Kimura’s disease of the elbows

Kimuras disease rarely involves a location outside the head and neck. We report a case of Kimuras disease in a young Asian man involving both elbows. Magnetic resonance imaging showed a soft-tissue mass of irregularly infiltrative strands in the subcutaneous fat accompanied with medial epitrochlear lymphadenopathy. The MRI appearance is described and the entity is briefly reviewed.     

Magnetic resonance imaging findings in Kimura’s disease

Although early diagnosis of Kimuras disease, a rare chronic inflammatory disorder most commonly presenting with asymmetric swelling in the head and neck region, is helpful in avoiding unnecessary diagnostic tests and starting prompt treatment, only a few reports emphasized radiological findings in detail. Magnetic resonance imaging findings showing the infiltrative nature of the disease and diffuse loss of fat tissue even in nonpalpable normally appearing regions of the head and neck in a young man with Kimuras disease are presented in this report.     

Kimura’s disease involving a long bone

Kimura’s disease is a rare, benign lymphoproliferative disorder of unknown etiology. It occurs most often in Asian men, usually in the second or third decade of life. Most lesions occur in the head and neck followed by the axilla, groin, popliteal region, and arm. The lesions are commonly found in soft tissues. To the best of our knowledge, there has been only one case report of bone involvement in Kimura’s disease presented on plain radiography. We report a case of Kimura’s disease that involved the proximal meta-diaphysis of the humerus and adjacent soft tissue shown on radiography and MR imaging.     

Role of DWI and MRS in diagnosis of Alzheimer’s and pre-Alzheimer’s disease

Background and purpose

Alzheimer’s disease (AD) is a major cause of dementia in elderly affecting about 30% above the age of 85 years, while mild cognitive impairment (MCI) is the impairment in cognitive functions with intact daily life activities which is described as the preclinical phase of AD.

Uptake of 99mTc-labeled chondroitin sulfate by chondrocytes and cartilage: a promising agent for imaging of cartilage degeneration?

Chondroitin sulfate (CS) is used in the treatment of human osteoarthritis as a slow-acting symptomatic drug. For this reason, we performed uptake studies with ^99mTcCS using different chondrocyte cultures, as well as cartilage tissue in vitro.For uptake studies, adherent monolayer cultures of human chondrocytes (2.7×10⁴ cells/well) and ^99mTcCS (1 μCi) were used. In parallel, we also performed uptake studies with cell suspensions of human chondrocytes at 1×10⁶ cells/well incubated with ^99mTcCS (5 μCi) under identical conditions. Uptake was studied also in cartilage tissue samples and frozen tissue sections for autoradiography. The uptake was monitored for 10–240 min, every 10–30 min for cell cultures and for cartilage tissue up to 72 h. As the commercially available drug Condrosulf (IBSA, Lugano, Switzerland) contains magnesium (Mg) stearate as additive, we investigated the uptake with and without this additive. The washout of the tracer was assessed after the uptake experiments with PBS buffer for different time intervals (10 min–3 h).Tracer uptake in monolayer±additives with low number of cells was low. With the use of chondrocytes in culture suspensions with higher number of cells, a higher uptake of 5.9±0.65% and 1.0±0.1% (n=6) was found, with and without additive, respectively. The saturation was achieved after 100 min. With the use of human rib cartilage, the uptake of ^99mTcCS was continuously increasing with time and was very high with additive amounting to 101.8±5.2% vs. 53.0±8.3% (n=6) without after 72 h and showing delayed saturation up to 30 h. Thus, not only the resorption of the drug is enhanced by Mg-stearate, but also the uptake. The washout of the tracer from cartilage after 3 h of uptake amounted to 3.75±1.5% with additive vs. 13.1±2.1% without. After 24 h, washout was lower amounting to 1.75±0.15% vs. 3.25±0.25%, respectively. The autoradiographic studies paralleled the results of in vitro cartilage tissue uptake.These data show that ^99mTcCS accumulates in cartilage tissue, either by acting as a substrate for proteoglycan synthesis or by adsorption to cartilage. ^99mTcCS could therefore be a possible agent to target and radioimage osteoarthritis.     

Use of ACE-inhibitors and falls in patients with Parkinson’s disease

Falls represent a major concern in patients with Parkinson’s disease (PD); however, currently acknowledged treatments for PD are not effective in reducing the risk of falling. The aim was to assess the association of use of ACE-inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with falls among patients with PD.We analysed data of 194 elderly with PD attending a geriatric Day Hospital. Self-reported history of falls that occurred over the last year, as well as use of drugs, including ACEIs and angiotensin II receptor blockers (ARBs) were recorded. The association of the occurrence of any falls with use of ACEIs, and ARBs was assessed by logistic regression analysis. The association between the number of falls and use of ACEIs, and ARBs was assessed according to Poisson regression.In logistic regression, after adjusting for potential confounders, use of ACEIs was associated with a reduced probability of falling over the last year (OR = 0.15, 95% CI = 0.03–0.81; P = 0.028). This association did not vary with blood pressure levels (P for the interaction term = 0.528). Also, using Poisson regression, use of ACEIs predicted a reduced number of falls among participants who fell (PR = 0.31; 95% CI = 0.10–0.94; P = 0.039). No association was found between use of ARBs and falls.Our results indicate that use of ACEIs might be independently associated with reduced probability, and a reduced number of falls among patients with PD. Dedicated studies are needed to define the single agents and dosages that might most effectively reduce the risk of falling in clinical practice.     

SPECT and PET imaging in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Beta-amyloid (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein are the pathological hallmarks of the disease, accompanied by other pathological processes such as microglia activation. Functional and molecular nuclear medicine imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques provides valuable information about the underlying pathological processes, many years before the appearance of clinical symptoms. Nuclear neuroimaging in AD has made great progress in the past two decades and has extended beyond the traditional role of brain perfusion and glucose metabolism evaluation. Intense efforts in radiopharmaceuticals research have led to the development of various probes able to detect Aβ deposits, tau protein accumulation, microglia activation and neuroinflammation. As a result, SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in mild cognitive impairment (MCI) subjects.     

Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson’s disease patients

^99mTc-TRODAT-1 is the first clinical routine ^99mTc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). ¹⁸ F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects.MethodsEighteen subjects (8 HC and 10 PD) were recruited for ^99mTc-TRODAT-1 SPECT, ¹⁸ F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts − 1). The nonparametric Mann–Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities.ResultsThe SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p < 0.001), and showed significant different between HC and PD subjects. Of note, the ¹⁸ F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to ^99mTc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from ¹⁸ F-AV-133 image as compared to ^99mTc-TRODAT-1 especially at the substantia nigra region.Conclusion¹⁸ F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical characteristics than that of ^99mTc-TRODAT-1 SPECT. ¹⁸ F-AV-133 PET also showed additional information in substantia nigra integrity in PD subjects by voxelwise analysis. Collectively, ¹⁸ F-AV-133 could be a promising and better tracer for clinical use to detect monoaminergic terminal reduction in PD patients.     

SPECT neuroimaging and neuropsychological functions in different stages of Parkinson’s disease

Purpose  

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson’s disease (PD).     

Utility of susceptibility-weighted MRI in differentiating Parkinson’s disease and atypical parkinsonism

Introduction  

Neuropathological studies report varying patterns of brain mineralization in Parkinson’s diseases (PD), progressive supranuclear palsy (PSP), and Parkinson variant of multiple system atrophy (MSA-P). Susceptibility-weighted imaging (SWI) is the ideal magnetic resonance imaging (MRI) technique to detect mineralization of the brain. The purpose of this study was to test if SWI can differentiate PD, PSP, and MSA-P.     

Neuroimaging in Huntington’s disease

Huntington’s disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded trinucleotide CAG sequence in huntingtin gene (HTT) on chromosome 4. HD manifests with chorea, cognitive and psychiatric symptoms. Although advances in genetics allow identification of individuals carrying the HD gene, much is still unknown about the mechanisms underlying the development of overt clinical symptoms and the transitional period between premanifestation and manifestation of the disease. HD has no cure and patients rely only in symptomatic treatment. There is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease modifying drugs. Over the past years, neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have provided important advances in our understanding of HD. MRI provides information about structural and functional organization of the brain, while PET can detect molecular changes in the brain. MRI and PET are able to detect changes in the brains of HD gene carriers years ahead of the manifestation of the disease and have also proved to be powerful in assessing disease progression. However, no single technique has been validated as an optimal biomarker. An integrative multimodal imaging approach, which combines different MRI and PET techniques, could be recommended for monitoring potential neuroprotective and preventive therapies in HD. In this article we review the current neuroimaging literature in HD.     

Memorcise and Alzheimer’s disease

Alzheimer’s disease (AD) is a debilitating disease influencing a multitude of outcomes, including memory function. Recent work suggests that memory may be influenced by exercise (‘memorcise’), even among those with AD. The present narrative review details (1) the underlying mechanisms of AD; (2) whether exercise has a protective effect in preventing AD; (3) the mechanisms through which exercise may help to prevent AD; (4) the mechanisms through which exercise may help attenuate the progression of AD severity among those with existing AD; (5) the effects and mechanisms through which exercise is associated with memory among those with existing AD; and (6) exercise recommendations for those with existing AD. Such an understanding will aid clinicians in their ability to use exercise as a potential behavioral strategy to help prevent and treat AD.     

Non-motor predictors of freezing of gait in Parkinson’s disease

BackgroundThe etiology of freezing of gait in Parkinson’s disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait.Research questionWe aimed to determine the predictive value of non-motor features in freezing of gait development.MethodsData were obtained from the Parkinson’s Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales.ResultsPatients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time.SignificanceOur findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.     

Myonecrosis of Behcet’s disease

Behcet’s disease is an inflammatory disease of unknown cause characterized by intermittent episodes of acute inflammation manifested by oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. We report a rare case of myonecrosis associated with Behcet’s disease. Myonecrosis of Behcet’s disease can mimic soft tissue abscess and therefore awareness of this entity in the appropriate clinical setting is important for initiation of appropriate and timely treatment.     

Distinct spatiotemporal patterns for disease duration and stage in Parkinson’s disease

Purpose

To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson’s disease (PD).

Methods

This retrospective study included 970 consecutive patients undergoing ¹²³I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4?±?11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7?±?8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.

Results

Increasing disease stage was associated with an exponential decrease in ¹²³I-ioflupane uptake (R ² ?=?0.1501) particularly in the head of the ipsilateral caudate nucleus (p?<?0.0001), whereas increasing disease duration was associated with a linear decrease in ¹²³I-ioflupane uptake (p?<?0.0001; R ² ?=?0.1532) particularly in the contralateral anterior putamen (p?<?0.0001).

Conclusion

We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 ¹²³I-ioflupane SPECT scans can be used for clinical and research applications.

     

Current status of PET imaging in Huntington’s disease

Purpose

To review the developments of recent decades and the current status of PET molecular imaging in Huntington’s disease (HD).

Methods

A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading “Huntington Disease” combined with text and key words “Huntington Disease”, “Neuroimaging” and “PET”. Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded.

Results

A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([¹⁸F]FDG and [¹⁵O]H₂O), presynaptic ([¹⁸F]fluorodopa, [¹¹C]β-CIT and [¹¹C]DTBZ) and postsynaptic ([¹¹C]SCH22390, [¹¹C]FLB457 and [¹¹C]raclopride) dopaminergic function, phosphodiesterases ([¹⁸F]JNJ42259152, [¹⁸F]MNI-659 and [¹¹C]IMA107), and adenosine ([¹⁸F]CPFPX), cannabinoid ([¹⁸F]MK-9470), opioid ([¹¹C]diprenorphine) and GABA ([¹¹C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail.

Conclusion

Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed for monitoring potential neuroprotective and preventive treatment in HD.

     

Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer’s disease

Purpose

We aimed to determine the amyloid (Aβ) and tau biomarker levels associated with imminent Alzheimer’s disease (AD) - related metabolic decline in cognitively normal individuals.

Methods

A threshold analysis was performed in 120 cognitively normal elderly individuals by modelling 2-year declines in brain glucose metabolism measured with [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) as a function of [¹⁸F]florbetapir Aβ positron emission tomography (PET) and cerebrospinal fluid phosphorylated tau biomarker thresholds. Additionally, using a novel voxel-wise analytical framework, we determined the sample sizes needed to test an estimated 25% drugeffect with 80% of power on changes in FDG uptake over 2 years at every brain voxel.

Results

The combination of [¹⁸F]florbetapir standardized uptake value ratios and phosphorylated-tau levels more than one standard deviation higher than their respective thresholds for biomarker abnormality was the best predictor of metabolic decline in individuals with preclinical AD. We also found that a clinical trial using these thresholds would require as few as 100 individuals to test a 25% drug effect on AD-related metabolic decline over 2 years.

Conclusions

These results highlight the new concept that combined Aβ and tau thresholds can predict imminent neurodegeneration as an alternative framework with a high statistical power for testing the effect of disease-modifying therapies on [¹⁸F]FDG uptake decline over a typical 2-year clinical trial period in individuals with preclinical AD.