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ABSTRACT: Patients with liver cirrhosis without overt hepatic encephalopathy (OHE) show alterations of cognitive function and metabolism which seem to not be fully reversible after liver transplantation (OLT), but the long-term outcomes have not be studied.
Fourteen cirrhotic subjects including alcoholic (n = 4), viral (n = 4), mixed (n = 5), and cholestatic (n = 2) without OHE were evaluated for OLT as well as 8 age-matched normal controls. All subjects underwent cerebral positron emission tomography (PET) with 18F-fluorodeoxyglucose to quantify cerebral glucose metabolism and neuropsychological evaluation to test memory, intelligence, and cerebral frontal functions. Transplanted patients underwent repeat evaluations at 1 and 10 years after liver transplantation.
Compared with the controls patients with liver cirrhosis showed significantly reduced cerebral glucose metabolism in all cerebral cortical and subcortical regions. This observation correlated with the presence of alterations in neuropsychological tests evaluating memory, frontal tasks, and visuospatial memory. Among 12 patients who were transplanted, 10 underwent repeat neuropsychological evaluation at 1 year; in addition 5 underwent PET). At 10 years the 7 living patients had repeat neuropsychological evaluation. One year after OLT, transplanted patients showed significant amelioration of cerebral glucose metabolism in all cerebral regions with significant improvements in neuropsychological tests, despite 20% of patients showing residual defects in frontal tasks. The cognitive function did not further improve at 10 years after OLT.
Patients with liver cirrhosis show altered cerebral function and metabolism that revert after successful liver transplantation, but with residual mild deficits in cerebral frontal functions, which seem to not improve in the long term.
Transplantation Proceedings 06/2009; 41(4):1295-6. · 1.00 Impact Factor
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ABSTRACT: Studies using brain-imaging techniques have shown changes in regional blood flow (rCBF) in patients with liver cirrhosis. It remains unknown whether the aetiology of liver disease accounts for these changes.
To evaluate whether the aetiology of liver cirrhosis is associated with different patterns of rCBF.
A total of 50 patients with end-stage liver disease and no overt encephalopathy were studied. Thirteen age-matched subjects admitted to the neurology department for headache were used as controls. Exclusion criteria were focal brain lesions, severe brain atrophy and any abnormalities found on computed tomography scan suggesting other central nervous system diseases, alcohol intake or use of neuroactive drugs for at least 6 months. rCBF was assessed using single-positron-emission tomography (SPECT) with 99mTc-hexamethylpropylene amine oxime (99mTc-HM-PAO) as a tracer in all patients and controls. The Mann-Whitney U test was used for statistical analysis.
The liver-disease aetiology was as follows: alcoholic (A) in 19 patients; viral (V) (hepatitis B virus, hepatitis D virus, hepatitis C virus) in 14 patients; alcoholic with concomitant viral (A + V) in five patients; and cholestatic (C) (primary biliary cirrhosis, primary sclerosing cholangitis) in 12 patients. SPECT showed significantly lower rCBF in cirrhotic patients than in controls for most cortical and subcortical regions and in alcoholic and viral patients than in cholestatic liver disease patients for some cortical regions. When patients were grouped according to previous alcohol abuse (including cases with a concomitant viral aetiology), rCBF was significantly lower in the frontal superior, medial and temporal inferior regions in the alcoholic group.
Cerebral blood flow is significantly lower in patients with liver cirrhosis than in controls and, among cirrhotics, it is lower in alcoholic and viral cirrhosis than in cholestatic liver disease. In patients with previous alcohol abuse, cerebral blood flow was significantly more reduced in the frontal and temporal regions compared with patients without previous alcohol abuse.
European Journal of Gastroenterology & Hepatology 10/2004; 16(9):885-90. · 1.76 Impact Factor
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ABSTRACT: In the last 20 years a cholinergic dysfunction has been the major working hypothesis for the pharmacology of memory disorders. Cholinergic antagonists and lesions impair and different classes of cholinomimetics (i.e. acetylcholine precursors, cholinergic agonists and acetylcholinesterase inhibitors) enhance attention and memory in experiment animals, healthy human subjects and Alzheimer disease patients. In addition, acetylcholinesterase inhibitors improve different cognitive (i.e. visuospatial and verbal) functions in a variety of unrelated disorders such as dementia with Lewy bodies, Parkinson disease, multiple sclerosis, schizoaffective disorders, iatrogenic memory loss, traumatic brain injury, hyperactivity attention disorder and, as we recently reported, vascular dementia and mild cognitive impairment. In animals, different cholinomimetics dose-dependently increased regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF), two indices of neuronal function, more markedly in subcortical regions (i.e. thalamus, hippocampus and visual system nuclei). In both healthy human subjects and Alzheimer disease patients acetylcholinesterase inhibitors increased rCMRglc and rCBF in subcortical and cortical brain regions at rest but attenuated rCBF increases during cognitive performances. Hence, acetylcholinesterase inhibitors may enhance cognition and rCMRglc by acting primarily on subcortical regions that are involved in attentional (i.e. thalamus) and memory (i.e. hippocampus) processes; such an effect probably is not specific for Alzheimer disease and can be beneficial in patients suffering from a wide array of neuropsychiatric disorders.
Acta Neurovegetativa 06/2002; 109(5-6):857-70. · 2.73 Impact Factor
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ABSTRACT: The currently used assessment techniques for measuring neurological deficits are time consuming and may lack of sensibility and repeatability. Previous studies suggested that the cinematic analysis of the movement, might represent a reliable alternative instrument for documenting the degree of motor impairment. To verify this hypothesis we investigated motor/functional progress in 20 post-stroke patients, undergoing rehabilitation therapy, by means of a widely used clinical test (Fugl-Meyer scale), and by evaluating kinematics of arm motion. After rehabilitation therapy, velocity and duration of reaching movements significantly improved with respect to baseline values. Before and after rehabilitation there was a significant correlation between each cinematic parameter and the clinical scale scores. These results, suggests that the cinematic analysis of movement can be proposed as a precise and objective assessment tool to be used in clinical practice.
Studies in health technology and informatics 02/2001; 81:386-92.
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ABSTRACT: The wide therapeutic spectrum of fluoxetine (e.g., antidepressant, antipanic, antiphobic, antiobsessive, analgesic, antimigraine) requires long-term administration and adaptive changes. To test whether adaptation involves the serotonin (5-HT) transporters, we measured the effects of fluoxetine on the regional cerebral metabolic rate for glucose (rCMRglc) in control rats or in rats pretreated for 2 weeks with fluoxetine (8 mg/kg, i.p., daily, 2 days wash out); rCMRglc was measured in 56 brain regions, using the quantitative [14C]deoxyglucose technique, at 30 min after i.p. administration of fluoxetine 0.4, 4 or 40 mg/kg, i.p., to non-pretreated rats or fluoxetine 4 mg/kg to pretreated rats. In non-pretreated rats, fluoxetine reduced rCMRglc in a dose-dependent fashion in 4 (7%, mean decrease 11%), 28 (50%, mean decrease 23%) and 37 (66%, mean decrease 32%) brain regions. In chronic fluoxetine-pretreated rats, fluoxetine decreased rCMRglc to a substantially lesser degree (eight regions, 14%; mean decrease, 10%). Subcortical brain regions (i.e., hypothalamic paraventricular, locus coeruleus and basal ganglia nuclei) that mediate the physiological responses to stress were very sensitive to fluoxetine acutely and subsensitive after chronic treatment. As kinetic tolerance to fluoxetine does not occur during chronic administration, the diminished rCMRglc responsivity to fluoxetine reflects dynamic, adaptive tolerance of 5-HT transporters and, consequently, increased synaptic 5-HT concentrations; the findings suggest that fluoxetine may be therapeutic by increasing the 5-HT-negative modulation upon areas that drive the abnormally hyperactive responses to stress found in several neuropsychiatric conditions.
Brain Research 02/2000; 854(1-2):35-41. · 2.73 Impact Factor
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The Italian Journal of Neurological Sciences 11/1998; 19 Suppl 1:S15.
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ABSTRACT: Previous studies showed contrasting results with regard to alterations of regional cerebral blood flow/metabolism in subjects with liver cirrhosis. The aim of the study was to extend these findings in a larger series of patients. In addition, we wanted to determine whether such alterations are reversed by successful liver transplantation.
The study group comprised 23 patients with liver cirrhosis and 13 normal controls. At entry to the study, all subjects underwent a complete neurological examination, EEG recordings and SPECT scanning. The severity of liver disease was determined according to the Child-Pugh score. Fourteen patients underwent a second SPECT examination 1 year after liver transplantation.
Significant rCBF reductions, ranging from 6% to 7%, were found in the majority of the cortical regions of the whole group of patients with cirrhosis, as compared to controls. These reductions were more diffuse in patients with alcoholic liver disease, comprising almost all the assayed regions. Liver transplantation normalized cortical rCBF deficits so that postoperative perfusion indexes were superimposable on control values. However, the frontal cortex remained significantly more impaired in patients with alcoholic cirrhosis than in those with non-alcoholic cirrhosis. The differences in frontal rCBF between the two groups of patients ranged from 6 to 11%.
Liver cirrhosis was associated with rCBF defects that depend upon the etiology of liver disease and that subsided after successful liver transplantation. The frontal defects in alcoholic cirrhosis either before or after surgery may imply a neurotoxic, possibly irreversible, action of ethanol.
Journal of Hepatology 08/1998; 29(1):78-84. · 9.26 Impact Factor
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ABSTRACT: Study was performed in Fischer-344 rats to test the effects of the intravenous anesthetic propofol on cerebral content of high-energy metabolites, glucose, and lactate in normoxic and severely hypoxic rats. General and local anesthetics (isoflurane, N(2)O 70%, pancuronium bromide, bupivacaine hydrochloride) were used for surgery (tracheostomy, femoral artery and vein cannulation, skull exposure, ligature of right-sided carotid and EEG needle electrodes only in rats devoted to the hypoxia study). For normoxia study, four groups of 7 rats each were treated for 60 min as it follows: the control group with N(2)O plus propofol vehicle and the other three with propofol 12.5, 25, or 50 mg x kg(-1) x h(-1) respectively. For the hypoxia-study five groups of 7 rats each were planned to have two control (one normoxic) and three propofol-treated groups, drug treatments being the above indicated and of 80 min. During the last 20 min Pa(O(2)) was lowered to 15-20 mmHg. Pa(CO(2)) was maintained between 35-40 mmHg, rectal temperature at 37 degrees C, MABP near to 100 mmHg and pH on the basal values during the whole procedure. Then brains were frozen in vivo, and cortical tissue was excised and analyzed for labile metabolites using fluorometric techniques. Propofol, at all the doses tested, did not alter the concentrations of adenine nucleotides, phosphocreatine, lactate, pyruvate, or glucose in normoxic rats. In rat brain, hypoxia did not produce significant changes in the concentrations of adenine nucleotides. PCr concentration was decreased both in the ligated and unligated side, and lactate levels exceeded 21 and 18 micromol/g in the right and left cortices, respectively. While the lowest dose of propofol was ineffective in preventing PCr decrease and lactate increase, both 25 and 50 mg x kg(-1) x h(-1) significantly reduced those adverse effects of hypoxia.
Life Sciences 02/1997; 60(16):1349-57. · 2.53 Impact Factor
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ABSTRACT: Many patients with Alzheimer's disease (AD) develop parkinsonian symptoms, suggesting an overlapping between AD and Parkinson's disease (PD). However, pathologic and neurochemical studies indicate that the involvement of the dopamine system may be different in the two conditions. Using single photon emission tomography, we determined the relative specific striatal uptake (striatum to cerebellum ratio) of the D2 receptor ligand [123I]-IBZM in 15 AD patients without overt extrapyramidal symptoms (three subjects presented mild rigidity and bradykinesia) and nine age-matched controls. Mean specific activity in striatal regions of AD patients (1.35 +/- 0.09) was significantly reduced from control mean (1.59 +/- 0.03). Because such changes were evident even in the absence of overt parkinsonian symptomatology, our data indicate that alterations of striatal D2 receptors may be part of the pathologic abnormalities of AD. In addition, the mechanisms underlying extrapyramidal symptoms in AD (decline of postsynaptic striatal dopamine receptors) appear different from the prevalent presynaptic nigrostriatal alterations typical of PD.
Neurology 11/1996; 47(4):1065-8. · 8.31 Impact Factor
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ABSTRACT: In animals, drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions. It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans. We evaluated the effects of the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical therapy.
Fifty-two severely disabled hemiplegic subjects were randomly assigned to three treatment groups; during 3 months of physical therapy, patients were treated with placebo, maprotiline (150 mg/d), or fluoxetine (20 mg/d). Before and at the end of the observation period, we assessed activities of daily living by the Barthel Index, degree of neurological deficit by a neurological scale for hemiplegic subjects, and depressive symptomatology by the Hamilton Depression Rating Scale.
The diverse treatments ameliorated walking and activities of daily living capacities to different extents. The greatest improvements were observed in the fluoxetine-treated group and the lowest in the maprotiline-treated group. Furthermore, fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo. These effects of the drugs were not related to their efficacy in treating depressive symptoms.
Fluoxetine may facilitate or, alternatively, maprotiline may hinder recovery in poststroke patients undergoing rehabilitation. The effects of fluoxetine as an adjunct to physical therapy warrant further investigation, since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone.
Stroke 08/1996; 27(7):1211-4. · 5.73 Impact Factor
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Advances in neurology 02/1996; 69:467-73.
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Advances in neurology 02/1996; 69:551-5.
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ABSTRACT: To determine if reported reductions of regional cerebral metabolic rates for glucose (rCMRglc) induced by the tryciclic antidepressant clomipramine (CMI) (10 mg/kg) are due to a presynaptic action on serotonin (5-HT) terminals, 3-month-old Fischer-344 rats were given parachloroamphetamine (PCA), a serotonin neurotoxin. rCMRglc was measured 3 weeks later in 55 brain regions after the administration of saline or CMI using the quantitative autoradiographic [14C]2-deoxyglucose procedure. PCA alone increased rCMRglc in the visual cortex. CMI alone reduced rCMRglc in 18 (33%) of the studied regions, including telencephalic, diencephalic, limbic, and brain stem areas. In PCA-lesioned rats, metabolic responses to CMI (10 mg/kg) were greatly reduced, and significant rCMRglc decreases were observed only in 4 (7%) of the brain areas, including the hippocampus and raphe nuclei. Abolition by PCA of the metabolic responses to CMI confirms that CMI, at the dose studied, reduces rCMRglc via a presynaptic mechanism, likely the 5-HT reuptake sites.
Neuropsychopharmacology 12/1995; 13(3):215-22. · 7.99 Impact Factor
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ABSTRACT: In this study we compared the effects of the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic [14C]2-deoxyglucose technique, at 10 min after i.p. injection of DPAT (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas DPAT produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in limbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT1A agonist DPAT and suggest that low dose buspirone activates preferentially 5-HT1A receptors. Hence, this receptor subtype may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic D2 antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Research 05/1995; 677(2):213-20. · 2.73 Impact Factor
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ABSTRACT: Single photon emission tomography with the ligand [123I]-IBZM was used to image central dopamine D2 receptors in Parkinson's disease patients. The aim was to assess striatal receptor densities in relation to response to L-Dopa therapy. In the parkinsonian patients group who were untreated until SPET study and in the group of patients with a sustained response to chronic L-Dopa, striatal [123I]-IBZM uptake did not differ significantly from mean values of the control group. On the contrary, significantly diminished uptake of [123I]-IBZM was found in the basal ganglia regions of the group of patients who developed a complicated/fluctuating response to chronic L-Dopa treatment. Our results indicate that striatal D2 receptor alterations in Parkinson's disease may contribute to the altered response to L-Dopa.
Journal of neural transmission. Supplementum 02/1995; 45:113-22. · 1.07 Impact Factor
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Transplantation Proceedings 01/1995; 26(6):3677-8. · 1.00 Impact Factor
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ABSTRACT: Using the quantitative autoradiographic [14C]2-deoxyglucose technique, regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats at 1, 2, 3, 4 and 6 h after administration of GM1 30 mg/kg and at 3 h after GM1 150 or 300 mg/kg. GM1 is a natural compound that is able to prevent neuron degeneration induced by exposure to excitatory amino acids in vitro and by ischemia or neurotoxins in vivo. GM1 30 mg/kg, a dose very effective in preventing excitatory amino acid-induced neurotoxicity, produced minimal rCMRglc change over a 6 h period. GM1 150 and 300 mg/kg reduced rCMRglc, in 14 (31%) and in 29 (64%) brain regions, respectively. Maximal metabolic effects occurred in hippocampal areas which possess, in specific subfields, the highest brain concentrations of different excitatory amino acid receptor subtypes. This finding suggests an effect by GM1 on postreceptor mechanisms common to different excitatory amino acids.
Brain Research 10/1993; 621(1):175-9. · 2.73 Impact Factor
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ABSTRACT: Rehabilitation therapy is believed to be useful during the first few months after stroke when recovery usually takes place. However, evidence exists that this may not be the rule for all stroke victims. Therefore, we investigated, in a selected group of poststroke patients, the profile of recovery in response to long-term rehabilitation therapy.
Fifty-one hemiplegic subjects unable to walk 3 months after stroke were enrolled in this study. Patients underwent consecutive periods of rehabilitation up to 2 years after the cerebrovascular accident. Autonomy in daily living activities and the degree of neurological compromission were periodically assessed with the Barthel Index and a neurological scale designed for hemiplegic subjects. The main features of the patients were also evaluated as a possible predictor of outcome.
In a consistent percentage of the patients, significant gains in gait and daily living abilities were observed during the first year and, in individual cases, during the second year after stroke. At the end of the study, 74% of the patients regained their capacity to walk without assistance, and up to 79% had a Barthel Index score above 70. Sphincter function, level of neurological impairments, and capacity in daily living activities are significantly related to the outcome of the patients as a whole but were not useful to anticipate the outcome of each patient.
These results suggest that disabled poststroke subjects may attain significative functional improvements in response to prolonged restorative therapy. However, the possibility of predicting the outcome of individual patients appears the major problem to solve in order to assign to long-term rehabilitation programs only patients who will benefit from the therapy.
Stroke 09/1993; 24(8):1186-91. · 5.73 Impact Factor
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Transplantation Proceedings 07/1993; 25(3):2218-9. · 1.00 Impact Factor
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ABSTRACT: Single photon emission tomography (SPET) with the novel ligand [123I]-IBZM was used to image central dopamine D2 receptors in Parkinson's disease (PD) patients. The aim was to assess basal ganglia (BG) receptor densities in relation to the response to L-dopa therapy. To better characterize the clinical potential of [123I]-IBZM SPET, each patient underwent a second study with the regional perfusion tracer [99mTc]-HM-PAO. Tracer activity ratios were calculated for caudate and putamen with mean activity over the cerebellar hemispheres as internal standard. In PD patients we found a significant decline of mean caudate [123I]-IBZM activity, as compared with age-matched control subjects. However, when patients were grouped according to their therapeutic behavior, the [123I]-IBZM uptake in BG ganglia regions of the PD patient group with a poor and fluctuating response to L-dopa was significantly reduced from mean values of patients with a sustained response to L-dopa therapy. [99mTc]-HM-PAO caudate and putamen uptake indexes in PD were similar to control values, even in patients with deteriorated therapeutic response. Our results indicate that BG D2 receptor alterations in PD may contribute to the altered response to L-dopa.
European Neurology 02/1993; 33(2):143-8. · 1.81 Impact Factor
