Dopamine receptor D4 (DRD4) polymorphisms with reduced functional potency intensify atrophy in syndrome-specific sites of frontotemporal dementia.

OBJECTIVE: We aimed to understand the impact of dopamine receptor D4 (DRD4) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRD4dampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD4 is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration. METHODS: 337 subjects, including healthy controls, patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) underwent genotyping, structural MRI, and cognitive/behavioral testing. We conducted whole-brain voxel-based morphometry to examine the relationship between DRD4 genotypes and brain atrophy patterns within and across groups. General linear modeling was used to evaluate relationships between genotype and cognitive/behavioral measures. RESULTS: DRD4 dampened-variants predicted gray matter atrophy in disease-specific regions of FTD in anterior cingulate, ventromedial prefrontal, orbitofrontal and insular cortices on the right greater than the left. Genotype predicted greater apathy and repetitive motor disturbance in patients with FTD. These results covaried with frontoinsular cortical atrophy. Peak atrophy patterned along regions of neuroanatomic vulnerability in FTD-spectrum disorders. In AD subjects and controls, genotype did not impact gray matter intensity. CONCLUSIONS: We conclude that DRD4 polymorphisms with reduced functional potency exacerbate neuronal injury in sites of higher receptor density, which intersect with syndrome-specific regions undergoing neurodegeneration in FTD.

Dependence of the frequency distribution around a vessel on the voxel orientation.

In this work the frequency distribution around a vessel inside a cubic voxel is investigated. Therefore, the frequency distribution is calculated in dependence on the orientation of the voxel according to the external magnetic field. The frequency distribution exhibits an interesting peak structure that cannot be explained by the established Krogh's vessel model. The results were validated with phantom measurements and in vivo measurements that agree very well with the developed theory.

The influence of spatial patterns of capillary networks on transverse relaxation.

Tissue-inherent relaxation parameters offer valuable information about the arrangement of capillaries: in an external field, capillaries act as magnetic perturbers to generate local inhomogeneous fields due to the susceptibility difference of deoxygenated blood and the surrounding tissue. These field inhomogeneities influence the free induction decay in a characteristic way, and, conversely, the above tissue parameters can be recovered by multi-parametric fits of adequate theoretical models to experimentally sampled free induction decays. In this work we study the influence of different spatial patterns of capillary positions on the free induction decay. Starting from the standard single capillary approximation (Krogh cylinder) for a symmetric array of capillaries, the free induction decay is analyzed for increasingly random capillary positions, using a previously described Gibbs point field model. The effects of diffusion are implemented with a flexible and fast random walk simulation. We find that the asymmetric form of the obtained frequency distribution is more robust against variations of capillary radii than against shifts of capillary positions, and further that, for an inclusion of diffusion effects, the single capillary approximation models the uniform alignment of capillaries in the hexagonal lattice to great accuracy. An increase in randomization of capillary positions then leads to a significant change in relaxation times. This effect, however, is found less pronounced than that of changes in the off-resonance field strengths which are controlled by the oxygen extraction fraction, thus indicating that observed changes in BOLD imaging are more likely to be attributed to changes in oxygenation than to capillary alignment.

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial.

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

[Vision Screening in Zurich]. / Sehscreening in der Stadt Zürich.

BACKGROUND: In the city of Zurich, vision screening is performed by school medical services as part of the legally compulsory preventive medical examinations. We retrospectively evaluated the results of the 2011-2012 school year. PATIENTS AND METHODS: Preventive medical examinations by the school medical services were performed in all kindergartens. The examinations were mandatory for first, second and eighth grade children, whilst those for the fourth grade were voluntary. The basic diagnostic testing consisted of monocular visual acuity (Snellen E chart) for all age groups and the stereopsis test (TNO test) in kindergartens. RESULTS: Vision screening was performed on 7499 children. 1471 first graders (55 %), 201 fourth graders (11 %) and 211 eighth graders (12.3 %) did not pass the examinations. In 33.7 % of the children who underwent the follow-up examination from an ophthalmologist, amblyogenic potential was found. CONCLUSIONS: Vision screening by the school medical services enrols most of the children from a single age group. The Snellen E charts used for the monocular distance acuity, together with the TNO stereo test, appear to constitute an effective testing combination. Ophthalmological follow-up examinations of the affected children revealed that one third were afflicted by amblyogenic factors.

Malposition of Teeth and Jaws in Patients with Congenital Superior Oblique Palsy.

BACKGROUND: Patients with congenital superior oblique palsy tend to adopt a head tilt to the contralateral side to maintain binocular single vision. It has long been recognised that facial asymmetries may be caused by a head tilt. The aim of this study was to describe the effect of habitual head tilt due to congenital superior oblique palsy on dental occlusion. PATIENTS AND METHODS: The study was designed as a descriptive cohort study. Ten patients with congenital superior oblique palsy (3 female, 7 male; mean age 51.7 (y) ± 15.8 SD, ranging from 19 to 69 (y)) underwent orthodontic examination. Orthodontic findings and values for vertical, torsional and horizontal deviation measured with the Harms tangent screen and stereopsis using a random dot test were compared. RESULTS: Three orthodontic parameters were found to correlate significantly or at least as trend with orthoptic parameters. Midline deviation of the upper jaw to the face (rho = 0.623; p = 0.054) and anterior positioning of upper first molar in the sagittal plane (rho = 0.594; p = 0.07) correlate with the vertical deviation; overbite correlates with horizontal deviation measured in the primary position (rho = 0.768; p = 0.016). CONCLUSIONS: In this small study, three orthodontic parameters correlated with orthoptic findings in patients with congenital superior oblique palsy. Further studies are needed to establish whether congenital superior oblique palsy is more frequent in patients exhibiting abnormal values of these orthodontic parameters.

Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder.

Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation.

Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer's Disease--Results of a Phase I Study.

OBJECTIVE: The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status. DESIGN: A 1-year phase I proof-of-concept study. SETTING: The Department of Psychiatry and Psychotherapy at the University of Cologne. PARTICIPANTS: We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. INTERVENTION: Bilateral low-frequency DBS of the nucleus basalis of Meynert. MEASUREMENTS: Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate. RESULTS: With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042). CONCLUSION: Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.

[Three horizontal muscle surgery for infantile esotropia and decompensated microtropia]. / Horizontale Dreimuskelchirurgie bei frühkindlichem Innenschielen und dekompensiertem Mikrostrabismus.

BACKGROUND: Surgical management of large-angle infantile esotropia and decompensated microtropia has been controversially debated. There seems to be a relative bias against surgery on more than two horizontal muscles to avoid overcorrections. In our study we report on the sensory and motor outcomes after three horizontal muscle surgery. Furthermore we aim to suggest a table to guide surgery amounts. PATIENTS AND METHODS: This study was a retrospective interventional cohort of 27 patients (16 female, 11 male; mean age 7.9 [years], ranging from 1 to 27 [years]) with infantile esotropia and decompensated microtropia who underwent three horizontal muscle surgery (bilateral medial rectus muscle recession and lateral rectus muscle plication) between 2005 and 2013. RESULTS: Preoperative deviation in primary position measured 30.2 [°] (mean; range 21.9 to 48.0). Postoperatively esotropia was significantly reduced to 2.6 [°] (mean; range -16.7 to 16.7). After six months deviation measured 5.5 [°] (mean, range -14.1 to 21.9). An effect of 1.63°/mm was calculated for the combined three muscle surgery. CONCLUSIONS: For the correction of large-angle infantile esotropia and decompensated microtropia three horizontal muscle surgery is associated with a high success rate. Only a very low rate of consecutive exotropia does occur.

Measurement of Optic Nerve Sheath Diameter: Differences between Methods? A Pilot Study.

BACKGROUND: Quantification of the optic nerve sheath diameter is a promising approach for the detection of elevated intracranial pressure. The comparability of current methods is unclear. The objective of this study was to assess the relationship between optic nerve sheath diameter as measured with computed tomography, magnetic resonance tomography and ultrasound in patients without known optic nerve disease or increased intracranial pressure. PATIENTS AND METHODS: 15 patients (60.8 [years]±16.73 SD; 7 female) with paranasal sinus pathology in whom computed tomography and magnetic resonance imaging were performed underwent optic nerve sheath diameter measurements by ultrasound, as well as an ophthalmological examination. Ultrasound-, computed tomography- and magnetic resonance imaging-derived maximal optic nerve sheath diameter values 3 mm behind the globe were compared. RESULTS: Optic nerve sheath diameter measured (n=30) by ultrasound (mean 6.2 [mm]±0.84 SD) was significantly (p<0.01) higher than optic nerve sheath diameter in computed tomography (5.2±1.11) or magnetic resonance imaging (5.3±1.14). There was no significant (p=0.24) difference between optic nerve sheath diameter measured in computed tomography and magnetic resonance tomography. CONCLUSIONS: The comparability of optic nerve sheath diameter measurements in patients without known optic nerve disease and assumed normal intracranial pressure appears to be given between computed tomography and magnetic resonance tomography, while comparability between ultrasound and computed tomography or magnetic resonance tomography seems to be less reliable.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

Inferior oblique muscle anteriorization in congenital superior oblique palsy.

BACKGROUND: Inferior oblique muscle overaction of variable amounts is usually present with congenital superior oblique palsy. Inferior oblique muscle anteriorization has been described as a suitable surgical procedure in this entity. The aim of this study was to investigate the effect of inferior oblique muscle anteriorization in patients with congenital superior oblique palsy on vertical, torsional and horizontal alignment. PATIENTS AND METHODS: The study was designed as an institutional retrospective cohort study. 45 patients with congenital superior oblique palsy (15 female, 30 male; mean age 36 years ± 19.2 SD, ranging from 6 to 75 years) underwent inferior oblique muscle anteriorization between 2000 and 2010. Preoperative amounts of vertical, torsional and horizontal deviation (using Harms tangent screen), measurements of Bielschowsky head tilt phenomenon as well as stereopsis (Lang test) were compared with findings three months and one year postoperatively. RESULTS: Preoperative vertical deviation in primary position measured 10.1° (mean; range 0-19). Three months postoperatively vertical deviation was significantly reduced (p<0.001) to 4° (mean; range 0-20). After one year vertical deviation measured 3.5° (mean; range 0-15). The values three months postoperatively did not significantly differ from those one year postoperatively (p=0.46). CONCLUSIONS: Inferior oblique muscle anteriorization leads to a significant and sustained improvement of ocular alignment in patients with congenital superior oblique palsy of various degrees of severity. Thus the procedure is recommendable as a first line treatment in this clinical situation.

Management and outcome of pallidal deep brain stimulation in severe Huntington's disease.

Neurodegenerative movement disorders, such as Huntington's disease (HD), have become a promising field for Deep Brain Stimulation (DBS). This study aims to contribute to the establishment of a well-grounded database including both expected and unexpected effects of pallidal DBS in HD, and to discuss the ethical and legal restrictions of DBS in cognitively limited patients. Evaluation of the outcome data indicates that pallidal DBS exerted an independent effect on motor symptoms but probably also on the patient's cognitive and affective state. The cognitive decline, however, that characterizes the late stage of neurodegenerative disorders implicates ethical and legal problems given the patients' inability to give informed consent to DBS.

Modulation of local field potential power of the subthalamic nucleus during isometric force generation in patients with Parkinson's disease.

Investigations of local field potentials of the subthalamic nucleus of patients with Parkinson's disease have provided evidence for pathologically exaggerated oscillatory beta-band activity (13-30 Hz) which is amenable to physiological modulation by, e.g., voluntary movement. Previous functional magnetic resonance imaging studies in healthy controls have provided evidence for an increase of subthalamic nucleus blood-oxygenation-level-dependant signal in incremental force generation tasks. However, the modulation of neuronal activity by force generation and its relationship to peripheral feedback remain to be elucidated. We hypothesised that beta-band activity in the subthalamic nucleus is modulated by incremental force generation. Subthalamic nucleus local field potentials were recorded intraoperatively in 13 patients with Parkinson's disease (37 recording sites) during rest and five incremental isometric force generation conditions of the arm with applied loads of 0-400 g (in 100-g increments). Repeated measures analysis of variance (ANOVA) revealed a modulation of local field potential (LFP) power in the upper beta-band (in 24-30 Hz; F(3.042)=4.693, p=0.036) and the gamma-band (in 70-76 Hz; F(4)=4.116, p=0.036). Granger-causality was computed with the squared partial directed coherence and showed no significant modulation during incremental isometric force generation. Our findings indicate that the upper beta- and gamma-band power of subthalamic nucleus local field potentials are modulated by the physiological task of force generation in patients with Parkinson's disease. This modulation seems to be not an effect of a modulation of peripheral feedback.

Endocrine and visual function after fractionated stereotactic radiotherapy of perioptic tumors.

PURPOSE: To find out whether the use of stereotactic techniques for fractionated radiotherapy reduces toxicity to the endocrine and visual system in patients with benign perioptic tumors. PATIENTS AND METHODS: From 1993 to 2009, 29 patients were treated with fractionated stereotactic radiotherapy. The most frequent tumor types were grade I meningioma (n = 11) and pituitary adenoma (n = 10, 7 nonfunctioning, 3 growth hormone-producing). Patients were immobilized with the GTC frame (Radionics, USA) and the planning target volume (PTV; median 24.7, 4.6-58.6 ml) was irradiated with a total dose of 52.2 Gy (range, 45.0-55.8 Gy) in 1.8-Gy fractions using a linear accelerator (6 MeV photons) equipped with a micro-multileaf collimator. Maximum doses to the optic system and pituitary gland were 53.4 Gy (range, 11.5-57.6 Gy) and 53.6 Gy (range, 12.0-57.9 Gy). RESULTS: Median follow-up was 45 months (range, 10-105 months). Local control was achieved in all but 1 patient (actuarial rate 92% at 5 years and 10 years). In 9 of 29 patients (31%), partial remission was observed (actuarial response rate 40% at 5 years and 10 years). In 4 of 26 patients (15%) with at least partial pituitary function, new hormonal deficits developed (actuarial rate 21% at 5 years and 10 years). This rate was significantly higher in patients treated for a larger PTV (< /> 25 ml: 0% vs. 42% at 5 years and 10 years, p = 0.028). Visual function improved in 4 of 15 patients (27%) who had prior impairment. None of the patients developed treatment-related optic neuropathy, but 2 patients experienced new disease-related visual deficits. CONCLUSION: Fractionated stereotactic radiotherapy for benign tumors of the perioptic and sellar region results in satisfactory response and local control rates and does not affect the visual system. The assumption that patients can be spared hypophyseal insufficiency only holds for small tumors.

Early onset of acquired comitant non-accommodative esotropia in childhood.

BACKGROUND: The aim of this study was to describe the clinical characteristics and surgical outcome of acquired comitant non-accommodative esotropia without obvious cause in children with an early onset ≤ three years of age. PATIENTS AND METHODS: 24 consecutive patients (13 females) with acquired comitant non-accommodative esotropia underwent strabismus surgery. Outcome measures included amount of deviation and level of binocularity at last follow-up. RESULTS: An acute onset of strabismus was observed in 83 % of patients. Accompanying features such as diplopia, covering one eye or stumbling were observed in 40 % of the children. Cycloplegic retinoscopy revealed a mild to moderate hypermetropia in all children (mean hypermetropia + 2.2 diopters). 90.5 % of children were aligned within 8 PD of orthotropia. 81 % regained normal stereovision (Lang I/II). CONCLUSIONS: All children exhibited the typical features of acute acquired comitant esotropia (AACE) type II (Burian-Franceschetti). Collective characteristics of this form of strabismus are a comitant and relatively large deviation, mild hypermetropia, a potential of normal binocular cooperation and absence of an accommodative component and neurological pathology. Time and suddenness of strabismus onset may be less helpful in defining this entity.