phosphatase may provide a therapeutic target for the treatment of AD.

NMO-IgG, the auto-antibody specific to the aquaporin-4 (AQP4) water channel associated with the autoimmune inflammatory disease neuromyelitis optica (NMO), is considered to be an accurate serum biomarker and is thought to be an important contributor to NMO pathology. In this review, we summarize recent evidences from our group and others indicating that NMO-IgG can be implicated at several levels in the immuno-pathology of NMO. NMO-IgG/anti-AQP4 antibodies may compromise the integrity of the blood-brain barrier and consequently facilitate and enhance the perivascular inflammation characteristic of NMO. Lastly, NMO-IgG can induce astrocyte injury which may lead to accumulation of excitatory/toxic molecules and accordingly damage oligodendrocytes and compromise myelin integrity.

Artificial grammar learning (AGL) is one of the most extensively employed paradigms for the study of learning. Grammaticality is one of the most common ways to index performance in AGL. However, there is still extensive debate on whether there is a distinct psychological process which can lead to grammaticality knowledge. An application of the COVIS model of categorization in AGL suggests that grammaticality might arise from a hypothesis-testing system (when grammaticality is appropriately balanced with other knowledge influences), so that prefrontal cortex damage should be associated with impaired grammaticality and intact chunk strength performance. This prediction was confirmed in a study of traumatic brain injury (TBI) patients and matched controls. The TBI patient cohort had diffuse prefrontal cortex damage as evidenced by the history of their injury, CT scans, and severe executive functioning problems. Our results allow a novel interpretation of grammaticality and AGL in general.

Background: Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by clinical investigations and animal experiments. It has been posited that elevated levels of Hcy mediate DNA damage, brain atrophy, and excitotoxicity. The current study sought to elucidate the effect of vitamin E on ethanol-induced hyperhomocysteinemia, DNA damage, and atrophy in the developing hippocampus and cerebellum of rats. Methods: Pregnant Wistar rats received ethanol with or without vitamin E from gestation day 7 throughout lactation. Weight changes in the brain, hippocampus and cerebellum, DNA damage, and Hcy levels in the plasma, hippocampus, and cerebellum of male offspring were measured at the end of lactation. Results: The results revealed that along with a significant decrease in brain, cerebellum, and hippocampus weights in animals that received alcohol, the levels of DNA damage and Hcy significantly increased. Significant amelioration of brain atrophy and DNA damage as well as restoration of the elevated level of Hcy to that of controls were found in vitamin E-treated rats. Conclusions: These findings strongly support the idea that ethanol intake by dams during pregnancy and lactation induces Hcy-mediated oxidative stress in the developing hippocampus and cerebellum of offspring rats, and that these effects can be alleviated by vitamin E as an antioxidant.

In this report the epidemiologic aspects of epilepsy in Arab countries are systematically reviewed. MEDLINE and Embase were searched, and six papers were identified: one incidence report from Qatar and five prevalence reports (two from Sudan, and one from each of Libya, Tunisia, and Saudi Arabia). An incidence of 174 per 100,000 persons in 2001 was reported in a hospital-based study from Qatar. Prevalence ranged between 0.9/1,000 in Sudan and 6.5/1,000 in Saudi Arabia, with a median of 2.3/1,000. An approximate 724,500 people with epilepsy live in the Arab world. All the studies report higher prevalence in males, which was statistically significant in the Saudi study. The prevalence is approximately 2-fold higher in children and young adults, compared to the rates in middle age. Two studies showed a high prevalence in individuals older than 60 years of age. Primary generalized seizures are reported in 28-97% of cases, partial seizures in 3-43.8%, and unclassified seizures in 18-51%. Idiopathic epilepsy represents 73.5-82.6% of cases. Early childhood brain damage such as in cerebral palsy and mental retardation represented a major cause of symptomatic epilepsy, whereas infection was the main cause in Sudan. The epidemiologic data from Arab states are lacking, especially from populous countries like Egypt, Algeria, and Syria. Well-designed studies are needed to accurately determine the burden of epilepsy in the Arab world.

To investigate the possible ameliorating effect of recombinant human erythropoietin (rhEPO) on white matter damage, pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine Escherichia coli infection. E. coli was inoculated into uterine cervix of the time-pregnant rats and the control was injected with normal saline. Following maternal E. coli inoculation, the pups received a single intraperitoneal injection of rhEPO at a dose of 5000 IU/kg body weight immediately after birth. Immunohistochemical staining and Western blot analysis for 2′, 3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), neurofilament (NF) and glial fibrillary acidic protein (GFAP) were performed to assess white matter damage in pup brains at post-natal day 1 (P1), P3 and P7. Pro-inflammatory cytokines and chemokines were detected by real-time quantitative RT-PCR at the mRNA levels to evaluate the inflammatory response in pup brains at P1, P3 and P7. A single dose of rhEPO treatment (5000 IU/kg body weight) attenuated white matter damage in developing rat brain after intra-uterine E. coli infection. The protein levels of CNPase and NF in pup brains at P7 significantly increased after post-natal rhEPO treatment as compared with the intra-uterine E. coli-treated group. Also, post-natal rhEPO injection markedly attenuated the intra-uterine E. coli infection-induced increases in GFAP protein expression and the mRNA levels of pro-inflammatory cytokines and chemokines. Post-natal EPO administration as a single dose may exert a neuroprotective effect on white matter damage by reducing pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine E. coli infection.

The most widely accepted indication for a stat EEG (stEEG) is the suspicion of nonconvulsive status epilepticus (NCSE). NCSE has been reported with surprising frequency in a wide variety of acute structural and metabolic brain injuries and significantly increases the risk of permanent brain damage and death. This risk rises and the effectiveness of treatment decreases with delays in diagnosis and increased duration of NCSE. Recent evidence confirms that more than half of NCSE patients improve with anti-seizure treatment. The emergence of NCSE as a common, dangerous, time-urgent, and treatable problem has positioned it as a target for emergency therapeutic intervention. NCSE can only be diagnosed by EEG testing, and stEEG has demonstrated value in improving NCSE management. As a result, in the near future, EEG laboratories will see increasing demands for stEEG related to NCSE. The two main obstacles to an effective stEEG program are EEG technologist coverage and electroencephalographer availability after work hours. We recommend three simple but fundamental changes in the traditional approach to stEEGs in order to overcome these obstacles: the use of EEG set-up templates by onsite personnel, easy access to EEG instruments after hours, and remote stEEG connectivity for real-time, off-site electroencephalographer interpretation.

Patients having surgical procedures are at risk for anoxia that may cause cognitive impairment. Continuous monitoring of cerebral oxygenation and perfusion with an instrument such as a cerebral oximeter is desirable. The data it provides give insight into the cause of the cerebral insults along with the cerebral response to specific interventions, all of which could help prevent damage to the brain. This critical review of the literature on the efficacy, mechanics, and usefulness of the cerebral oximeter will be helpful to anesthesia providers in evaluating the controversy surrounding its use. A comprehensive understanding of the factors involved in cerebral perfusion and available equipment, such as the cerebral oximeter to monitor cerebral oxygenation, allows anesthetists to provide the best protection for the brain.