Neurological Conditions Causing Orthostatic Hypotension
The primary neurological causes of orthostatic hypotension are neurodegenerative disorders affecting the autonomic nervous system, including multiple system atrophy, Parkinson's disease with autonomic failure, pure autonomic failure, and peripheral autonomic neuropathies (most commonly diabetic autonomic neuropathy). 1, 2
Primary Autonomic Failure Syndromes
These represent the core neurological causes where the autonomic nervous system itself degenerates:
- Multiple system atrophy (Shy-Drager syndrome) involves widespread autonomic degeneration with neurologic deterioration, postural tachycardia, and muscular rigidity 3, 1
- Pure autonomic failure affects peripheral autonomic nerves selectively, causing orthostatic hypotension without other neurological features 3, 1
- Parkinson's disease with autonomic failure develops when Parkinson's disease progresses to include autonomic dysfunction, causing neurogenic orthostatic hypotension 3, 1, 4
- Dementia with Lewy bodies can present with autonomic failure as part of its clinical spectrum 3
Secondary Autonomic Neuropathies
Neurological damage from systemic diseases represents another major category:
- Diabetic autonomic neuropathy is the most common endocrine cause of neurogenic orthostatic hypotension, representing an advanced stage of autonomic dysfunction 1, 5, 2
- Amyloidosis causes orthostatic hypotension through autonomic nerve infiltration 3, 1
- Autoimmune autonomic neuropathy results from immune-mediated damage to autonomic ganglia 3
- Paraneoplastic autonomic neuropathy occurs as a remote effect of malignancy 3
- Spinal cord injuries disrupt descending autonomic pathways 3
Hereditary Autonomic Disorders
- Familial dysautonomia (Riley-Day syndrome, hereditary sensory and autonomic neuropathy type III) is a genetic disorder with abnormalities of sensory and autonomic nerves, decreased pain sensation, and decreased tear production 3
Key Distinguishing Features of Neurogenic Orthostatic Hypotension
The hallmark that separates neurogenic from non-neurogenic causes:
- Blunted heart rate response upon standing (typically <10 beats per minute increase) occurs because cardiovascular sympathetic fibers fail to increase total peripheral vascular resistance and heart rate appropriately 3, 1
- In contrast, non-neurogenic causes (volume depletion, medications) show preserved or enhanced heart rate increases 3, 1
Age-Related Neurological Changes
While not a discrete disease entity, aging causes neurological deterioration that predisposes to orthostatic hypotension:
- Impaired compensatory vasoconstrictor reflexes develop with aging 1
- Baroreflex dysfunction from age-related changes contributes to orthostatic hypotension 1
- Reduced cerebral autoregulation occurs as an age-related neurological change 1
Clinical Pitfalls
- Unexplained syncope may be the first manifestation of neurodegenerative disorders such as Parkinson's disease, before other motor symptoms become apparent 6
- Up to 40% of elderly patients with syncope have amnesia for loss of consciousness, making diagnosis challenging and often presenting as unexplained falls rather than classic syncope 6
- Carotid sinus hypersensitivity is an under-recognized neurological cause of syncope in the elderly that can contribute to backward falls 6
- Supine hypertension commonly coexists with neurogenic orthostatic hypotension in autonomic failure, complicating treatment goals 5
Diagnostic Approach for Neurological Causes
When neurogenic orthostatic hypotension is suspected:
- Cardiovascular autonomic reflex tests (CARTs) including heart rate variability testing, Valsalva maneuver, and deep breathing tests confirm autonomic dysfunction 5
- Neurological examination should assess gait, balance (eyes open and closed), and signs of Parkinsonism or other neurodegenerative features 3, 6
- Referral for autonomic evaluation is useful to improve diagnostic and prognostic accuracy in patients with syncope and known or suspected neurodegenerative disease 3