Thermoregulatory and sweating dysfunctions are often encountered in the setting of autonomic disorders. Both hypo- and hyperhidrosis (reduced and increased sweat production, respectively) may occur with a variable distribution.

Patients may complain of hypohidrosis as reduced tolerance to heat exposure and skin dryness. If global anhidrosis occurs, the inability of dissipating heat may, in turn, lead to hyperthermia with potentially fatal consequence [6].

Hyperhidrosis may manifest as drenching sweat, if the whole body is affected, or as localized sweating in the axillae, palms, soles of feet, and face. Secretomotor dysfunction may also cause gustatory sweating, which is a pathological sweating in response to stimuli that usually activate salivation, such as eating or food aroma [15].

Seborrhea may be reported, but causes other than dysautonomia, e.g., endocrinological, may be more relevant in its pathogenesis [37].

Alterations in skin vasomotor control are responsible for altered venous return, which results in peripheral edema, cold hands/feet, and Raynaud-like phenomena, with blueish or blanched extremities. Inappropriate vasodilation may manifest as paroxysmal cutaneous flushes.

In complex regional pain syndrome (formerly known as reflex sympathetic dystrophy), regional sweating and vasomotor abnormalities may occur together with sensory deficits, dystonic postures, and myoclonic jerks, following traumatic limb injury or without an apparent cause [8].

Hypohidrosis occurs as a common side effect of drugs with anticholinergic properties such as tricyclic antidepressants, oxybutynin, and botulinum toxin, the latter being the treatment of choice for local hyperhidrosis. Sweating disturbances may be also caused by a variety of conditions, from alcohol or drug withdrawal to thyroid dysfunction. Hyperthyroidism is usually characterized by excessive sweating, while a reduced thyroid function is responsible for hypohidrosis and reduced heat tolerance. Drenching sweats may be a common sign of hypercatabolic states linked to systemic infections or neoplasms. Sweat glands may be involved in the course of primary dermatological disorders, vasculitis (Sjogren’s syndrome), or burns and radiation therapy, resulting in regional or global anhidrosis. Congenital dysplasia of ectodermal-derived tissues may be a fairly rare cause of anhidrosis in children [6].

Normal urinary function consists of a storage phase, in which the bladder detrusor is inactivated and activation of urethral sphincter muscles prevents urine leak, and a voiding phase, in which bladder detrusor contraction and urethral sphincter relaxation promote passing of urine. Both the storage and the voiding phase are under involuntary and voluntary control. Neurogenic disorders may result in a variable combination of detrusor overactivity or underactivity, with or without sphincter dysfunction [46, 60].

Impairment of the urinary storage phase results in nocturia, urinary frequency, and urgency, with or without incontinence.

Symptoms of voiding phase dysfunction are reported as feeling of incomplete bladder emptying and need for a double voiding, along with hesitancy and interrupted or poor stream. Since post-void urine residual volume increases in case of voiding impairment, retention and overflow incontinence may superimpose.

The abovementioned lower urinary tract symptoms usually worsen during the course of chronic autonomic disorders and may even shift, e.g., from a storage dysfunction to a voiding or mixed one over time [60]. Recurrent lower urinary tract infections, retrograde pyelonephritis, and eventually urosepsis are frequent complications of neurogenic bladder disturbances. In case of large post-void residual urine volume, hydronephrosis and bladder and kidney stones may also occur.

Sexual dysfunction frequently accompanies urological autonomic failure. Erectile dysfunction in men often remains undiagnosed, but it has been reported that isolated erectile dysfunction may precede urinary symptoms over years in atypical parkinsonian symptoms like multiple system atrophy, actually belonging to the earliest, though unspecific, premotor disease signs [14]. Ejaculatory disorders may also be reported, including premature or delayed ejaculation or complete absence of semen emission if retrograde ejaculation takes place. Women may complain either of genital hyposensitivity with anorgasmia or pain during sexual activity due to poor vaginal lubrication [39].

Lower urinary tract symptoms are a frequent complaint in the aging population of both genders, resulting from structural to functional disorders of the pelvic district, and clinical manifestations may overlap with those of urogenital autonomic failure.

Laboratory tests to exclude urinary tract infections are mandatory in case of acute onset of lower urinary tract symptoms, especially if dysuria is present, since infection is the most common, reversible cause. On the other hand, when recurrent infections occur, an underlying urodynamic disturbance should be excluded.

The most common etiology for lower urinary tract symptoms in men is represented by benign prostatic hyperplasia, whose prevalence has an exponential rise from the sixth decade of life. Obstructive symptoms, like poor or interrupted stream with hesitancy, are the most frequent complaints, but frequency and urgency can occur, as well as incomplete emptying and retention, in the case of superimposing atonic bladder [18].

In women, urinary symptoms may develop as a consequence of pelvic floor relaxation and prolapses, especially after multiple labors, or in the presence of pelvic masses and scars.

Major pelvic surgery or pelvic radiation may produce urogenital symptoms in both sexes.

Bladder dysfunction occurring together with low-back pain, saddlelike sensory deficit, and variable motor and sensory loss in the lower extremities, is highly suspicious for a cauda equina syndrome and should prompt further investigation to rule out caudal entrapment (vertebral disc prolapses, fractures, neoplasms).

Aging is accompanied by an exponential increase in sexual disturbances as a result of multiple pathophysiological mechanisms. Poor vaginal lubrication or pain during sexual intercourse in a postmenopausal woman may reflect genital atrophy due to the physiological reduction in hormone levels. Chronic diseases, medications, and atherosclerotic changes may underlie an erectile dysfunction in older men. Thyroid disorders, prolactinomas, and gonadic hormone deficiency may manifest with sexual dysfunction, among others. Classical cardiovascular risk factors like smoking, hypertension, and dyslipidemia are further risk factors for erectile dysfunction of vascular origin. Failure in both erection and ejaculation phases may also occur as a consequence of prostate surgery or radiotherapy. Retrograde ejaculation is a recognized side effect of many drugs, especially sympatholytic agents.

Symptoms of gastrointestinal autonomic dysfunction may arise at every level of the gastrointestinal tract and are divided into symptoms of the upper and of the lower gastrointestinal tract. Autonomic dysfunction of the upper gastrointestinal tract may manifest with:

Symptoms of the lower gastrointestinal tract may produce a variety of symptoms. Constipation and colic pain are by far the most reported. A long-standing constipation may, in turn, promote bacterial overgrowth, which results in intermittent diarrhea. Apart from constipation, dissynergic contraction of pelvic muscles and anal sphincter may contribute to evacuation difficulties or to involuntary loss of stool [13]. Rarely, focal dystonia of the striated anal sphincter may result in refractory constipation [26].

A detailed pharmacological anamnesis is the first step in the evaluation of salivary disturbances. Dry mouth is a common side effect of anticholinergic drugs, whereas benzocaine (contained in cough drops and over-the-counter medications for mouth ulcers) may cause sialorrhea. Xerostomia is a key feature of Sjögren’s disease and associated connective tissue disorders. Dryness may involve also the eyes both in Sjogren’s disease and autonomic failure. Reduced salivary production may follow surgery and radiotherapy for head and neck tumors. Drooling is frequently encountered in the setting of altered neuromuscular control of swallowing, such as bulbar form of amyotrophic lateral sclerosis, myasthenia gravis, or cerebral palsy.

Symptoms of chronic, delayed bolus transit may result from anatomical obstructions and should prompt exclusion of malignancies. Mesenteric vascular insufficiency should also be considered as a likely cause of gastroparesis in the elderly. Medications (Ca²⁺ blockers, antidepressants) and metabolic disturbances (hypothyroidism and hypercalcemia) should be excluded as common causes of chronic constipation. Rare etiologies for obstructive colonic symptoms are represented by Chagas’ disease and Hirschsprung’s disease, respectively, an infective and hereditary cause of enteric nervous system degeneration. Systemic sclerosis with visceral involvement may also be a rare case of gastrointestinal obstruction, especially at esophageal level.

Respiratory symptoms may be an early manifestation of autonomic failure in patients with multiple system atrophy (MSA), though commonly associated with advanced stages and, overall, constituting a poor prognostic predictor [25]. Obstructive sleep apnea is generally an early manifestation, while central sleep apnea may develop later on, when degeneration of brainstem breathing relays occurs [48]. Sleep-related breathing disorders are typically reported by the patient’s bed partner, while the patient himself may be less aware of them. These include enhanced or new-onset snoring and stridor, a harsh and strained high-pitched inspiratory sound that occurs especially, but not only, at nighttime, which is due to pathological adduction of the vocal cords and is typically accompanied by chronic dysphonia. Sleep is not restorative in these patients, who also complain about sleepiness and sleep attacks during daytime.

In patients with severely impaired central respiratory drive, awake breathing rhythm alterations, like periodic inspiratory gasps or agonic respiratory patterns, may occur, as well as respiratory insufficiency of “pump failure” type [35].

When sleep-related disorders precede other autonomic or motor manifestations, they cannot be distinguished from idiopathic sleep-related disordered breathing. Anecdotal reports of surgical intervention for snorers, who were eventually diagnosed with multiple system atrophy (MSA), underline the importance of a careful differential diagnosis [25].

Chronic stridor and other inspiratory disorders result from a partial obstruction of the upper respiratory tract, usually at glottic or supraglottic levels [38]. Clinical examination by the otorhinolaryngologist is required to exclude neoplastic, cystic, or inflammatory lesions of the larynx. Extrinsic stenosis may be caused by disorders of the adjacent structures, such as thyroid goiter or cancer, or result from neck surgery and radiotherapy. Soft tissue swelling secondary to acromegaly is a less common cause of obstruction and sleep apnea. Unilateral vocal cord palsy may be caused by chest or mediastinal neoplasm entrapping the recurrent laryngeal nerve or by accidental lesion of the recurrent laryngeal nerve during thyroid surgery.

Autonomic disorders may affect both lacrimation and pupillomotor function. Patients may complain of xerophthalmia, dry eyes, which results from impaired cholinergic stimulation of lacrimal glands.