The impact of early surgical treatment of tracheal stenosis on neurorehabilitation outcome in patients with severe acquired brain injury.

INTRODUCTION: Acquired tracheal stenosis (TS) is a potentially life-threatening condition following prolonged intubation and/or tracheostomy in adult patients with severe Acquired Brain Injury (sABI), requiring a tracheal resection and reconstruction. METHODS: We included 38 sABI adult patients with TS, admitted at a post-acute Neurorehabilitation Hospital. Disability Rating Scale (DRS) and other functional assessment measures were recorded at admission (t1), before TS surgical treatment (t2), and at discharge (t3). Patients were defined as 'improved' when they changed from a more severe to a less severe disability, between time t2 and time t3, and as "not improved" when they did not show any further improvement between t2 and t3, or they already exhibited a disability improvement since time interval t1-t2. RESULTS: Time interval between the injury onset and TS surgical treatment (t2-t0) was associated with the patient's disability improvement, suggesting the t2-t0 time interval ≤ 115 days as a cutoff value for a possible functional recovery. A t2-t0 time interval ≤ 170 days is also associated to absence of persistent dysphagia. CONCLUSIONS: Early TS surgical treatment within 115 days from the injury onset contributes to the improvement of the disability level in patients with sABI, optimizing their functional outcomes and recovery potential.

TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKß/VPS34 pathway.

The lysosomal calcium channel TRPML1, whose mutations cause the lysosomal storage disorder (LSD) mucolipidosis type IV (MLIV), contributes to upregulate autophagic genes by inducing the nuclear translocation of the transcription factor EB (TFEB). Here we show that TRPML1 activation also induces autophagic vesicle (AV) biogenesis through the generation of phosphatidylinositol 3-phosphate (PI3P) and the recruitment of essential PI3P-binding proteins to the nascent phagophore in a TFEB-independent manner. Thus, TRPML1 activation of phagophore formation requires the calcium-dependent kinase CaMKKß and AMPK, which increase the activation of ULK1 and VPS34 autophagic protein complexes. Consistently, cells from MLIV patients show a reduced recruitment of PI3P-binding proteins to the phagophore during autophagy induction, suggesting that altered AV biogenesis is part of the pathological features of this disease. Together, we show that TRPML1 is a multistep regulator of autophagy that may be targeted for therapeutic purposes to treat LSDs and other autophagic disorders.

A CMOS application-specified-integrated-circuit for 40 GHz high-electron-mobility-transistors automatic biasing.

This paper presents the design and the experimental results of a CMOS Automatic Control System (ACS) for the biasing of High-Electron-Mobility-Transistors (HEMT). The ACS is the first low-power mixed-signal Application-Specified-Integrated-Circuit (ASIC) able to automatically set and regulate the operating point of an off-chip 6 HEMT Low-Noise-Amplifiers (LNAs), hence it composes a two-chip system (the ACS+LNAs) to be used in the Large Scale Polarization Explorer (LSPE) stratospheric balloon for Cosmic Microwave Background (CMB) signal observation. The hereby presented ACS ASIC provides a reliable instrumentation for gradual and very stable LNAs characterization, switching-on, and operating point (<4 mV accuracy). Moreover, it simplifies the electronic instrumentation needed for biasing the LNAs, since it replaces several off-the-shelf and digital programmable device components. The ASIC prototype has been implemented in a CMOS 0.35 µm technology (12 mm2 area occupancy). It operates at 4 kHz clock frequency. The power consumption of one-channel ASIC (biasing one LNA) is 3.6 mW, whereas 30 mW are consumed by a single LNA device.

Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness.

BACKGROUND: Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are involved in airway hyperresponsiveness (AHR) and inflammation. However, the role of nociceptin at modulating the inflammatory immune microenvironment in asthma is still unclear. OBJECTIVE: To understand the role of N/OFQ in the regulation of a Th2-like environment, we used a conventional murine model of AHR. METHODS: Balb/c and CD1 mice were sensitized to ovalbumin (OVA) and treated with saline solution or N/OFQ, at days 0 and 7. A group of Balb/c mice were killed at 7 and 14 days from the first sensitization for the inflammatory profile evaluation while a group of Balb/c and CD1 mice were aerosol-challenged from day 21 to 23 with OVA and killed 24 h later for functional evaluations. RESULTS: In OVA-sensitized mice, N/OFQ significantly reduced IL-4+ CD4+ T cells in lymph nodes (LN) and IL-13 in the lungs, while it induced IFN-γ increase in the lung. The efflux of dendritic cells (DCs) to the mediastinic LN and into the lung of OVA-sensitized mice was reduced in N/OFQ-treated and sensitized mice. N/OFQ reduced the expression of CD80 on DCs, indicating its ability to modulate the activation of DCs. In a less prone Th2-like environment mice strain, such as CD1 mice, N/OFQ did not modify lung resistances as observed in BALB/c mice. Finally, spectroscopic data showed the N/OFQ was able to interact onto the membrane of DCs obtained from Balb/c rather than CD1 mice, indicating its ability to modulate AHR in a Th2-like environment with a direct activity on DCs. CONCLUSIONS AND CLINICAL RELEVANCE: Our data confirmed the capability of N/OFQ to modulate the immune microenvironment in the lung of Th2-biased, OVA-sensitized Balb/c mice, suggesting N/OFQ-NOP axis as a novel pharmacological tool to modulate the inflammatory immune microenvironment in asthma.

Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI.

Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

Could four-dimensional contrast-enhanced ultrasound replace computed tomography angiography during follow up of fenestrated endografts? Results of a preliminary experience.

OBJECTIVE: To evaluate four-dimensional contrast-enhanced ultrasound (4D-CEUS) as an alternative imaging method to computed tomography angiography (CTA) during follow up of fenestrated endovascular aneurysm repair (FEVAR) for juxta- and para-renal abdominal aortic aneurysms (AAA). METHODS: Between October 2011 and March 2012, all consecutive patients who underwent FEVAR follow up were included in the study and evaluated with both 4D-CEUS and CTA. The interval between the two examinations was always ≤ 30 days. Endpoints were the comparison of postoperative AAA diameter, AAA volume, presence of endoleaks, revascularized visceral vessel (RVV) visualization, and patency. Comparative analysis was performed using Bland-Altman plots and McNemar's Chi-square test. RESULTS: Twenty-two patients (96% male, 4% female; mean age 74 ± 7 years; American Society of Anesthesiologists grade III/IV 82%/18%) were enrolled. Seventy-eight RVV (fenestrations: 60; scallops: 17; branches: 1) were analyzed. The mean AAA diameter evaluated by 4D-CEUS and CTA was 45 ± 10 mm (range 30-69 mm) and 48 ± 9 mm (range 32-70 mm), respectively. The mean difference was 3 ± 3 mm. The mean AAA volume evaluated by 4D-CEUS and CTA was 150 ± 7 cc (range 88-300 cc) and 159 ± 68 cc (range 80-310 cc), respectively. The mean difference was 7 ± 4 cc; a Bland-Altman plot revealed agreement in AAA diameter and volume evaluation (p < .01) between 4D-CEUS and CTA. The observed agreement for the detection of endoleaks was 95%. McNemar's Chi-square test confirmed that 4D-CEUS and CTA were equivalent (p > .05) at detecting endoleaks. The first segment of six (8%) RVVs (four renal and two superior mesenteric arteries) was not directly visualized by 4D-CEUS owing to obesity, but the contrast enhancement into the distal part of vessel or into the relative parenchyma gave indirect information about their patency. McNemar's Chi-square test demonstrated the superiority of CTA (p = .031) in visualizing RVVs. The patency of 77/78 RVVs was confirmed with both techniques. McNemar's Chi-square test confirmed that 4D-CEUS and CTA were equivalent in their ability to detect visceral vessel patency. CONCLUSIONS: The data suggest that 4D-CEUS is as accurate as CTA in the evaluation of postoperative AAA diameter and volume, endoleak detection, and RVV patency after FEVAR. Four-dimensional CEUS could provide hemodynamic information regarding RVVs, and reduce radiation exposure and renal impairment during follow up. Obesity limits the diagnostic accuracy of 4D-CEUS.

Elucidation of the molecular mechanism and the efficacy in vivo of a novel 1,4-benzoquinone that inhibits 5-lipoxygenase.

BACKGROUND AND PURPOSE: 1,4-Benzoquinones are well-known inhibitors of 5-lipoxygenase (5-LOX, the key enzyme in leukotriene biosynthesis), but the molecular mechanisms of 5-LOX inhibition are not completely understood. Here we investigated the molecular mode of action and the pharmacological profile of the novel 1,4-benzoquinone derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id) in vitro and its effectiveness in vivo. EXPERIMENTAL APPROACH: Mechanistic investigations in cell-free assays using 5-LOX and other enzymes associated with eicosanoid biosynthesis were conducted, along with cell-based studies in human leukocytes and whole blood. Molecular docking of RF-Id into the 5-LOX structure was performed to illustrate molecular interference with 5-LOX. The effectiveness of RF-Id in vivo was also evaluated in two murine models of inflammation. KEY RESULTS: RF-Id consistently suppressed 5-LOX product synthesis in human leukocytes and human whole blood. RF-Id also blocked COX-2 activity but did not significantly inhibit COX-1, microsomal PGE2 synthase-1, cytosolic PLA2 or 12- and 15-LOX. Although RF-Id lacked radical scavenging activity, reducing conditions facilitated its inhibitory effect on 5-LOX whereas cell stress impaired its efficacy. The reduced hydroquinone form of RF-Id (RED-RF-Id) was a more potent inhibitor of 5-LOX as it had more bidirectional hydrogen bonds within the 5-LOX substrate binding site. Finally, RF-Id had marked anti-inflammatory effects in mice in vivo. CONCLUSIONS AND IMPLICATIONS: RF-Id represents a novel anti-inflammatory 1,4-benzoquinone that potently suppresses LT biosynthesis by direct inhibition of 5-LOX with effectiveness in vivo. Mechanistically, RF-Id inhibits 5-LOX in a non-redox manner by forming discrete molecular interactions within the active site of 5-LOX.

Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator.

Mismanaged protein trafficking by the proteostasis network contributes to several conformational diseases, including cystic fibrosis, the most frequent lethal inherited disease in Caucasians. Proteostasis regulators, as cystamine, enable the beneficial action of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators in ΔF508-CFTR airways beyond drug washout. Here we tested the hypothesis that functional CFTR protein can sustain its own plasma membrane (PM) stability. Depletion or inhibition of wild-type CFTR present in bronchial epithelial cells reduced the availability of the small GTPase Rab5 by causing Rab5 sequestration within the detergent-insoluble protein fraction together with its accumulation in aggresomes. CFTR depletion decreased the recruitment of the Rab5 effector early endosome antigen 1 to endosomes, thus reducing the local generation of phosphatidylinositol-3-phosphate. This diverts recycling of surface proteins, including transferrin receptor and CFTR itself. Inhibiting CFTR function also resulted in its ubiquitination and interaction with SQSTM1/p62 at the PM, favoring its disposal. Addition of cystamine prevented the recycling defect of CFTR by enhancing BECN1 expression and reducing SQSTM1 accumulation. Our results unravel an unexpected link between CFTR protein and function, the latter regulating the levels of CFTR surface expression in a positive feed-forward loop, and highlight CFTR as a pivot of proteostasis in bronchial epithelial cells.

The Golgi apparatus: an organelle with multiple complex functions.

Remarkable advances have been made during the last few decades in defining the organizational principles of the secretory pathway. The Golgi complex in particular has attracted special attention due to its central position in the pathway, as well as for its fascinating and complex structure. Analytical studies of this organelle have produced significant advances in our understanding of its function, although some aspects still seem to elude our comprehension. In more recent years a level of complexity surrounding this organelle has emerged with the discovery that the Golgi complex is involved in cellular processes other than the 'classical' trafficking and biosynthetic pathways. The resulting picture is that the Golgi complex can be considered as a cellular headquarters where cargo sorting/processing, basic metabolism, signalling and cell-fate decisional processes converge.

Functional transcranial Doppler assessment of cerebral blood flow velocities changes during attention tasks.

BACKGROUND AND PURPOSE: Aim of our study was to evaluate cerebral hemodynamic changes during performance of attention tasks and to correlate them with reaction time (RT) and percentage of right answers. METHODS: Mean flow velocity (MFV) in middle cerebral arteries was monitored in 30 subjects by transcranial Doppler during tonic alertness, phasic alertness, focused and divided attention tasks. RESULTS: Mean flow velocity increase was significantly higher during divided attention with respect to other tasks (P < .001). MFV increase was higher in the right than in the left side (P < .001). Asymmetry during attention tasks resulted significantly higher than that observed in tonic alertness condition. RT was increased during focused attention tasks (P < .001 vs. both alert tasks), with further increase during divided attention tasks (P < .001 vs. focused attention task). RT was inversely related to MFV increase only during tonic alertness (P = 0.012 for left side; P = 0.008 for right side). During the divided attention tasks, an association was found between MFV increase and correct answers (r = 0.39, P = 0.033). CONCLUSIONS: These data show a relationship between RT, correct answers and changes in blood flow velocity and suggest that this method of cerebral blood flow investigation could be a useful approach during assessment of patients with attention deficit.

Phosphoinositides as regulators of membrane trafficking in health and disease.

Membrane trafficking is crucial in the homeostasis of the highly compartmentalized eukaryotic cells. This compartmentalization occurs both at the organelle level, with distinct organelles maintaining their identities while also intensely interchanging components, and at a sub-organelle level, with adjacent subdomains of the same organelle containing different sets of lipids and proteins. A central question in the field is thus how this compartmentalization is established and maintained despite the intense exchange of components and even physical continuities within the same organelle. The phosphorylated derivatives of phosphatidylinositol, known as the phosphoinositides, have emerged as key components in this context, both as regulators of membrane trafficking and as finely tuned spatial and temporal landmarks for organelle and sub-organelle domains. The central role of the phosphoinositides in cell homeostasis is highlighted by the severe consequences of the derangement of their metabolism caused by genetic deficiencies of the enzymes involved, and from the systematic hijacking of phosphoinositide metabolism that pathogens operate to promote their entry and/or survival in host cells.

Contrast-enhanced US of the prostate with time/intensity curves: Preliminary results.

PURPOSE: To evaluate the diagnostic performance of ultrasonography using second-generation contrast agent in the study of patients with focal prostate lesions and increased serum prostate-specific antigen (PSA) level. MATERIALS AND METHODS: SIX CONSECUTIVE PATIENTS (AGE RANGE: 72-87 years) with increased PSA (≥4 ng/ml) underwent transrectal ultrasonography (TRUS) followed by contrast-enhanced ultrasonography (CEUS) with injection of second-generation contrast agent. All patients showed areas of abnormal echostructure suspicious for neoplastic lesions. On the basis of CEUS, a time/intensity curve of the suspected area was compared to that of a normal-appearing distant area of the gland and to the results of biopsy of the hypoechoic area. RESULTS: AT CEUS TWO DIFFERENT PATTERNS OF ENHANCEMENT WERE IDENTIFIED AND CONSIDERED TO BE SIGNIFICANT: pattern 1 characterized by a rapid rise in the time/intensity curve of the suspected area compared with the normal gland. Two out of six patients had this pattern and biopsy showed cancer in the biopsied area. Pattern 2 was characterized by a similar rise in the time/intensity curve of the suspected area compared with the normal gland. Four out of six patients had this pattern and biopsy showed prostatitis in the biopsied area. CONCLUSIONS: CEUS using second-generation contrast agent can on the basis of time/intensity curves show differences in vascularization in normal and pathological tissue. Evaluation of the two patterns seems to be useful for identifying areas requiring biopsy, particularly when peripheral hypoechoic areas are observed at TRUS. Our data need to be confirmed in a larger patient population.

Cerebral blood flow velocity changes during meaningful and meaningless gestures--a functional transcranial Doppler study.

The aim of the study was to use functional transcranial Doppler to investigate the possibility of revealing different activation patterns during healthy subjects' performance of meaningful and meaningless actions. Mean flow velocity (MFV) changes were recorded in middle cerebral arteries (MCAs) of 26 normal subjects during a rest phase and during performance of meaningful and meaningless actions. The meaningful task consisted of pouring sugar into a cup with a teaspoon. The meaningless action was an arm movement similar to that necessary for pouring sugar in a cup but without any tool and thus without a goal. Performing actions with or without meaning was associated with different patterns of MFV changes, as documented by the triple interaction condition x performing arm x side of recording [F(1, 25)=10.977; P=0.003]. During the meaningful action, MFV in MCAs increased significantly more than during the meaningless action. During the meaningless action, the MFV increase was significantly higher in the contralateral than in the ipsilateral MCA to the arm performing the task and the meaningful action determined a bilateral MFV increase only when the task was performed with the left arm. When the same task was performed with the right arm, the MFV increase was significantly higher in the contralateral than in the ipsilateral MCA. These findings suggest that the content of an action can influence MFV changes and further confirm the usefulness of transcranial Doppler in neuropsychological investigation.

Early clinical predictive factors during coma recovery.

In severe brain injury patients few studies have examined the role of early clinical factors emerging before recovery of consciousness. Patients suffering from vegetative state and minimally conscious state in fact may need variable periods of time for recovery of the ability to follow commands. In a previous study we retrospectively examined a population of very severe traumatic brain injury patients with coma duration of at least 15 days (prolonged coma), and we found, as significant predictive factors for the final outcome, the time interval from brain injury to the recovery of the following clinical variables: optical fixation, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia during coma recovery were also favourable prognostic factors for the final outcome. In a further study, also as for the neuropsychological recovery, the clinical variable with the best significant predictive value was the interval from head trauma to the recovery of safe oral feeding. In the present study the presence of psychomotor agitation diagnosed by means of LCF (score 4 = confused-agitated) at the admission time in rehabilitation predicted a statistically significant better outcome at the discharge time in comparison with patients without agitation.

Protein-lipid interactions in membrane trafficking at the Golgi complex.

The integrated interplay between proteins and lipids drives many key cellular processes, such as signal transduction, cytoskeleton remodelling and membrane trafficking. The last of these, membrane trafficking, has the Golgi complex as its central station. Not only does this organelle orchestrates the biosynthesis, transport and intracellular distribution of many proteins and lipids, but also its own function and structure is dictated by intimate functional and physical relationships between protein-based and lipid-based machineries. These machineries are involved in the control of the fundamental events that govern membrane traffic, such as in the budding, fission and fusion of transport intermediates, in the regulation of the shape and geometry of the Golgi membranes themselves, and, finally, in the generation of "signals" that can have local actions in the secretory system, or that may affect other cellular systems. Lipid-protein interactions rely on the abilities of certain protein domains to recognize specific lipids. These interactions are mediated, in particular, through the headgroups of the phospholipids, although a few of these protein domains are able to specifically interact with the phospholipid acyl chains. Recent evidence also indicates that some proteins and/or protein domains are more sensitive to the physical environment of the membrane bilayer (such as its curvature) than to its chemical composition.

FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P.

The molecular mechanisms underlying the formation of carriers trafficking from the Golgi complex to the cell surface are still ill-defined; nevertheless, the involvement of a lipid-based machinery is well established. This includes phosphatidylinositol 4-phosphate (PtdIns(4)P), the precursor for phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). In yeast, PtdIns(4)P exerts a direct role, however, its mechanism of action and its targets in mammalian cells remain uncharacterized. We have identified two effectors of PtdIns(4)P, the four-phosphate-adaptor protein 1 and 2 (FAPP1 and FAPP2). Both proteins localize to the trans-Golgi network (TGN) on nascent carriers, and interact with PtdIns(4)P and the small GTPase ADP-ribosylation factor (ARF) through their plekstrin homology (PH) domain. Displacement or knockdown of FAPPs inhibits cargo transfer to the plasma membrane. Moreover, overexpression of FAPP-PH impairs carrier fission. Therefore, FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery that controls generation of constitutive post-Golgi carriers.

Photorefractive keratectomy for compound myopic astigmatism with the MEL-70 G-Scan excimer laser.

PURPOSE: To assess the safety, efficacy, predictability and stability of photorefractive keratectomy in compound myopic astigmatism with a moderate and high cylinder component. METHODS: Photorefractive keratectomy was done in 42 eyes with compound myopic astigmatism with the spherocylindrical algorithm of the MEL-70 excimer laser, with wide ablation zones. RESULTS: Spherical equivalent refraction changed from -4.19 +/- 1.65D to -0.05 +/- 0.31D, refractive cylinder from -2.01 +/- 0.71D to -0.09 +/- 0.20D and mean sphere from -3.22 +/- 1.76D to -0.02 +/- 0.26D. Mean uncorrected visual acuity rose from 0.12 +/- 0.17 to 0.91 +/- 0.10. No eye lost lines of spectacle-corrected visual acuity. The safety index was 1.03 and the efficacy index 0.98. Six months from the treatment all eyes were within +/- 1D, 8.9% of eyes were within 0.50D and 44% were plano of target refraction. Refractive and topographical stability were achieved between one and three months after treatment. Transient haze was observed between one and three months after PRK. CONCLUSIONS: Photorefractive keratectomy with the MEL-70 excimer laser to correct myopic astigmatism was a safe and effective procedure with good stability at six months' follow-up. Refractive and visual outcome confirmed that excellent predictability can be expected.

Emotional processing in Parkinson's disease. A study using functional transcranial doppler sonography.

This study evaluated the use of transcranial Doppler ultrasonography for detecting selective changes in cerebral blood flow velocity during emotional processes. The aim was to investigate the possibility of obtaining functional information on the neuropsychology of emotions in patients with Parkinson's disease (PD). For this reason, blood flow velocity changes were investigated in both middle cerebral arteries (MCA) during a rest condition and when viewing non emotional (tasks 1 and 3) and emotional (task 2) slide sequences. The study included 12 PD patients and 12 healthy subjects. All patients were in treatment with levodopa or dopamine agonist. Investigation of PD patients was performed during an on-phase. The three tasks produced significantly different effects on the right and left side in the PD patients compared with the control group. During the two non emotion-related tasks the increase of mean flow velocity (MFV) compared with the basal values was similar in the two middle cerebral arteries in both groups [(PD Patients: Task 1: left MCA = 3.95 % 2.2, Right MCA = 4.33 % +/- 2.3, Task 3: left MCA = 3.04 % +/- 1.9, Right MCA = 2.71 % +/- 2.2) (control group: Task 1: left MCA = 4.57 % +/- 1.4, Right MCA = 4.46 % +/- 1.7, Task 3: left MCA = 2.32 % +/- 0.9, Right MCA = 2.52 % +/- 1.2)] The negative emotional task was accompanied by a significantly higher increase in the right (10.53 % +/- 3.2) than in the left middle cerebral artery (4.52 % +/- 1.51) only in the control group. The PD patients showed a bilateral and symmetrical increase of MFV (left MCA = 4.28 % +/- 2.3 and right MCA 5.77 % +/-3.8). To determine whether there was a dysfunction in cerebrovascular reactivity and a deficit in the ability to activate both hemispheres in response to non emotion-related stimuli in the PD patients, the protocol study included a cerebrovascular reactivity test to apnea, a motor task (thumb-to-finger opposition), a cognitive task (word fluency and visual discrimination of objects), performed by both patients and controls. The pattern of MFV changes during these tasks was not statistically significantly different in the two experimental groups. In order to evaluate the possible influence of drug treatment on cerebrovascular reactivity, seven patients were also evaluated during an off-phase, after a 48-hour wash-out period. Changes in MFV during every task were similar to that observed during the on-phase. These findings show the possibility of obtaining specific functional information from bilateral transcranial Doppler and suggest the selective and specific deficit of PD patients in emotional processing.