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Supplements Understanding the Diagnosis, Management, and Treatment Options for Neurogenic Orthostatic Hypoten

Neurogenic Orthostatic Hypotension: Pathophysiology and Diagnosis

Phillip A. Low, MD
Several factors may contribute to the diag-nosis of NOH being missed. One reason is that symptoms of lightheadedness may be absent. Additionally, patients may instead have subtle symptoms, such as cognitive slowing.38 Another reason is that a patient may truly be asymptomatic, due to expansion of the autoregulated range.46 Awareness of this rare disease also presents a problem because it is understandably low among both clinicians and patients. In addition, patients may attribute NOH symptoms to their primary disorder. An online survey collected data from 178 patients with disorders that may be affected by NOH (PD, MSA, PAF, dopamine beta-hydrox-ylase deficiency, and nondiabetic autonomic neuropathy) and their caregivers (n = 180).68 Although most patients reported experiencing at least 1 symptom of NOH, 24% of patients and 22% of caregivers had never heard of NOH.

Tools for Assessing NOH Symptoms

Two self-report questionnaires have been developed specifically to assess symptoms in patients with NOH: the Orthostatic Grading Scale (OGS; Table 337) and the Orthostatic Hypotension Questionnaire (OHQ; Figure 1a, 1b, 1c69).37,69 These instruments may be used in diagnosis to assess progres-sion of NOH and to assess the response to pharmaco-therapy in clinical practice.41 The OHQ has been used to evaluate the clinical efficacy of droxidopa and midodrine for NOH in clinical trials.70,71 The OGS, which was adapted from the autonomic symptom profile, has 5 items that address the frequency and severity of orthostatic symptoms, relationship of symptoms to orthostatic stressors, and impact of symptoms on activities of daily living and standing time.2,37 Scores for each item are summed to provide a total score for the instrument, ranging from 0 for no impairment to 20 for maximal impairment. The OGS robustly correlated with autonomic deficits on the CASS in patients undergoing full autonomic laboratory evaluation. Using a CASS adrenergic subscore of at least 3, an OGS score of at least 9 had sensitivity of 65.6% and specificity of 69.2%.37

The OHQ has 2 domains: OH symptoms and their impact on walking.69 The 6-item Orthostatic Hypotension Symptom Assessment (OHSA) asks about dizziness/ lightheadedness, vision disturbance, weakness, fatigue, trouble concentrating, and head or neck discomfort. The 4-item Orthostatic Hypotension Daily Activity Scale (OHDAS) assesses the interference of NOH with daily activities: standing a short time, standing a long time, walking a short time, and walking a long time. Patients score items on a scale of 0 to 10 for the average severity of symptoms over the past week. Two factors raise questions about content validity of the OHQ: the questionnaire asks patients to rate only symptoms related to their low blood pressure problem and to average the severity of their symptoms over the past week.72 An improvement of 0.8 to 1.0 units is considered a minimal important change on the OHSA, OHDAS, and OHQ composite score.69

A study in 201 patients with PD evaluated the rela-tionship between the orthostatic drop, standing blood pressure, and symptoms of OH as characterized by the OHQ. Using the criteria of a 20/10 mm Hg drop in blood pressure for the diagnosis of NOH, 50% of patients in the cohort met the diagnosis and 33% of them were symptom-atic. Using the criteria of a 30/15 mm Hg drop in blood pressure, 30% of patients met the diagnosis and 44% were symptomatic. A mean standing blood pressure lower than 75 mm Hg had 97% sensitivity and 98% specificity for detecting symptomatic OH. The authors propose a mean standing blood pressure lower than 75 mm Hg as a marker for determining if OH symptoms are substantial enough for pharmacotherapy.73

Author affiliation: Mayo Clinic.

Funding source: This activity is supported by an educational grant from Lundbeck, LLC. Author disclosure: Dr. Low has no relevant commercial financial relationships or affiliations to disclose.

Authorship information: Concept and design, analysis and interpreta-tion of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, statistical analysis, and supervision.

Address correspondence to: low@mayo.edu.
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