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Phillip A Low

Publications and source records attributed to Phillip A Low.

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↗
PubMed2007

Vasovagal syncope in patients with reduced left ventricular function.

Vasovagal syncope (VVS) is mediated by arterial mechanoreceptors, resulting in reflexive changes in heart rate and vascular tone. The Bezold-Jarisch reflex was originally described as enhanced contraction and activation of left ventricular mechanoreceptors, but later studies implicated other triggers, including coronary, carotid, and cerebral arterial mechanoreceptors. VVS is uncommon in patients with left ventricular dysfunction. We hypothesized that VVS could occur in this subset and examined patient characteristics and hemodynamic responses during tilt table testing. From 1996 through 1998, 128 consecutive patients with ejection fraction <40% underwent tilt table testing (70 degrees , 45 min). A total of 15 patients (11.7%) had a positive neurocardiogenic response thought to be the cause of syncope. Clinical data and hemodynamic responses were reviewed. Mean patient age (+/-SEM) was 70.1 +/- 12.2 years. Nine patients were male. Mean ejection fraction was 27.7% +/- 7.1%. Thirteen had electrophysiologic studies with normal findings or abnormal findings insufficient to account for syncope. Hemodynamic analysis of 14 patients who had a vasovagal response during passive tilt table testing showed a mean time to positive response of 17.6 +/- 12.7 min. Cardioinhibitory responses (pauses >3 sec or heart rate < 40 beats/min for > or =10 sec) were not observed. Five responses were classified as mixed type (>10% decrease in heart rate without a cardioinhibitory response) and 9 as vasodepressor type (< or =10% decrease in heart rate). VVS occurs in patients who have clinically significant left ventricular dysfunction. Although this study had a small cohort size, the predominantly vasodepressor response without a cardioinhibitory component warrants further investigation into mechanisms of VVS in these patients.

Aged↗
PubMed2006

Association between angiotensin-converting enzyme gene polymorphisms and QT duration in a multiethnic population in Hawaii.

OBJECTIVES: Recent studies have suggested that heart-rate corrected QT interval (QTc) in normal populations may be influenced by genetic factors. We report findings of a study of the relationship between QTc, increased QTc (> 440 ms) and angiotensin-converting enzyme (ACE) genotype in a multiethnic, population-based study completed in rural Hawaii. METHODS: Blood samples were obtained while fasting and after an oral glucose challenge from 1452 individuals between 1997 and 2000. The clinical examination included an electrocardiogram. Medical histories, behavioral and socio-demographic information were obtained during the interview. Ethnicity was estimated by self-report. The insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction (PCR) from a random sample of 588 participants. Multiple linear and logistic regression was used to test for associations between QTc and ACE gene polymorphisms. RESULTS: The overall crude prevalence of increased QTc was 21.2%. The prevalence of increased QTc was lowest among those with ACE DD genotype, and highest among those with ACE insertion/insertion (II) genotype. The adjusted odds ratio for increased QTc was 2.29 (95% CI 1.02-5.12) and 3.61 (95% CI 1.60-8.13) for ID and II genotypes, respectively, compared to the DD genotype. The test for trend was highly significant (p < 0.001). CONCLUSIONS: The ACE insertion allele was associated with increased prevalence of prolonged QTc independent of ethnicity, age, gender, and BMI. These findings may implicate the ACE gene as an important genetic risk factor for cardiovascular disease morbidity and mortality.

Adult↗
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

Multiple effects of hypothermia on inflammatory response following ischemia-reperfusion injury in experimental ischemic neuropathy.

Hypothermia is neuroprotective in peripheral nerve ischemia, but the mechanism(s) of neuroprotection are not well known. A major mechanism of ischemia-reperfusion (IR) injury is the inflammatory response. We therefore dissected the effects of hypothermia on inflammatory mediators in peripheral nerve ischemia of rats. Following functional and pathological evaluations for the effect of hypothermia on IR injury, we undertook immunohistochemical studies of inflammatory cells, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor kappa B (NF-kappaB) in nerve subjected to IR under defined hypothermic conditions with varying time delays (0, 1, 3, and 4 h) and depth of hypothermia (28 degrees C, 32 degrees C, and 35 degrees C). Functionally and pathologically, significant hypothermic neuroprotection was confirmed in the intraischemically treated groups but not in the postischemically treated groups. In endoneurial microvessels, intraischemic hypothermia inhibited ICAM-1 upregulation but not TNF-alpha, NF-kappaB, and IL-6 expressions. We demonstrated significantly reduced granulocyte and mononuclear phagocyte infiltration into nerve with intraischemic hypothermia but not with postischemic hypothermia. Cytokine (TNF-alpha and IL-6) positive cells were significantly decreased in both epineurium and endoneurium with intraischemic hypothermia. Excess NF-kappaB expression was seen in both Schwann cell and axon under normothermia (35 degrees C) but was inhibitable with deep hypothermia (28 degrees C). We conclude that intraischemic hypothermia significantly attenuates the inflammatory response by its effect on multiple key mediators including cytokines, ICAM-1, and NF-kappaB.

Action Potentials↗
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

Enhanced inflammatory response via activation of NF-kappaB in acute experimental diabetic neuropathy subjected to ischemia-reperfusion injury.

Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in diabetic nerves compared to control normoglycemic nerves. The mechanism of this excessive susceptibility is unclear. Since reperfusion injury results in an inflammatory response, we tested the hypothesis that the diabetic state increases the inflammatory cascade. We used an animal model of unilateral ischemia-reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to evaluate the density and localization of mediators of the inflammatory response using selective immunolabeling methods (for nuclear factor kappa B (NF-kappaB), intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We studied a 1-month diabetic group and an age-matched control group (n=6 each). The right limb underwent 3 h ischemia at 35 degrees C and 7 days reperfusion. This was achieved by ligating the supplying arteries and collaterals to the right sciatic-tibial nerve for 3 h, followed by releasing the ties. Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF-kappaB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was significantly increased over that of controls subjected to identical IR injury. We observed a nearly 2-fold increase in density of NF-kappaB and ICAM-1 expression in microvessels of diabetic nerve compared with control nerve. Extensive infiltration of monocyte macrophages (1C7) was observed in the endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS 48) occurred in the endoneurium of diabetic tibial nerves. This study provides evidence for an enhanced inflammatory response in diabetic nerves subjected to IR injury apparently via NF-kappaB activation.

Acute Disease↗
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

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

Acetylcholinesterase inhibition in patients with orthostatic intolerance.

The efficacy of current therapeutic measures in orthostatic intolerance (OI) varies among patients and is oftentimes unsatisfactory. New approaches to alleviate symptoms of OI are therefore clearly needed. Recent reports have demonstrated that acetylcholinesterase inhibition is effective in the treatment of orthostatic hypotension with the presumed mechanism of enhancing sympathetic ganglionic transmission. Based on the hypothesis that acetylcholinesterase inhibition, by improving the safety factor of cholinergic transmission, will result in enhanced vascular adrenergic tone and a vagal shift in cardiac sympathovagal balance, we evaluated the role of acetylcholinesterase inhibition in the treatment of patients with OI. We monitored heart rate (HR), blood pressure, and indexes for cardiac output, end-diastolic volume, and systemic resistance continuously in 18 patients with OI during supine rest and during 5 minutes of 70 degrees head-up tilt before and 1 hour after oral administration of 60 mg pyridostigmine. Plasma catecholamines and baroreflex sensitivity were determined for the supine and upright position before and after medication. Patients scored orthostatic symptoms for both tilt studies. The excessive HR response to orthostatic stress was significantly blunted after pyridostigmine administration. HR was significantly lower in the supine and more so in the upright position. Baroreflex sensitivity in the upright position was significantly higher after pyridostigmine. Norepinephrine was increased in both supine and upright position. These changes were associated with significant improvement of orthostatic symptoms. We conclude that pyridostigmine improves orthostatic tolerance in patients with OI. Our findings support the suggested mechanisms of enhanced sympathetic ganglionic neurotransmission and a vagal shift in cardiac sympathovagal balance. Acetylcholinesterase inhibition could be a new useful concept in the treatment of OI.

Adolescent↗
PubMed2006

Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial.

OBJECTIVE: The aim of this trial was to evaluate the effects of alpha-lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP). RESEARCH DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg (n = 45) (ALA600), 1,200 mg (n = 47) (ALA1200), and 1,800 mg (ALA1800) of ALA (n = 46) or placebo (n = 43) for 5 weeks after a 1-week placebo run-in period. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Secondary end points included individual symptoms of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score (NIS), and patients' global assessment of efficacy. RESULTS: Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in ALA1800 compared with 2.9 points (32%) in the placebo group (all P < 0.05 vs. placebo). The corresponding response rates (>/=50% reduction in TSS) were 62, 50, 56, and 26%, respectively. Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain, the NSC score, and the patients' global assessment of efficacy. The NIS was numerically reduced. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo. CONCLUSIONS: Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio.

Administration, Oral↗
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

A screen of candidate genes and influence of beta2-adrenergic receptor genotypes in postural tachycardia syndrome.

OBJECTIVE: To screen candidate genes, encoding beta2-adrenergic receptor (beta2AR), alpha2C-adrenergic receptor (alpha(2C)AR), norepinephrine transporter (NET), and mitochondrial complex I (COI), for common single nucleotide polymorphisms (SNPs) in patients with postural tachycardia syndrome (POTS); alterations could potentially cause or aggravate orthostatic tachycardia and to relate beta2AR SNPs, known to effect venomotor tone, to heart rate (HR) and blood pressure measurements during 10-min head-up tilt. METHODS: (a) DNA extraction from leukocytes of 29 patients with POTS; (b) Denaturing high performance liquid chromatography analysis to screen for the 12-bp deletion (Del322-325) in alpha(2C)AR and for the alanine to proline mutation at amino acid 457 (Ala457Pro) in NET; (c) Systematic direct sequence analysis to screen for SNPs in beta2AR, NET, and COI. RESULTS: Three common polymorphisms were abundant in at least one allele in beta2AR resulting in a cysteine to arginine in the 5' promoter region (72% of patients), an arginine to glycine at amino acid-16 (Gly16; 86%), and a glutamine to glutamic acid at amino acid-27 (Glu27; 66%), a frequency that was no different to the normal Caucasian population. Orthostatic HR was significantly greater in patients with Glu27. Diastolic blood pressure (DBP) was significantly lower in a subset of patients with Gly16 whose HR were > or =120 beats/min with head-up tilt. All patients did not show the Ala457Pro mutation of NET; all sequence variants detected in alpha(2C)AR, NET, and COI were not considered causally related to POTS. CONCLUSIONS: Of the candidate genes screened, none harbored a SNP considered to be causally related to POTS. There was significant association of HR and DBP with SNPs of the gene encoding beta2AR; Gly16 or Glu27 could aggravate orthostatic tachycardia by excessive venous pooling.

Adult↗
PubMed2005

Stability of acetylcholine chloride solution in autonomic testing.

Acetylcholine (ACh) is the neurotransmitter used as an agent to evoke a sudomotor axon reflex response in autonomic testing. Adequate stimulus of postganglionic axons requires ACh solutions to be stable, but its stability in the clinical laboratory is uncertain. We evaluated the stability of standard (0.55 M) ACh solutions stored at temperatures of -20 degrees C, 4 degrees C, 25 degrees C, and 50 degrees C for 10 time points between 0 and 84 days. ACh and choline (Ch) were measured by reverse-phase HPLC with electrochemical detection using an Acetylcholine/Choline Assay Kit. Linear regressions of ACh and Ch standards were used to calculate the levels in the stored samples. The inherent levels of Ch were used as the internal standard. Regression analyses were used to examine the effects of length of storage and temperature. The samples of ACh stored at -20 degrees C and 4 degrees C showed an extremely small breakdown over the 84-day period and had no evidence to show the regression lines differed. ACh solution stored at 25 degrees C was stable for about 28 days, after such time, modest breakdown occurs. At a temperature of 50 degrees C, ACh showed a rapid breakdown after 1 day. We conclude ACh solution should not be stored at room temperature for more than 28 days and should not be exposed to higher temperatures to assure an adequate axon stimulus.

Acetylcholine↗
PubMed2005

Spectral analysis of slow modulation of EEG amplitude and cardiovascular variables in subjects with postural tachycardia syndrome.

OBJECTIVE: Previous studies have reported slow (<0.5 Hz) modulation of electroencephalographic (EEG) background amplitude and suggested that this reflects periodic neuronal activity in the brainstem, such as may be recorded from cardiovascular and respiratory centers in animals. We searched for a relationship between EEG amplitude modulation and modulation of simultaneously recorded cardiovascular variables and attempted to determine whether this relationship was altered in subjects with postural tachycardia syndrome (POTS). METHODS: We recorded EEG, blood flow velocity in the middle cerebral artery (MCA), heart rate, respirations, and blood pressure from subjects with POTS and controls during head-up tilt. Time-frequency analysis of 0.512-s epochs of EEG was performed to determine peak alpha amplitude. Spectra were divided into 3 bands: ultraslow, middle, and respiratory. RESULTS: EEG alpha amplitude modulation in all frequency bands was reduced in POTS subjects while supine. EEG modulation decreased in controls with head-up tilt but not in POTS subjects. Heart rate modulation in the respiratory frequency band decreased with head-up tilt and was significantly less (P<0.02) in ultraslow and respiratory frequency bands in POTS subjects after head-up tilt. Blood pressure and MCA flow velocity modulation in middle and respiratory bands increased with head-up tilt to a greater degree in POTS subjects. Blood pressure and MCA flow velocity modulation frequencies were moderately correlated, but correlations between EEG and cardiovascular variable modulation frequencies were generally low, being highest in the respiratory band but not statistically significant. CONCLUSION: There are subtle differences in EEG amplitude modulation in subjects with POTS. Altered EEG amplitude modulation in POTS may reflect altered brainstem physiology in this disorder.

Adult↗
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↗