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Pages 317-356

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From page 317...
... Appendix B Commissioned Paper THE FUNCTIONAL IMPACT OF ORTHOSTATIC INTOLERANCE IN EHLERS-DANLOS SYNDROME Peter C
From page 318...
... 318 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE between orthostatic intolerance and other disabling conditions, including heritable disorders of connective tissues. We then review the therapeutic measures to attenuate the impact of circulatory dysfunction on daily activities for affected children and adults, moving on to discuss the determinants of the ability to work or attend school.
From page 319...
... APPENDIX B 319 TABLE B-1 Symptoms of Orthostatic Intolerance Due (largely) to the Hyperadrenergic Due to ↓ CBF Response to ↓ CBF Lightheadedness Dyspnea Syncope Chest discomfort Diminished concentration Palpitations Headache Tremulousness Blurred vision Anxiety Fatigue Diaphoresis Exercise intolerance Nausea NOTE: CBF = cerebral blood flow.
From page 320...
... 320 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE FIGURE B-1  Pathophysiologic factors in orthostatic intolerance. NOTE: BP = blood pressure; dOH = delayed orthostatic hypotension; HR = heart rate; NMH = neurally mediated hypotension; OH = orthostatic hypotension; POTS = postural tachycardia syndrome.
From page 321...
... APPENDIX B 321 the return of blood to the heart and a markedly increased catecholamine response (Benditt et al., 2003; Rosen and Cryer, 1982)
From page 322...
... 322 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE during the first 10 minutes upright as an additional criterion (Fedorowski, 2019)
From page 323...
... APPENDIX B 323 pathophysiology of NMH involves reduced venous return, which then initiates a series of neural responses that result in withdrawal of sympathetic tone and a relatively unopposed vagal response. These responses lead to slowing of the heart rate and vasodilation, which can result ultimately in a profound drop in blood pressure or syncope if the individual remains upright.
From page 324...
... 324 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE Head-Up Tilt Table Testing Modern head-up tilt table testing is conducted using a motorized table with a footboard for weight-bearing (Benditt et al., 1996)
From page 326...
... 326 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE BOX B-1 Methods and Reporting Form for the Passive Standing Test PASSIVE STANDING TEST: The following is a modification of the passive standing test (Hyatt et al., 1975) that has been used in the Chronic Fatigue Clinic at Johns Hopkins Hospital since the mid-1990s.
From page 327...
... APPENDIX B 327 DEFINITIONS: Postural tachycardia syndrome (POTS) : an increase in heart rate of at least 30 beats per minute (bpm)
From page 328...
... 328 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE BOX B-1 Continued STANDING TEST DATA SHEET Name: Date of Test: ___________ Medications in last 2 weeks: ________________________________________ ________________________________________________________________ Blood Comments/Symptom Heart Rate Pressure ratings SUPINE 1 min 2 min 3 min 4 min 5 min STANDING 1 min change in heart rate in those with POTS than does active standing (Plash et al., 2013)
From page 329...
... APPENDIX B 329 2 min 3 min 4 min 5 min 6 min 7 min 8 min 9 min 10 min SUPINE 1 min 2 min Abbreviations: ACRO = acrocyanosis, COG = cognitive difficulties, FTG = fatigue, HA = head ache, HOT = warmth/hot flash, LH = lightheadedness, NAU = nausea, PALL = pallor, PN = muscle pain/ache, SOB = trouble breathing, SW = sweating. ASSOCIATION OF ORTHOSTATIC INTOLERANCE WITH OTHER DISABLING CONDITIONS Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Among those with ME/CFS or the related condition fibromyalgia, orthostatic stress consistently provokes fatigue and other symptoms (IOM, 2015; Martinez-Lavin, 2006; van Campen et al., 2020a)
From page 330...
... 330 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE with as little as 20 degrees of upright stress (van Campen 2020c; Wyller et al., 2007)
From page 331...
... APPENDIX B 331 FIGURE B-2 Changes in cerebral blood flow during 30 minutes of head-up tilt compared to supine values in 44 healthy controls and 429 adults with ME/CFS. The dotted column is mid-tilt and the hatched column is end-tilt.
From page 332...
... 332 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE In subsequent work, van Campen and colleagues (2020b) have shown that sitting can provoke a clinically important reduction in cerebral blood flow.
From page 333...
... APPENDIX B 333 De Wandele and colleagues (2014a) performed the largest and most comprehensive study of the association between autonomic dysfunction and heritable disorders of connective tissue.
From page 334...
... 334 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE FIGURE B-3  Reductions in cerebral blood flow (CBF) from supine values after 30 minutes of head-up tilt in 100 hypermobile and 100 nonhypermobile adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
From page 335...
... APPENDIX B 335 Nonpharmacologic Measures Nonpharmacologic treatment for orthostatic intolerance is focused in four main areas. Individuals need to (1)
From page 336...
... 336 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE promote increased calf muscle contraction. We advise against sitting on a high stool with the legs dangling freely, as that position provides no resistance to blood pooling in the legs.
From page 337...
... APPENDIX B 337 drinks) can help symptoms by acting as a vasoconstrictor, but some patients experience adverse effects, such as excessive stimulation or diuretic effects.
From page 338...
... 338 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE TABLE B-2 Medications for Orthostatic Intolerance Medication Usual Adolescent Dose Comments/Indications Vasoconstrictors Midodrine 2.5 mg every 4 hours while Suggested as first-line therapy for awake. Increase every 3–7 days those with baseline hypotension.
From page 339...
... APPENDIX B 339 TABLE B-2 Continued Medication Usual Adolescent Dose Comments/Indications Desmopressin 0.1 mg at bedtime, increasing to Suggested for those with nocturia. acetate 0.2 mg daily.
From page 340...
... 340 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE (Boehm et al., 1997)
From page 341...
... APPENDIX B 341 Ivabradine A variety of medications can be used to combat the vasoconstriction defect, improve blood volume, or affect the release or impact of catecholamines. Ivabradine is a newer medication introduced for the treatment of tachycardia in the setting of congestive heart failure (DiFrancesco, 2010)
From page 342...
... 342 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE overall function by trying to perform too much exercise before her circulatory dysfunction had been treated. For this patient, increases in ivabradine were associated with gradual lowering of her resting heart rate to 72 bpm.
From page 343...
... APPENDIX B 343 In earlier work among adults, VanNess and colleagues (2010) evaluated 25 females with ME/CFS and 23 sedentary controls after a maximal cardiopulmonary exercise test (duration 5–15 minutes)
From page 344...
... 344 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE of ligamentous instability at the skull base (including atlantoaxial and craniocervical instability) (Henderson et al., 2021; Milhorat et al., 2007)
From page 345...
... APPENDIX B 345 distinguish between diseased and nondiseased individuals, it is less useful to define the disability level for individual patients, especially in light of the variation of the number of steps per day for a certain value of the PFS (van Campen et al., 2020d)
From page 346...
... 346 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE individuals with EDS or hypermobility spectrum disorder, 9 had multiple episodes of syncope and presyncope weekly, which would create a risk of injury and be incompatible with steady classroom attendance or employment. Surgical stabilization, however, significantly decreased the frequency of syncope and presyncope.
From page 347...
... APPENDIX B 347 CONCLUDING COMMENTS Orthostatic intolerance is common in individuals with EDS and hypermobility spectrum disorders and can be associated with heterogeneous blood pressure and heart rate responses to orthostatic stress, including POTS, orthostatic hypotension, and NMH. Importantly, as measured by Doppler techniques, orthostatic reductions in cerebral blood flow can be present even in those with a normal heart rate and blood pressure response to upright posture.
From page 348...
... 348 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE REFERENCES Arnold, L
From page 349...
... APPENDIX B 349 De Wandele, I., P Calders, W
From page 350...
... 350 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE Grubb, B
From page 351...
... APPENDIX B 351 Legge, H., M Norton, and J
From page 352...
... 352 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE Ocon, A
From page 353...
... APPENDIX B 353 Rowe, P
From page 354...
... 354 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE Smith, J
From page 355...
... APPENDIX B 355 van Campen, C., P
From page 356...
... 356 SELECTED HERITABLE DISORDERS OF CONNECTIVE TISSUE Walker, L

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