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P Sandroni

Publications and source records attributed to P Sandroni.

At least 19 recordsLinked to original sources

Involvement of vagal autonomic nuclei in multiple system atrophy and Lewy body disease.

BACKGROUND: Multiple system atrophy (MSA) and Lewy body disorders (LBDs) are associated with impaired control of gastrointestinal and cardiac functions. The dorsal vagal nucleus (DMV) innervates enteric neurons, whereas the ventrolateral nucleus ambiguus (NAmb) innervates the heart. The relationship between DMV and NAmb involvement and the gastrointestinal or cardiovagal manifestations in MSA and LBD is unclear. METHODS: The authors counted the cholinergic neurons in the DMV and NAmb in 15 cases of neuropathologically confirmed MSA, 14 of LBD (4 brainstem, 3 limbic, and 7 neocortical), and 12 control cases. All MSA and 8 of the 14 LBD cases had gastrointestinal symptoms; 8 of 12 MSA and 1 of 4 LBD cases had laboratory evidence of cardiovagal failure; 5 of the MSA and no LBD cases had laryngeal stridor. RESULTS: There was loss of cholinergic DMV neurons in all MSA and LBD cases. The degree of DMV cell loss was similar in LBD patient with or without gastrointestinal symptoms. In MSA but not in LBD cases, there was neuronal loss in the ventrolateral NAmb, with lower counts in patients with cardiovagal failure. CONCLUSIONS: There is comparable involvement of the dorsal vagal nucleus (DMV) in multiple system atrophy (MSA) and different stages of Lewy body disorders (LBDs). The relationship of DMV involvement and gastrointestinal symptoms is uncertain. Loss of neurons in the ventrolateral nucleus ambiguus may explain the more consistent cardiovagal failure in MSA than in LBD.

Aged↗

The North American Multiple System Atrophy Study Group.

The North American Multiple System Atrophy Study Group involves investigators in 12 US medical centers funded by a grant from the National Institutes of Health. The objectives are to examine the environmental and genetic risk factors for MSA; elucidate pathogenic mechanisms underlying the disorder; and refine evaluations used for assessment. During its first year, the group enrolled 87 patients, implemented four cores, and initiated four scientific projects. Most patients among the 87 had parkinsonian features, which frequently began asymmetrically and remained asymmetrical; one-third responded to levodopa and many developed levodopa complications; almost two-thirds of the patients had cerebellar dysfunction, of these 90% had ataxia; urinary incontinence occurred commonly, and sleep disorders affected most. The investigators studied the effects of oxidative and nitrative stress upon the formation of alpha-synuclein inclusions; generated transgenic models of alpha-synuclein accumulation that recapitulate several behavioral and neuropathological features of MSA; and compared the severity of the autonomic features of MSA, Parkinson's disease and dementia with Lewy bodies.

Animals↗

Autonomic dysfunction in dementia with Lewy bodies.

OBJECTIVE: To assess autonomic function in patients with dementia with Lewy bodies (DLB). METHODS: The authors compared data from 20 DLB patients evaluated from 1995 to 2000 to 20 age-matched multiple system atrophy (MSA) and Parkinson disease (PD) patients evaluated from 1999 to 2002. Analysis of variance, Fisher exact test, and Student t-test were applied to compare disease characteristics, autonomic symptoms, and function tests on the Composite Autonomic Scoring Scale (CASS) and Thermoregulatory Sweat Test (TST). RESULTS: In DLB, mean age at onset of autonomic symptoms was 70.3 +/- 8.9 years. Orthostatic symptoms were common and orthostatic hypotension occurred in 10/20 DLB, 17/20 MSA, and 1/20 PD patients (p = 0.023, 0.003). CASS-sudomotor for DLB, MSA, and PD were 1.6 +/- 1.2, 2.5 +/- 0.7, and 0.9 +/- 0.8 (p < 0.00001). CASS-cardiovagal were 1.4 +/- 0.9, 2.1 +/- 0.8, and 0.7 +/- 0.6 (p < 0.00001). CASS-adrenergic function were 2.4 +/- 1.2, 3.5 +/- 0.9, and 0.5 +/- 0.6 (p < 0.00001). Total CASS were 5.2 +/- 2.0, 8.1 +/- 1.3, and 2.2 +/- 1.2 (p < 0.00001). The most common pattern of TST in DLB was distal anhidrosis. Mean duration of follow-up was 3.0 +/- 1.8 years. Six patients needed medication to maintain blood pressure and five had good response. CONCLUSIONS: Autonomic dysfunction is frequent in dementia with Lewy bodies and the severity is intermediate between that of multiple system atrophy and Parkinson disease.

Acetylcholine↗

Aphrodisiacs past and present: a historical review.

The drug Viagra (sildenafil) has drawn public attention to aphrodisiacs. The search for such substances dates back millennia. Aphrodisiacs can be classified by their mode of action into 3 types: those that increase (1) libido, (2) potency, or (3) sexual pleasure. Various substances of animal and plant origin have been used in folk medicines of different cultures; some have been identified pharmacologically, allowing for understanding of their mechanisms of action. For increasing libido, ambrein, a major constituent of Ambra grisea, is used in Arab countries. This tricyclic triterpene alcohol increases the concentration of several anterior pituitary hormones and serum testosterone. Bufo toad skin and glands contain bufotenine (and other bufadienolides), a putative hallucinogenic congener of serotonin. It is the active ingredient in West Indian "love stone" and the Chinese medication chan su. The aphrodisiac properties are likely of central origin, as are the other effects of the drug. For increasing potency, Panax ginseng used in traditional Chinese medicine, works as an antioxidant by enhancing nitric oxide synthesis in the endothelium of many organs, including the corpora cavernosa; ginsenosides also enhance acetylcholine-induced and transmural nerve stimulation-activated relaxation associated with increased tissue cyclic guanosine monophosphate, hence the aphrodisiac properties. For increasing sexual pleasure, cantharidin ("Spanish fly") is a chemical with vesicant properties derived from blister beetles, which have been used for millennia as a sexual stimulant. Its mode of action is by inhibition of phosphodiesterase and protein phosphatase activity and stimulation of beta-receptors, inducing vascular congestion and inflammation. Morbidity from its abuse is significant. The ingestion of live beetles (Palembus dermestoides) in Southeast Asia and triatomids in Mexico may have a basis similar to cantharidin. It is of paramount importance for the physician to be aware of the options available to help his or her patients, and to advise them in using the correct drugs while avoiding "miracle" remedies that could be potentially harmful.

Aphrodisiacs↗

Involvement of GABA(A) receptors in myoclonus.

Alterations in multiple neurochemical systems have been reported in animal and human studies of posthypoxic myoclonus. It is impossible, however, to establish causative relationships between the observed changes and the myoclonic movements from these studies. Therefore, to establish causative links between neurochemical changes and myoclonus, ligands that target neurotransmitter systems that are altered in posthypoxic myoclonus were microinjected into the lateral ventricles of normal rats to identify the changes that can produce myoclonus. Of the ligands that were tested, only the GABA(A) antagonists produced myoclonus after intracerebroventricular administration, suggesting the importance of disinhibition of GABAergic systems in myoclonus. To further examine the role of GABA in myoclonus, GABAergic antagonists were microinjected into the nucleus reticularis of the thalamus (NRT), an area of the brain in which extensive pathologic changes are seen in posthypoxic animals. GABA(A), but not GABA(B), antagonists produced myoclonus after microinjection into the NRT. Earlier investigators have further reported the ability of GABA(A) antagonists to produce myoclonus after microinjection into the caudate. The data therefore suggest that disruption of activity at GABA(A) receptors at any one of a number of levels in the neural axis can produce myoclonus.

Animals↗

Mechanisms of blood pressure alterations in response to the Valsalva maneuver in postural tachycardia syndrome.

The postural tachycardia syndrome (POTS) is characterized clinically by orthostatic lightheadedness and tachycardia. When these patients perform a Valsalva maneuver, there is an excessive blood pressure increment after cessation of the maneuver (phase IV) that is sometimes associated with headaches. It is not known whether excessive phase IV is due to excessive peripheral vascular tone (an alpha-adrenergic mechanism) or is a manifestation of increased beta-adrenergic tone (hyperadrenergic state). The authors undertook a pharmacologic study evaluating the effect of intravenous phentolamine (alpha-adrenergic antagonist) and propranolol (beta-adrenergic antagonist) on the different phases of the Valsalva maneuver in a group of patients with POTS and age-matched normal control subjects. Patients with POTS had mean phases, when compared with controls, that were characterized by more negative II_E (p = 0.07), smaller II_L (p = 0.04), and significantly larger phase IV (p = 0.001). The effect of phentolamine was qualitatively and quantitatively different in POTS when compared with controls. Ten mg phentolamine in controls resulted in a significant accentuation of phase II_E (p = 0.001), attenuation of phase II_L (p = 0.002), and increase of phase IV (57.6 vs 30.7 mm Hg; p = 0.025). These changes resembled those of patients with POTS at baseline. In patients with POTS, the phase II abnormalities, already present, were further accentuated (p <0.001), and phase IV became smaller (50.6 vs 73.8 mm Hg; p = 0.09). Propranolol had no significant effect on phases II_E and II_L, but significantly reduced phase IV in both controls (p <0.05) and in patients with POTS (p <0.001) and improved the headache symptoms, when present, during and after phase IV. The authors conclude that phase IV is mainly under beta-adrenergic regulation and that the exaggerated phase IV in POTS is a result of a hyperadrenergic state.

Adrenergic alpha-Antagonists↗

Postural tachycardia syndrome: clinical features and follow-up study.

OBJECTIVE: To define the clinical features and outcome of postural tachycardia syndrome (POTS). MATERIALS AND METHODS: In this cross-sectional study of the autonomic symptom profile, inclusion criteria were orthostatic heart rate increment of 30 beats/min or greater, orthostatic symptoms, completion of a standardized autonomic test battery, and follow-up of 18 months or longer. We used 2 instruments. The first part was a structured and validated autonomic symptom profile (108 patients). The second part was a structured questionnaire focused on autonomic status on prospective follow-up (40 patients) (mean +/- SD follow-up, 67+/-52 months). RESULTS: Most patients had frequent, persistent, and at least moderately severe symptoms for less than 5 years. The following orthostatic symptoms occurred in more than 75% of subjects: light-headedness or dizziness, lower extremity or diffuse weakness, disequilibrium, tachycardia, and shakiness. Nonorthostatic symptoms included dry eyes or mouth, gastrointestinal complaints of bloating, early satiety, nausea, pain, and alternating diarrhea and constipation. Half of the patients reported an antecedent illness presumed to be of viral origin. On follow-up, 80 % of patients were improved, 60% were functionally normal, and 90% were able to return to work. Patients who had an antecedent event appeared to do better than those with spontaneous POTS. Salt supplementation and beta-blockers were the most efficacious therapies. CONCLUSION: In the majority of patients, POTS is self-resolving, especially in those with a triggering event.

Adult↗

Complex regional pain syndrome I (CRPS I): prospective study and laboratory evaluation.

OBJECTIVE: To relate clinical features to autonomic laboratory indices used in the diagnosis of Complex Regional Pain Syndrome type I (CRPS I) (reflex sympathetic dystrophy) to generate improved diagnostic criteria. DESCRIPTION: CRPS I is a chronic pain syndrome, characterized by diffuse limb pain with allodynia and prominent vasomotor and sudomotor dysfunction. METHODS: We conducted a prospective study on 102 patients referred for possible CRPS I. These patients completed a structured questionnaire and underwent neurologic examination, with special attention to the evaluation of clinical features of vasomotor, sudomotor, motor, and sensory, including pain, dysfunction. All patients were tested using a standard autonomic protocol that compared side-to-side skin temperature, resting sweat output, and quantitative sudomotor axon reflex test (QSART) measurements. Composite autonomic clinical (CRPS-Sx) and laboratory (CRPS-LAB) scores were defined. The clinical (subjective and objective) and the laboratory data were analyzed using Pearson's correlation analysis and Bonferroni's probability value to assess concordance and their value in correctly diagnosing CRPS I. RESULTS: All cases occurred after limb injury. One-third of cases did not fulfill our criteria of CRPS I. Highly significant correlations (p<.001) were found among certain clusters of symptoms and signs that shared unifying pathophysiologies. CRPS-Sx correlated with CRPS-LAB (p = .035). The indices that correlated most reliably with clinical data and with each other were RSO, QSART, and skin temperature reductions. CONCLUSION: Clinical and autonomic laboratory probability scores correlate in an internally consistent manner. Both CRPS-Sx and CRPS-LAB are sensitive and reliable tools to formulate a correct diagnosis of CRPS I and can be combined to provide an improved set of diagnostic criteria for CRPS I.

Adult↗

Certain cardiovascular indices predict syncope in the postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) represent a patient population with orthostatic intolerance; some are prone to syncope, others are not. The underlying neurocardiovascular mechanisms are not completely understood. The current study was undertaken to assess if certain cardiovascular indices are predictive of syncope in POTS. We compared the response to tilt-up and the Valsalva maneuver in four groups: POTS patients who fainted (POTS-f; n = 11;31 +/- 11 years): POTS patients who did not faint (POTS-nf; n = 9; 29 +/- 9 years); normal controls (NLS; n = 13; 39 +/- 11 years); patients with generalized autonomic failure with orthostatic hypotension and syncope (n = 10; 59 +/- 14 years). Beat-to-beat heart rate (HR), systolic arterial pressure, diastolic arterial pressure (DAP) and pulse pressure (PP) were monitored using Finapres. Cardiac output, stroke volume (SV) and end-diastolic volume (EDV), and calculated total peripheral resistance (TPR) were recorded using thoracic electrical bioimpedance. An autonomic reflex screen which quantitates the distribution and severity of autonomic failure was also done. With the patient supine, all POTS patients (POTS-nf; POTS-f) had increased HR (p < 0.001) and reduced SV/EDV (p < 0.001) when compared with NLS. On tilt-up, POTS-f patients were significantly different from both NLS and POTS-nf patients; the most consistent alteration was a fall instead of an increase in TPR; other changes were a greater reduction in PP, a reduction (instead of an increment) in DAP, and a different pattern of changes during the Valsalva maneuver (excessive early phase II, attenuated or absent late phase II). Our results suggest alpha-adrenergic impairment with increased pooling or hypovolemia in POTS-f patients. We conclude that it is possible to identify the mechanism of syncope in POTS patients, and perhaps other patients with orthostatic intolerance and an excessive liability to syncope.

Adult↗

Diphenhydramine is effective in the treatment of idiopathic dystonia.

OBJECTIVE: To assess the effectiveness of diphenhydramine hydrochloride (Benadryl) in the treatment of patients with idiopathic truncal dystonia. DESIGN: Before-and-after trial. SETTING: University referral center. PATIENTS: Five consecutive patients with idiopathic truncal dystonia who were poorly treated with conventional pharmacotherapies. No patients were withdrawn from the trial for adverse side effects. INTERVENTIONS: Treatments with diphenhydramine hydrochloride (50 mg intravenously or up to 500 mg/kg orally). Follow-up for up to 20 months. MAIN OUTCOME MEASURE: Dystonia evaluation. RESULTS: Diphenhydramine therapy was associated with minimal side effects, and it was most effective in treating patients with dystonia who experienced lightning jerks. Treatment with intravenous diphenhydramine may have a predictive value on a future response to oral therapy. CONCLUSION: Diphenhydramine should be considered a therapeutic option for idiopathic truncal dystonia with lightning jerks.

Adult↗

Readiness to respond in a target detection task: pre- and post-stimulus event-related potentials in normal subjects.

Brain potentials were recorded from 12 normal subjects engaged in an auditory target detection task (target stimulus probability of 0.2, stimulus rate of 1 every 2 sec) when instructions were (1) to press a response button with the thumb of the dominant hand to each target or (2) to keep a mental count of each target. A pre-stimulus slow negative potential was identified before every stimulus except non-targets immediately after targets. The amplitude of the pre-stimulus negativity was significantly affected by task instructions and was up to 4 times larger during the button press than the mental count condition. In contrast, the amplitudes and latencies of the event-related components (N100, P200, N200 and P300), when slow potentials were removed by filtering, were not different as a function of press or count instructions. The immediately preceding stimulus sequence affected both the amplitude and onset latency of the pre-stimulus negativity; both measures increased as the number of preceding non-targets increased. The amplitude of the pre-stimulus negative shift to targets also increased significantly as RT speed decreased. The major portion of the pre-stimulus negative potential is considered a readiness potential (RP) reflecting preparations to make a motor response. The amplitude of the RP during the target detection task did not significantly lateralize in contrast to the RP accompanying self-paced movements.

Adult↗

Tremor: classification, diagnosis and management.

Tremor can range from imperceptible physiologic movements to severely handicapping shaking. It can be a single entity, or it can occur in association with a disease that affects the basal ganglia, brainstem, cerebellum or peripheral nervous system. Tremors can be classified according to their anatomic location, the circumstances under which they occur, their frequency and amplitude, and whether they are physiologic or pathologic. As an isolated disorder, tremor should be treated only when it impairs the patient's ability to perform activities. Successful treatment requires the identification of precipitating factors, as well as associated signs and symptoms.

Humans↗

'Fatigue' in patients with multiple sclerosis. Motor pathway conduction and event-related potentials.

Ten patients with a definite diagnosis of multiple sclerosis and complaints of "fatigue" were studied using (1) reaction times and event-related potentials accompanying the performance of auditory memory tasks (target detection, verbal short-term memory) and (2) motor conduction velocities of the pyramidal tract elicited by cerebral and cervical magnetic stimulation. Patients were studied when "rested" and when fatigued. Reaction times of the patients when rested were significantly delayed in the short-term memory but not the target-detection tasks when compared with normal controls. When patients were fatigued, their reaction times became significantly longer in all tasks compared with when they were rested. Event-related potentials in these tasks consist of N1/P2 sensory components and P3a and P3b cognitive components. The N1 component latency was longer and P3a and P3b amplitudes were reduced in patients compared with controls. Fatigue in patients with multiple sclerosis was accompanied by a shortening of P3a latency and an increase in P3a and P3b amplitudes compared with these measures when patients were rested. Pyramidal tract conduction velocities did not differ between rested and fatigued conditions. Thus, fatigue in patients with multiple sclerosis was associated with a slowing of performance (reaction time) on memory tasks, whereas brain potentials reflecting neural events of stimulus encoding and classification were either unchanged or paradoxically speeded up in latency in the fatigued compared with the rested conditions. We postulate that, in patients with multiple sclerosis, fatigue affects neural processes acting after stimulus evaluation but before activation of the primary motor pathways.

Adult↗

Autonomic involvement in extrapyramidal and cerebellar disorders.

We reviewed the clinical and autonomic features of all patients with extrapyramidal and cerebellar disorders studied in the Mayo Autonomic Reflex Laboratory from 1983 to 1989. Patients were grouped into the following categories (number in parentheses): Parkinson's disease (35); parkinsonism-plus (54); multiple system atrophy (75); hereditary multisystem degenerations (eleven); progressive supranuclear palsy (32); non-familial cerebellar degeneration (eleven); nonspecific sporadic multisystem degeneration (73). Severe autonomic failure occurred in 97% of patients with multiple system atrophy and 53% of the nonspecific sporadic multisystem degeneration patients respectively. Autonomic involvement was mild or absent in Parkinson's disease while parkinsonism-plus and non-familial cerebellar degeneration patients had moderate autonomic failure. Orthostatic blood pressure reduction, percentage of anhidrosis on thermoregulatory sweat test, quantitative sudomotor axon reflex test, forearm response and heart rate response to deep breathing strongly regressed with severity. A response to levodopa treatment in patients with parkinsonism was more likely if cerebellar signs and cognitive deficits were absent. The presence of levodopa induced dyskinesia was also a marker for a clinically favourable levodopa response. We conclude that there is a spectrum of autonomic involvement in these degenerative disorders and that autonomic studies are useful in separating them and monitoring their course.

Adult↗

Pharmacological dissection of components of the Valsalva maneuver in adrenergic failure.

The arterial blood pressure (BP) components of the Valsalva maneuver (VM) were analyzed to ascertain whether they could be used as an index of adrenergic regulation of the circulation. We studied a control and three age- and sex-matched patient groups. Sympathetic adrenergic failure was graded on the basis of the degree of systolic BP (SBP) reduction during tilt: orthostatic hypotension (OH; SBP greater than 30 mmHg), borderline OH (BOH; 30 less than SBP greater than 10 mmHg), and sympathetic sudomotor failure (SSF). Controls exhibited a biphasic phase II, consisting of a modest decrement (early phase II) followed by a rise in BP (late phase II; II1) above resting values. All the patient groups including SSF exhibited a significant reduction in II1. An excessive BP fall in phase II and an absent phase IV overshoot were observed in the OH group. BOH and, to a lesser extent, SSF groups showed a significant reduction in phase IV overshoot. We conclude that BP changes during VM will detect adrenergic vasoconstrictor failure with greater sensitivity than orthostatic BP recordings.

Adult↗

Hemianopia, hemianesthesia, and spatial neglect: a study with evoked potentials.

We recorded somatosensory or visual evoked potentials (SEPs, VEPs) to stimuli contralateral and ipsilateral to the lesion in three right-brain-damaged patients with left spatial hemineglect and in three left-brain-damaged patients without evidence of neglect, as assessed by visual exploratory tasks. All patients had contralateral homonymous hemianopia or hemianesthesia. The three neglect patients showed normal SEPs or VEPs to stimuli delivered to the left half-field or to the left hand, without conscious perception and verbal report of the stimulation. By contrast, the three left-brain-damaged patients without neglect showed no recognizable cortical evoked response to contralateral visual or somatosensory stimuli. In all patients, the cortical evoked responses to ipsilateral stimulation were normal. In patients with spatial hemineglect, hemianopia and hemianesthesia may be manifestations of the neglect syndrome (visual and somatosensory hemi-inattention), rather than representing primary sensory deficit. Visual and somatosensory hemi-inattention may be due to defective access to the neural processes subserving conscious perception by information that has undergone early sensory processing.

Aged↗