Enuresis

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Editor(s)-in-Chief: C. Michael Gibson, M.S.,M.D. [1] Phone:617-632-7753; Angela Botts, M.D., Beth Israel Deaconess Medical Center Geriatric Medicine [2]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [3]

Overview

Enuresis is the involuntary urination beyond the age of anticipated control. The two major forms of enuresis are diurnal enuresis (or daytime wetting), and nocturnal enuresis (bedwetting or nighttime wetting). Enuresis impacts the child and is associated with poor scholastic performance. It also has a major psychosocial burden on the family and this results in poorer quality of life in parents. This condition vastly affects the whole family. Treatment of enuresis should be holistic by managing enuresis in children, and providing psychotherapeutic support to the parents.

Historical Perspective

• Enuresis has been a major social problem since ancient times.
• Initially enuresis was considered a manifestation of psychiatric disturbance. It has been followed by the clearer theory of maturational delay with the role of hereditary factors.
• After multiple studies, it has been found that enuresis may be the cause and not the result of a psychiatric disorder.
• As early as 1550 BC, the problem of childhood incontinence was described in the Ebers papyrus.
• Prayers became an important supplemental component of the treatment options in the middle ages.
• Belladonna, camphor, opium, and ergot were administered to enhance the bladder muscle tone in the eighteenth century.
• In 1948, a direct conditioning based treatment modality called the alarm or bell-and-pad system was introduced.
• Initially, psychotherapy was accepted as the only possible method to treat enuresis, and there was a lot of skepticism about the conditioning treatment.

Classification

• Enuresis is broadly divided in two types: daytime wetting and nocturnal enuresis.
• According to International Children’s Continence Society (ICCS), enuresis consists of wetting by a child who has passed his or her fifth birthday.
• Enuresis is considered significant if it occurs more than once per month and at a frequency of at least three times per three months. Enuresis is termed frequent if there are more than three episodes a week.
• If there are concomitant daytime voiding symptoms such as incontinence, frequency, urgency, or low voided volume, the condition is termed nonmonosymptomatic enuresis (NMEN). If bedwetting and nocturia are the only symptoms, the condition is known as monosymptomatic enuresis (MEN).
• MEN occurs without any other symptoms of bladder dysfunction whereas NMEN is associated with dysfunction of the lower urinary tract with or without daytime incontinence.
• Primary enuresis is used for a child that was never continent, whereas the term secondary enuresis is used for new-onset symptoms after a dry period of at least six months.

Pathophysiology

• Some of the underlying pathophysiological mechanisms for enuresis are:
  • Altered antidiuretic hormone profile
  • Sleep arousal failure
  • Delayed bladder maturation
  • Abnormal bladder function
  • Detrusor instability
  • Excess urine production during sleep
• Nocturnal enuresis may be associated with lower urinary tract symptoms such as urgency, frequency, and wetting – with reduced bladder storage, and an overactive bladder. These may be further associated with constipation.
• Nocturnal enuresis often occurs early in the night, mainly in sleep stage 2 and deep sleep. Children with nocturnal enuresis and nocturnal polyuria differ in hemodynamics and autonomic activation at night compared to healthy controls.
• Children with nocturnal enuresis often have sleep-disordered breathing and disturbed sleep due to awakenings and arousal. Periodic limb movements (PLM) have also been seen in children with refractory enuresis.

Differential Diagnosis

Enuresis should be differentiated from other causes

• Medication side effects
• Neurogenic bladder
• Renal diseases
• Constipation
• Diabetes Mellitus
• Detrussor areflexia or overactivity
• Urinary tract infection
• Posterior urethral valve
• Emotional disturbances
• Underlying conditions resulting in polyuria such as sickle cell disease, and diabetes insipidus
• Spinal dysraphism
• Nephronopthisis
• Psychogenic polydipsia
• Pinworm infection
• Upper airway tract obstruction
• Other urological dysfunction
• Other neurological diseases

Epidemiology and Demographics

Prevalence

• The prevalence of enuresis is
  • 5,000-10,000 per 100,000 (5%-10%) among children 5 years of age
  • 3,000-5,000 per 100,000 (3%-5%) among children 10 year of age
  • 1,000 per 100,000 (1%) among individuals 15 years of age or older

Age

• Enuresis is found to be more prevalent in the first born children.
• If enuretic symptoms persist into adulthood, they are probably less likely to resolve with time.
• Primary nocturnal enuresis in adult may represent a more pronounced form and have a more serious social and psychological effect on affected individuals.

Gender

• Most studies show a predominance of enuresis in males, whereas some others show no gender predominance.

Race

• Sickle-cell anemia (SCA) is the most common inherited hemoglobinopathy in the African population. It has been found that children and adolescents with SCA are at increased risk of nocturnal enuresis.

Risk Factors

• The risk factors for the development of enuresis are
  • Delayed or lax toilet training
  • Genetic predisposition
  • Encopresis
  • Psychosocial stressors
  • Family history of enuresis (such as maternal history, and sibling history of bedwetting)
  • Low socioeconomic status
  • Snoring
  • Heavy and late supper
  • Deep sleeper
  • Sleepwalking
  • Being introverted and shy

Natural History, Complications, and Prognosis

• Most children with enuresis eventually obtain bladder control.
• It has been found that the prevalence of nocturnal enuresis gradually decreases with increasing age and many may achieve spontaneous resolution.
• The link between childhood enuresis and adult detrusor instability is observed to be stronger for men than women.
• If intranasal desmopressin is used in the treatment of enuresis, some patients may develop seizures or altered mental status within 14 days of starting the medication.
• The accidental poisoning of young children by medications (tricyclic antidepressants) prescribed for enuresis have been reported.
• The prognosis of secondary nocturnal enuresis due to cystitis, constipation, diabetes mellitus, seizure disorder, acquired urethral obstruction, and hyperthyroidism, is excellent once the underlying cause has been treated successfully.
• Patients with nocturnal enuresis due to psychological causes generally improve over time with psychosocial alterations or successful psychotherapy.

Comorbidities

• Enuresis exists with various comorbid conditions
  • Attention-deficit hyperactivity disorder (ADHD)
  • Obstructive sleep apnea syndrome
  • Sickle cell anemia
  • Childhood obesity
  • Oppositional-defiant disorder (ODD)
  • Tic disorder
  • Conduct disorder
  • Bipolar affective disorder
  • Post-traumatic stress disorder (PTSD)

Diagnostic Criteria

DSM-5 Criteria for Enuresis

• Enuresis is included under the elimination disorders.
• The diagnostic guidelines are
  • Repeated voiding of urine into bed or clothes, either involuntary or intentional.
  • The behavior is clinically significant as manifested by either a frequency of at least twice a week for at least three consecutive months or the presence of clinically significant distress or impairment in social, academic (occupational), or other areas of functioning.
  • Chronological age is a minimum of 5 years.
  • The behavior is not attributable to the physiological effects of a substance (such as a diuretic, an antipsychotic ) or another medical condition (Such as diabetes, spina bifida,or seizure disorder).

• Specify if:
  • Nocturnal only: Passage of urine only during nighttime sleep.
  • Diurnal only: Passage of urine only during waking hours.
  • Nocturnal and diurnal: A combination of the two subtypes.

ICD-10 Criteria

• The criteria for the diagnosis of nonorganic enuresis are described in the section 'F98.0'.
• It emphasizes that enuresis should not be diagnosed in a child under the age of five years or under the mental age of four years.
• This category includes urinary incontinence of nonorganic origin or functional enuresis.

Treatment

• Medications are usually avoided in children under seven years of age.
• Parents should be reassured about the physical and emotional health of their children and counseled about eliminating guilt, and punishment.
• The patients are treated by behavioral modifications, medications, or a combination of both.
• It is extremely important that the psychosocial consequences of the symptom be recognized and addressed with sensitivity during the treatment of enuresis.

Non-pharmacological management

• Enuresis alarms are effective in patients with primary nocturnal enuresis and should be considered for older, highly motivated children from cooperative families.
• In the long-term follow-up, the enuretic alarm device also provided a full response rate in children with primary nocturnal enuresis.
• Hypnotherapy is found to be an effective alternative or adjunctive form of treatment for enuresis in children.
• Acupressure administered by the parents could be an alternative non-drug treatment. It has the advantages of being non-invasive, cost-effective, and painless.

Pharmacological management

• Desmopressin, an antidiuretic hormone (ADH) analog, or arginine vasopressin (AVP), can resolve primary nocturnal enuresis by reducing urine production at the night.
• Patients respond to desmopressin more quickly than to alarm systems. However, it has been observed that more children improve from psychological (urine alarm) than from pharmacological interventions.
• Imipramine is useful for enuresis when other treatment options such as desmopressin, alarm, and anticholinergics have failed in older children.
• Tricyclics and desmopressin are effective in reducing the number of wet nights while taking the drugs, but most children relapse after stopping active treatment. On the contrary, relapse rates are lower after alarm treatment.
• It has been found that structured withdrawal program from sublingual formulation of fast-melting oral desmopressin lyophilisate (MELT) therapy doesn't offer advantages compared to abrupt discontinuation in patients with nocturnal enuresis.
• Oxybutinin has shown partial response in the management of nocturnal enuresis.

Combined

• It is effective for resistant cases.
• The combination of desmopressin and alarm is helpful for severe cases and those with other behavioural problems.
• Combined therapy (enuresis alarm, bladder training, motivational therapy, and pelvic floor muscle training) is more effective than each component used alone.
• Pharmacotherapy can provide early relief, while behavioral intervention may lead to more long-term benefits. Utilizing this, the positive effect of achieving dry nights with pharmacotherapy can encourage the patient to sustain behavioral therapy.

References

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