Cerebral Palsy

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.

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).

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.

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.

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.

We demonstrate a reduction in enzymatic divalent immature and trivalent pyridinium cross-links and an increase in the nonenzymatic cross-link, pentosidine (Pen), in rabbits with methionine (Met)-induced hyperhomocysteinemia. Such detrimental cross-link formation in bone was ameliorated by raloxifene (RLX) treatment. INTRODUCTION: Collagen cross-links are determinants of bone quality. Homocysteine (Hcys) interferes with collagen cross-linking. Because RLX is thought to ameliorate bone quality, we investigated whether RLX ameliorated hyperhomocysteinemia-induced cross-link abnormalities using a Met-rich diet rabbit model. METHODS: We divided New Zealand white rabbits into six groups (n = 6 per group): baseline control, sham operation, sham + 1% Met diet, ovariectomy (OVX), 1% Met diet + OVX, OVX + RLX (10 mg/kg/day), and 1% Met diet + OVX + RLX. RLX was administered for 16 weeks. We measured the amount of enzymatic immature and mature pyridinium cross-links and the nonenzymatic cross-link, Pen, and correlated the cross-link content to bone strength. RESULTS: Hcys levels were significantly higher in the Met diet groups than in the normal diet groups. Met-fed rabbits with or without OVX showed a significant reduction of enzymatic cross-links, whereas an increase in Pen was observed in Met-fed rabbits with OVX. The cross-link content of the RLX-treated Met-fed rabbits with OVX was restored to similar levels as the sham group, accompanied by an improvement of bone strength. CONCLUSION: These results demonstrate that hyperhomocysteinemia reduced bone strength via a reduction of enzymatic cross-links and an increase of nonenzymatic cross-links. RLX may ameliorate hyperhomocysteinemia-induced detrimental cross-linking in rabbits with OVX and may improve bone strength via the amelioration of collagen cross-links.

Hydronephrosis is one of the most common abnormalities detected on routine prenatal ultrasounds, being noted in up to 1% of fetuses. Rarely, severe hydronephrosis coexists with oligohydramnios, which portends a poor prognosis. We review the most recent literature on the results of prenatal intervention in this setting. Presently, the first randomized controlled trial to address whether prenatal vesicoamniotic shunting improves survival and renal function is underway, and should address the value of prenatal intervention.

Huntington’s disease (HD) is an inherited, progressive neurological disorder caused by a CAG/polyglutamine repeat expansion, for which there is no effective disease modifying therapy. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression. Administration of histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) have consistently shown therapeutic potential in models of HD, at least partly through increasing the association of acetylated histones with down-regulated genes and by correcting mRNA abnormalities. The HDAC enzyme through which SAHA mediates its beneficial effects in the R6/2 mouse model of HD is not known. Therefore, we have embarked on a series of genetic studies to uncover the HDAC target that is relevant to therapeutic development for HD. HDAC7 is of interest in this context because SAHA has been shown to decrease HDAC7 expression in cell culture systems in addition to inhibiting enzyme activity. After confirming that expression levels of Hdac7 are decreased in the brains of wild type and R6/2 mice after SAHA administration, we performed a genetic cross to determine whether genetic reduction of Hdac7 would alleviate phenotypes in the R6/2 mice. We found no improvement in a number of physiological or behavioral phenotypes. Similarly, the dysregulated expression levels of a number of genes of interest were not improved suggesting that reduction in Hdac7 does not alleviate the R6/2 HD-related transcriptional dysregulation. Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7.

Background and purpose: Previous studies suggested that biochemical markers of brain damage could act as prognostic factors in ischaemic stroke. The aim of the present study was to assess predictive value of the selected biomarkers S100B protein, neuron-specific enolase (NSE), C-reactive protein (CRP) and D-dimers, as well as GABA and excitatory amino-acids (EAA) measured in blood for 3-month functional outcome in ischaemic stroke patients. Material and methods: We investigated 54 patients with ischaemic stroke (mean age: 73.3 +/-11.7). Serum con-centrations of S100B, NSE, CRP, EAA and GABA, as well as plasma concentrations of D-dimers, were assessed in blood samples taken at admission and at 12, 24, and 72 hours after stroke onset. Functional status was measured with modified Rankin Scale (mRS) 3 months after stroke onset. Results: Significant independent predictors of outcome in ischaemic stroke patients 3 months after stroke were: S100B level at 12 h (OR: 1.7; 95% CI: 0.5-7.0; p = 0.007), NSE at 12 h (OR: 2.4; 95% CI: 0.7-8.1; p = 0.037), 24 h (OR: 10.2; 95% CI: 2.4-43.2; p = 0.0007), and 72 h (OR: 10.2; 95% CI: 2.3-45.0; p = 0.0001), CRP at 72 h (OR: 8.3; 95% CI: 1.5-45.4; p = 0.009) and D-dimers at admission (OR: 4.8; 95% CI: 1.1-20.7; p = 0.02), 24 h (OR: 5.5; 95% CI: 1.4-20.9; p = 0.004), and 72 h after stroke onset (OR: 2.7; 95% CI: 0.6-11.8; p = 0.01). Conclusions: The results of the present study are consistent with previous evidence indicating that selected biomarkers could help in prediction of the outcome in ischaemic stroke early after symptoms onset.

Visually based reading disorders are frequently encountered in patients with acquired brain damage. Homonymous visual field defects, impaired elementary visual capacities (acuity, contrast sensitivity, convergent fusion, ocular motor disorders), visual neglect or Balint-Holmes syndrome are the most frequent causes of such reading disorders. Reading is not only an important prerequisite for vocational and private life, but is also indispensable for subsequent cognitive abilities such as verbal working memory and long-term memory. Despite this importance no comprehensive system exists for the standardised assessment and treatment of visually based reading capacities in the German-speaking area. Here, we describe the basic properties of such a system (READ). After a short survey of the main causes of visually based reading disorders after brain damage, the anamnesis, diagnostic facilities, normative data as well as a variety of treatment techniques of the novel system are described. Selected results from ongoing clinical group studies as well as case examples highlight the diagnostic sensitivity and therapeutic efficiency of the new system for better management of visually based reading disorders after brain damage.