Phenotypic variability of a distinct deletion in McLeod syndrome

The X‐linked McLeod neuroacanthocytosis syndrome strongly resembles Huntington's disease and has been reported in various countries world‐wide. Herein, we report two Chilean brothers with predominant psychiatric features at disease onset including schizophrenia‐like psychosis and obsessive compulsive disorder. Molecular genetic analysis revealed a small deletion in the XK gene (938‐942delCTCTA), which has been already described in a North American patient of Anglo‐Saxon descent and a Japanese family, presenting with seizures, muscle atrophy or chorea yet absence of psychiatric features. These findings argue against a founder effect and indicate a profound phenotypic variability associated with the 938‐942delCTCTA deletion. Our report supports the inclusion of McLeod syndrome in the differential diagnosis of Huntington's disease as well as acute psychosis in male subjects. © 2007 Movement Disorder Society     

Do commonly used oral antihypertensives alter fetal or neonatal heart rate characteristics? A systematic review.

OBJECTIVE: To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy. METHODS: A systematic review of randomized controlled trials (RCTs), observational studies (N >/= 6 women), and animal studies. Data were abstracted (two reviewers) to determine relative risk (RR) (or risk difference (RD) for low event rates) and 95% CI. RESULTS: Eighteen RCTs (1858 women), one controlled observational study (N = 22), and seven case series (N = 117) were reviewed. Most hypertension was pregnancy-induced (N = 14 studies). The FHR was assessed by cardiotocogram (CTG) (N = 17 studies (visual interpretation); 1 study (computerized CTG), or umbilical artery velocimetry (N = 4). Four studies examined neonatal heart rate. In placebo-controlled RCTs (N = 192 women), adverse FHR effects did not differ between groups [9/101 (drugs) vs. 7/91 (placebo); RD 0.02, 95% CI (- 0.06, 0.11); chi2 = 1.02]. In six drug vs. drug RCTs (295 women), adverse FHR effects did not differ between groups [29/144 (methyldopa) vs. 42/151 (other drugs); RR 0.72, 95% CI (0.49, 1.07); chi2 = 0.69]. In one labetalol vs. placebo trial, neonatal bradycardia did not differ between groups [4/70 (labetalol) vs. 4/74 (placebo); OR 1.06, 95% CI (0.26, 4.39)], while in three drug vs. drug RCTs, neonatal bradycardia was not observed (0/24 vs. 0/26). CONCLUSIONS: Available data are inadequate to conclude whether oral methyldopa, labetalol, nifedipine, or hydralazine adversely affect fetal or neonatal heart rate and pattern. Until definitive data are available, FHR changes cannot be reliably attributed to drug effect, but may be due to progression of the underlying maternal or placental disease.     

Umschriebene Sprachentwicklungsstörungen

This paper gives an overview of the diagnostics and therapy of specific developmental language disorders. In addition, the present understanding of etiology and in particular genetics is discussed. For the classification of a specific language impairment both the linguistic and the general cognitive abilities have to be evaluated.For this purpose, standardised tests should be used instead of informal methods. Hearing impairment has to be ruled out for each language retarded child. If a decrease or stagnation of the language ability is observed, it is necessary to initiate detailed cerebral diagnostics. In the therapy the language symptoms must be directly treated,whereas a training of basic, non-linguistic abilities does not appear to be effective.Additional symptoms, in particular hyperactivity, conduct and emotional disorders, should be considered sufficiently in the treatment.Parents should be included in the therapeutic process more strongly than has been the case in the past.     

Maplets for correspondence-based object recognition.

We present a correspondence-based system for visual object recognition with invariance to position, orientation, scale and deformation. The system is intermediate between high- and low-dimensional representations of correspondences. The essence of the approach is based on higher-order links, called here maplets, which are specific to narrow ranges of mapping parameters (position, scale and orientation), which interact cooperatively with each other, and which are assumed to be formed by learning. While being based on dynamic links, the system overcomes previous problems with that formulation in terms of speed of convergence and range of allowed variation. We perform face recognition experiments, comparing ours to other published systems. We see our work as a step towards a reformulation of neural dynamics that includes rapid network self-organization as essential aspect of brain state organization.     

Accommodative convergence in hypermetropia

We compared the clinical characteristics of esotropic, hypermetropic children whose strabismus was fully corrected with spectacles (refractive accommodative esotropia) with those who remained orthotropic (that is, had no manifest strabismus on the cover test) in the presence of uncorrected hypermetropia. In addition to a standard ophthalmologic and orthoptic examination, we determined the stimulus accommodative convergence/accommodation (AC/A) ratio by using the gradient method over a range of 6 diopters, the near point of accommodation, and random dot stereopsis. Hypermetropic patients without esotropia or significant esophoria were found to have a low AC/A ratio in contrast to those patients with refractive accommodative esotropia. This finding explains why esodeviations may be absent in some hypermetropic patients with uncorrected vision. We found a high prevalence of abnormally low near points of accommodation and defective or absent stereopsis in both groups of patients.     

Ultrasound for the assessment of the embolic risk of carotid plaques

In a prospective study we compared duplex-ultrasound characteristics of symptomatic internal carotid artery (ICA) stenoses with cranial computerized tomographic (CCT) findings in 82 patients suffering from completed or transient middle cerebral artery symptoms. The aim was to assess the pathogenic role of ICA plaque morphology and the potential embolic risk of ICA plaques. The degree of carotid stenosis was estimated by spectral analysis of the pulsed Doppler signal. The CCT findings were classified as being either normal, lacunar lesions, hemodynamically induced low-perfusion infarctions, or territorial embolic infarctions. According to their ultrasonic features we characterized the ICA plaque surface as smooth or irregular and their structure as homogeneous or heterogeneous. Plaques with an irregular surface and heterogeneous echogenicity dominated significantly in CCT-territorial infarctions (p < 0.01), whereas hemodynamically induced low-perfusion infarctions showed no relationship with any plaque characteristic. High degree ICA stenoses (> 50>%) dominated in both territorial infarctions and low-perfusion infarctions, as compared to ipsilateral normal CCT or lacunes (p < 0.05). Normal CCT and lacunar infarctions were associated with homogeneous and smooth plaques (both p < 0.05). We conclude that > 50% ICA stenoses can cause both hemodynamically induced low-perfusion infarctions as well as thromboembolic territorial infarctions, whereas ulcerated and heterogeneous plaques constitute a high risk factor for arterio-arterial embolic stroke. Furthermore, carotid ultrasound may help to estimate the clinical significance of carotid lesions.     

Lymphocyte subclasses and function in patients with optic neuritis in childhood with special reference to multiple sclerosis

Ten patients with childhood optic neuritis (5 with a single attack of ON and 5 with later MS) were studied at various stages of the disease. Lymphocyte count and function were analysed in the peripheral blood of all patients, 3 repeatedly, and in one they were also analysed in the CSF. T-lymphocytes counts were normal in all but 2 MS cases who had high counts. In acute stages the T4/T8 ratio were high in 1/3 determinations, in recovery low in 2/2 determinations, and in stable stages normal in 6/8 determinations. Lymphocyte function, measured by PHA, ConA and PWM stimulation, was normal in all but one. One patient showed significantly higher T-cell percentages and a high number of stimulated lymphocytes in CSF but a lower count of suppressor cells than in the blood. We found no abnormalities specific to MS nor to childhood MS or to disease activity stage. Rather than peripheral blood, it would seem more worthwhile to study CSF to clarify the pathogenesis of ON and MS.     

Expression and distribution of vascular endothelial growth factor protein in human brain tumors

Marked neovascularization is a hallmark of many neoplasms in the nervous system. Recent reports indicate that the endothelial mitogen vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation in malignant gliomas. Using novel monoclonal antibodies to the VEGF polypeptide we have determined the expression and cellular distribution of VEGF protein in a representative series of 171 human central nervous system (CNS) tumors by immunohistochemistry and immunoblotting. In agreement with previous in situ hybridization data, 19 out of 20 glioblastomas (95%) showed immunoreactivity for VEGF, whereas both the percentage of immunoreactive tumors and the extent of immunoreactivity for VEGF were significantly lower in astrocytomas. Of the pilocytic astrocytomas (WHO grade I) 44% were immunoreactive for VEGF, but we observed several cases with pronounced vascular proliferates in the absence of VEGF. In ependymomas, meningiomas, hemangioblastomas, and primitive neuroectodermal tumors, there was no correlation between VEGF expression, vascular endothelial proliferation and the grade of malignancy. Oligodendrogliomas and the oligodendroglial component of mixed gliomas lacked immunoreactive VEGF, indicating that endothelial growth factors other than VEGF may regulate tumor angiogenesis in these neoplasms. Western blot analysis showed a predominant VEGF protein species of 23 kDa and confirmed the immunohistochemical data in all cases. Our findings demonstrate that VEGF is expressed in a wide spectrum of brain tumors in which it may induce neovascularization. However, other angiogenic factors also appear to contribute to the vascularization of CNS neoplasms. Received: 18 April 1996 / Revised, accepted: 20 August 1996