Spatial reorganization of putaminal dopamine D2-like receptors in cranial and hand dystonia

The putamen has a somatotopic organization of neurons identified by correspondence of firing rates with selected body part movements, as well as by complex, but organized, differential cortical projections onto putamen. In isolated focal dystonia, whole putaminal binding of dopamine D(2)-like receptor radioligands is quantitatively decreased, but it has not been known whether selected parts of the putamen are differentially affected depending upon the body part affected by dystonia. The radioligand [(18)F]spiperone binds predominantly to D(2)-like receptors in striatum. We hypothesized that the spatial location of [(18)F]spiperone binding within the putamen would differ in patients with dystonia limited to the hand versus the face, and we tested that hypothesis using positron emission tomography and magnetic resonance imaging. To address statistical and methodological concerns, we chose a straightforward but robust image analysis method. An automated algorithm located the peak location of [(18)F]spiperone binding within the striatum, relative to a brain atlas, in each of 14 patients with cranial dystonia and 8 patients with hand dystonia. The mean (left and right) |x|, y, and z coordinates of peak striatal binding for each patient were compared between groups by t test. The location of peak [(18)F]spiperone binding within the putamen differed significantly between groups (cranial dystonia z<hand dystonia z, p = 0.016). We conclude that in isolated focal dystonia, dopamine D(2)-like receptors are distributed differently in the putamen depending on the body part manifesting dystonia

The Denominator Matters! Lessons from Large Database Research in Neonatology

Observational studies from large datasets are becoming more common in neonatology. In this review, we highlight the importance of the denominator in study design and interpretation including examples of bias from source data, weight-based categories, age-related bias, and diagnosis-based denominators

Two-Year Outcomes of Infants with Stage 2 or Higher Retinopathy of Prematurity: Results from a Large Multicenter Registry.

OBJECTIVE:  To define the incidence of ophthalmologic morbidities in the first 2 years of life among infants diagnosed with stage 2 or higher retinopathy of prematurity (ROP). STUDY DESIGN:  We prospectively enrolled premature infants with stage 2 or higher ROP. The infants were followed up for 2 years, and we report on data collected from outpatient ophthalmology and primary care visits. RESULTS:  We enrolled 323 infants who met inclusion criteria, of which 112 (35%) received treatment with laser surgery (90) or bevacizumab (22). Two-year follow-up was available for 292 (90%) of the cohort. The most common ophthalmologic conditions at follow-up were hyperopia (35%), astigmatism (30%), strabismus (21.9%), myopia (19.2%), anisometropia (12%), and amblyopia (12%). Severe ophthalmologic morbidities such as retinal detachment and cataracts were rare, but occurred in both treated and untreated infants. Overall, 22.6% of the infants were wearing glasses at 2 years, including 8.5% of the untreated infants. CONCLUSION:  Patients with stage 2 or higher ROP remain at significant risk for ophthalmological morbidity through 2 years of age. Infants with regression of subthreshold ROP who do not require treatment represent an underrecognized population at long-term ophthalmological risk. CLINICALTRIALS. GOV IDENTIFIER:  NCT01559571

Somatotopy represented on a coronal section of the putamen.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088121#pone-0088121-g003" target="_blank">Fig. 3A</a> from ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088121#pone.0088121-Nambu1" target="_blank">[43]</a>, used by permission.</p

Mean location in atlas space of peak [¹⁸F]spiperone binding, by group (mm).

<p>Mean location in atlas space of peak [¹⁸F]spiperone binding, by group (mm).</p

Coronal view of peak [¹⁸F]spiperone binding in striatum in cranial and hand dystonia.

<p>The location of peak [¹⁸F]spiperone binding in striatum is plotted for each dystonic subject by atlas |<i>x</i>| and <i>z</i> coordinates according to which part of the body is affected by dystonia. On average, the peak was 2.1 mm more superior in the hand cramp group (red triangles) than in the group with dystonia affecting the face (blue circles). The mean location for each dystonia group is indicated by a plus sign; note that the mean (and median) cranial dystonia peak lies inferior to every hand cramp peak. The three left-handed subjects are indicated by dashed symbols. The large black lines intersect at the mean peak location for the control group.</p

Peak putaminal [¹⁸F]spiperone binding does not vary significantly with age.

<p>The location of peak [¹⁸F]spiperone binding in striatum (atlas <i>z</i> coordinate) is graphed versus age, for a group of normal volunteers. There is no meaningful correlation of this measure with age, and the line that best fits the data has a nearly flat slope.</p