Enrico Fazzini, D.O., Ph.D.

Pulmonary manifestations of Kaposi's sarcoma. 1987
Garay, S M; Belenko, M; Fazzini, E; Schinella, R
2009 Nov;136(5 Suppl):e30-e30, Chest
— id: 132475, year: 2009, vol: 136, page: e30, stat: Journal Article,

Transtelephonic home blood pressure to assess the monoamine oxidase-B inhibitor rasagiline in Parkinson disease
White, William B; Salzman, Phyllis; Schwid, Steven R; Fazzini, Enrico
2008 Sep;52(3):587-593, Hypertension
Monoamine oxidase inhibitors are associated with dietary tyramine interactions that can induce hypertensive crises. Rasagiline mesylate is a novel irreversible selective monoamine oxidase type B inhibitor for Parkinson disease that may have a low risk of interaction with dietary tyramine because of its selectivity. To study interactions of rasagiline with diets unrestricted in tyramine-containing foods, we incorporated transtelephonic, self-monitoring of the blood pressure (BP) into a randomized, placebo-controlled trial of rasagiline 0.5 and 1.0 mg daily in 414 levodopa-treated Parkinson patients with motor fluctuations. The proportion of patients with a systolic BP increase of >30 mm Hg was the primary BP end point. In 13 968 self-measured readings at baseline, the proportion of systolic BP values that increased by >30 mm Hg after a meal ranged from 9.5% to 12.9% in the 3 treatment groups. In 25 733 BPs obtained postrandomization, the proportion of values with a >30-mm Hg systolic postprandial increase was 15% in the placebo group, 15% in the rasagiline 0.5-mg group, and 11% in the rasagiline 1-mg group after 3 weeks of double-blind therapy and 13%, 14%, and 12%, respectively, after 26 weeks of treatment (P value was not significant for all of the comparisons among treatment groups). A postprandial increase in systolic BP to >180 mm Hg at any time after randomization was seen in 3.3%, 2.6%, and 2.9% of the placebo, 0.5-mg, and 1.0-mg rasagiline groups, respectively. These data demonstrate that rasagiline did not induce postprandial hypertension in patients with Parkinson disease who were on an unrestricted diet
— id: 130418, year: 2008, vol: 52, page: 587, stat: Journal Article,

Rotigotine Transdermal System as adjunctive therapy to levodopa in patients with advanced-stage Parkinson's disease. Results of a randomized, double-blind, placebo-controlled, multicenter, multinational trial
Boroojerdi, B; LeWitt, PA; Nausieda, PA; Chang, F; Fazzini, E; Truong, DD; Carpenter, M
2005 NOV 15 ;238(6):S353-S353, Journal of the neurological sciences
— id: 63299, year: 2005, vol: 238, page: S353, stat: Journal Article,

A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study
Fazzini, E
2005 Feb;62(2):241-248, Archives of neurology
BACKGROUND: Rasagiline (n-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD). OBJECTIVE: To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations. DESIGN: Multicenter, randomized, placebo-controlled, double-blind, parallel-group study. PATIENTS: Parkinson disease patients (N = 472) with at least 21/2 hours of daily 'off' (poor motor function) time, despite optimized treatment with other anti-PD medications. INTERVENTIONS: Rasagiline, 1.0 or 0.5 mg/d, or matching placebo. MAIN OUTCOME MEASURES: Change from baseline in total daily off time measured by patients' home diaries during 26 weeks of treatment, percentage of patients completing 26 weeks of treatment, and adverse event frequency. RESULTS: During the treatment period, the mean adjusted total daily off time decreased from baseline by 1.85 hours (29%) in patients treated with 1.0 mg/d of rasagiline, 1.41 hours (23%) with 0.5 mg/d rasagiline, and 0.91 hour (15%) with placebo. Compared with placebo, patients treated with 1.0 mg/d rasagiline had 0.94 hour less off time per day, and patients treated with 0.5 mg/d rasagiline had 0.49 hour less off time per day. Prespecified secondary end points also improved during rasagiline treatment, including scores on an investigator-rated clinical global impression scale and the Unified Parkinson's Disease Rating Scale (activities of daily living in the off state and motor performance in the 'on' state). Rasagiline was well tolerated. CONCLUSIONS: Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated PD patients. In light of recently reported benefits in patients with early illness, rasagiline is a promising new treatment for PD
— id: 130417, year: 2005, vol: 62, page: 241, stat: Journal Article,

Standard osteopathic manipulative treatment acutely improves gait performance in patients with Parkinson's disease
Wells MR; Giantinoto S; D'Agate D; Areman RD; Fazzini EA; Dowling D; Bosak A
1999 Feb;99(2):92-98, Journal of the American Osteopathic Association
Patients with Parkinson's disease exhibit a variety of motor deficits which can ultimately result in complete disability. The primary objective of this study was to quantitatively evaluate the effect of osteopathic manipulative treatment (OMT) on the gait of patients with Parkinson's disease. Ten patients with idiopathic Parkinson's disease and a group of eight age-matched normal control subjects were subjected to an analysis of gait before and after a single session of an OMT protocol. A separate group of 10 patients with Parkinson's disease was given a sham-control procedure and tested in the same manner. In the treated group of patients with Parkinson's disease, statistically significant increases were observed in stride length, cadence, and the maximum velocities of upper and lower extremities after treatment. There were no significant differences observed in the control groups. The data demonstrate that a single session of an OMT protocol has an immediate impact on Parkinsonian gait. Osteopathic manipulation may be an effective physical treatment method in the management of movement deficits in patients with Parkinson's disease
— id: 18380, year: 1999, vol: 99, page: 92, stat: Journal Article,

Cognitive functioning after pallidotomy for refractory Parkinson's disease [see comments]
Perrine K; Dogali M; Fazzini E; Sterio D; Kolodny E; Eidelberg D; Devinsky O; Beric A
1998 Aug;65(2):150-154, Journal of neurology neurosurgery & psychiatry
BACKGROUND: Earlier approaches to pallidotomy for refractory Parkinson's disease had significant complication rates. More recent approaches show fewer complications, but the effect of pallidotomy on cognition is unclear. The current study was conducted to examine the neuropsychological effects of unilateral pallidotomy. METHODS: Neuropsychological testing was performed on patients with medically refractory, predominantly unilateral Parkinson's disease at baseline and after unilateral ventral pallidotomy (n=28) or after an equivalent period without surgery in control patients (n=10). RESULTS: Pallidotomy patients showed no significant changes from baseline to retesting relative to the control group for any measure. Across all of the tests administered, only five of the surgery patients showed a significant decline, and of these five none declined on more than one test. Depression did not relate to preoperative or postoperative cognition. The pallidotomy group showed a significant improvement in motor functioning and activities of daily living whereas the control group did not. These measures were not associated with the neuropsychological test scores at baseline or retest. CONCLUSIONS: Stereotactic unilateral ventral pallidotomy does not seem to produce dramatic cognitive declines in most patients
— id: 7740, year: 1998, vol: 65, page: 150, stat: Journal Article,

Selection criteria for unilateral posteroventral pallidotomy
Alterman RL; Kelly P; Sterio D; Fazzini E; Eidelberg D; Perrine K; Beric A
1997 ;68(5):18-23, Acta neurochirurgica. Supplementum
In an attempt to refine the indications for posteroventral pallidotomy (PVP) the authors instituted strict selection criteria which are based on the experience gained from the first 60 pallidotomy patients treated at their institution. In addition to clinical evaluation, all pallidotomy candidates undergo neuropsychological testing and 18F-fluoro-deoxyglucose utilization positron emission tomography (FDG/PET). The data from which these criteria were developed are presented as are early clinical results. The authors demonstrate that these criteria enhance the efficacy of the procedure by assuring therapeutic response and reducing the incidence of post-operative dementia. Their indications and contraindications for pallidotomy are discussed
— id: 25191, year: 1997, vol: 68, page: 18, stat: Journal Article,

Metabolic correlates of pallidal neuronal activity in Parkinson's disease
Eidelberg D; Moeller JR; Kazumata K; Antonini A; Sterio D; Dhawan V; Spetsieris P; Alterman R; Kelly PJ; Dogali M; Fazzini E; Beric A
1997 Aug;120 ( Pt 8)(2):1315-1324, Brain
We have used [18F]fluorodeoxyglucose and PET to identify specific metabolic covariance patterns associated with Parkinson's disease and related disorders previously. Nonetheless, the physiological correlates of these abnormal patterns are unknown. In this study we used PET to measure resting state glucose metabolism in 42 awake unmedicated Parkinson's disease patients prior to unilateral stereotaxic pallidotomy for relief of symptoms. Spontaneous single unit activity of the internal segment of the globus pallidus (GPi) was recorded intraoperatively in the same patients under identical conditions. The first 24 patients (Group A) were scanned on an intermediate resolution tomograph (full width at half maximum, 8 mm); the subsequent 18 patients (Group B) were scanned on a higher resolution tomograph (full width half maximum, 4.2 mm). We found significant positive correlations between GPi firing rates and thalamic glucose metabolism in both patient groups (Group A: r = 0.41, P < 0.05; Group B: r = 0.69, P < 0.005). In Group B, pixel-based analysis disclosed a significant focus of physiological-metabolic correlation involving the ventral thalamus and the GPi (statistical parametric map: P < 0.05, corrected). Regional covariance analysis demonstrated that internal pallidal neuronal activity correlated significantly (r = 0.65, P < 0.005) with the expression of a unique network characterized by covarying pallidothalamic and brainstem metabolic activity. Our findings suggest that the variability in pallidal neuronal firing rates in Parkinson's disease patients is associated with individual differences in the metabolic activity of efferent projection systems
— id: 18381, year: 1997, vol: 120 ( Pt 8), page: 1315, stat: Journal Article,

Stereotactic pallidotomy for Parkinson's disease: a long-term follow-up of unilateral pallidotomy
Fazzini E; Dogali M; Sterio D; Eidelberg D; Beric A
1997 May;48(5):1273-1277, Neurology
Eleven patients suffering from Parkinson's disease were followed for up to 4 years after unilateral pallidotomy. We observed persistent contralateral improvement and unexpected ipsilateral improvement of motor symptoms. In addition, there was a protracted relief of contralateral dyskinesias and maintenance of relatively stable levodopa dosage
— id: 7143, year: 1997, vol: 48, page: 1273, stat: Journal Article,

Preoperative indicators of clinical outcome following stereotaxic pallidotomy
Kazumata K; Antonini A; Dhawan V; Moeller JR; Alterman RL; Kelly P; Sterio D; Fazzini E; Beric A; Eidelberg D
1997 Oct;49(4):1083-1090, Neurology
We assessed the utility of preoperative clinical assessment and functional brain imaging with 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in predicting the clinical outcome of stereotaxic pallidotomy for the treatment of advanced Parkinson's disease (PD). Twenty-two PD patients undergoing posteroventral pallidotomy were assessed preoperatively with the Core Assessment Program for Intracerebral Transplantation (CAPIT) ratings measured on and off levodopa; quantitative FDG/PET was also performed before surgery. Preoperative clinical and metabolic measurements were correlated with changes in off-state CAPIT ratings determined 3 months after surgery. Clinical outcome following pallidotomy was also correlated with intraoperative measures of spontaneous pallidal single-unit activity as well as postoperative MRI measurements of lesion volume and location. We found that unilateral pallidotomy resulted in variable clinical improvement in off-state CAPIT scores for the contralateral limbs (mean change 30.9 +/- 15.5%). Postoperative MRI revealed that pallidotomy lesions were comparable in location and volume across the patients. Clinical outcome following surgery correlated significantly with preoperative measures of CAPIT score change with levodopa administration (r = 0.60, p < 0.005) and with preoperative FDG/PET measurements of lentiform glucose metabolism (r = 0.71, p < 0.0005). Operative outcome did not correlate with intraoperative measures of spontaneous pallidal neuronal firing rate. We conclude that preoperative measurements of lentiform glucose metabolism and levodopa responsiveness may be useful indicators of motor improvement following pallidotomy. Both preoperative quantitative measures, either singly or in combination, may be helpful in selecting optimal candidates for surgery
— id: 25190, year: 1997, vol: 49, page: 1083, stat: Journal Article,

Characteristics of pallidal neuronal discharges in Parkinson's disease patients
Beric A; Sterio D; Dogali M; Fazzini E; Eidelberg D; Kolodny E
1996 ;69:123-128, Advances in neurology
— id: 12696, year: 1996, vol: 69, page: 123, stat: Journal Article,

Effects of posteroventral pallidotomy on Parkinson's disease
Dogali M; Sterio D; Fazzini E; Kolodny E; Eidelberg D; Beric A
1996 ;69(4):585-590, Advances in neurology
— id: 18386, year: 1996, vol: 69, page: 585, stat: Journal Article,

Regional metabolic correlates of surgical outcome following unilateral pallidotomy for Parkinson's disease
Eidelberg D; Moeller JR; Ishikawa T; Dhawan V; Spetsieris P; Silbersweig D; Stern E; Woods RP; Fazzini E; Dogali M; Beric A
1996 Apr;39(4):450-459, Annals of neurology
Stereotaxic ventral pallidotomy has been employed in the symptomatic treatment of patients with advanced Parkinson's disease (PD). To understand the pathophysiology of clinical outcome following this procedure, we studied 10 PD patients (5 men and 5 women; mean age 60.0 +/- 6.1 years; mean Hoehn and Yahr stage 3.8 +/- 1.0) with quantitative 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). All patients were scanned preoperatively; 8 of 10 patients were rescanned 6 to 8 months following surgery. Clinical performance was assessed off medications before and after surgery using standardized timed motor tasks. We found that preoperative lentiform metabolism correlated significantly with improvement in contralateral motor tasks at 1 week, 3 months, and 6 months following unilateral pallidotomy (p<0.03). Postoperatively, significant metabolic increases were noted in the primary motor cortex, lateral premotor cortex, and dorsolateral prefrontal cortex (p<0.01) of the hemisphere that underwent surgery. Improvement in contralateral limb motor performance correlated significantly with surgical declines in thalamic metabolism (p<0.01) and increases in lateral frontal metabolism (p<0.05). Principal components analysis disclosed a significant covariance pattern characterized by postoperative declines in ipsilateral lentiform and thalamic metabolism associated with bilateral increase in supplementary motor control metabolism. Subject scores for this pattern correlated significantly with improvements in both contralateral and ipsilateral limb performance (p<0.005). These results suggest that pallidotomy reduced the preoperative overaction of the inhibitory pallidothalamic projection. Clinical improvement may be associated with modulations in regional brain metabolism occurring remote from the lesion site
— id: 18385, year: 1996, vol: 39, page: 450, stat: Journal Article,

Deprenyl and levodopa and Parkinson's disease progression
Fowler JS; Fazzini E; Volkow ND
1996 Aug;40(2):267-268, Annals of neurology
— id: 18383, year: 1996, vol: 40, page: 267, stat: Journal Article,

Current trends in the pharmacologic and surgical treatment of Parkinson's disease
Galler RM; Hallas BH; Fazzini E
1996 Apr;96(4):228-232, Journal of the American Osteopathic Association
Recently, there has been a surge in the research regarding the pharmacologic and surgical treatment of Parkinson's disease. This article reviews the latest modes of medical and surgical therapy for Parkinson's disease. The latest drug therapy has consisted of levodopa, a combination of levodopa and carbidopa (Sinemet/Sinemet CR), and monoamine oxidase type B (MAO-B) inhibitors (selegiline hydrochloride). The surgical treatment modalities have been stereotaxic implantations of dopamine-producing tissues (such as adrenal medulla and fetal mesencephalon) into the caudate nucleus and ventral pallidotomy of patients with Parkinson's disease. The most recent work has been in the field of gene therapy. The implantation of cells genetically modified to express trophic factors and tyrosine hydroxylase for the synthesis of L-dopa from tyrosine has been proposed as a possible route for the treatment of Parkinson's disease. Although the etiology of the disease is still unknown, two recent theories are discussed
— id: 18384, year: 1996, vol: 96, page: 228, stat: Journal Article,

Cholinesterase inhibition in Parkinson's disease
Hutchinson M; Fazzini E
1996 Sep;61(3):324-325, Journal of neurology neurosurgery & psychiatry
— id: 18382, year: 1996, vol: 61, page: 324, stat: Journal Article,

Electrognathographics (EEG): A quantitative measure for diagnosis of Parkinson Disease (PD)
Silverman, SI; Weinreb, H; Fazzini, E
1996 FEB ;75(2):80-80, Journal of dental research
— id: 53059, year: 1996, vol: 75, page: 80, stat: Journal Article,

Central motor loop oscillations in parkinsonian resting tremor revealed by magnetoencephalography
Volkmann J; Joliot M; Mogilner A; Ioannides AA; Lado F; Fazzini E; Ribary U; Llinas R
1996 May;46(5):1359-1370, Neurology
A variety of clinical and experimental findings suggest that parkinsonian resting tremor results from the involuntary activation of a central mechanism normally used for the production of rapid voluntary alternating movements. However, such central motor loop oscillations have never been directly demonstrated in parkinsonian patients. Using magnetoencephalography, we recorded synchronized and tremor-related neuromagnetic activity over wide areas of the frontal and parietal cortex. The spatial and temporal organization of this activity was studied in seven patients suffering from early-stage idiopathic Parkinson's disease (PD). Single equivalent current dipole (ECD) analysis and fully three-dimensional distributed source solutions (magnetic field tomography, MFT) were used in this analysis. ECD and MFT solutions were superimposed on high-resolution MRI. The findings indicate that 3 to 6 Hz tremor in PD is accompanied by rhythmic subsequent electrical activation at the diencephalic level and in lateral premotor, somatomotor, and somatosensory cortex. Tremor-evoked magnetic activity can be attributed to source generators that were previously described for voluntary movements. The interference of such slow central motor loop oscillations with voluntary motor activity may therefore constitute a pathophysiologic link between tremor and bradykinesia in PD
— id: 7056, year: 1996, vol: 46, page: 1359, stat: Journal Article,

Anatomic and physiological considerations in pallidotomy for Parkinson's disease
Dogali M; Beric A; Sterio D; Eidelberg D; Fazzini E; Takikawa S; Samelson DR; Devinsky O; Kolodny EH
1995 ;64:9-12, Acta neurochirurgica. Supplementum
Our ongoing study of ventral pallidotomy for the control of Parkinson's disease in selected patients has provided the opportunity to explore the topographical and somatotopic organization of the human globus pallidus. Utilizing microelectrode techniques we have obtained recordings which were correlated with data from MPTP-parkinsonian primates. In addition, we performed pre- and post-operative FDG/PET scans in these patients. Our studies reveal similarities between the MPTP-parkinsonian primate model and human Parkinson's disease in terms of physiologic recordings and responses. However, we have encountered significant differences between dominant and non-dominant hemisphere representations, particularly for the hand, in the human. In addition, our PET studies confirmed, as in previous parkinsonian primate models, glucose hypermetabolism in the lenticular area of Parkinson's disease patients. This hypermetabolism is dramatically altered by creation of a lesion in the globus pallidus medialis. This is demonstrated by follow-up PET scans which reveal not only a decrease in metabolism of the operated lenticular region, but also in the frontal cortical projections. These combined observations of the cellular activity in the globus pallidus and the observed changes in PET metabolism support the selection of the pallidum for lesioning and control of Parkinson's disease, and offer insight into the underlying physiology of this disorder. The above physiological and PET data will be clinically correlated with our ongoing series of 35+ patients
— id: 12822, year: 1995, vol: 64, page: 9, stat: Journal Article,

Stereotactic ventral pallidotomy for Parkinson's disease
Dogali M; Fazzini E; Kolodny E; Eidelberg D; Sterio D; Devinsky O; Beric A
1995 Apr;45(4):753-761, Neurology
Eighteen patients with medically intractable Parkinson's disease that was characterized by bradykinesia, rigidity, and marked 'on-off' fluctuations underwent stereotactic ventral pallidotomy under local anesthesia. Targeting was aided by anatomic coordinates derived from the MRI, intraoperative cell recordings, and electrical stimulation prior to lesioning. A nonsurgically treated group of seven similarly affected individuals was also followed. Assessment of motor function was made at baseline and at 3-month intervals for 1 year. Following the lesioning, patients improved in bradykinesia, rigidity, resting tremor, and balance with resolution of medication-induced contralateral dyskinesia. When compared with preoperative baseline, all quantifiable test scores after surgery improved significantly with the patients off medications for 12 hours: UPDRS by 65%, and CAPIT subtest scores on the contralateral limb by 38.2% and the ipsilateral limb by 24.2%. Walk scores improved by 45%. Medication requirements were unchanged, but the patients who had had surgery were able to tolerate larger doses because of reduced dyskinesia. Ventral pallidotomy produces statistically significant reduction in parkinsonism and contralateral 'on' dyskinesia without morbidity or mortality and with a short hospitalization in Parkinson's disease patients for whom medical therapy has failed
— id: 12789, year: 1995, vol: 45, page: 753, stat: Journal Article,

The Effects of unilateral ventral posterior medial pallidotomy in patients with
Fazzini E; Dogali M; Beric A; Eidelberg D; Sterio D; Gianutsos J; Newman B; Kluger A
Therapy of Parkinson's disease New York: Dekker, 1995,
— id: 2605, year: 1995, vol: , page: 353, stat: Chapter,

Neuropsychiatric and neuropsychological findings in conduct disorder and attention-deficit hyperactivity disorder
Aronowitz, B; Liebowitz, M; Hollander, E; Fazzini, E; Durlach-Misteli, C; Frenkel, M; Mosovich, S; Garfinkel, R; Saoud, J; DelBene, D
1994 Summer;6(3):245-249, Journal of neuropsychiatry & clinical neurosciences
Neuropsychiatric and neuropsychological evaluations were performed in a pilot study of adolescents with DSM-III-R disruptive behavior disorders, including conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). The following comparisons were made: 1) CD comorbid with ADHD vs. CD only; 2) all subjects with ADHD vs. all non-ADHD; and 3) all subjects with CD vs. all non-CD. The CD + ADHD group had increased left-sided soft signs compared with the CD group. CD + ADHD subjects significantly underperformed CD subjects on several executive functioning measures, with no differences on Verbal IQ subtests. Results are discrepant with previous findings of deficient verbal functioning in delinquent populations. However, findings may not be generalizable because of sampling limitations
— id: 130416, year: 1994, vol: 6, page: 245, stat: Journal Article,

Pharmacokinetics and in vivo specificity of [11C]dl-threo-methylphenidate for the presynaptic dopaminergic neuron
Ding YS; Fowler JS; Volkow ND; Gatley SJ; Logan J; Dewey SL; Alexoff D; Fazzini E; Wolf AP
1994 Oct;18(2):152-160, Synapse
dl-threo-Methylphenidate (Ritalin) was labeled with carbon-11 (t1/2:20.4 minutes) in order to measure its pharmacokinetics, to evaluate it as a radiotracer for the presynaptic dopaminergic neuron, and to examine its sensitivity to the loss of dopaminergic neurons. Positron emission tomographic (PET) studies were carried out in the baboon to determine specificity for the presynaptic dopaminergic neuron and in humans to assess sensitivity to neuronal loss. Studies with [11C]dl-threo-methylphenidate ([11C]MP) in baboon demonstrated high regional uptake in the striatum. Peak uptake (0.04%/cc) occurred at 5-15 minutes post-injection. The half-time for clearance from peak uptake for [11C]MP was 60 minutes and the ratio between the radioactivity in the striatum and that in the cerebellum (ST/CB) ranged from 2.2 to 2.6 at 40 minutes. Repeated measures in the same baboon showed < or = 8% variability in the ST/CB ratio. Pretreatment with unlabeled methylphenidate (0.5 mg/kg) or GBR12909 (1.5 mg/kg) 30 minutes prior to [11C]MP injection markedly reduced the striatal but not the cerebellar uptake of [11C]MP, demonstrating the saturable and specific binding of [11C]MP to a site on the dopamine transporter in the brain. In both cases, the ratio of striatum to cerebellum (ST/CB) after pretreatment was reduced by about 43%. The ratios of distribution volumes at the steady-state for the striatum to cerebellum (ST/CB) for these two separate studies in the same baboon were reduced by 37 and 38%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 63163, year: 1994, vol: 18, page: 152, stat: Journal Article,

Anatomic and physiological considerations in pallidotomy for Parkinson's disease
Dogali M; Beric A; Sterio D; Eidelberg D; Fazzini E; Takikawa S; Samelson DR; Devinsky O; Kolodny EH
1994 ;62(1-4):53-60, Stereotactic & functional neurosurgery
Our ongoing study of central pallidotomy for the control of Parkison's disease in selected patients has provided the opportunity to explore the topographical and somatotopic organization of the human globus pallidus. Utilizing microelectrode techniques we have obtained recordings which were correlated with data from MPTP-parkinsonian primates. In addition, we performed pre- and postoperative FDG/PET scans in these patients. Our studies reveal similarities between the MPTP-parkisonian primate model and human Parkinson's disease in terms of physiological recordings and responses. However, we have encountered significant differences between dominant and nondominant hemisphere representations, particularly for the hand, in the human. In addition, our PET studies confirmed, as in previous parkinsonian primate models, glucose hypermetabolism in the lenticular area of Parkinson's disease patients. This hypermetabolism is dramatically altered by creation of a lesion in the globus pallidus medialis. This is demonstrated by follow-up PET scans which reveal not only a decrease in metabolism of the operated lenticular region, but also in the frontal cortical projections. These combined observations of the cellular activity in globus pallidus and the observed changes in PET metabolism support the selection of the pallidum for lesioning and control of Parkinson's disease, and offer insight into the underlying physiology of this disorder. The above physiological and PET data will be clinically correlated with our ongoing series of 35+ patients
— id: 13043, year: 1994, vol: 62, page: 53, stat: Journal Article,

Slow recovery of human brain MAO B after L-deprenyl (Selegeline) withdrawal
Fowler, J S; Volkow, N D; Logan, J; Wang, G J; MacGregor, R R; Schyler, D; Wolf, A P; Pappas, N; Alexoff, D; Shea, C; Fazzini, E
1994 Oct;18(2):86-93, Synapse
L-Deprenyl (Selegeline) is an enzyme-activated irreversible inhibitor of monoamine oxidase B (MAO B; EC 1.4.3.4). It is used to treat Parkinson's disease at a dose of 5 mg twice a day. Since enzyme inhibition is irreversible, the recovery of functional enzyme activity after withdrawal from L-deprenyl requires the synthesis of new enzyme. We have measured a 40 day half-time for brain MAO B synthesis in Parkinson's disease and in normal subjects after withdrawal from L-deprenyl. This is the first measurement of the synthesis rate of a specific protein in the living human brain. L-Deprenyl is currently used by 50,000 patients with Parkinson's disease in the United States and its use is expected to increase with reports that it may be beneficial in Alzheimer's disease. The slow turnover of brain MAO B suggests that the current clinical dose of L-deprenyl may be excessive and that the clinical efficacy of reduced dosing should be evaluated. Such an evaluation may have mechanistic importance as well as an impact on reducing the side effects and the costs arising from excessive drug use
— id: 130419, year: 1994, vol: 18, page: 86, stat: Journal Article,

Neurophysiological properties of pallidal neurons in Parkinson's disease
Sterio D; Beric A; Dogali M; Fazzini E; Alfaro G; Devinsky O
1994 May;35(5):586-591, Annals of neurology
Neuronal properties of the human globus pallidus (GP) are not known. Since GP is the major output of the basal ganglia, it may be involved in the pathophysiology of Parkinson's disease. We studied 12 patients with medically resistant Parkinson's disease by using single cell recording of the GP during stereotaxic pallidotomy to define neuronal firing rate and its modulation during active and passive movements. Different frequency and pattern of single cell activity was found in globus pallidus externus compared with globus pallidus internus. Discharge rates of 19% of GP cells were modulated by passive contralateral movements. Pallidal units were most often related solely to single joint movement. Different patterns of activity in relation to the two different movements of the same joint were often observed. We identified somatotopically arranged cell clusters that alter discharge rate with related movements. These findings suggest at least a partial somatotopic organization of the human GP and similarity with experimental results in both healthy and MPTP monkeys, providing a rationale for surgical or pharmacological targeting of GP for treating Parkinson's disease
— id: 12968, year: 1994, vol: 35, page: 586, stat: Journal Article,

Dominantly inherited, early-onset parkinsonism: neuropathology of a new form
Dwork AJ; Balmaceda C; Fazzini EA; MacCollin M; Cote L; Fahn S
1993 Jan;43(1):69-74, Neurology
We report postmortem findings in a 46-year-old man with dominantly inherited parkinsonism whose symptoms started at age 28. At least 13 other family members in three generations have been affected, some from early childhood. Dystonia is a prominent feature in several of the youngest patients, but was not present in this patient. After several years of successful treatment with medication, he developed severe on-off fluctuations and dyskinesias. At age 45, the patient underwent stereotaxic implantation of autologous adrenal medullary tissue into the left corpus striatum and lateral ventricle. He improved considerably over the following 6 months, but then developed glioblastoma multiforme and died 1 year after transplantation. There was severe neuronal loss in the pars compacta and pars reticulata of the substantia nigra, with prominent gliosis in the pars reticulata. The nigral neurons remaining in the pars compacta were poorly pigmented. Neither Lewy bodies nor neurofibrillary tangles were present, and we identified no other degenerative neuropathologic changes. This combination of pathologic and clinical features differs from any previously reported case
— id: 18375, year: 1993, vol: 43, page: 69, stat: Journal Article,

Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease
Eidelberg D; Takikawa S; Moeller JR; Dhawan V; Redington K; Chaly T; Robeson W; Dahl JR; Margouleff D; Fazzini E; et al.
1993 May;33(5):518-527, Annals of neurology
Regional and global metabolic rates for glucose were estimated using 18F-fluorodeoxyglucose and positron emission tomography in 10 patients with a clinical likelihood of striatonigral degeneration (2 men and 8 women; mean age, 61.8 +/- 6.9 years; mean disease duration, 4.7 +/- 2.2 years; mean Hoehn and Yahr score, 3.5 +/- 0.8). Measures of brain glucose metabolism in these patients were compared with those for 10 age-matched normal volunteers, 10 disease severity-matched patients with Parkinson's disease (PD), and 10 disease duration-matched patients with PD. Normalized glucose metabolism was significantly reduced in the caudate (p < 0.03) and putamen (p < 0.003) as compared with that in normal and PD control subjects, and discriminated patients with striatonigral degeneration from control subjects (p < 0.002). Putamenal hypometabolism in patients with striatonigral degeneration correlated significantly with quantitative ratings of motor disability (p < 0.02). These results suggest that quantitative 18F-fluorodeoxyglucose positron emission tomography techniques may be useful in supporting a diagnosis of striatonigral degeneration in life, and in objectively assessing disease severity and potential therapeutic interventions
— id: 18387, year: 1993, vol: 33, page: 518, stat: Journal Article,

Multiple System Atrophy Associated with Progressive Autonomic Failure; The Shy-Drager Syndrome: A New Classification Scheme
Fazzini E
Parkinsonian syndromes New York : Marcel Dekker, 1993,
— id: 5640, year: 1993, vol: , page: ?, stat: Chapter,

Stereotaxic Implantation of Autologous Adrenal Medulla into Caudate Nucleus in Four Patients with Parkinsonism: One-year Follow-up
Fazzini E
1992 ;?:6-7, Parkinson/Alzheimer digest
— id: 130415, year: 1992, vol: ?, page: 6, stat: Journal Article,

Transplantation in the treatment of paralysis agitans (Parkinson's disease)
Fazzini E
1992 Oct;92(10):1255-1260, Journal of the American Osteopathic Association
Over the past 3 years, there has been great interest in transplantation therapy in the treatment of Parkinson's disease. Following the impressive results reported by Madrazo in the spring of 1987, more than 350 cases of adrenal medullary implantation have been performed worldwide. There has been a significant reduction in 'off' time and an increase in 'on' time without chorea in 40% of patients having this procedure. The duration of effect is 1 year in half of these cases, with the other half (20% of all patients) still demonstrating significant improvement 3 years after the procedure. The mechanism of the bilateral beneficial improvement is unknown. The survival of adrenal medullary tissue has not been demonstrated at autopsy. It is thought that the mechanism of improvement involves either regenerative sprouting of the remaining dopamine producing neurons as a consequence of the release of neurotrophic factors or an interruption of the striatal pallidal output inhibitory influence of the basal ganglia on the thalamus (or both). Fetal mesencephalic implantation has also been attempted in more than 100 cases worldwide. The improvements when seen are not any more dramatic than those following the best results of adrenal medullary implantation. Graft survival has not been proved; it remains a possibility that interruption of the putamino-subthalamic pallidal pathway or a trophic influence of the tissue provides an alleviation in parkinsonism. The ethical controversy, need for long-term immunosuppression, and difficulty with obtaining tissue of the appropriate age and delivering the appropriate quantity to the putamen have made this technique less than adequate.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 18376, year: 1992, vol: 92, page: 1255, stat: Journal Article,

Cerebrospinal fluid antibodies to coronavirus in patients with Parkinson's disease
Fazzini E; Fleming J; Fahn S
1992 ;7(2):153-158, Movement disorders
The etiology of Parkinson's disease remains unknown, and a search for environmental agents continues. In 1985, Fishman induced infection of the basal ganglia by a coronavirus in mice. Although coronavirus is recognized primarily as a respiratory pathogen in humans, its affinity for the basal ganglia led us to investigate its possible role in human Parkinson's disease. The cerebrospinal fluid of normal controls (CTL) (n = 18), and patients with Parkinson's disease (PD (n = 20) and other neurological disease (OND) (n = 29) was analyzed in a blinded manner by enzyme-linked immunosorbent assay [measurements in optical density (OD) units] for antibody response to four coronavirus antigens: mouse hepatitis virus JHM (J) and A59 (A), and human coronavirus 229E (E) and OC43 (O). When compared with CTL, PD patients had an elevated (p less than 0.05) mean OD response to J (0.0856 vs. 0.0207) and A (0.1722 vs. 0.0636). Response (p greater than 0.05) to O (0.0839 vs. 0.0071) was greater than that to E (0.1261 vs. 0.0743). When compared to OND, PD patients had an elevated mean OD response to J (0.0856 vs. 0.0267, p less than 0.05). Responses (p greater than 0.05) to A (0.1722 vs. 0.0929) and O (0.0839 vs. 0.0446) were greater than that to E (0.1261 vs. 0.0946). These results suggest that there may be an association between coronavirus and PD
— id: 18377, year: 1992, vol: 7, page: 153, stat: Journal Article,

Magnetic recording of resting tremor related brain activity in Parkinson's disease
Volkmann, J.; Lado, F.; Ioannides, A.; Mogilner, A.; Joliot, M.; Ribary, U.; Fazzini, E.; Llinas, R. R.
1992 ;18(1-2):936-936, Abstracts (Society for Neuroscience)
— id: 92367, year: 1992, vol: 18, page: 936, stat: Journal Article,

Stereotaxic implantation of autologous adrenal medulla into caudate nucleus in four patients with parkinsonism. One-year follow-up
Fazzini E; Dwork AJ; Blum C; Burke R; Cote L; Goodman RR; Jacobs TP; Naini AB; Pezzoli G; Pullman S; et al.
1991 Aug;48(8):813-820, Archives of neurology
Four patients with levodopa-responsive parkinsonism (aged 26, 35, 45, and 49 years) received autologous adrenal medullary implants into or near the left caudate nucleus by stereotaxic implantation after flank adrenalectomy. All patients had an immediate response to implantation lasting several days, during which parkinsonian signs and symptoms decreased. This period was followed by a gradual reappearance of symptoms in all but one patient. This patient had had a dramatic increase in 'on' time without dyskinesias and a decrease in the severity and duration of 'off' time. He died of multifocal glioblastoma 1 year after transplantation. Autopsy revealed no surviving adrenal cells. In one case, the stereotaxic implantation missed the basal ganglia, resulting in the placement of the adrenal medullary tissue into the medial thalamus and near the third ventricle; the patient did not improve. In the other two cases, a modest but definite increase in 'on' time without dyskinesia and a reduction in the severity and duration of 'off' time has been observed. The role of autologous adrenal medullary transplantation in patients with parkinsonism remains to be determined. Patients with a family history of cerebral malignancy may be at increased risk for the development of transplant-induced malignancy
— id: 18378, year: 1991, vol: 48, page: 813, stat: Journal Article,

United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: presurgical, and 1- and 2-year follow-up
Goetz, C G; Stebbins, G T 3rd; Klawans, H L; Koller, W C; Grossman, R G; Bakay, R A; Penn, R D; Fazzini, E
1991 Nov;41(11):1719-1722, Neurology
Thirteen centers participated in a multicenter database with systematic evaluation of US and Canadian patients who had adrenal medullary transplantation for Parkinson's disease. This voluntary registry collected demographic, safety, and efficacy data using the same scoring measures over a 2-year follow-up period. Baseline data on 61 patients and 2-year follow-up data on 56 patients were compared. Eighteen percent died during the study period, and one-half of these deaths were related or questionably related to the surgery. Of the remaining 45 patients with data, global improvement, defined as an improved summed score of the 'on' and 'off' motor and activities of daily living functions from the Unified Parkinson's Disease Rating Scale, occurred in 32% of the patients at 2 years after surgery. At follow-up, significant group improvement persisted in the amount of daily 'on' time and the quality of 'off' function, but other measures were no better than baseline. When the global improvement calculation was based on the total sample and included deaths and patients lost to follow-up as 'not improved,' only 19% were improved 2 years after surgery. Twenty-two percent of survivors had persistent psychiatric morbidity not present prior to surgery. These data document a modest group improvement in 'off' function after neurotransplantation, but a serious level of mortality and morbidity
— id: 130414, year: 1991, vol: 41, page: 1719, stat: Journal Article,

Experience with selegiline and levodopa in advanced Parkinson's disease
Lieberman A; Fazzini E
1991 ;136(8):66-69, Acta neurologica Scandinavica. Supplementum
We compared the results of treatment with selegiline (deprenyl, Eldepryl) in 17 patients with advanced Stage 4 Parkinson Disease (PD) who were on levodopa (as Sinemet) with 65 Stage 2 or 3 patients with early PD who were also on levodopa. The first group consisted of 17 patients with advanced Stage 4 PD without response fluctuations ('wearing off' or 'on off' phenomena). Their mean age was 72.1 +/- 7.5 years, their mean duration of PD was 7.4 +/- 3.2 years. The second group consisted of 65 patients with Stage 2 or 3 PD who had recently been started on levodopa. Their mean age was 63 +/- 12.1 years, their mean duration of PD was 7.4 +/- 3.2 years. The mean dose of selegiline was 10.0 +/- 1.8 mg per day (range 5-20 mg). The mean duration of treatment was 1.5 +/- 0.8 years. During the four years of observation 55.3 +/- 8.0% of the Stage 2 or 3 patients improved while only 14.3 +/- 13.5% of the Stage 4 patients improved. This difference was significant (p less than 0.05). During this time 22.0 +/- 6.7% of the Stage 2 or 3 patients worsened and 60.7 +/- of the Stage 4 patients worsened. This degree of worsening was significant (p less than 0.05). Adverse effects were minor and reversible. Our observations suggest that selegiline is more effective (higher percent of patients improving, lower percent of patients worsening) when it is added earlier with patients on levodopa than when it is added later
— id: 18379, year: 1991, vol: 136, page: 66, stat: Journal Article,

GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice
Fazzini, E; Durso, R; Davoudi, H; Szabo, G K; Albert, M L
1990 Oct;99(1):59-68, Journal of the neurological sciences
We investigated the effect of GM1 gangliosides on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Five groups of mice (saline, GM1 (30 mg/kg), MPTP, MPTP + GM1 (15 mg/kg), MPTP + GM1 (30 mg/kg] were compared. GM1 was given daily via intraperitoneal injection before and during 13 daily doses of MPTP (30 mg/kg). Mice were tested for locomotion (1) within 2 h of an MPTP dose (to measure reduced motor activity), and (2) within 24 h of an MPTP dose (after animals had recovered and exhibited hyperactivity). We found that mice given GM1 gangliosides exhibited significantly less MPTP-induced behavior. This effect was most evident with the 15 mg/kg GM1 dose. GM1 also appeared to attenuate MPTP-induced neurochemical changes. GM1 effects indicating enhancement of DA turnover and preservation of DA, DOPAC and HVA concentrations in the striatum were found after the 8th MPTP dose. These latter neurochemical changes, however, were transient and not present after the 13th MPTP dose. Our data would suggest that gangliosides may reduce acute MPTP-induced neurotoxicity in mice either through an increase in DA neuron survival and/or the augmentation of striatal DA activity
— id: 130412, year: 1990, vol: 99, page: 59, stat: Journal Article,

The effect of gangliosides on a neurotoxin (MPTP) induced model of Parkinson's disease in mice
Fazzini, Enrico Anthony
[S.l. : s.n.], 1989,
Thesis (Ph. D.)--Boston University, 1989
— id: 2243, year: 1989, vol: , page: , stat: ,

Recovery of Function in Aphasia
Fazzini E; Bachman D; Albert M
1986 ;2(1-2):15-46, Journal of neurolinguistics
A neurobiological model for recovery of function in aphasia is proposed. features and contributing factors are systematically reviewed: aphasia type, time course, etiology, sex, age, handedness, cerebral asymmetries, depression, epilepsy, perseveration. The role of the right hemisphere is investigated: language recovery and the right hemisphere, crossed aphasia, transfer of language dominance, right hemisphere language. Mechanisms of recovery are considered: localizationist theories (redundancy, vicarious function, multiple control, substitution) and diaschisis (anatomy and physiology, experimental evidence). Evidence for a new theory of recovery of function in aphasia is then provided: sprouting, supersensitivity., chemical anatomy (noradrenergic and serotonergic systems, mesocortical dopaminergic system), release of right hemisphere potential, latent synapses (pharmacological deblocking, environmental deblocking). A more active intervention into recovery from aphasia is suggested
— id: 130420, year: 1986, vol: 2, page: 15, stat: Journal Article,

3H-N-n-propylnorapomorphine: a novel agonist ligand for central dopamine receptors
Creese, I; Padgett, L; Fazzini, E; Lopez, F
1979 Jul 1;56(4):411-412, European journal of pharmacology
— id: 130413, year: 1979, vol: 56, page: 411, stat: Journal Article,