Autonomic Failure

Unfortunately there is no causal therapy of autonomic dysfunction available. Therefore the therapeutic strategy is defined by clinical symptoms and impairment of quality of life in these patients. Because of the progressive course of MSA, a regular review of the treatment is mandatory to adjust measures according to clinical needs.

The concept to treat symptoms of orthostatic hypotension is based on the increase of intravascular volume and the reduction of volume shift to lower body parts when changing to upright position. The selection and combination of the following options depend on the severity of symptoms and their practicability in the single patient, but not on the extent of blood pressure drop during tilt test. Nonpharmacological options include sufficient fluid intake, high salt diet, more frequent, but smaller meals per day to reduce postprandial hypotension by spreading the total carbohydrate intake, and custom-made elastic body garments. During the night, head-up tilt increases intravascular volume up to 1 L within a week, which is particularly helpful to improve hypotension early in the morning. This approach is successful in particular in combination with fludrocortisone, which further supports sodium retention.

The next group of drugs to consider are the sympathomimetics. These include ephedrine (with both direct and indirect effects), which is often valuable in central autonomic disorders such as MSA. With higher doses, side effects include tremulousness, loss of appetite, and urinary retention in men.

Among the large number of vasoactive agents that have been evaluated in MSA, only one, the directly acting a-adrenergic agonist midodrine, meets the criteria of evidence-based medicine (178180). Side effects are usually mild and only rarely lead to discontinuation of treatment because of urinary retention or pruritus, predominantly on the scalp.

Another promising drug appears to be the norepinephrine precursor L-threo-dihydroxy-phenylserine (L-threo-DOPS), which has been used in this indication in Japan for years and efficacy of which has now been shown by a recent open, dose-finding trial (181).

In case the above-mentioned drugs do not produce the desired effects, selective targeting is needed. The somatostatin analog, octreotide, is often beneficial in postprandial hypotension (182), presum-

Table 3

Practical Management of MSA

  1. Pharmacotherapy
  2. For akinesia-rigidity
  • Levodopa up to 800-1000 mg/d, if tolerated
  • Dopamine agonists as second-line anti-parkinsonian drugs (dosing as for PD patients)
  • Amantadine as third-line drug, 100 mg up to three times daily II. For focal dystonia
  • Botulinum toxin A

III. For orthostatic hypotension

  • Head-up tilt of bed at night
  • Elastic stockings or tights
  • Increased salt intake
  • Fludrocortisone 0,1-0, 3 mg/d
  • Ephedrine 15-45 mg t.i.d
  • L-threo-DOPS (300 mg b.i.d.)
  • Midodrine 2.5 |4g-10 mg t.i.d.

IV. For postprandial hypotension

  • Octreotide 25-50 |J,g s.c. 30 min before a meal V. For nocturnal polyuria
  • Desmopressin (spray: 10-40 mg/night or tablet: 100-400 mg/night) VI. For bladder symptoms
  • Oxybutynin for detrusor hyperreflexia (2.5-5 mg b.i.d-t.i.d.)
  • Intermittent self-catheterization for retention or residual volume >100 ml

B. Other therapies

  • Physiotherapy
  • Speech therapy
  • Occupational therapy
  • Percutaneous endoscopic gastrostomy (PEG) (rarely needed in late stage)
  • Provision of wheelchair
  • CPAP (rarely tracheostomy for inspiratory stridor

Reproduced with kind permission from John Wiley & Sons, Inc.: Wenning et al., Multiple System atrophy: an update. Mov Disord 2003;18(suppl 6):34-42.

ably because it inhibits release of vasodilatory gastrointestinal peptides (183); importantly it does not enhance nocturnal hypertension (182).

The vasopressin analogue, desmopressin, which acts on renal tubular vasopressin-2 receptors, reduces nocturnal polyuria and improves morning postural hypotension (184).

The peptide erythropoietin may be beneficial in some patients by raising red cell mass, secondarily improving cerebral oxygenation (185,186).

A broad range of drugs (Table 3) have been used in the treatment of postural hypotension (187). Unfortunately, the value and side effects of many of these drugs have not been adequately determined in MSA patients using appropriate endpoints.

In the management of neurogenic bladder including residual urine clean intermittent catheteriza-tion three to four times per day is a widely accepted approach to prevent secondary consequences of failure to micturate. It may be necessary to provide the patient with a permanent transcutaneous suprapubic catheter if mechanical obstruction in the urethra or motor symptoms of MSA prevent uncomplicated catheterization.

Pharmacological options with anti- or pro-cholinergic drugs or a-adrenergic substances are usually not successful to adequately reduce postvoid residual volume in MSA, but anticholinergic agents like oxybutynin can improve symptoms of detrusor hyperreflexia or sphincter-detrusor dyssynergy in the early course of the disease (50). Recently, a-adrenergic receptor antagonists (prazosin and moxisylyte) have been shown to improve voiding with reduction of residual volumes in MSA patients (188). Urological surgery must be avoided in these patients because postoperative worsening of bladder control is most likely (50).

The necessity of a specific treatment for sexual dysfunction needs to be evaluated individually in each MSA patient. Male impotence can be partially circumvented by the use of intracavernosal papav-erine, prostaglandin E1, or penile implants (189). Preliminary evidence in PD patients (190) suggests that sildenafil may also be successful in treating erectile failure in MSA: a recent trial confirmed the efficacy of this compound in MSA, but also suggested caution because of the frequent cardiovascular side effects (191). Erectile failure in MSA may also be improved by oral yohimbine (50).

Constipation can be relieved by increasing the intraluminal volume, which may be achieved by using macrogol-water-solution (192).

Inspiratory stridor develops in about 30% of patients. Continuous positive airway pressure (CPAP) may be helpful in some of these patients (193). In only about 4% a tracheostomy is needed and performed.

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