Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes Clinical Presentation

Features of autonomic disturbance in any of these conditions may include orthostasis, nausea, constipation, urinary retention or incontinence, nocturia, impotence, heat intolerance, and dry mucous membranes. Less commonly, patients experience periods of apnea or inspiratory stridor. Postural orthostatic tachycardia syndrome (POTS) results in prominent excessive adrenergic symptoms, especially tachycardia.

• Symptoms of decreased sympathetic function may include the following:

  • Orthostatic hypotension
  • Decreased sweating
  • Ejaculatory dysfunction
  • Ptosis associated with Horner syndrome
• Symptoms of decreased parasympathetic function may include the following:

  • Constipation
  • Nausea
  • Urinary retention
  • Erectile dysfunction
• Pure autonomic failure (PAF)

  • PAF is by definition not associated with CNS symptoms. Careful questioning is required to exclude symptoms of CNS dysfunction, such as gait disturbance or spasticity. Patients should also be questioned in detail about sensory loss or neuropathic pain, which may suggest autoimmune autonomic neuropathy (AAN).
  • In older literature, the terms PAF and idiopathic orthostatic hypotension were sometimes used interchangeably. Orthostatic hypotension is the most common complaint in this group of patients.
  • Abnormalities of urination, salivation, sweating, and defecation can occur, though these are less common in PAF than in AAN.
• Autoimmune autonomic neuropathy

  • Patients with apparent PAF should be questioned carefully regarding dry mouth or dry eyes.
  • Such sicca symptoms may be associated with ganglionic AChR autoantibodies.
  • Mild sensory disturbances may be present and overshadowed by autonomic dysfunction.
• Multiple system atrophy

  • MSA is a chronic, progressive disorder with mixed features of chronic autonomic dysfunction, parkinsonism, and ataxia.^[1]
  • Autonomic dysfunction is a common finding in MSA and in the absence of pathological findings essential to the diagnosis.
  • A subset of patients with PAF may eventually develop MSA, but no clinical or diagnostic markers identify this group at the outset.
  • Depending on their clinical features, patients with MSA may be categorized as parkinsonian (MSAp) or cerebellar (MSAc) variants, depending on the most prominent symptoms and findings on physical examination.
• Postural orthostatic tachycardia syndrome

  • POTS is a relatively benign disorder that is often self-limiting.
  • Patients may complain of dizziness, blurry vision, weakness, lightheadedness, and fatigue upon standing. Palpitations, tremulousness, and anxiety can also be seen.
  • Other associated symptoms include neurocognitive or sleep disorders, exercise intolerance, hyperpnea, dyspnea, nausea, abdominal pain, and sweating.

• Pure autonomic failure

  • Cardiovascular manifestations include orthostatic hypotension with an inappropriate lack of compensatory increase in heart rate with standing. Orthostatic hypotension is defined as a decrease of at least 20 mm Hg in systolic blood pressure or at least 10 mm Hg in diastolic blood pressure within 3 minutes of standing.
  • Gastroparesis is common and is associated with nausea or constipation. The abdomen may be distended, and patients may have discomfort on palpation. An acute abdomen is unusual. Diarrhea may also occur, with or without fecal incontinence.
  • Urinary retention is seen frequently and may cause bladder distention. A distended bladder can be detected on examination by percussion or palpation. Bladder emptying may be incomplete with post-void residuals of 100 mL or more.
  • Decreased sweating manifests as heat or exercise intolerance. Patients may have noticeably warm and/or dry skin.
  • The eyes may be affected. Careful ophthalmologic examination may reveal ptosis, anisocoria, Horner syndrome, or tonic pupils
  • Failure of either erection or ejaculation is a common physical manifestation in males. Female sexual dysfunction has not been well studied in these disorders.
• Autoimmune autonomic neuropathy: The overall physical findings are similar to those observed in PAF. Patients may have additional findings of sensory abnormalities, pain, or loss of deep tendon reflexes.
• Multiple system atrophy: Autonomic manifestations are similar to those observed in AAN and PAF. However, additional neurologic features may be present.

  • Pyramidal or cerebellar abnormalities including weakness, ataxia, incoordination, and eye-movement abnormalities may precede the autonomic features by as long as 2 years.
  • Patients with the MSA parkinsonian variant have variable parkinsonian findings, including rigidity, bradykinesia, tremor, and truncal instability, that do not respond to levodopa.
  • Patients with the MSA cerebellar variant have evidence of cerebellar dysfunction that manifests as ataxia, dysmetria, dysdiadokinesia, and incoordination. Eye-movement abnormalities are frequently present.
• Postural orthostatic tachycardia syndrome: A greater than 30-bpm increase in heart rate on standing, without a clinically significant decrease in blood pressure are diagnostic.

• Pure autonomic failure

  • Patients who are initially identified as having PAF may have underlying pathology consistent with MSA or Parkinson's disease, or they may be found to have AAN after extensive testing.
  • Involvement of the intermediolateral cell column with the loss of small sympathetic neurons has been observed in some patients.
• Autoimmune autonomic neuropathy

  • The cause of AAN is presumed to be autoimmune.
  • Autoantibodies against ganglionic AChRs are seen in one- to two-thirds of patients with this condition.^[2]
  • A preceding infection or other antecedent illness is noted in about 60% of cases.
  • In rare cases, patients have a coexisting thymus tumor.
• Multiple system atrophy

  • In MSA with autonomic involvement, changes in the intermediolateral cell column also may be seen; in addition, widespread abnormalities are apparent in the brain.
  • Histopathologically, alpha-synuclein immunostaining demonstrates glial cytoplasmic inclusions.
  • Associated clinical findings are related to the constellation of affected areas.
  • Neuronal loss may be noted in the basal ganglia, pons, cerebellum, substantia nigra, locus ceruleus, nucleus of Edinger-Westphal, hypothalamus, thalamus, and vestibular complex.
• Postural orthostatic tachycardia syndrome

  • A norepinephrine transporter deficiency has been identified in 1 family.
  • Polymorphisms in genes encoding the beta-2 adrenoreceptor and nitric oxide synthetase may play a role.
  • Beta-receptor supersensitivity, reduced vagal function, brainstem dysfunction, and deficient cerebral blood flow autoregulation are other proposed mechanisms.
  • Some patients have restricted autonomic neuropathy.