Mordechai Lorberboym

[123I]-FP-CIT SPECT and olfaction test in patients with combined postural and rest tremor

Summary.Mixed-type tremors pose a clinical diagnostic challenge. The aim of the study was to better characterize patients with combined postural and rest tremor. Patients were categorized into four groups: essential tremor (ET) (n = 7), combined rest + postural tremor (n = 17), PD (n = 17), and control subjects (n = 9). All underwent the University of Pennsylvania Smell Identification Test (UPSIT). The mixed-tremor group was also evaluated with SPECT imaging using the dopamine transporter (DaT) ligand 123I-labeled FP-CIT. There was no significant difference in olfaction scores between the mixed tremor and essential tremor groups (23.2 ± 6.6 vs 21.7 ± 4.9) or between these groups and controls (27.2 ± 5.0). The patients with PD had significantly lower scores than all the other groups (13.7 ± 5.4, p < 0.001). Of the 12 patients with mixed tremor evaluated by SPECT, 9 had normal findings. This study suggests that rest tremor is part of the spectrum of ET, even in patients with long-standing disease. However, in a minority of patients, there might be transformation of ET–PD.

Technetium 99m ethylcysteinate dimer single-photon emission computed tomography (SPECT) during intellectual stress test in children and adolescents with pure versus comorbid attention-deficit hyperactivity disorder (ADHD)

Children and adolescents with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of attention-deficit hyperactivity disorder (ADHD) can have comorbid conditions such as conduct disorder, oppositional defiant disorder, and obsessive-compulsive disorder (comorbid type). The purpose of our study was to compare the pattern of regional cerebral perfusion in these two groups of children with ADHD during a computerized performance test. Nineteen children and adolescents were enrolled in the study. Seven boys and one girl with pure ADHD (group 1: mean age 12 years, range 9—16 years) and nine boys and two girls with comorbid ADHD (group 2: mean age 11 years, range 8—16 years) were studied by single-photon emission computed tomography (SPECT). The patients were not receiving any medication for at least 48 hours prior to the study. All patients were injected with 99mTc- ethylcysteinate dimer while doing a computerized performance test. Nine age-matched control children (five boys and four girls, mean age 12 years, range 9—17 years) with a normal brain SPECT served as controls. All patients in group 2 showed significantly decreased perfusion in the temporal lobes (P < .005). Five patients had decreased frontal lobe perfusion. Additionally, two patients in group 2 had decreased perfusion in the basal ganglia (not significant). Four of eight patients in group 1 had decreased frontal lobe perfusion (not significant). In addition, two patients had bilateral temporal lobe abnormalities, whereas two patients had a normal SPECT. Three patients in group 1 also had decreased basal ganglia perfusion. In contrast to previous studies of brain perfusion in ADHD that focused mainly on frontal and prefrontal cortical abnormalities, our study demonstrates that temporal lobe perfusion abnormalities are more common in patients with the comorbid type of ADHD. We postulate that these findings can have therapeutic implications and explain the decreased response to stimulants in this group of patients. (J Child Neurol 2004; 19: 91—96).

Perspective: Identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson's disease.

Parkinsons disease (PD) is slowly progressive, and heterogeneity of its severity among individuals may be due to endogenous mechanisms that counterbalance the striatal dopamine loss. In this perspective paper, we introduce a neuroimaging-genetic approach to identify genetic variants, which may contribute to this compensation. First, we briefly review current known potential compensatory mechanisms for premotor and early disease PD, located in the striatum and other brain regions. Then, we claim that a mismatch between mild symptomatic disease, manifested by low motor score on the Unified PD Rating Scale (UPDRS), and extensive Nigro-Striatal (NS) degeneration, manifested by reduced uptake of [(123)I]FP-CIT, is indicative of compensatory processes. If genetic variants are associated with the severity of motor symptoms, while the level of striatal terminals degeneration measured by ligand uptake is taken into account and controlled in the analysis, then these variants may be involved in functional compensatory mechanisms for striatal dopamine deficit. To demonstrate feasibility of this approach, we performed a small proof of concept study (candidate gene design) in a sample of 28 Jewish PD patients, and preliminary results are presented.

Association of the ZFPM2 gene with antipsychotic-induced parkinsonism in schizophrenia patients

RationaleAntipsychotic-induced parkinsonism (AIP) is a severe adverse affect of antipsychotic drug treatment. Recently, our group performed a genome-wide association study (GWAS) for AIP severity, and identified several potential AIP risk variants.ObjectivesThe aim of this study was to validate our original AIP-GWAS susceptibility variants and to understand their possible function.MethodsWe conducted a validation study of 15 single-nucleotide polymorphisms (SNPs) in an independent sample of 178 US schizophrenia patients treated for at least a month with typical or atypical antipsychotics. Then, a sample of 49 Jewish Israeli Parkinsons disease (PD) patients with available neuroimaging ([123I]-FP-CIT-SPECT) data was analyzed, to study association of confirmed AIP SNPs with level of dopaminergic deficits in the putamen.ResultsUsing logistic regression and controlling for possible confounders, we found nominal association of the intronic SNP, rs12678719, in the Zinc Finger Protein Multitype 2 (ZFPM2) gene with AIP (62 affected/116 unaffected), in the whole sample (pu2009=u20090.009; Pu2009=u20095.97u2009×u200910−5 in the GWAS), and in the African American sub-sample (Nu2009=u2009111; pu2009=u20090.002). The same rs12678719-G AIP susceptibility allele was associated with lower levels of dopaminergic neuron related ligand binding in the contralateral putamen of PD patients (pu2009=u20090.026).ConclusionsOur preliminary findings support association of the ZFPM2 SNP, rs12678719, with AIP. At the functional level, this variant is associated with deficits in the nigrostriatal pathway in PD patients that may be related to latent subclinical deficits among AIP-prone individuals with schizophrenia. Further validation studies in additional populations are required.

Use of a single [123I]-FP-CIT SPECT to predict the severity of clinical symptoms of Parkinson disease

The aim of this study was to assess the ability of a single SPECT performed in the early stage of Parkinson’s disease (PD) to predict disease severity in 19 patients with early PD. [123I]-FP-CIT striatal uptake was expressed as a ratio of specific:nonspecific uptake for defined brain areas. Clinical severity was determined by the UPDRS at baseline and 12–15xa0months following the SPECT procedure. [123I]-FP-CIT uptake in the contralateral putamen and striatum was correlated with UPDRS score at baseline, with a more significant correlation after 1-year interval. [123I]-FP-CIT uptake in all areas was correlated with bradykinesia and rigidity subscores only at follow up visit. Significant correlations were found between [123I]-FP-CIT uptake in the contralateral striatum, putamen and caudate and the difference between motor scores of 1-year interval (ΔUPDRS). These results suggest that disease severity might be anticipated by a single SPECT at an early stage of the disease.

The 'mouse face' appearance of the vertebrae in Paget's disease.

Pagets disease is occasionally found as an incidental finding on bone scans performed for the evaluation of metastatic disease, which causes a diagnostic and a subsequent therapeutic dilemma. We have previously described the Mouse Face appearance of vertebrae on bone scans (increased uptake in the vertebral body, posterior elements, and the spinous process), which was fairly specific for Pagets disease in a small series. This retrospective study was undertaken to determine if this observation holds true in a larger series. Bone scans performed in 2,881 patients were randomly selected, and were reviewed by 2 physicians. Thirty-nine cases with a Mouse Face appearance were identified. Diagnosis was established in 30 of the 39 patients by correlative radiographic studies and/or clinical follow-up. Twenty patients were referred for the evaluation of possible metastases, and 7 were found to have metastases at the sites of Mouse Face. The other 13 had Pagets disease. However, 6 of the 7 patients with metastases had extravertebral findings compatible with multiple metastases, and the remaining patient had a Mouse Face lesion only, with a question of metastases. Ten patients were evaluated for Pagets disease or others, and none of them had metastases at the site of the Mouse Face. The Mouse Face appearance is more suggestive of Pagets disease than metastases even in patients with cancer. These patients should be assumed unlikely to have vertebral metastases, unless proven by another correlative radiologic study.

Transient false-positive hepatobiliary scan associated with ceftriaxone therapy.

Drug related false-positive hepatobiliary imaging is uncommon. The authors present a case of a 54-year-old woman who was treated with intravenous ceftriaxone for bacterial meningitis. Symptoms of acute cholecystitis subsequently developed and a sonogram revealed a gallstone. A Tc-99m DISIDA hepatobiliary study was positive for cystic duct obstruction. After discontinuation of ceftriaxone, the patients clinical condition improved and, 2 weeks later, a repeat hepatobiliary scan was normal. High doses of ceftriaxone and prolonged administration may lead to formation of pseudocholelithiasis and signs of acute cholecystitis. Although this condition is usually benign and reversible, discontinuation of the drug is warranted when symptoms of acute cholecystitis are accompanied by a positive hepatobiliary scan.

Polyostotic fibrous dysplasia in McCune-Albright syndrome diagnosed by bone scintigraphy.

A 19-year-old woman with a history of chronic left lower extremity pain had exacerbation of her symptoms in the last 6 months. The pain was aggravated by walking and responded partially to anti-inflammatory drugs. The patient had a history of precocious puberty when she was 8 years old, but had no skin pigmentation. A bone scan showed extensive, irregular increased activity in the left hemipelvis, femur and tibia, but also in other sites that were not suspected clinically. Plain radiographs of the left hip, left femur, and left tibia were consistent with fibrous dysplasia.

Occult aortic arch mycotic aneurysm diagnosed by radiogallium scintigraphy.

Aortic arch mycotic aneurysm, an uncommon cause of sepsis, carries a grave prognosis. Clinical presentations as well as laboratory and radiologic examinations may be noncontributory and often misleading. In a patient with a fever of unknown origin, only the radiogallium study could enable an accurate diagnosis and pinpoint the anatomic localization of the mycotic aneurysm as the cause of fever.

False-positive uptake of TI-201 by an intracranial inflammatory pseudotumor

A 28-year-old man had recurrent episodes of headache, ophthalmoplegia, and ptosis. MR imaging showed a mass within the sphenoid sinus. TI-201 imaging showed intense uptake in the region of the sphenoid sinus and right middle fossa with moderate retention of activity, suggesting the diagnosis of a viable tumor. A biopsy specimen from the sphenoid sinus revealed dense inflammatory infiltrate dominated by plasma cells, consistent with inflammatory pseudotumor. After radiation therapy, the mass showed no significant change on MR imaging, but regressed in size and uptake on the follow-up TI-201 scan. TI-201 may accumulate in nonmalignant inflammatory lesions and could mimic a viable tumor. It is, therefore, suggested that before surgery and histologic diagnosis, any abnormal intracranial accumulation of TI-201 should be interpreted with caution.