Cerebral Palsy

Dysfunction of the central dopaminergic system is associated with neurodegenerative disorders and mental illnesses such as Parkinson’s disease and schizophrenia. Patients suffering from these diseases were reported to exhibit altered immune functions compared to healthy subjects and imbalance of the central dopaminergic system has been suggested as one causative factor for the immune disturbances. However, it is unclear whether the observed immune changes are primary or secondary to the disease. Here we demonstrate that central dopamine (DA) depletion in a rat model of Parkinson’s disease induced transient changes in blood leukocyte distribution and cytokine production that were apparent until four weeks after bilateral intrastriatal administration of the neurotoxin 6hydroxydopamine (6-OHDA). Eight weeks after treatment, no differences in blood immune parameters were anymore evident between neurotoxin-treated and control animals. Nevertheless, animals with a widespread damage of dopaminergic neurons in the nigrostriatal system showed an exacerbated pro-inflammatory response following in vivo challenge with bacterial lipopolysaccharide. Our data indicate that peripheral immune perturbations in the early phase after intrastriatal 6-OHDA administration might have been related to the neurodegenerative process itself whereas the increased sensitivity to the inflammatory stimulus seems to have resulted from an impaired dopaminergic control of prolactin (PRL) and corticosterone (CORT) secretion. The findings demonstrate that the brain dopaminergic system is involved in peripheral immune regulation and suggest that central dopaminergic hypoactivity bears the risk of excessive inflammation, e.g., during infection or tissue injury.

Tullberg M, Ziegelitz D, Ribbelin S, Ekholm S. White matter diffusion is higher in Binswanger disease than in idiopathic normal pressure hydrocephalus. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01165.x. (c) 2009 The Authors Journal compilation (c) 2009 Blackwell Munksgaard.Objectives – To explore diagnostic differences in periventricular white matter (PWM) and deep white matter (DWM) diffusion patterns in patients diagnosed with Binswanger disease (BD) and in patients diagnosed with probable idiopathic normal pressure hydrocephalus (INPH) using diffusion-weighted imaging (DWI). Materials and methods – Apparent diffusion coefficient (ADC) values were calculated in the PWM and DWM in patients with INPH (n = 14) and BD (n = 9) and in controls (n = 10) using an spin echo echo planar imaging single-shot diffusion sequence and region of interest (ROI) analysis. Results – Patients with BD had higher ADC values than patients with INPH in the PWM and DWM in the frontal and occipital regions (P < 0.05) and higher values than controls in the frontal PWM and DWM (P < 0.01). After shunt surgery, ADC values were reduced in the frontal PWM in patients with INPH (P < 0.05). Conclusions – Increased diffusion in the PWM and DWM in patients with BD may reflect irreversible breakdown of axonal integrity caused by the subcortical ischaemic vascular disease. By contrast, the normal white matter diffusion in patients with INPH indicates structurally intact axons, compatible with the reversibility of this disorder. DWI may be an important non-invasive diagnostic tool for differentiating between INPH and BD and identifying shunt responders and reversible brain damage in patients with INPH. However, the overlap between patients with INPH and BD in this study restricts the predictive value of the method.

Cerebrovascular diseases and especially ischemic stroke are a leading cause of death. They occur mostly due to an insufficient oxygen (O(2)) supply to the central neural tissue as a result of thromboembolic events and/or obstructive vessel disease. The primary damage of the brain tissue cannot be restored. However, adequate therapy could minimize secondary impairment of brain tissue and restore neuronal function in the so-called “penumbra region”. Apart from reopening occluded vessels, additional O(2) supply is essential for survival of malfunctioning neural tissue. Breathing of 100% O(2) under hyperbaric conditions, hyperbaric oxygenation (HBO), is the only method to increase the O(2) concentration in tissue with impaired blood supply. Experimental as well as clinical studies have reported a positive effect of HBO therapy. Survival rate has increased under HBO therapy and neurological outcome has improved. The optimal levels of pressure as well as duration and numbers of HBO sessions need to be specified to avoid undesirable effects. Unfortunately, many questions remain unanswered before routinely recommending HBO as additional therapy in clinical practice. In this review we consider the (patho-)physiological background of HBO-therapy, the latest results of experimental and clinical studies and stress the evidence in patients with cerebrovascular disease.

Stroke is a significant cause of long-term disability. Currently, once damage from a stroke is established little can be done to recover lost function. Cell transplantation emerged as possible alternative therapy, on the basis of animal studies showing that cells transplanted into the brain not only survive, but also lead to functional improvement in different neurodegenerative diseases. Stem cells have been tested in stroke patients as a possible treatment option. While initially stem cells seemed to work by a ‘cell replacement’ mechanism, it is emerging that cell therapy works mostly by providing trophic support to the injured tissue and brain, fostering both neurogenesis and angiogenesis. This review summarizes clinical studies on stem cell transplantation in stroke patients to evaluate the safety, feasibility of administration and tolerability of this experimental treatment. At present there is little evidence to assess the applicability of this treatment in stroke patients and well designed clinical trials are necessary to evaluate safety and toxicity as well as optimal cell type, route and time of delivery.

Object Agitation and aggression are common after traumatic brain injury (TBI) and can hamper recovery and rehabilitative efforts. To date, there is no consensus on pharmaceutical intervention for these conditions after TBI. Ziprasidone has been reported efficacious in this population but the evidence is limited. The authors report their experience of using ziprasidone to treat posttraumatic brain injury agitation in 20 consecutive pediatric patients. A secondary objective of this case series was to attempt to establish an age-specific dosage and identify possible side effects of this medication. Methods This case series study was performed at a university hospital and pediatric trauma center. Over an 18-month period, all patients who presented to the pediatric intensive care unit with TBI and later developed agitation and/or aggression were treated with ziprasidone as the sole intervention. Pre- and posttreatment scores on the Riker Sedation-Agitation Scale (SAS) were recorded along with demographic data. Results Twenty children received ziprasidone for agitation and/or aggression during the immediate recovery period from TBI. The median patient age was 8 years (range 9 months-17 years). Children were stratified into 4 age groups: < 2 years old (Group 1), 2-6 years old (Group 2), 7-12 years old (Group 3), and >/= 13 years old (Group 4). The SAS score, before and 24 hours after the initiation of ziprasidone, demonstrated a significant reduction after initiation of the medication (p < 0.001). The initial dose for Groups 1-4 was 1.7, 0.9, 0.7, and 0.6 mg/kg, respectively, with final doses of 1.8, 1.5, 1.7, and 0.07 mg/kg, respectively. The duration of therapy for Groups 1-4 was 5, 8, 6, and 3 days, respectively. All patients received continuous cardiac and blood-pressure monitoring. No adverse events were reported in any of the age groups. Conclusions Based on this limited patient series, ziprasidone appears to be safe and effective in pediatric patients with closed head injuries who develop agitation and/or aggression in the immediate postinjury period. Ziprasidone consistently lowered SAS scores and did so in all age groups. There were minimal dose adjustments and the duration of therapy was relatively brief. No adverse events were reported. A prospective trial of ziprasidone in this population appears warranted.

Few urinary screening studies have been performed to determine the incidence of urinary abnormalities in antiretroviral therapy-naive, HIV-infected outpatients. From published data, the incidence appears to be high, particularly when compared with populations outside sub-Saharan Africa. In South Africa, urinary screening in antiretroviral therapy clinics is not routinely practiced. The aim of this descriptive study was to screen antiretroviral therapy-naive, HIV-infected outpatients attending the HIV clinic for urinary abnormalities, namely leukocyturia, microscopic hematuria, and microalbuminuria/proteinuria. This study showed that 84% of the screened population had AIDS (CD4 count < 200 cells/ mm3), and the incidence of abnormalities on urinary dipstick testing was high: 30% had leukocyturia, 33% had microscopic hematuria, and 44% had microalbuminuria/proteinuria. In patients with leukocyturia, an infective organism was cultured in only 29.1% of cases, predominantly Escherichia coli (70%) with sterile leukocyturia comprising the remainder. There may be an association with tuberculosis (TB) or sexually transmitted infections (STI) in the sterile leucocyturia group, but this remains to be confirmed. In those with a culture positive result the most common organism was E. coli (70%), which exhibited 90% resistance to cotrimoxazole, demonstrating that cotrimoxazole prophylaxis is not effective to prevent urinary tract infection in this group. On the basis of these findings, it has been proposed that urinary screening be considered standard of care in HIV clinics in South Africa. An algorithm has been proposed for use in antiretroviral therapy clinics in South Africa to guide clinicians regarding the cost-effective management of urinary dipstick abnormalities.

AIM: Progressive posthaemorrhagic ventricular dilatation (PHVD) may induce abnormal amplitude-integrated electroencephalographic (aEEG) activity prior to clinical deterioration or significant cerebral ultrasound changes. These abnormalities might be ameliorated with cerebrospinal fluid (CSF) drainage. The aims of this study were to investigate the occurrence of aEEG-abnormalities with progressive PHVD in relation to clinical and cerebral ultrasound changes and to evaluate whether CSF drainage results in aEEG improvement. METHODS: aEEG and cerebral ultrasound scans were performed in 12 infants with PHVD, before and after CSF drainage, until normalization of aEEG occurred. RESULTS: aEEG was abnormal with progressive PHVD in all patients. Concurrently, 60% of the patients were clinically stable without deterioration in ultrasonographic cerebral abnormalities. Post drainage, continuous pattern was restored in all but one patient, whereas the frequency of discontinuous pattern decreased in nine patients and burst-suppression pattern decreased in all but one patient. Low-voltage pattern was only observed in one patient who suffered severe grade IV IVH and died one week after EVD placement. Sleep-wake cycling matured in 75%. CONCLUSION: These findings demonstrate the impact of CSF drainage on compromised aEEG-activity associated with PHVD. aEEG changes indicative of impaired cerebral function were apparent before clinical deterioration or major ultrasound changes. These changes were reversible with CSF drainage. aEEG should therefore be used in addition to clinical observation and ultrasound when monitoring PHVD.

Adult T-cell leukemia/lymphoma (ATLL) is a malignant tumor caused by latent human T-lymphotropic virus 1 (HTLV-1) infection. We previously identified a common breakpoint cluster region at 10p11.2 in acute-type ATLL by spectral karyotyping. Single nucleotide polymorphism array comparative genomic hybridization analysis of the breakpoint region in three ATLL-related cell lines and four patient samples revealed that the chromosomal breakpoints are localized within the enhancer of polycomb 1 (EPC1) gene locus in an ATLL-derived cell line (SO4) and in one patient with acute-type ATLL. EPC1 is a human homologue of the E(Pc) enhancer of polycomb gene of Drosophila. Inappropriate expression of the polycomb group gene family has been linked to the loss of normal gene silencing pathways, which can contribute to the loss of cell identity and malignant transformation in many kinds of cancers. In the case of the SO4 cell line, which carried a der(10)t(2;10)(p23;p11.2) translocation, EPC1 was fused with the additional sex combs-like 2 (ASXL2) gene at 2p23.3 (EPC1/ASXL2). In the case with an acute-type ATLL, who carried a der(10)del(10)(p11.2)del(10)(q22q24) translocation, a putative truncated EPC1 gene (EPC1tr) was identified. Overexpression of EPC1/ASXL2 enhanced cell growth in T-leukemia cells, and a GAL4-EPC1/ASXL2 fusion protein showed high transcriptional activity. Although a GAL4-EPC1tr fusion protein did not activate transcription, overexpression of EPC1tr accelerated cell growth in leukemia cells, suggesting that the EPC1 structural abnormalities in the SO4 cell line and in the patient with acute-type ATLL may contribute to leukemogenesis. (c) 2009 Wiley-Liss, Inc.

To improve long-term outcome of de novo acute myeloid leukemia (AML) patients by intermediate dose of cytarabine integrated in induction therapy and to explore the impact of cytogenetic abnormalities on the prognosis. Eighty-seven AML patients were treated with HAD regimen containing intermediate dose cytarabine (IDAra-C) as induction therapy, 83 from which with karyotype results were divided into three cytogenetic groups according to SWOG criteria. Complete remission (CR) rate, disease-free survival (DFS), and overall survival (OS) among different groups were evaluated. The CR rate of the 87 cases was 80/87 (92%). Median DFS and OS have not reached (NR). DFS rates at 1 and 3 years were 76.3% and 63.4%, respectively. OS rates at 1 and 3 years were 86.0% and 58.7%, respectively. According to SWOG criteria, CR rate, median DFS, and OS were 100%, NR and NR for the favorable group; 88.9%, NR, and 16 months for the intermediate group; 83.3%, 4.5 months, and 7.5 months for the adverse group. The differences among the three groups were statistically significant excepting for CR rate between adverse and intermediate groups. HAD regimen containing IDAra-C as induction chemotherapy regimen is effective in de novo AML of adult patients and can achieve higher CR rate and longer survival than standard dose of cytarabine (SDAra-C) regimen. Most of the patients were able to endure the therapy. Cytogenetics is still an important prognostic factor despite of the incorporation of IDAra-C in induction chemotherapy. The differences among the three groups were statistically significant. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

Huntington’s disease (HD) is associated with a variety of cognitive deficits, as well as motor and psychiatric disturbances. As clinical trials for HD evolve, briefer screening instruments will be needed to determine cognitive effects of interventions. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may fill this gap. A total of 75 participants diagnosed with HD were evaluated with the RBANS, as well as several other scales typically used in HD. RBANS performances for these participants fell significantly below expectations for the Total Scale score, all five Indexes, and 11 of the 12 individual subtests. Cognitive scores on the RBANS were also significantly related to other markers of HD, including motor abnormalities, functional abilities, and other cognitive scores. Although additional research is needed, the current study supports the clinical applicability of the RBANS in patients with HD.