NEURO­GENIC BLADDER

Urinary symptoms are experienced by nearly all MSA patients and can be one of the earliest signs of the disease. Symptoms include trouble voiding, incontinence, increased frequency and urgency and leakage. In MSA, urinary tract problems are thought to occur due to a decline of neuronal control from the cerebellum. These problems can lead to a lack of control of the urinary sphincter and a change in activity of the detrusor muscle found in the wall of the bladder, leading to incontinence and an inability to fully empty the bladder. These problems can lead to repeated urinary tract infections and kidney infection if not properly treated.

1. Non-pharmacologic treatments of neurogenic bladder include:

  • Catheterization can help to control the symptoms of neurogenic bladder. Intermittent catheterization can be used when residual urine volume is >100ml. This can be performed by the patient or caregiver at regular intervals during the day to drain excess urine from the bladder to prevent infection. When urinary symptoms progress, a permanent catheter may need to be placed.
  • Surgery is an option when catheterization doesn’t work or is not feasible. A permanent suprapubic catheter can be surgically placed to drain urine. In men, surgery may remove the external sphincter to prevent urinary retention. Stents can also be placed into the urethra to maintain a patent pathway for voiding and to prevent urine retention.
  • There are lifestyle modifications that can also help with urinary symptoms of MSA. Avoidance of diuretics, including caffeine and alcohol, can limit the frequency of urination. Adequate exercise and the use of compression stockings can also decrease edema, which can lead to increased urination, especially at night.
  • bladder diary is an important way to discern symptoms and the progression of symptoms in MSA patients. A bladder diary can track urinary tract symptoms, fluid intake, urine output, and time to voids.

2. Medications used to control neurogenic bladder include:

  • Anticholinergic agents are used when post-void urine volume is <100ml. These medications block the neurotransmitter acetylcholine and the muscle contraction it causes, and can ameliorate symptoms of urgency, frequency and incontinence, but increase the risk of urine retention. Drugs in this class include propiverine, which can increase bladder capacity, oxybutynin, which not only increases bladder capacity, but can also decrease the activity of the detrusor muscle. Oxybutynin has the added benefit of being available as an extended release capsule or a transdermal patch. Tolterodinesolifenacin and darifenacin are other drugs in this class that have been shown to decreases symptoms of neurogenic bladder.
  • Alpha-adrenergic blockers, such as alfuzosine chlorhydrate and tamsulosine chlorhydrate, can be used to reduce post-void urine residuals when there is an impaired urinary sphincter muscle. Given the worsening of orthostatic hypotension that may occur with this class of medication, care must be taken using these.
  • Nitrous oxide induces vasodilation and has been shown to relax the muscles of the bladder and increase bladder capacity. Drugs that mimic the mechanism of action of nitrous oxide include sildenafiltadalafil and vardenafil and have been shown to be effective both for neurogenic bladder and erectile dysfunction.
  • Tamsulosin can be used in conjunction with tadalafil to assist with voiding, decreasing residual urine volume and increase bladder storage capacity.
  • Botulinum injection into either the detrusor muscle or urethral sphincter can be used when medications don’t work. This can decrease overactivity in the detrusor muscle and increase bladder capacity and can be used in the urethral sphincter to assist in bladder emptying.
  • Desmopressin can be used to decrease urine volume and is especially useful in treating excessive nighttime urination, while having the additional benefit of improving orthostatic hypotension, but given its high rate of hyponatremia and cognitive impairment, it is not recommended.

References

  1. Sakakibara R, Hattori T, Uchiyama T, et al. Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation?. J Neurol Neurosurg Psychiatry. 2000;68(1):65–69.
  2. Perez-Lloret S, Flabeau O, Fernagut PO, et al. Current Concepts in the Treatment of Multiple System Atrophy. Mov Disord Clin Pract. 2015;2(1):6–16.
  3. Yu Y, de Groat WC. Nitric oxide modulates bladder afferent nerve activity in the in vitro urinary bladder-pelvic nerve preparation from rats with cyclophosphamide induced cystitis. Brain Res. 2013;1490:83–94.
  4. Palma JA, Norcliffe-Kaufmann L, Martinez J, Kaufmann H. Supine plasma NE predicts the pressor response to droxidopa in neurogenic orthostatic hypotension. Neurology. 2018;91(16):e1539–e1544.
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