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Purpose: Macular telangiectasia type 2 (MacTel) is a bilateral neurodegenerative disorder of the central macula. Previous findings indicated more functional impairment in low light conditions. We sought to further characterize retinal dysfunction using dark-adapted two-color fundus-controlled perimetry ("scotopic microperimetry")., Methods: Participants of the MacTel Natural History Observation Registry study and age-matched healthy controls underwent retinal imaging including dual wavelength autofluorescence macular pigment optical density (MPOD) measurement. Retinal sensitivity was assessed with scotopic microperimetry using cyan (505 nm) and red (627 nm). Disease was graded into classes of MPOD loss (0 to 3). For perimetry analysis, the differences of the mean sensitivities (MacTel minus controls) were compared at each test location and the results were aggregated to global indices., Results: Thirty-four eyes (19 patients, mean age 62.2 years) were compared with 25 eyes (25 controls, mean age 61.5 years). Both cyan and red sensitivity were lower in MacTel. This was more pronounced at one- and three-degree eccentricity. Eyes with MPOD class 0 did not exhibit a functional deficit. Class 1 had impaired cyan, but normal red sensitivity. Class 2 and 3 behaved similarly and had impaired cyan and red sensitivity with a relatively higher cyan impairment., Conclusions: Rods might be compromised to a greater extent than cones. Linking to previous studies, our results might also hint toward (postreceptoral) dysfunction of the cone system in very early disease stages. Macular pigment loss and global perimetry indices seemed to reflect functional impairment and might be useful as adjunct measures for disease progression.

Background/aim: Macular pigment optical density (MPOD) is centrally depleted early on in macular telangiectasia type 2 (MacTel). Contrast sensitivity (CS) might be related to MPOD, and thus impaired in early MacTel. The effect of low luminance was assessed on both CS and best corrected visual acuity (BCVA)., Methods: This is a cross-sectional study. Pelli-Robson charts were used for CS testing at 1 m in photopic (110 lux) and mesopic (1 lux) conditions. BCVA was tested with ETDRS charts and low luminance visual acuity (LLVA) with a 2.0 log unit neutral density filter. MPOD was obtained with dual-wavelength autofluorescence., Results: One hundred and three eyes of 52 patients with MacTel (mean±SD age 62.9±10.2, range 35-77) were compared with 34 healthy eyes of 17 controls (mean±SD age 65.2±7.4, range 53-78). CS was significantly lower in the eyes with MacTel. This impairment was higher in low light conditions (low light contrast sensitivity (LL-CS)). Eyes at the early stages of MacTel had significantly lower LL-CS than controls, but normal (photopic) CS. The results were similar but less pronounced for BCVA/LLVA. Decrease in CS was correlated with loss of MPOD., Conclusions: Low light conditions have a detrimental effect on visual performance in MacTel. Impaired CS might correlate with MPOD depletion as a pathognomonic finding in MacTel. Functional impairment might precede structural disintegration, indicating dysfunction at the cellular level. The applied tests might be useful as additional functional assessments in clinical routine and as outcome measures in future interventional clinical trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In patients with macular telangiectasia Type 2, blue light reflectance imaging reveals an oval, parafoveal area in the macula that has increased reflectance compared with its surrounding. Here, we examine how dark adaptation and photobleaching can affect the blue light reflectance imaging pattern., Methods: Prospective study of patients with macular telangiectasia enrolled in the MacTel Natural History Observation Study. After dark adaptation, a sequence of images was obtained with a confocal scanning laser ophthalmoscope at 488 nm. Change of reflectance patterns was analyzed over time., Results: Eighteen eyes from 16 patients were analyzed. Initially, increased reflectivity in the parafoveal area resulted in higher gray values compared with the paramacular surrounding on blue light reflectance imaging. The difference between parafoveal and paramacular reflectance intensity decreased steadily during imaging, from 17.7 gray-value units (95% confidence interval: 12.1-23.2) down to 2.8 (95% confidence interval: -0.8 to 6.5) after around 30 seconds, and recovered after 5 minutes of dark adaptation., Conclusion: A bleaching effect was evident in our study. Understanding these changes is important for both diagnosis and assessment of blue light reflectance phenotype in patients with macular telangiectasia and could also provide further insights into the pathophysiology of this disease.

Purpose: Pigment in the midretina is a characteristic sign in Type 2 idiopathic macular telangiectasia (MacTel) and is considered to characterize the late stage of the disease. Our aim was to investigate its incidence, and relationship with risk factors for MacTel, including outer retinal vascularization and subretinal neovascular proliferation (SRNV)., Methods: Pigment extent was measured in fundus autofluorescence images of 150 eyes of 75 MacTel probands, using the Region Finder tool of Heidelberg Eye Explorer. A linear mixed model was used to analyze the dynamics of pigment and its associations with other features of the phenotype. The relative incidence of pigment and of outer retinal outer retinal vascularization and SRNV was analyzed within the full MacTel Study cohort (1,244 probands)., Results: Mean pigment area at baseline was 0.157 mm (range = 0-1.295 mm, SD = 0.228 mm, n = 101). Progression demonstrated a nonlinear pattern (P < 0.001) at an overall rate of 0.0177 mm/year and was associated with the initial plaque size and with SRNV. There was a strong correlation between fellow eyes (P ≤ 0.0001). In approximately 25% of all SRNV cases, SRNV may coincide with or precede pigment., Conclusion: Our data may be useful for refining the current system for staging disease severity in MacTel.

Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10 -8 ) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10 -17 ; rs715 at 2q34, P = 9.97 × 10 -14 ; rs477992 at 1p12, P = 2.60 × 10 -12 ) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10 -6 ) and serine (P = 2.48 × 10 -4 ) between MacTel cases and controls.

Background: The majority of Huntington's disease (HD) mutation carriers experience some psychopathology during their lifetime, varying from irritability to psychosis, but prevalences of particular symptoms vary widely due to diverse study populations in different stages of HD and the use of different assessment methods., Methods: The study population consisted of 1993 HD mutation carriers from 15 European countries, all participating in the observational REGISTRY study. The behavioural section of the Unified HD Rating Scale was used to examine the prevalence and correlates of five neuropsychiatric features: depression, irritability/aggression, obsessive/compulsive behaviours, apathy and psychosis., Results: Twenty-seven per cent of the participants did not have any neuropsychiatric symptom in the last month. Moderate to severe apathy occurred in 28.1% of the participants, whereas moderate to severe depression was found in 12.7%. Irritable/aggressive symptoms were present in 13.9% of the participants, and 13.2% showed obsessive/compulsive behaviours. Moderate to severe psychotic symptoms were found in only 1.2%. Only 54.9% of all participants with moderate to severe depression used antidepressants, suggesting undertreatment of depression. Obsessive/compulsive behaviours and irritability/aggression were inversely correlated with the Total Functional Capacity score, but with apathy showing the strongest inverse association., Conclusions: A variety of neuropsychiatric symptoms are highly prevalent in different stages of HD in this European HD population, with apathy as the most frequent symptom. Depression, irritability/aggression and OCBs are prevalent in all stages of HD. Apathy was the key neuropsychiatric symptom occurring most often in advanced HD stages. Due to possible selection of relatively healthy participants, prevalences reported in this study might be an underestimation of prevalence in the entire HD population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Depressive symptoms and religious/spiritual (R/S) practices are widespread around the world, but their intersection has received relatively little attention from mainstream mental health professionals. This paper reviews and synthesizes quantitative research examining relationships between R/S involvement and depressive symptoms or disorders during the last 50 years (1962 to 2011). At least 444 studies have now quantitatively examined these relationships. Of those, over 60% report less depression and faster remission from depression in those more R/S or a reduction in depression severity in response to an R/S intervention. In contrast, only 6% report greater depression. Of the 178 most methodologically rigorous studies, 119 (67%) find inverse relationships between R/S and depression. Religious beliefs and practices may help people to cope better with stressful life circumstances, give meaning and hope, and surround depressed persons with a supportive community. In some populations or individuals, however, religious beliefs may increase guilt and lead to discouragement as people fail to live up to the high standards of their religious tradition. Understanding the role that R/S factors play in preventing depression, facilitating its resolution, or leading to greater depression will help clinicians determine whether this is a resource or a liability for individual patients.

People with MCI suffer from a moderate memory impairment, from deficits in attention and cognitive flexibility but do not fulfil the diagnostic criteria of dementia. These patients feel forgetful, and sometimes may have problems with their jobs and families because of their forgetfulness. In many cases (10-15% per year), MCI is leading to Alzheimer's disease. The sooner MCI is diagnosed and treated, the better the transition into Alzheimer's disease may perhaps be delayed. The diagnostic instruments are the same as for the diagnosis of Alzheimer's disease: biomarkers of the cerebrospinal fluid, neuroimaging and neuropsychological testing. Neuropsychological testing already shows deficits, even when neuroimaging findings still seem to be normal. Therapy of MCI is basically like the treatment of Alzheimer's disease: symptomatic treatment with cholinesterase-inhibitors or antioxidants, and compensatory psychological approaches.

The few reports available on olanzapine in Huntington's disease (HD) are insufficiently documented and/or insufficiently dosed. We describe a 30-year-old woman with genetically confirmed HD who presented with severe chorea. She was not able to eat or dress without help and did not respond to haloperidol; the motor scale of the Unified HD Rating Scale (UHDRS-I) revealed 65 of a possible 124 points. After admission, we treated the patient with a high dose of olanzapine (30 mg daily). The chorea almost ceased in the next 2 days, she was able to eat and walk without assistance (UHDRS-I of 21 points), and fine motor tasks improved, as well as gait and eye movements. This effect lasted for 5 months. We conclude that high-dose olanzapine appears to be useful in grave choreatic attacks.

Advances in neuroradiological and neurosurgical techniques have lead to a growing interest in functional neurosurgical interventions for medically intractable movement disorders. The majority of these procedures are performed in patients with hypokinetic movement disorders, especially Parkinson's disease. However, relatively few interventions were done in hyperkinetic disorders such as Huntington's disease (HD), mainly owing to the lack of an adequate target nucleus. We have recently described the case of a reversible chorea in a genetically confirmed HD patient. We subsequently identified a marked bilateral degeneration of the substantia nigra as the probable reason for choreatic cessation. We therefore suggest that primary striatal atrophy causing hyperkinesia and secondary substantia nigra atrophy favouring hypokinesia were balanced in this patient, thus resulting in a close-to-physiologic GABAergic basal ganglia output. We postulate that deep brain stimulation of the substantia nigra pars compacta may ameliorate hyperkinesia in choreatic movement disorders, thus representing the first effective therapy in Huntington's chorea. Several lines of evidence in recent neurophysiological research support our hypothesis and are discussed below., (Copyright 2001 Harcourt Publishers Ltd.)

There are only a few reliable objective methods of diagnosing peripheral neuronal damage suitable for routine use; the most important is based on measurement of nerve conduction velocity, which only shows changes when severe disturbances are already present. However, it is precisely at this stage that the possibilities of therapy are no longer satisfactory. As small fibres are affected earlier in the course of most forms of PNP than the large ones, assessment of afferent as well as efferent C-fibre function gains importance in the management of this widespread disease. In assessment of autonomic dysfunction, variability of the heartbeat with deep breathing or the Valsalva manoeuvre is a good and generally accepted test, although not strongly associated with other PNP test abnormalities. However, axonal degeneration starts in the most distal parts of the axon due to impaired axonal transport. Therefore, the longest C-fibres, i.e. in the lower extremities, are affected first, and incipient changes are most prominent there. For this reason HLDF, a reflex response of the skin blood flow stimulated by heat, has advantages in assessment of early C-fibre dysfunction. Considering the fact that the afferent and efferent sympathetic C-fibres are involved in regulation of microcirculation, the skin blood flow regulation is investigated by means of laser Doppler flowmetry. The microcirculation is stimulated by heat and the reaction of microcirculation is assessed as a value for the function of afferent and efferent (sympathetic) C-fibres. The results of this method are in close correlation with electrophysiologic tests, which is not achieved with sudomotor function.

Object: Whereas the removal of subarachnoid blood is possible during early-stage aneurysm surgery, this cannot be achieved in aneurysms treated by endovascular means. The levels of potential spasmogens in the cerebrospinal fluid (CSF) in patients receiving endovascular treatment might therefore be higher, with the potential for more severe post-subarachnoid hemorrhage (SAH) vasospasm., Methods: Serum and CSF concentrations of big endothelin (ET)-1 were serially measured in patients with SAH receiving one of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgical treatment (15 patients), 2) early endovascular treatment (17 patients), or 3) no intervention in the acute phase (12 patients). In patients suffering delayed infarctions higher levels of big ET-1 CSF were demonstrated than in those without infarctions (p = 0.01). In patients in whom surgery was performed in the acute phase lower big ET-1 CSF concentrations were demonstrated than in those who received embolization treatment or no treatment (p = 0.02). Subgroup analysis demonstrated that in patients receiving early endovascular treatment, higher big ET-1 CSF concentrations were revealed than in those undergoing early aneurysm surgery; this was true for patients with (microsurgerytreated, 1.84 +/- 0.83 pg/ml; and embolization-treated 2.19 +/- 0.54 pg/ml) and without (microsurgery-treated 1.76 +/- 0.61 pg/ml; and embolization-treated 2.01 +/- 0.48 pg/ml) delayed infarctions., Conclusions: Among patients with SAH who received treatment during the acute phase, those undergoing early aneurysm surgery were shown to have lower big ET-1 CSF levels than those receiving embolization and no treatment (that is, the nonsurgical treatment groups). The clinical significance of this finding remains to be established in future clinical trials, because in the present study the trend toward lower levels of big ET-1 CSF in the microsurgically treated group was not paralleled by a lower delayed stroke rate or an improvement in neurological outcome.

The article describes the development of symptoms in a 59-year-old patient. Dyskinesia and speech disorder were the only clinical features in the beginning. Increased immunological parameters and only slight hypokinetic-rigid signs for a long time made the diagnostical and therapeutical process more difficult, as well as atypical findings in neuroimaging techniques. Corticobasal degeneration was diagnosed about 6 years after onset of clinical symptoms.

The recommendations for the dietary allowance of iodine are 150 micrograms per day for adolescents and adults. Thyrotropin (TSH) and thyroglobulin (Tg) can be used as surveillance indicators for assessing iodine deficiency disorders. We compared the relation between TSH and Tg, free triiodothyronine, and thyroxine serum levels with urinary iodine excretion in 2311 untreated euthyroid patients using our modified cericarsenite method. An adequate iodine intake may be assumed when TSH and Tg values are at the lower end of the normal range. Patients were grouped according to urinary iodine excretion and goiter size. In the group with an iodine excretion between 201 and 300 micrograms of iodine per gram of creatinine, the lowest TSH values and even low Tg levels could be shown. We conclude that an iodine intake of approximately 250 micrograms/day is associated with the lowest TSH stimulation to thyrocytes. In the groups separated according to thyroid size, significantly higher Tg levels were found in the patients with uninodular and multinodular goiter as a result of longstanding iodine deficiency, whereas actual urinary iodine excretion did not differ significantly. Additionally, iodine excretion of 39,913 euthyroid patients between 1984 was 1996 was examined. In Austria iodized salt (10 mg KI/kg) was introduced by law in 1963 and increased to 20 mg KI/kg salt in 1990. An initial increase of iodine excretion until 1993 was followed by a decrease in 1994 and 1995 without further changes in 1996. These results show that iodine intake has improved since 1984; however, in 1996 iodine excretion in one-third of the investigated patients was under 100 micrograms per gram of creatinine and more than 80% had less than 200 micrograms per gram of creatinine.

The aim of this study was to evaluate the incidence of cognitive and affective problems in the treatment of children suffering from myodystrophy. It was hypothesised that psychomotory assessment taking appropriate account of data regarding the evaluation of cognitive and affective development might allow an adequate and realistic therapeutic protocol to be defined. For this purpose the authors examined 55 myodystrophic patients aged between 6 and 10 years old during the period January 1980 and June 1993 using traditional psychomotory tests (Stanford-Binet and/or WISC in relation to the various age groups), projective tests (CAT, TAT) and graphic tests. The latter were also evaluated according to Koppitz's criterion which enabled emotional indicators (EI) to be assessed. All 55 cases were evaluated in collaboration with the 1st Pediatric Clinic of the Neuro-Psychomotory Unit of "G. Gaslini" Institute. Psychomotory treatment, which by definition is addressed to the entire person, specifically took cognitive and affective data into consideration. In fact, as observed by Johnson and Alexander, in myodystrophy functional skills are more often limited by cognitive and motivational factors than by actual menomation. The results showed that the concentration on psychological aspects in the rehabilitation of myodystrophic children allows the neuropsychological component of movement (practognosia) to be preserved for as long as possible despite the progress of instrumental deficit (anatomic degeneration). In the authors' experience and in comparison to that of other Authors, it was possible to state that a "personalized" approach allows the subjects to improve their own "presence in the world".

We studied central and peripheral hemodynamics and exercise tolerance in 24 patients with left ventricular dysfunction. All were in NYHA class II or III, and echocardiographic left ventricular ejection fraction was < 35% without pharmacologic influences. Patients underwent to treadmill test (Naughton protocol), cardiopulmonary upright bicycle test, and supine bicycle test with haemodynamic measurements. All tests were exhaustive. Average exercise time was 9 +/- 3.4 min, (range 3-20). Average ejection fraction (.28 +/- 0.65) dis not correlate with working capacity (r = .32), nor did left ventricular filling pressure (pulmonary capillary wedge pressure) at rest and at peak exercise (r = .29 and r = .02). Stroke volume and stroke volume index were on average depressed, with no variations during work; cardiac output and cardiac index were also depressed, with a significant increase at peak exercise (both p < .001). Systemic and pulmonary resistances were increased, but systemic resistances tended to decrease during effort (p < .001), while pulmonary resistances did not (p = NS). We subdivided patients according to systemic vascular resistances lower or higher than 1500 dynes.cm.sec-5 at rest; this identifies two different working capacities (low systemic vascular resistances 11.7 +/- 4.4 min, high systemic vascular resistances 6.9 +/- 3.2 min, p < .05). Patients were then divided in two groups: group I (rest stroke volume > 60 ml) and group II (rest stroke volume < 60 ml). Group I worked 11 +/- 5 min, group II 8.5 +/- 3 min (p < .05). We performed a linear regression analysis between cardiac output and systemic vascular resistances at rest and during exercise in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

In the present study we evaluated the influence of intravenous thrombolysis and patency of the infarct-related coronary artery on both markers of ventricular electrical instability and incidence of late arrhythmic events after acute myocardial infarction (AMI). Ninety one patients surviving a first AMI who consecutively performed coronary angiography were enrolled in the present study; 44 patients (48%) received thrombolysis, 47 patients (52%) were treated conventionally. Of 91 patients, 90 (99%) had signal-averaged electrocardiogram (SAECG), and 40 (44%) programmed ventricular stimulation. No significant difference was observed between thrombolytic-treated and control group in late potential rate, SAECG determinants and ventricular arrhythmia inducibility. Of 91 patients, 40 (44%) had occlusion of the infarct-related artery: of these, 15 (37%) had late potentials compared with 5 of 51 patients (9%) with a patent artery (p < 0.01). Mean left ventricular ejection fraction was not significantly different between the two groups (0.50 +/- 0.15 vs 0.55 +/- 0.12; p = NS). No significant difference was present between the two groups of patients with regard to inducibility of sustained ventricular tachyarrhythmias, however an odds ratio of 3.5 was observed in the group with a closed vessel.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: The appearance or the increase of repolarization abnormalities in the EKG during post exercise (ET) recovery phase (R) is considered a marker of ischemia., Methods: In order to evaluate the real meaning of these changes we compared the EKG data with eventual modifications of left ventricular kinesis analyzed by 2D-ECHO. 10 male patients with previous myocardial infarction, mean age 50 +/- 4.8 y, underwent exercise testing on a treadmill (Bruce's protocol) and continuous 2D-ECHO observation from the end of exercise along the whole R. Patients were divided in two groups: Group A (6 patients) and Group B (4 patients), all free of symptoms., Results: Group A showed ischemic EKG markers during exercise which increased during R; Group B showed ischemic EKG markers only during R. The 2D-ECHO showed in Group A an impairment of left ventricular kinesis at peak exercise without increase or extension during R (WMSI at rest 1.32; peak ET 1.60; R 1.60); in Group B the kinetic alterations appeared only in R (WMSI at rest 1.33, peak ET 1.42; R 1.80), strictly related to EKG markers., Conclusions: The data suggest : 1) that the increase of EKG abnormalities already present during exercise do not seem to imply more severe ischemia; 2) that EKG changes appearing during R are markers of ischemia which occur in the R.

The influence of intravenous thrombolysis on both prevalence of ventricular late potentials and incidence of late arrhythmic events was evaluated in 174 consecutive patients surviving a first acute myocardial infarction; 106 patients (61%) received thrombolysis (group A) and 68 (34%) had conventional therapy (group B). In group A, 18 patients (17%) had late potentials compared with 23 (34%) in group B (p less than 0.05); mean left ventricular ejection fraction was not different (0.50 +/- 0.09 vs 0.50 +/- 0.10; p = not significant [NS]). Of 63 patients who underwent coronary arteriography because of postinfarction ischemia, 28 (44%) had a closed infarct-related artery; of these, 11 (39%) had late potentials compared with 3 of 35 (9%) with a patent artery (p less than 0.01). Mean left ventricular ejection fraction was not significantly different between the 2 groups (0.49 +/- 0.09 vs 0.53 +/- 0.09; p = NS). At a mean follow-up of 14 +/- 8 months, 8 of 161 patients (5%) had a late arrhythmic event; 6 of 8 (75%) with and 28 of 153 (18%) without events had late potentials (p less than 0.001). In group A, 4 of 99 patients (4%) had events compared with 4 of 62 (6%) in group B (p = NS, relative risk 1.6). Of 24 patients with anterior wall AMI and left ventricular dyskinesia, 6 events occurred. In this group of patients, a higher rate of events was observed (25%); 3 of 16 (19%) treated with thrombolysis had an event compared with 3 of 8 (37%) treated conventionally (p = NS, relative risk 2.6).(ABSTRACT TRUNCATED AT 250 WORDS)

The antiprogestin RU 486 converts the early pregnant uterus by increasing the sensitivity of the myometrium to prostaglandin (PG). These effects of antiprogestin have resulted in the development of nonsurgical procedures to abort embryos based on a combination of RU 486 and different PG-analogues administered vaginally or intramuscularly. RU 486 also has a softening effect on the cervix which may be used as pretreatment in second and third trimester abortions. The effects, mode of action, dangers, and the many other postulated clinical implications (like breast cancer, meningioma, ectopic pregnancy, fetal death in utero, induction of labour, initiation and promotion of lactation, endometrial or ovarian cancers, leukemia, Cushing's syndrome, uterine adenomyosis, acute uremia, leiomyosarcoma, hypertension, etc.) are discussed.