Progression of Nigrostriatal Denervation in Cerebellar Multiple System Atrophy: A Prospective Study

Background and Objectives:Nigro-striatal dopaminergic denervation (NSDD) remains poorly characterized in cerebellar multiple system atrophy (MSA-C). We aimed to study NSDD progression in MSA-C and evaluate the capacity for [123I]-FP-CIT-SPECT and parkinsonism to differentiate MSA-C from idiopathic late-onset cerebellar ataxia (ILOCA).Material and methods:We included 85 patients successively referred for sporadic late-onset cerebellar ataxia (SLOCA). Every six months, SARA, UPDRS-III and SDFS scores were measured, and MSA-C diagnostic criteria were searched for. Striatal/occipital dopaminergic binding ratio was evaluated every year with [123I]-FP-CIT-scintigraphy.Results:After a mean follow-up of 33.8 months, 33 patients had probable MSA-C, 8 possible MSA-C and 44 ILOCA. SARA and UPDRS-III scores worsened faster in the probable MSA-C group (p<0.01) compared to the ILOCA group. Baseline striatal/occipital ratio was lower (2.3 vs 2.97; p<0.01) and more decreasing among probable MSA-C patients (p<0.01). Weighting dysautonomia and parkinsonism and/or NSDD as additional and principal criterion, respectively, in the possible MSA-C diagnostic criteria slightly improved their specificity (81.6% vs 76.9%) and sensitivity (77.8% vs 72.2%) to predict a final diagnosis of probable MSA-C.Conclusions:Rapid symptoms worsening and NSDD existence and progression predict MSA-C among SLOCA patients. Parkinsonism, NSDD and dysautonomia should be considered equivalent for possible MSA-C diagnosis.

A Novel Automatic Approach for Calculation of the Specific Binding Ratio in [I-123]FP-CIT SPECT

A fully automatic method for specific binding ratio (SBR) calculation in [123I]ioflupane single-photon emission computed tomography (SPECT) studies was proposed by creating volumes of interest of the striatum (VOIst) and reference region (VOIref) without manual handling to avoid operator-induced variability. The study involved 105 patients (72 ± 10 years) suspected of parkinsonian syndrome (PS) who underwent [123I]ioflupane SPECT. The 200 images from our previous study were used for evaluation and validation of the new program. All patients were classified into PS and non-PS groups according to the results of clinical follow-up. A trapezoidal volume of interest (VOIt) containing all striatal intensive counts was created automatically, followed by VOIst setting using the previous method. SBR values were calculated from the mean values of VOIst and VOIref determined by the whole brain outside of VOIt. The low count voxels in the VOIref were excluded using an appropriate threshold. The SBR values from the new method were compared with the previous semi-automatic method and the Tossici–Bolt (TB) method. The SBRs from the semi- and fully automatic methods showed a good linear correlation (r > 0.98). The areas under the curves (AUCs) of receiver operating characteristic analysis showed no significant difference between the two methods for both our previous (AUC > 0.99) and new (AUC > 0.95) data. The diagnostic accuracy of the two methods showed similar results (>92%), and both were better than the TB method. The proposed method successfully created the automatic VOIs and calculated SBR rapidly (9 ± 1 s/patient), avoiding operator-induced variability and providing objective SBR results.

Synthesis of New Tetra Triazole Functionalized Calix[4]resorcinarene and Chemosensing of Copper Ions in Aqueous Medium

A new tetra triazole functionalized calix[4]resorcinarene macrocycle (5) is synthesized and utilized for the detection of copper ions in the aqueous medium. The photophysical potential of compound (5) is examined by a range of cations (Ba2+, Ca2+, Co2+, Hg2+, K+, Mg2+, Mn2+, Na+, NH4 + and Pd2+). The triazole based calix[4]resorcinarene macrocycle (5) has interacted with Cu2+ ion in preference of other cations. A significant quenching has been observed after the addition of 15 μM Cu2+ ion solution, which produced 4.2 folds drift in the absorption intensity of compound (5). Tetra triazole functionalized calix[4]resorcinarene macrocycle showed high selectivity towards copper ion chemosensing without any interference in competitive studies. The pH studies of compound (5) with Cu2+ indicated the maximum chelation between 7- 7.5 pH. The compound (5) is capable to recognize Cu2+ at 1 μM detectable limit. Copper ion was detected in tap water with 15 μM concentration. Job’s plot showed 1:2 binding ratio between macrocycle (5) and Cu2+.

Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.