Jacob G. Dubroff

Neuroimaging of traumatic brain injury.

Head trauma requires several different neuroimaging modalities for adequate evaluation and determination of treatment. This article considers the importance of anatomical and functional imaging modalities in the initial evaluation, treatment planning, and long-term management of patients with head injury. These modalities include computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. Each modality offers specific advantages and potential disadvantages. However, it is important to understand the capabilities of each modality, and how and when each one might provide the most valuable information as one evaluates such patients.

An open-label efficacy trial of escitalopram for night eating syndrome ☆

OBJECTIVE Night eating syndrome (NES) has become increasingly recognized as a disorder in need of effective treatments. Selective serotonin reuptake inhibitors have shown efficacy in previous trials, so we sought to expand our understanding of the efficacy of escitalopram in the current trial. METHOD Thirty-one adults with NES participated in a 12-week open-label trial of escitalopram. Outcome measures included the Night Eating Symptom Scale (NESS), percent of daily intake after the evening meal (% intake) and number of nocturnal ingestions/week (NI), weight, total awakenings/week, mood, and quality of life. Mixed-effects models were used to assess change over time. RESULTS Significant reductions were observed from week 0 to week 12 for the NESS (30.2 to 15.2), % intake (46% to 17%), NI (5.8 to 1.2), weight (90.2 to 88.6 kg), awakenings (8.1 to 2.7), and BDI-II (12.1 to 7.7). Outcomes did not differ significantly by gender, age, race, or psychiatric co-morbidity status. Eighteen of 31 completed 12 weeks of treatment. DISCUSSION This open-label trial of escitalopram showed significant reductions in symptoms associated with NES. Randomized controlled trials are warranted to test these findings. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT01401595.

Taste function in early stage treated and untreated Parkinson’s disease

Since brain stem regions associated with early Parkinson’s disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated whole-mouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue. The PD cohort was tested both on and off dopamine-related medications in counterbalanced test sessions. While whole-mouth taste identification test scores for all stimuli were, on average, nominally lower for the PD patients than for the controls, a trend in the opposite direction was noted for the intensity ratings at the lower stimulus concentrations for all stimuli except caffeine. Moreover, regional testing found that PD subjects tended to rate the stimuli, relative to the controls, as more intense on the anterior tongue and less intense on the posterior tongue. No significant associations were evident between taste test scores and UPDRS scores, L-DOPA medication equivalency values, or [99mTc]TRODAT-1 SPECT imaging of dopamine transporter uptake within the striatum and associated regions. Our findings suggest that suprathreshold measures of taste function are influenced by PD and that this disease differentially influences taste function on anterior (CN VII) and posterior (CN IX) tongue regions. Conceivably PD-related damage to CN IX releases central inhibition on CN VII at the level of the brainstem, resulting in enhanced taste intensity on the anterior tongue.

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism

The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (α4β2* subtype) availability using PET imaging of the radiotracer 2-18F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-18F-FA-85380, or 2-18F-FA). Methods: Twenty-four smokers—12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR ≥ 0.26)—underwent 2-18F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans. Results: Thalamic nAChR α4β2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability. Conclusion: The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine.

Use of Standardized Uptake Value Ratios Decreases Interreader Variability of [18F] Florbetapir PET Brain Scan Interpretation

BACKGROUND AND PURPOSE: Fluorine-18 florbetapir is a recently developed β-amyloid plaque positron-emission tomography imaging agent with high sensitivity, specificity, and accuracy in the detection of moderate-to-frequent cerebral cortical β-amyloid plaque. However, the FDA has expressed concerns about the consistency of interpretation of [18F] florbetapir PET brain scans. We hypothesized that incorporating automated cerebral-to-whole-cerebellar standardized uptake value ratios into [18F] florbetapir PET brain scan interpretation would reduce this interreader variability. MATERIALS AND METHODS: This randomized, blinded-reader study used previously acquired [18F] florbetapir scans from 30 anonymized patients who were enrolled in the Alzheimers Disease Neuroimaging Initiative 2. In 4 separate, blinded-reading sessions, 5 readers classified 30 cases as positive or negative for significant β-amyloid deposition either qualitatively alone or qualitatively with additional adjunct software that determined standardized uptake value ratios. A κ coefficient was used to calculate interreader agreement with and without the use of standardized uptake value ratios. RESULTS: There was complete interreader agreement on 20/30 cases of [18F] florbetapir PET brain scans by using qualitative interpretation and on 27/30 scans interpreted with the adjunct use of standardized uptake value ratios. The κ coefficient for the studies read with standardized uptake value ratios (0.92) was significantly higher compared with the qualitatively read studies (0.69, P = .006). CONCLUSIONS: Use of standardized uptake value ratios improves interreader agreement in the interpretation of [18F] florbetapir images.

Suprathreshold odor intensity perception in early‐stage Parkinson's disease

Whether Parkinsons disease (PD) influences suprathreshold changes in perceived odor intensity is unknown. In patients with Alzheimers disease, patients with schizophrenia, and the elderly, such perception is reportedly normal. If generally true, this could reflect a core element of the olfactory system insulated to some degree from age‐ and disease‐related pathological conditions.

Frequency and clinicopathological characteristics of presenilin 1 Gly206Ala mutation in Puerto Rican Hispanics with dementia.

The frequency and clinical and pathological characteristics associated with the Gly206Ala presenilin 1 (PSEN1) mutation in Puerto Rican and non-Puerto Rican Hispanics were evaluated at the University of Pennsylvanias Alzheimers Disease Center. DNAs from all cohort subjects were genotyped for the Gly206Ala PSEN1 mutation. Carriers and non-carriers with neurodegenerative disease dementias were compared for demographic, clinical, psychometric, and biomarker variables. Nineteen (12.6%) of 151 unrelated subjects with dementia were discovered to carry the PSEN1 Gly206Ala mutation. Microsatellite marker genotyping determined a common ancestral haplotype for all carriers. Carriers were all of Puerto Rican heritage with significantly younger age of onset, but otherwise were clinically and neuropsychologically comparable to those of non-carriers with AD. Three subjects had extensive topographic and biochemical biomarker assessments that were also typical of non-carriers with AD. Neuropathological examination in one subject revealed severe, widespread plaque and tangle pathology without other meaningful disease lesions. The PSEN1 Gly206Ala mutation is notably frequent in unrelated Puerto Rican immigrants with dementia in Philadelphia. Considered together with the increased prevalence and mortality of AD reported in Puerto Rico, these high rates may reflect hereditary risk concentrated in the island which warrants further study.

Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia

Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

Postsurgical atypical F-18 fluorodeoxyglucose positron emission tomography uptake.

False positive recognition is crucial for proper interpretation of FDG-PET studies. The authors present a case of a woman who underwent surgery over a month prior to PET/CT imaging which revealed significant tracer uptake within muscles and soft tissue in several sites contralateral to the location of surgery. The FDG-PET images of this case illustrate the importance of communication between physicians ordering and physicians reading FDG-PET/CT scans as well as atypical FDG-PET findings that could be interpreted as concerning but are, in fact, innocuous. This study also demonstrates the unusual glucose metabolic patterns which may arise following treatment be it surgical, chemotherapeutic or radiation.

Selectivity of probes for PET imaging of dopamine D3 receptors

Dopamine D3 receptors have key roles in behavioral reward, addiction, Parkinsons disease, and schizophrenia, and there is interest in studying their role in these disorders using PET. However, current PET radiotracers for studying D3 receptors in humans all bind to both D2 and D3 due to similarities between the two receptors. Selective D2 and D3 radioligands would aid investigation of the differences between D2 and D3 circuitry in the central nervous system. While there are currently in vitro measures of ligand D3/D2 selectivity, there is a need for an in vivo PET measure of D3/D2 selectivity. This review discusses current PET imaging of dopamine D2/D3 receptors and proposes methodology for quantitating in vivo selectivity of probes for PET imaging of dopamine D3 receptors.