Cerebral Palsy

In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134-147 ms; normal <118 ms. We hypothesize that elevated GABA in ocular tissue of SSADH patients leads to a use-dependent downregulation of the major GABAergic receptor in eye, GABA(C), and that the VEP recordings' abnormalities, as evidenced by P100 latency and/or amplitude measurements, may be reflective of abnormalities within visual systems. This is a preliminary finding that may suggest the utility of performing VEP analysis in a larger sample of SSADH-deficient patients, and encourage a neurophysiological assessment of GABA(C) receptor function in Aldh5a1(-/-) mice to reveal new pathophysiological mechanisms of this rare disorder of GABA degradation.

AIMS/HYPOTHESIS: Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima-media thickness (CIMT). METHODS: We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. RESULTS: CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46-69%; p = 0.004-0.043). In people with type 1 diabetes, FMD was reduced by 45% (p < 0.001) and CIMT increased by 25% (p < 0.001), these being correlated (r = -0.25, p = 0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r = 0.25, p = 0.037) and CD34+ (r = 0.34, p = 0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r = -0.27, p = 0.028 and r = -0.24, p = 0.048, respectively). CONCLUSIONS/INTERPRETATION: These findings suggest that abnormalities of endothelial function in addition to pro-inflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events.

INTRODUCTION: Alexander disease is a rare disorder of the central nervous system with characteristic symmetric white matter abnormalities with frontal predominance on magnetic resonance (MR) images. Histopathology shows a lack of myelin in the affected white matter, variably interpreted as hypomyelination or demyelination. To increase our insight into the nature of the pathology leading to the MR imaging findings in Alexander disease, we applied serial MR imaging, spectroscopy, magnetization transfer (MT) imaging (MTI), and diffusion tensor imaging (DTI) in six patients with juvenile Alexander disease. METHODS: The MR imaging protocol comprised T1- and T2-weighted spin echo images and fluid-attenuated inversion recovery images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and MT ratio (MTR) maps were generated, and MR spectroscopy concentrations were quantified for several metabolites. RESULTS: MR imaging showed similar cerebral white matter abnormalities in all patients, with only minor increase on prolonged follow-up, despite sometimes serious clinical progression. MR spectroscopy showed highly elevated levels of myo-inositol, lactate, and choline-containing compounds and decreased total N-acetyl-aspartate and N-acetyl-aspartyl-glutamate levels in the abnormal white matter. High values of ADC were observed, and both FA and MTR were attenuated. CONCLUSION: The sequential MR imaging findings in Alexander disease provide strong evidence against active demyelination as sole explanation for the underlying pathology. An alternative explanation for our spectroscopic, DTI, and MTI findings-which would suggest demyelination-could be hyperplasia and hypertrophy of astrocytes, as seen in low grade gliomas.

BACKGROUND: The purpose of this retrospective study was to assess the frequency of magnetic resonance imaging (MRI) signs of iliotibial band friction (ITBF) in patients with advanced medial compartment knee osteoarthritis. MATERIAL AND METHODS: Proton density-weighted (PDw) fat-saturated (fatsat) MR images (1.5 T, slice thickness (SL) 2.5-3 mm, eight-channel phased array coil) of 128 patients with isolated advanced osteoarthritis of the medial knee compartment and complete or subtotal (>80%) loss of cartilage were evaluated. There were 41 men and 87 women. Mean age was 63 years, range 34-89 years. The control group consisted of 94 patients with medial meniscus degeneration without cartilage loss (56 men and 38 women, mean age 50 years, range 16-89 years). MRI signs of ITBF were evaluated in both groups [poorly defined abnormalities of signal intensity and localized fluid collection lateral, distal or proximal to the lateral epicondyle; signal intensity abnormalities superficial to or deep by the iliotibial band (ITB)]. Transverse images were evaluated separately. Consensus evaluation using all imaging planes was performed. RESULTS: Of 128 patients with osteoarthritis, 95 had moderate or advanced MRI signs of ITBF (74.2%). Eighty-nine patients (69.5%) had advanced degeneration of the meniscus. In the control group, 26 of 94 patients had only moderate MRI signs of ITBF. There was a statistically significant difference between both groups for the presence of MR signs of ITBF (P </= 0.01). CONCLUSION: MRI signs of ITBF were frequently present in patients with severe medial compartment osteoarthritis of the knee. Joint space narrowing with varus knee deformity may be a cause of ITBF. LEVEL OF EVIDENCE: Level 4 (Historic, non-randomized, retrospective, cohort study with a control group).

PURPOSE: We evaluated the accuracy of magnetic resonance imaging (MRI) in young women with primary amenorrhoea with suspected Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome (congenital absence of both vagina and uterus and presence of normal ovaries). MATERIALS AND METHODS: Fifty-eight women (age range 14-30 years, mean 20.9) with primary amenorrhea were studied with MRI performed with a 1.0-T superconducting magnet (Philips NT Intera). All patients were examined in the supine position using a phased-array coil (four channels). Turbo spin-echo T2-weighted images were acquired in the sagittal, axial and coronal planes with the following parameters: TR 4,750-6,686, TE 100-120, FOV 350-375, 4- to 5-mm sections with a 0.4- to 0.5-mm intersection gap and NSA 6. T1-weighted images were acquired in the axial and coronal planes (TR 470, TE 15, FOV 350, 4-mm sections with a 0.6-mm intersection gap, NSA 3). Two experienced radiologists evaluated all the examinations in consensus to assess the presence, position and morphology of vagina, uterus, ovaries and kidneys and any pelvic abnormalities. MRI results were judged on the basis of laparoscopic findings in 41 patients. RESULTS: MRKH syndrome was confirmed in 56 patients with 100% sensitivity and specificity. MRI identified bilateral Müllerian buds in 34/56 (61%) and unilateral in 10/56 (18%) patients. MRI sensitivity was 81.42%, and there was good agreement with laparoscopy (k=0.55) and full agreement in the identification of cavitation between MRI and intraoperative sonography. Both ovaries were visualised in 54 patients, with regular morphology in 46 (82.1%), polycystic in 10 (17.8%), pelvic in 47 (83.6%) and extrapelvic in eight (14.5%). We found associated abnormalities of the upper urinary tract in six patients (solitary kidney in four and ptosis in two). CONCLUSIONS: MRI is a useful diagnostic tool in the preoperative evaluation of MRKH syndrome and is less expensive and invasive than laparoscopy. Strong cooperation between radiologists and surgeons is highly recommended.

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.

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.

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.

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.

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.