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Phillip A Low

Publications and source records attributed to Phillip A Low.

At least 37 records · Page 2Linked to original sources
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

What is the minimum duration of head-up tilt necessary to detect orthostatic hypotension?

OBJECTIVE: There is uncertainty as to the minimum duration of head-up tilt (HUT) needed to detect orthostatic hypotension (OH). The orthostatic duration has variably been recommended to be 1, 2, 3, and 5 minutes. The purpose of the current study was 1) to determine the minimum duration of HUT necessary to detect OH and 2) to identify different patterns of orthostatic blood pressure (BP) response in patients with OH. DESIGN/METHODS: We evaluated the medical records of 66 consecutive patients (mean age 70.0+/-10.1 years; 64% male) seen at Mayo Clinic-Rochester from 2000-2001 who fulfilled the criteria for OH (systolic blood pressure [SBP] reduction > or = 20 mmHg within 3 minutes of HUT) during routine clinical autonomic studies. All patients completed an autonomic reflex screen with continuous monitoring of heart rate and BP during supine rest and 5 minutes of 70 degree HUT. Severity of autonomic deficits was quantified with the Composite Autonomic Severity Score (CASS). RESULTS: Overall, BP was the lowest at 1 minute with gradual and partial recovery over the following 4 minutes. Eighty-eight percent of patients (N=58) developed OH by 1 minute of HUT, with an additional 11% (N=7) developing OH by 2 minutes and the remaining 1% (N=1) developing OH by 3 minutes. We identified two broad patterns of SBP response to HUT. Forty-eight percent (N=32) of patients demonstrated an initial drop in SBP (> or = 20 mm Hg),which remained stable until tilt-back. Thirty-six percent (N=24) demonstrated an initial drop (> or = 20 mmHg) followed by a progressive decline in SBP until tilt-back. Repeated measures analysis of variance confirmed that the SBP change in response to HUT differed significantly among patients with a stable vs. progressive pattern [F(3,32)=25.1, p<0.001). Patients with the progressive pattern also had more severe adrenergic impairment on the CASS (p=0.03) and were more likely to have their tilt test terminated early (prior to 5 minutes) due to presyncope (p<0.0001) than patients with the stable pattern. CONCLUSIONS: One minute of HUT will detect OH in the great majority (88%) of patients and three minutes will detect the balance. Orthostatic stress beyond 2 minutes is necessary to detect the pattern of progressive OH. Since this group has more severe adrenergic deficits than the group with stable OH, we suggest that the progressive pattern is due to greater impairment of compensatory reflexes. Recognition of the group with progressive fall in BP is important since this group may be at greater risk of orthostatic syncope.

Aged↗
PubMed2005

Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.

The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Electrodiagnosis↗
PubMed2005

The therapeutic window of hypothermic neuroprotection in experimental ischemic neuropathy: protection in ischemic phase and potential deterioration in later reperfusion phase.

Hypothermia will neuroprotect peripheral nerve from ischemia-reperfusion (IR) injury, but the therapeutic window of hypothermic neuroprotection has not been defined. Unilateral IR injury was produced by the ligation and release of nooses tied around supplying arteries to the right sciatic-tibial nerve of the rat. Using this model, 114 rats were divided into 12 groups according to the delay (0, 1, 3, and 4 h) and the depth of hypothermia (28, 32, and 35 degrees C). All rats were subjected to 3 h ischemia and 7 days reperfusion followed by behavioral, electrophysiological, and pathological evaluations. We demonstrated significant hypothermic neuroprotection with both deep (28 degrees C) and mild (32 degrees C) hypothermia initiated during ischemia (0 and 1 h delay), but not hypothermia initiated during reperfusion (3 and 4 h delay) in both behavioral and electrophysiological evaluations. In addition, the pathologically significant differences were observed between deep hypothermia (28 degrees C) and normothermia (35 degrees C) initiated during ischemia. We conclude that the therapeutic window of hypothermic neuroprotection is optimal during the intraischemic period and that mild and deep hypothermia provide neuroprotection. Prolonged delay of hypothermic treatment results in worsening of IR injury.

Action Potentials↗
PubMed2005

Inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome, and overlapping syndromes.

BACKGROUND: Inappropriate sinus tachycardia (IAST) and postural orthostatic tachycardia syndrome (POTS) are syndrome complexes with some distinctive features, overlapping clinical manifestations, and potential common mechanisms. Pathogenesis of these overlapping syndromes is poorly understood. Diagnostic and therapeutic approaches have not been standardized. PURPOSE: This article provides an overview of the definition, clinical presentation, and proposed mechanisms of IAST and other overlapping syndromes. A stepwise diagnostic approach is suggested. A multidisciplinary management scheme is outlined. METHODS: A MEDLINE search for English-language articles on IAST, POTS, and chronic orthostatic intolerance published up to 2005 was performed. Published data incorporated with our clinical experience were synthesized and presented in this review. RESULTS: The population of IAST is heterogeneous and underlying mechanisms are complex and likely multifactorial. Evidence suggests that both cardiac and extracardiac causes are plausible. Regional and limited autonomic neuropathies, at least in part, can provide a mechanism-based explanation of the cardiovascular indices and clinical symptoms in a significant number of patients with IAST. The regional abnormalities can be detected by autonomic testing. Among patients with IAST and evidence of autonomic dysregulation, an integrated autonomic, cardiovascular, and psychiatric management approach appears to be logical and rational when appropriate. Sinus node ablation could be considered in patients with persistent IAST in the absence of autonomic neuropathy and multisystem symptoms. Data from long-term outcomes are lacking. CONCLUSION: The current understanding of IAST mechanisms is incomplete and management approach is not adequate. Significant effort needed in clinical research to improve therapeutic outcome.

Humans↗
PubMed2005

Acute blood pressure changes after the onset of atrioventricular nodal reentrant tachycardia: a time-course analysis.

INTRODUCTION: We aimed to characterize blood pressure (BP) response at the beginning of atrioventricular nodal reentrant tachycardia (AVNRT) and its relationship to orthostatic challenge and variable atrioventricular interval. METHODS AND RESULTS: In this prospective study of 17 consecutive patients with documented AVNRT, mean BP was analyzed in the supine and upright positions during sinus rhythm, AVNRT, and pacing with atrioventricular delay of 150 msec (AV150) and 0 msec (AV0). Mean BPs were compared at 3-5 seconds, 8-10 seconds, and 28-30 seconds after the onset of AVNRT or pacing. BP decreased immediately after AVNRT initiation, with gradual recovery during the first 30 seconds from 71.9 +/- 16.5 mmHg to 86 +/- 13.8 mmHg, P < 0.01. A similar pattern was observed during AV0, but not during AV150, pacing. While supine, mean BP decrease was more pronounced during AVNRT and AV0 pacing (-26.1% and -32.1%, respectively) than during AV150 pacing (-8%, P = 0.02 and P = 0.07, respectively). This difference subsided 30 seconds after the onset of AVNRT or pacing. When upright, the mean BP time course was similar, but mean BP recovery during AVNRT was slower, and the difference between mean BP during AVNRT and AV150 persisted at 30 seconds. CONCLUSIONS: The initial mean BP decrease during AVNRT recovered gradually within 30 seconds. A short atrioventricular interval is associated with a greater mean BP decrease at the onset of tachycardia. These observations may explain clinical symptoms immediately after the onset of AVNRT.

Adult↗
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↗
PubMed2004

Ischemia-reperfusion injury of peripheral nerve in experimental diabetic neuropathy.

The pathogenesis of human diabetic neuropathy likely involves the interplay of hyperglycemia, ischemia, and oxidative stress. Mild-moderate ischemia-reperfusion to streptozotocin (STZ)-induced diabetes results in florid fiber degeneration in diabetic but not in normal nerves. Uncertainty exists as to the influence of duration of diabetes on this susceptibility. We therefore studied diabetic tibial and sciatic nerves using a rat ischemia-reperfusion (IR) model after 1 month and 4 months of diabetes utilizing electrophysiological, behavioral, and neuropathological methods. Electrophysiological abnormalities were present in 1-month diabetic rats (D) and persisted over 4 months. Behavioral scores were decreased markedly at 4 months (p<0.05). Endoneurial edema and ischemia fiber degeneration (IFD) were observed at both the 1-month (p<0.01 and p<0.001) and 4-month (p<0.001) durations in diabetic nerves, whereas only mild or no damage was observed in age-matched control nerves. These findings demonstrate that STZ-induced diabetes exacerbates the morphological and electrophysiological pathology in peripheral nerve to IR injury both in the early timepoint of 1 month and late timepoint of 4 months, although there was a gradation of injury, which is more severe at the later timepoint. Reperfusion exaggerated morphological pathology in 1-month STZ-induced diabetic peripheral nerve.

Action Potentials↗
PubMed2004

Passive transfer of autoimmune autonomic neuropathy to mice.

Autoimmune autonomic neuropathy (AAN) is an acquired, often severe, form of dysautonomia. Many patients with AAN have serum antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (AChR). Rabbits immunized with a fusion protein corresponding to the N-terminal extracellular domain of the ganglionic AChR alpha3 subunit produce ganglionic AChR antibodies and develop signs of experimental AAN (EAAN) that recapitulate the cardinal autonomic features of AAN in man. We now demonstrate that EAAN is an antibody-mediated disorder by documenting sympathetic, parasympathetic, and enteric autonomic dysfunction in mice injected with rabbit IgG containing ganglionic AChR antibodies. Recipient mice develop transient gastrointestinal dysmotility, urinary retention, dilated pupils, reduced heart rate variability, and impaired catecholamine response to stress. The autonomic signs are associated with a reversible failure of nicotinic cholinergic synaptic transmission in superior mesenteric ganglia. Mice injected with IgG from two patients with AAN (of three tested) demonstrated a milder phenotype with evidence of urinary retention and gastrointestinal dysmotility. The demonstration that ganglionic AChR-specific IgG causes impaired autonomic synaptic transmission and autonomic failure in mice implicates an antibody-mediated pathogenesis for AAN. The antibody effect is potentially reversible, justifying early use of immunomodulatory therapy directed at lowering IgG levels and abrogating IgG production in patients with AAN.

Animals↗
PubMed2004

Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody.

BACKGROUND: The clinical characteristics of autoimmune autonomic neuropathy are only partially defined. More than 50% of patients with high levels of ganglionic acetylcholine receptor (AChR) autoantibodies have a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal tract symptoms, and neurogenic bladder. OBJECTIVE: To compare patients with idiopathic autonomic neuropathy who were seropositive (n = 19) and seronegative (n = 87) for ganglionic AChR antibodies. DESIGN: Retrospective review of autonomic programmatic database. SETTING: Autonomic Disorders Program Project at Mayo Clinic College of Medicine, Rochester, Minn. PATIENTS: We evaluated a cohort of 87 patients with idiopathic autonomic neuropathy who had undergone full autonomic testing and neurological evaluation and who had a complete panel of paraneoplastic and ganglionic AChR antibodies. We compared patients seropositive (n = 19) and seronegative (n = 87) for ganglionic AChR antibodies. RESULTS: The seropositive group had a significant overrepresentation of abnormal pupillary responses (12/18 [67%] vs 12/87 [14%]; P<.001), sicca complex (9/15 [60%] vs 11/47 [23%]; P =.01), and lower gastrointestinal tract dysautonomia (16/19 [84%] vs 48/85 [56%]; P =.02). A subacute mode of onset was more common in the seropositive group (12/19 [63%] vs 23/84 [27%]; P =.004). Results of quantitative autonomic function tests differed significantly in the 2 groups only in the cardiovagal domain. Because subacute onset was overrepresented in the seropositive group, we analyzed the data separately, controlling for temporal profile (ie, the relationship between antibody status and symptoms while controlling for rate of onset). The relationships between antibody status and clinical profile (eg, presence of sicca complex, pupillary abnormalities, and lower gastrointestinal tract symptoms) generally remained significant regardless of onset rate, indicating that the associations are not due to temporal profile. CONCLUSIONS: These observations support the concept that ganglionic AChR antibodies are diagnostically and pathophysiologically important. Patients with orthostatic hypotension and prominent cholinergic dysautonomia are most likely to be seropositive for ganglionic AChR antibody.

Autoantibodies↗
PubMed2004

Involvement of medullary serotonergic groups in multiple system atrophy.

We sought to determine whether medullary serotonergic neurons were affected in multiple system atrophy (MSA). Immunostaining for tryptophan hydroxylase was performed on serial 50 microm sections of the medulla of brains obtained at autopsy from six control subjects, eight subjects with clinical diagnosis of MSA, and four with Parkinson's disease. There was a severe depletion of serotonergic neurons in the nucleus raphe magnus, raphe obscurus, raphe pallidus, and ventrolateral medulla in MSA. Depletion of serotonergic neurons may contribute to impaired control of sympathetic outflow and other abnormalities in MSA.

Aged↗
PubMed2004

Schwann cell is a target in ischemia-reperfusion injury to peripheral nerve.

Ischemia-reperfusion (IR) causes oxidative injury and ischemic fiber degeneration due to injury of the neuron and axon. In this study, we explore the effect of oxidative stress on Schwann cells, as a specific peripheral nerve target, using our established rat model for IR injury. Fifty-six rats were used. Six groups (N = 8 each) underwent complete hindlimb ischemia for 4 h, followed by reperfusion durations of 0 h, 3 h, 7 days, 14 days, 28 days, and 42 days. One group underwent sham operation (N = 8). We evaluated immunohistochemical labeling for oxidative injury using anti-8-hydroxydeoxyguanosine (8-OHdG). To identify cells committed to apoptosis, we studied immunolabeling to caspase-3 and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) positivity. Only minimal positivity was seen in the sham, 0-h, and 3-h groups. Positivity to 8-OHdG, caspase-3, and TUNEL increased significantly in groups undergoing longer reperfusion (8-OHdG, 7-28 days; caspase-3, 14-42 days; TUNEL, 14-42 days). The positive cells surrounding axons were identified as being Schwann cells by their configuration and colabeling with S-100. We conclude that apoptosis of Schwann cells occurs during reperfusion and continues even when axons regenerate. Schwann cell apoptosis could contribute to impairment of axonal function and efficiency of fiber regeneration. Both these abnormalities are known to occur in experimental and human diabetic nerves.

Animals↗
PubMed2004

Myeloneuropathy and anemia due to copper malabsorption.

Dietary deficiency of copper results in a progressive ataxic myelopathy in ruminants called swayback. Menkes disease is a human disease due to an inherited defect in copper absorption; survival into adulthood is typically not known to occur. We report a 63-year-old woman who was evaluated by us for a myeloneuropathy that occurred in the setting of copper malabsorption. Her neurological deterioration stopped with copper supplementation. The limited literature on neurological manifestations of acquired copper deficiency suggests that the clinical presentation resembles the myeloneuropathy seen with vitamin B12 deficiency.

Anemia↗
PubMed2004

Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction.

The aim of this study was to investigate in patients with neurogenic orthostatic hypotension the mechanism and usefulness of abdominal compression to increase standing blood pressure. In three protocols, 23 patients underwent abdominal compression. Protocol 1 evaluated in a 40-60 degrees head-up-tilt position, the effect of abdominal compression on caval vein and femoral diameter, arterial blood pressure and hemodynamics. Protocol 2 documented the relationship between the level of compression and the arterial pressure response. Protocol 3 investigated the ability to maintain standing blood pressure by an elastic binder. During head-up-tilt, compression (40 mm Hg) resulted in a reduction in diameter of the caval vein (mean -2.6mm, range -1.4 to 0.6), without a change in femoral vein diameter. Stroke volume increased by 14 % (range -1 to 23) and blood pressure (systolic/diastolic) by 30/14 mmHg (range 7/2 to 69/36), both p < 0.05; 40 mmHg compression was associated with a higher pressure response than 20 mmHg (mean 18/8 mmHg, range 6/2 to 43/20 vs. mean 9/4 mmHg, range -1/0 to 18/8, p < 0.05). Elastic abdominal binding increased standing blood pressure with 15/6 mmHg (range -3/3 to 36/14, p < 0.05). We conclude that in patients with neurogenic orthostatic hypotension, abdominal compression increases standing blood pressure to a varying degree by increasing stroke volume.

Abdomen↗
PubMed2004

Pacing does not improve hypotension in patients with severe orthostatic hypotension--a prospective randomized cross-over pilot study.

BACKGROUND: Tachypacing has been suggested to compensate for drop in blood pressure as a technique to improve symptoms in patients with severe orthostatic hypotension secondary to autonomic dysfunction. To date, however, no randomized controlled studies have been performed to validate the approach. METHODS AND RESULTS: Six patients with severe orthostatic hypotension and chronotropic incompetence secondary to autonomic dysfunction underwent a prospective randomized cross-over tilt table study with no pacing and with temporary DDD pacing at 90 and 110 bpm. Time to syncope or pre-syncopal symptoms, blood pressure changes, stroke volume and cardiac output were recorded using real time hemodynamic monitoring and echocardiography. All patients, except for one, had a drop in blood pressure and syncope or pre-syncopal symptoms during tilt regardless of whether they were paced or not. There was also no difference in any of the measured hemodynamic and vasomotor parameters with pacing. CONCLUSIONS: Pacing did not produce any benefits in terms of symptoms or in any of the measured hemodynamic variables during tilt for patients with severe orthostatic hypotension secondary to autonomic dysfunction in this limited pilot study.

Aged↗
PubMed2004

Zonisamide and associated oligohidrosis and hyperthermia.

Zonisamide is an antiepileptic agent that is indicated as adjunctive therapy for the treatment of partial seizures in adults. Oligohidrosis has been reported in a small number of patients receiving zonisamide and, in a proportion of these patients, hyperthermia has occurred. Most reports of hyperthermia have been in children, typically occurring during the summer months. However, the mechanism of zonisamide-associated oligohidrosis is not fully understood. Thirteen events of oligohidrosis, or hyperthermia, associated with zonisamide were reported in the US during the 3 years after zonisamide was approved, an estimated incidence of 1 case per 4590 patient-years. These events happened mostly in children. In Japan, all reported cases of zonisamide-associated oligohidrosis or hyperthermia have been in children, with an incidence of 1 case per 10,000 pediatric-years during the first 11 years of marketing. In each case, oligohidrosis was reversible upon discontinuation of zonisamide. Ensuring that children remain cool and well hydrated during hot weather can minimize the potential for hyperthermia resulting from oligohidrosis.

Adult↗