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Paola Sandroni

Publications and source records attributed to Paola Sandroni.

At least 19 recordsLinked to original sources
PubMed2007

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy.

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in approximately 1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA.

Cerebellum↗
PubMed2006

Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety.

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P < 0.01). LBNP with trouser inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P < 0.05), but they were not related to the HR responses during LBNP or mental stress (P > 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.

Adult↗
PubMed2006

Involvement of hypocretin neurons in multiple system atrophy.

Hypocretin/Orexin (Hcrt/Orx) neurons of the posterolateral hypothalamus have been implicated in control of sleep and autonomic function. Sleep disorders and autonomic failure are important manifestations of multiple system atrophy (MSA). We sought to determine whether Hcrt/Orx neurons were involved in this disorder. Hypothalamus was obtained from seven subjects with neuropathologically confirmed MSA, and seven age-matched controls. 50 mum sections obtained throughout the posterior hypothalamus were immunostained for Hcrt-1 and alpha-synuclein. In MSA, there was a marked reduction of the total numbers of Hcrt/Orx neurons compared to controls (1,009 +/- 190 cells in MSA vs. 3,206 +/- 185 in controls, P < 0.0001). There were abundant glial cytoplasmic inclusions in the area of distribution of Hcrt/Orx neurons in MSA. This is the first demonstration of loss of Hcrt/Orx neurons in MSA, which is consistent with a system degeneration of neurons involved in homeostatic function, including sleep and autonomic regulation, in this disorder.

Adult↗
PubMed2006

Differential involvement of hypothalamic vasopressin neurons in multiple system atrophy.

We sought to determine whether there is differential involvement of different groups of hypothalamic arginine-vasopressin (AVP) synthesizing neurons in multiple system atrophy (MSA). Hypothalamus was obtained from five subjects with clinical diagnosis of MSA confirmed neuropathologically and five age-matched controls. Sections were immunostained for AVP, and cells with visible nuclei were counted in the posterior portion of the paraventricular nucleus (PVNp), supraoptic nucleus (SON), magnocellular PVN and suprachiasmatic nucleus (SCN). Sections of the hypothalamus and medulla were also immunostained for tyrosine hydroxylase (TH). There was a significant loss of AVP neurons in the PVNp in MSA compared with controls (17 +/- 3 versus 59 +/- 10 cells/section, P < 0.01). There was preservation of AVP- and TH-immunoreactive neurons in the SON and magnocellular PVN in all MSA cases. In contrast, there was marked depletion of TH-immunoreactive fibres innervating these magnocellular AVP neurons, coincident with a loss of neurons in the A1 area (6 +/- 1 versus 13 +/- 1 cells/section, P < 0.01). There was loss of AVP neurons in the SCN in MSA compared with control cases (14 +/- 3 versus 71 +/- 16 cells/section, P < 0.02). Our results indicate that, in MSA, loss of AVP neurons in the PVNp may contribute to sympathetic failure, whereas loss of catecholaminergic input from the brainstem to the magnocellular AVP neurons may contribute to impaired AVP secretion in response to orthostatic stress. Loss of AVP neurons in the SCN may contribute to impaired circadian regulation of endocrine and autonomic functions.

Aged↗
PubMed2006

Congenital idiopathic inability to perceive pain: a new syndrome of insensitivity to pain and itch with preserved small fibers.

Individuals vary widely in their sensitivity to painful stimuli. Some exhibit heightened reactions to pain (hyperpathia), while others show relative indifference. Although multiple factors may be responsible for these differences, varying sensitivities to pain also can be due to underlying differences in nociceptive neurophysiology. We present here the case of an individual with an apparent congenital inability to perceive pain. This patient appears to be different from other reported cases of insensitivity to pain described in the medical literature. He exhibited no evidence of an abnormality of the peripheral or autonomic nervous system and no apparent abnormality of the central nervous system other than isolated deficits in pain and temperature perception. Since pain is a subjective phenomenon, there is no definitive way to assess this patient's reported inability to perceive painful somatic stimulation, but available evidence suggests he has a defect in the supraspinal processing of nociceptive stimuli which renders him insensitive to pain. This raises the possibility of either deficient central nociceptive functioning or aberrant endogenous anti-nociceptive functioning.

Adult↗
PubMed2006

Pyridostigmine treatment trial in neurogenic orthostatic hypotension.

BACKGROUND: Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension. OBJECTIVE: To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo. DESIGN: We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given. RESULTS: No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms. CONCLUSIONS: Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.

Adolescent↗
PubMed2006

Thermoregulatory sweat testing in patients with erythromelalgia.

OBJECTIVES: To examine the results of thermoregulatory sweat testing in patients with erythromelalgia and to compare them with the results of other neurophysiologic tests of small-fiber nerve function. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Thirty-two consecutive patients with erythromelalgia who had thermoregulatory sweat testing in addition to vascular and nerve testing. INTERVENTION: The following information was abstracted for each patient: demographics, clinical presentation, and results of thermoregulatory sweat testing, vascular (noninvasive) testing, and nerve testing (electromyography and autonomic reflex screen, including quantitative sudomotor axon reflex test). MAIN OUTCOME MEASURES: Results of thermoregulatory sweat testing to evaluate small-fiber neuropathy, compared with other tools used to estimate small-fiber neuropathy. RESULTS: Thermoregulatory sweat testing results were abnormal in 28 (88%) of 32 patients, and quantitative sudomotor axon reflex test results were abnormal in 22 patients (69%). Abnormalities noted on thermoregulatory sweat testing varied from local hypohidrosis or anhidrosis to global anhidrosis. Global or almost-global anhidrosis was present in 8 patients (25%); in 19 patients (59%) the anhidrosis was distal, and 1 other patient (3%) had a less specific pattern of anhidrosis (multifocal or regional). The area of anhidrosis generally corresponded to the area that was symptomatic of the erythromelalgia. CONCLUSIONS: Small-fiber neuropathy is prevalent in most patients with erythromelalgia. Thermoregulatory sweat testing is a sensitive and useful marker of small-fiber neuropathy in these patients.

Adolescent↗
PubMed2006

Detection of small-fiber neuropathy by sudomotor testing.

The symptoms of burning sensation affecting the feet, thought to be due to a distal small-fiber neuropathy (DSFN) affecting somatic unmyelinated fibers, are usually accompanied by vasomotor or sudomotor changes suggestive of involvement of autonomic fibers. We therefore examined the relationship between pattern of anhidrosis and DSFN and its etiology, comparing patients with "pure" DSFN (with normal nerve conduction) to those with clinical DSFN (minor conduction abnormalities). We reviewed 125 cases with a clinical phenotype of DSFN. These patients had distal burning discomfort, variable sensory deficits, and intact motor function. All had undergone assessment with thermoregulatory sweat test (TST), autonomic reflex screen (ARS), and nerve conduction studies and electromyography (NCS/EMG). TST showed a distal pattern of anhidrosis in 74%. The quantitative sudomotor axon reflex test (QSART) was abnormal in 74%, with 80% of those having a length-dependent pattern of anhidrosis/hypohidrosis. In total, 93% of patients had a distal pattern of abnormality on QSART or TST. The Composite Autonomic Severity Score (CASS) was used to quantify the severity and distribution of autonomic deficits: 98% had CASS abnormality (sudomotor, 98%; adrenergic, 43%; cardiovagal, 35%). EMG was normal or showed unrelated abnormalities in 75%. The most common etiologies of DSFN were idiopathic (73%), presumed hereditary (18%), and diabetes (10%). Sudomotor examination is thus a highly sensitive detection tool in DSFN. Autonomic involvement is mainly distal, and additionally may involve adrenergic and the long cardiovagal fibers.

Adult↗
PubMed2006

Histopathologic findings in primary erythromelalgia are nonspecific: special studies show a decrease in small nerve fiber density.

The histopathology of primary erythromelalgia has been poorly characterized. A total of 33 skin biopsy specimens from 29 patients with a diagnosis of primary erythromelalgia were re-examined. Histopathologic findings were nonspecific. Vascular thrombi were not identified. A relative decrease in small nerve fiber density was noted in specimens from 13 of 16 patients.

Adult↗
PubMed2005

Blood pressure recovery from Valsalva maneuver in patients with autonomic failure.

BACKGROUND: Blood pressure (BP) changes in response to the Valsalva maneuver (VM) reflect the integrity of the baroreflex that regulates BP, and the phases of VM are widely used indices of adrenergic evaluation. OBJECTIVE: To study the BP recovery time (PRT) following termination of VM back to baseline to determine if it could be an additional and better indicator of adrenergic function. METHODS: The authors evaluated three groups of patients with increasing degrees of adrenergic failure and an age-matched control group. Adrenergic failure was graded on the basis of systolic blood pressure (SBP) reduction to tilt: Group 1, orthostatic hypotension (OH; SBP > or = 30 mm Hg); Group 2, borderline OH (BOH; 30 > SBP > 10 mm Hg); and Group 3, sympathetic sudomotor failure. RESULTS: PRT was found to vary directly with severity of adrenergic impairment. PRT significantly correlated with previously utilized phases of the VM and baroreflex gain, with highest correlations with phases II_L (reflex vasoconstriction following initial fall in BP) and IV (BP overshoot following the VM). PRT extends the indices for the quantitation of adrenergic failure, since it will continue to parallel increasing adrenergic failure after phase II_L is lost and is a reliable index when II_L cannot be recorded. CONCLUSIONS: Pressure recovery time is a valuable index of adrenergic failure. It extends the value of the Valsalva maneuver by providing a quantitative index that is measurable in patients with severe adrenergic failure.

Autonomic Nervous System Diseases↗
PubMed2005

Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus.

Epidemiological evidence suggests decreased heat tolerance in patients with Type 2 diabetes mellitus (T2DM), but it is not known whether the mechanisms involved in thermoregulatory control of skin blood flow are altered in these patients. We tested the hypothesis that individuals with T2DM have a delayed internal temperature threshold for active cutaneous vasodilation during whole body heating compared with healthy control subjects. We measured skin blood flow using laser-Doppler flowmetry (LDF), internal temperature (T or) via sublingual thermocouple, and mean arterial pressure via Finometer at baseline and during whole body heating in 9 T2DM patients and 10 control subjects of similar age, height, and weight. At one LDF site, sympathetic noradrenergic neurotransmission was blocked by local pretreatment with bretylium tosylate (BT) to isolate the cutaneous active vasodilator system. Whole body heating was conducted using a water-perfused suit. There were no differences in preheating T(or) between groups (P > 0.10). Patients with T2DM exhibited an increased internal temperature threshold for the onset of vasodilation at both untreated and BT-treated sites. At BT-treated sites, T or thresholds were 36.28 +/- 0.07 degrees C in controls and 36.55 +/- 0.05 degrees C in T2DM patients (P < 0.05), indicating delayed onset of active vasodilation in patients. Sensitivity of vasodilation was variable in both groups, with no consistent difference between groups (P > 0.05). We conclude that altered control of active cutaneous vasodilation may contribute to impaired thermoregulation in patients with T2DM.

Adrenergic Antagonists↗
PubMed2005

Chronic inflammatory demyelinating polyneuropathy and respiratory failure.

Neuromuscular respiratory failure is not considered to be a clinical feature of chronic inflammatory demyelinating polyneuropathy (CIDP). We present 4 patients with CIDP who required respiratory assistance and mechanical ventilation. Two patients needed emergent intubation and one patient lapsed in a stupor from hypercapnia. Respiratory failure in CIDP should be considered exceptional, but more formal studies in CIDP may be needed to assess its prevalence.

Aged↗
PubMed2005

Involvement of medullary regions controlling sympathetic output in Lewy body disease.

We sought to determine the involvement of medullary regions controlling sympathetic output in pathologically confirmed diffuse Lewy body disease (LBD). We studied eight limbic or neocortical stage LBD and eight multiple system atrophy (MSA) cases, confirmed neuropathologically, and eight age-matched controls. Five of the LBD cases and all MSA cases had orthostatic hypotension. Serial 50-mum sections obtained from the medulla rostral to the obex were immunostained for tyrosine hydroxylase, tryptophan hydroxylase and alpha-synuclein. Analysis was focused on the ventrolateral medulla and medullary raphe nuclei. In LBD cases, there were Lewy bodies and neurites, as well as dystrophic neurons in the ventrolateral medulla, but the number of catecholaminergic and serotonergic neurons was not significantly reduced. All these groups were depleted in MSA. There were Lewy body pathology and dystrophic neurons in the raphe in all LBD cases. Cell numbers were reduced in both the raphe obscurus and raphe pallidus. Our findings suggest that, although LBD affects medullary autonomic areas, it does so less severely than MSA, particularly in the case of the VLM, which controls sympathetic outputs maintaining arterial pressure. In LBD, orthostatic hypotension may be due primarily to involvement of sympathetic ganglion neurons rather than ventrolateral medulla neurons.

Adult↗
PubMed2005

Depressive symptoms and life satisfaction in patients with multiple system atrophy.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by extrapyramidal signs, prominent autonomic failure, and a poor prognosis. In the absence of restorative treatment, management is aimed at improving quality of life. Little is known about modifiable factors, such as depression, that may affect quality of life in MSA. The present study investigated the rate of depressive symptoms and their relationship to life satisfaction in patients with MSA. Ninety-nine patients with MSA (54% women; mean age, 67.8 +/- 8.8) completed measures of depressive symptoms, life satisfaction, physical function, and disease and demographic factors. Objective autonomic indices were abstracted from the medical chart. Participants reported a high rate of depressive symptoms, with 39% endorsing moderate to severe depressive symptoms on the Beck Depression Inventory (BDI > or = 7). Reported life satisfaction was low, with a mean of 38.8 on a 100-point visual analogue scale (0 = Extremely Dissatisfied, 100 = Extremely Satisfied). The SF-36 Physical Component Scale was approximately 1.5 standard deviations below the mean of a normative sample of healthy adults the same age. Regression analysis revealed that autonomic disease parameters accounted for 22% of the variance in life satisfaction. Physical function did not account for any additional variance; however, depressive symptoms accounted for an additional 15%. Depressive symptoms are common, often severe, and an important determinant of life satisfaction in patients with MSA. Adequate treatment of comorbid depression may improve quality of life in this population, despite the presence of other debilitating deficits.

Aged↗
PubMed2005

Evaluation of orthostatic hypotension: relationship of a new self-report instrument to laboratory-based measures.

OBJECTIVE: To compare measured autonomic deficits (composite autonomic severity score [CASS]) with a brief self-report scale we developed to measure severity of symptoms of orthostatic hypotension. PATIENTS AND METHODS: Patients were recruited in 2 phases: from August to October 2002 and in April 2004. All patients underwent full evaluation in the autonomic laboratory, from which a CASS of autonomic deficits was derived. Patients also completed the 5-item self-report Orthostatic Grading Scale, which inquires about symptoms of orthostatic intolerance due to orthostatic hypotension (eg, severity, frequency, and interference with daily activities). RESULTS: Of 145 patients, 97 (67%) had orthostatic hypotension. The 5-item scale demonstrated strong internal consistency (coefficient alpha=.91). Patients with orthostatic hypotension had significantly higher scores on each questionnaire item and CASS subscores than those without orthostatic hypotension. The scale items correlated significantly with each of the CASS subscores, maximally with the CASS adrenergic subscore. CONCLUSIONS: Orthostatic hypotension is not the only cause of reduced orthostatic tolerance, and some patients may have orthostatic hypotension but be asymptomatic. Results of this study indicate that this 5-item questionnaire is a reliable and valid measure of the severity of symptoms of orthostatic hypotension and that it can supplement laboratory-based measures to provide a rapid, more complete clinical assessment. This questionnaire would also be useful as a brief screening device for orthostatic intolerance to aid physicians in identifying patients who may have orthostatic hypotension.

Activities of Daily Living↗