Mohs Defect Repair with Dehydrated Human Amnion/Chorion Membrane.

Importance: Reconstructing cosmetically sensitive defects in an aging population undergoing multiple Mohs micrographic surgeries (MMS) may be addressed with alternatives to surgery. Objective: Patients undergoing MMS with defect reconstruction in visually prominent areas receiving placental allograft were compared with traditional autologous tissue-based procedures-flaps and full-thickness skin grafts (FTSG). Design, Setting, and Participants: This retrospective case-control study evaluated patients who underwent MMS for removal of a basal or squamous cell carcinoma with same-day repair. Main Outcomes and Measures: The primary endpoint was the incidence and comparison of postoperative morbidity. Risk for developing medical or cosmetic sequelae was determined through multivariate logistic regression. Results: The study population consisted of 143 propensity score-matched pairs (n = 286) with moderate- to high-risk defects on the face, head, and neck. Compared with autologous tissue, placental allograft cases were associated with significantly lower risk for infection (p = 0.004), poor scar cosmesis (p < 0.0001), scar revision (p < 0.0001), or reoperation (p = 0.0007). Conclusions and Relevance: Postoperative complication rates for placental reconstructions did not exceed those demonstrated by autologous tissue counterparts, indicating this is a safe alternative to flap and FTSG in cosmetically sensitive repairs.

D3 dopamine receptor-preferring [11C]PHNO PET imaging in Parkinson patients with dyskinesia.

OBJECTIVE: To investigate whether levodopa-induced dyskinesias (LID) are associated with D3 overexpression in levodopa-treated humans with Parkinson disease (PD). METHODS: In this case-control study, we used PET with the D3-preferring radioligand [(11)C]-(+)-PHNO to estimate D2/3 receptor binding in patients with levodopa-treated PD with LID (n = 12) and without LID (n = 12), and healthy control subjects matched for age, sex, education, and mental status (n = 18). RESULTS: Compared to nondyskinetic patients, those with LID showed heightened [(11)C]-(+)-PHNO binding in the D3-rich globus pallidus. Both PD groups also showed higher binding than controls in the sensorimotor division of the striatum. In contrast, D2/3 binding in the ventral striatum was lower in patients with LID than without, possibly reflecting higher dopamine levels. CONCLUSIONS: Dopaminergic abnormalities contributing to LID may include elevated D2/3 binding in globus pallidus, perhaps reflecting D3 receptor upregulation. The findings support therapeutic strategies that target and diminish activity at D3 to prevent LID.

[¹¹C]-(+)-PHNO PET imaging of dopamine D(2/3) receptors in Parkinson's disease with impulse control disorders.

Dopamine agonist medications with high affinity for the D3 dopamine receptor are commonly used to treat Parkinson's disease, and have been associated with pathological behaviors categorized under the umbrella of impulse control disorders (ICD). The aim of this study was to investigate whether ICD in Parkinson's patients are associated with greater D3 dopamine receptor availability. We used positron emission tomography (PET) radioligand imaging with the D3 dopamine receptor preferring agonist [¹¹C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) in Parkinson's patients with (n = 11) and without (n = 21) ICD, and age-, sex-, and education-matched healthy control subjects (n = 18). Contrary to hypotheses, [¹¹C]-(+)-PHNO binding in D3 -rich brain areas was not elevated in Parkinson's patients with ICD compared with those without; instead, [¹¹C]-(+)-PHNO binding in ventral striatum was 20% lower (P = 0.011), correlating with two measures of ICD severity (r = -0.8 and -0.9), which may reflect higher dopamine tone in ventral striatum. In dorsal striatum, where [¹¹C]-(+)-PHNO binding is associated with D2 receptor levels, [¹¹C]-(+)-PHNO binding was elevated across patients compared with controls. We conclude that although D3 dopamine receptors have been linked to the occurrence of ICD in Parkinson's patients. Our findings do not support the hypothesis that D3 receptor levels are elevated in Parkinson's patients with ICD. We also did not find ICD-related abnormalities in D2 receptor levels. Our findings argue against the possibility that differences in D2/3 receptor levels can account for the development of ICD in PD; however, we cannot rule out that differences in dopamine levels (particularly in ventral striatum) may be involved.

Bilateral pallidal stimulation for x-linked dystonia parkinsonism.

OBJECTIVE: To report the clinical benefits of bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) in a patient with X-linked dystonia parkinsonism (XDP). DESIGN: Case report. SETTING: Tertiary referral center. Patient A 40-year-old Filipino man with genetically confirmed XDP and severely disabling generalized dystonia. Intervention Bilateral GPi DBS. MAIN OUTCOME MEASURES: The primary outcome measures were the Burke-Fahn-Marsden Dystonia Scale (BFMDS) severity and disability scores, and the secondary outcome measure was the Unified Parkinson Disease Rating Scores. RESULTS: At the 1-year postoperative follow-up, there was 80.4% improvement in the BFMDS severity score and 66.7% improvement in the BFMDS disability score. CONCLUSION: Bilateral GPi DBS seems to be very effective in improving dystonia in XDP.

Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-(+)-PHNO in drug-naive Parkinson's disease.

The D(3) dopamine (DA) receptor is a member of the D(2)-like DA receptor family. While the D(2) receptor is abundant especially in motor-regions of the striatum, the D(3) receptor shows a relative abundance in limbic regions and globus pallidus. This receptor is of current interest in neurology because of its potential involvement in psychiatric and motor complications in Parkinson's disease and the possibility that dopamine D(3)-preferring agonist therapy might delay progression of the disorder. Preclinical data indicate that striatal levels of the D(3) (but not the D(2)) DA receptor are decreased following lesion of nigrostriatal DA neurons; at present, there are no in vivo data on this receptor subtype in Parkinson's disease. The objective of this positron emission tomography study was to compare [(11)C]-(+)-PHNO (D(3) versus D(2) preferring) and [(11)C]raclopride (D(3) = D(2)) binding in brain of non-depressed, non-demented, dopaminergic drug-naïve patients with early-stage Parkinson's disease (n = 10), relative to matched-controls (n = 9). Parkinson's disease was associated with a trend for bilaterally decreased [(11)C]-(+)-PHNO (but not [(11)C]raclopride) binding in the D(3)-rich ventral striatum (-11%, P = 0.07) and significantly decreased binding in globus pallidus (-42%, P = 0.02). In contrast, in the primarily D(2)-populated putamen, both [(11)C]-(+)-PHNO (25%, P = 0.02) and [(11)C]raclopride (25%, P < 0.01) binding were similarly increased, especially on the side contra-lateral to the symptoms. In the midbrain, presumably containing D(3) receptors localized to the substantia nigra, [(11)C]-(+)-PHNO binding was normal. Decreased [(11)C]-(+)-PHNO to [(11)C]raclopride ratio correlated with motor deficits and lowered-mood (P < 0.02). Our imaging data suggest that brain DA neuron loss in the human causes region-specific differential changes in DA D(2) and D(3) receptors with D(3) receptor 'downregulation' possibly related to some motor and mood problems in Parkinson disease. D(3) receptor levels might be a determinant vulnerability factor underlying side-effects associated with treatment; hence, these initial findings provide valuable baseline information to understand the role of D(3) receptors in response to Parkinson's disease medication.

Granulomatous reaction to titanium alloy: an unusual reaction to ear piercing.

A 68-year-old man presented with 4 firm, flesh-colored, and slightly erythematous nodules located on the superior pole and lobule of each ear. Although reluctant to provide details, it was discovered he had pierced his ears approximately 10 years earlier, and the nodules developed at the sites of the piercings. Keloids were suggested clinically and the lesions were excised. Microscopic examination demonstrated epithelialized tracts surrounded by a granulomatous infiltrate of macrophages, lymphocytes, and plasma cells. Closer examination revealed minute brown-black particles within macrophages. Dark-field microscopy confirmed the metallic nature of the particles. Environmental scanning electron microscopy with energy dispersive spectroscopy revealed the particles to be composed of titanium, aluminum, and vanadium. It would appear that in rare circumstances titanium alloy used in body piercing may engender a granulomatous dermatitis. The rarity of such a response to titanium alloy is discussed and the literature appraised.

PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation.

Parkinson's disease may arise from multiple aetiologies, including genetic mutations that are for the most part uncommon. We describe here the positron emission tomography (PET) findings in clinically affected and asymptomatic, high-risk members of two autosomal dominantly inherited Parkinson's disease kindreds with recently described mutations at the PARK8 locus, in a novel gene encoding a leucine-rich repeat kinase (LRRK2). Affected family members have L-dopa-responsive parkinsonism with loss of dopaminergic nigral neurons and pleomorphic subcellular pathology. Fifteen family members underwent PET using: 18F-6-fluoro-L-dopa (18F-dopa) to assess dopamine (DA) synthesis and storage, 11C-(+/-)-dihydrotetrabenazine (11C-DTBZ) for the vesicular monoamine transporter, and 11C-d-threo-methylphenidate (11C-MP) for the membrane dopamine transporter (DAT). Measurements were compared with normal (n = 33) and sporadic Parkinson's disease (sPD) (n = 67) control groups. Four clinically affected members had findings similar to sPD, with impaired presynaptic DA function affecting the putamen more than the caudate. In two affected members, D2 dopamine receptor binding was intact. Two asymptomatic mutation carriers had abnormal DAT binding with another two developing such abnormalities over 4 years of follow-up. In these individuals, 18F-dopa uptake remained normal, although two of them also displayed abnormal 11C-DTBZ binding. Our study demonstrates that the in vivo neurochemical phenotype of LRRK2 mutations is indistinguishable from that of sPD, despite the pathological heterogeneity of the condition. Furthermore, we suggest that compensatory changes including downregulation of the DAT and upregulation of decarboxylase activity may delay the onset of parkinsonian symptoms.

Parkinson's disease: in vivo assessment of disease progression using positron emission tomography.

Over the past two decades, positron emission tomography (PET) has provided valuable insights into the mechanisms of nigrostriatal degeneration in Parkinson's disease (PD). Furthermore, it allows the in vivo assessment of disease progression and the evaluation of treatment interventions. In this review, we shall discuss some of the issues and concerns that arise with the use of PET as a surrogate marker of disease progression in Parkinson's disease.