Hyperhidrosis (increased sweating) in neurological practice
December 15th, 2009 by Administrator

The author: Professor Yasser Metwally


December 15, 2009 — The clinical spectrum of sweating disorders includes sudomotor excess and deficiency. Hyperhidrosis is characterized by sweating beyond that required to maintain a constant internal body temperature. Hypohidrosis and anhidrosis are distinguished by a reduced or absent ability to generate sweat for the purpose of evaporative heat dissipation. Whereas hyperhidrosis is usually benign, anhidrosis may predispose to hyperthermia. Either hyperhidrosis or anhidrosis may accompany a more serious underlying disorder. Correct diagnosis depends on determining the anatomical pattern of sweating and localizing the lesion within the autonomic nervous system. Sudomotor deficits may involve the frontal operculum, hypothalamus, brain stem, spinal cord, sympathetic chain ganglia, peripheral nerve, or eccrine sweat glands. Treatments for hyperhidrosis include topical aluminum chloride, oral anticholinergic agents, intradermal botulinum toxin for some localized syndromes, and thoracic ganglionic sympathotomy or sympathectomy for refractory palmar hyperhidrosis.

Eccrine gland sweating is the principal means of thermoregulatory heat dissipation in humans. If the body’s internal temperature exceeds the hypothalamic set point, activation of a sympathetic reflex results in generalized sweating, vasodilatation, and hyperpnea.[1] Evaporative heat loss thus maintains homeostasis by lowering core temperature to normal. The sweating pathway originates in the preoptic area of the anterior hypothalamus and descends uncrossed through the medial portion of the lateral funiculus of the brain stem to synapse upon preganglionic neurons in the intermediolateral column of the spinal cord.[2] Ipsilateral postganglionic sympathetic cholinergic fibers innervate the two to four million eccrine sweat glands distributed over the body surface. These sweat glands are most numerous on the palms and soles (600 to 700 glands/cm2) and least numerous on the back (64 glands/cm2).[3,4] The face and eyelid are supplied by spinal segments TI-T4, the upper limbs by segments T2-T8, the trunk by segments T4-TI2, and the lower limbs by segments TI0-L2.[5,6]

Disorders of sweating are divided into excessive sweating (hyperhidrosis, box 1) and decreased (hypohidrosis) or absent sweating (anhidrosis, box 2) in response to a proportionate thermal or pharmacologic stimulus. Hyperhidrosis is more socially than medically burdensome although it can be occupationally restrictive and rarely hazardous. Anhidrosis, in contrast, may become a medical emergency leading to hyperthermia, heat exhaustion, heat stroke, or death.


  • Generalized Hyperhidrosis

Essential or primary generalized hyperhidrosis is characterized by sweating that exceeds the amount necessary to maintain thermal regulation. Generalized sweating may occur at a lowered threshold with excessive volume loss of body fluids resulting in the potential for dehydration or electrolyte loss.[7] Hyperhidrosis may also be secondary and associated with any of numerous systemic processes and illnesses, including pheochromocytoma, thyrotoxicosis, diabetes mellitus, diabetes insipidus, hypopituitarism, anxiety, menopause, carcinoid syndrome, and drug withdrawal.[3,4,8] Nocturnal diaphoresis, in particular, may be a clue to the diagnosis of tuberculosis, lymphoma, endocarditis, diabetes, acromegaly, or Prinzmetal angina.[3,4] Amelioration of hyperhidrosis in these cases requires treatment of the underlying disease.

Penfield introduced the term "diencephalic epilepsy" to describe the syndrome of paroxysmal diaphoresis, flushing, hypertension, lacrimation, shivering, and respiratory changes in a patient with a tumor at the foramen of Monro.[9] Other authors have reported similar episodes in patients with head trauma,[10,11] neoplasia,[12] thalamic lesions,[13] and hydrocephalus.[14] Such episodes are not true epilepsy, as electroencephalography is normal and the episodes fail to respond to antiepileptic drugs. The term "paroxysmal sympathetic storms" more appropriately describes what are more likely to represent a release phenomenon or periodic functional hypothalamic disturbance that may respond to morphine or bromocryptine.[11] Shapiro syndrome is a related disorder characterized by episodic hyperhidrosis with hypothermia and is often associated with agenesis of the corpus callosum or other midline structural abnormalities.[15] These episodes may respond to clonidine,[16] glycopyrrolate,[17] or antiepileptic drugs.[7]

Several common medications occasionally produce hyperhidrosis. These include tricyclic and serotonin reuptake inhibitors, opioid analgesics, acyclovir, and naproxen.[18]

  • Focal Hyperhidrosis

Essential Hyperhidrosis

In contrast to the generalized distribution of thermoregulatory sweating due to exercise and heat exposure, sweating in response to emotional stimuli and mental effort involves the palms, soles, and axillae.[19,20] Sweating in these areas represents the most common form of focal hyperhidrosis. Patients with essential palmar hyperhidrosis complain of sweat constantly pouring from the skin surface and may be embarrassed to shake hands. In severe cases patients cannot use a pen without soaking the writing paper. There may be accompanying plantar hyperhidrosis with staining and damage to shoes. Topic antiperspirants containing 6 to 25% aluminum chloride in alcohol are the first line of therapy for axillary hyperhidrosis, yet are ineffective in the treatment of palmar or plantar hyperhidrosis because the skin is much thicker. Tap water iontophoresis is a safe and inexpensive therapeutic modality for palmar hyperhidrosis.[21] The mechanism may be poral plugging, and the effect is temporary, requiring ongoing therapy. Anxiolytics such as benzodiazepines may be helpful when hyperhidrosis is triggered by specific psychosocial stressors. Anticholinergic medications are seldom helpful.

Intradermal injection of botulinum toxin has been shown to decrease focal hyperhidrosis of the palms and axillae for 2 to 6 months and may be the treatment of choice for these conditions.[22-25] The treatment requires at least 20 injections per palm and can associated with transient weakness of the intrinsic hand muscles. For patients with severe, refractory palmar hyperhidrosis, satisfactory long-term results have been reported following endoscopic thoracic sympathectomy. Compensatory sweating elsewhere develops in many cases. In addition to hand dryness, side effects in a small proportion of patients include Horner syndrome, pneumothorax, gustatory hyperhidrosis, and chronic rhinitis.[26,27] The risk of adverse effects may be less with sympathotomy.[28] As the long-term recurrence rate is 7 to 17% for palmar hyperhidrosis compared with 65% for axillary hyperhidrosis, permanent abolition of the latter is achievable only by surgical resection of axillary skin.[26,27]

  • Hyperhidrosis with Peripheral Neuropathy

Hyperhidrosis frequently accompanies small-fiber peripheral neuropathies. Excessive sweating may occur as a compensatory phenomenon involving proximal regions, such as the head and trunk, that are spared in a dying-back neuropathy. In addition, patients with small-fiber peripheral neuropathies may have excessive distal sweating, presumably due to spontaneous firing of injured neurons.[29] Episodic hyperhidrosis also occurs commonly in patients with familial dysautonomia (Riley-Day syndrome), a hereditary sensory and autonomic neuropathy (HSAN III) that results from a splice defect in the IKBKAP gene on chromosome 9q31.[30]

  • Unilateral Circumscribed Idiopathic Hyperhidrosis

Unilateral circumscribed idiopathic hyperhidrosis is an idiopathic condition in which profuse sweating occurs episodically in an area of skin sharply demarcated from the surrounding dry skin. Typically the face or arms are the involved territory. Sweating may occur spontaneously or in response to heat, psychological stimuli, or spicy foods.[20,31] Therapeutic measures include topical aluminum chloride, oral anticholinergic agents, clonidine, or local sweat gland excision (box 3).[7,32]

  • Hyperhidrosis with Spinal Cord Disease

Autonomic dysreflexia is a potentially life-threatening syndrome affecting patients with spinal cord injury at or above the level of T6. In these patients spinal preganglionic sympathetic neurons disconnected from supraspinal regulation episodically exhibit unchecked reflexes. Ordinary stimuli such as bowel or bladder distension, visceral stimulation, skin irritation, or orthostatic hypotension provoke an exaggerated autonomic response characterized by hypertension; profuse sweating involving the face, neck, and upper trunk; facial flushing; pounding headache; nasal congestion; piloerection; and bradycardia.[33] Patients with syringomyelia may present with focal hyperhidrosis due to segmental hyperactivity of sympathetic preganglionic neurons.[34] In some patients excessive sweating occurs in regions above or below the level of the syrinx. Hyperhidrosis may subside as spinal cord damage progresses over time[34] or following surgical drainage of the syrinx.[35]

  • Hyperhidrosis with Thoracic Tumors

Unilateral hyperhidrosis involving the face, neck, and thorax may signal encroachment of an ipsilateral tumor on the sympathetic chain ganglia or postganglionic sympathetic fibers. The most common are pulmonary adenocarcinoma,[36-39] mesothelioma,[40] myeloma,[41] osteoma,[42] and cervical rib.[43] Associated signs may include Horner syndrome, upper limb weakness, and sensory loss (Pancoast syndrome). In other cases, normal preserved sweating contralateral to the sympathetic deficit may be misinterpreted as regional hyperhidrosis.

  • Hyperhidrosis with Cerebrovascular Disease

Hemihyperhidrosis in the paretic side of the body may follow cerebral hemispheric,[44,45] brain stem,[46,47] or hypothalamic[48] infarction. The hyperhidrosis is typically acute and transient.[45-49] Recognition of enduring asymmetry of sweating may be delayed pending the arrival of warm weather.[46] The mechanism in some cases may be interruption of a crossed sympathoinhibitory pathway originating in the frontal operculum. In other cases normal sweating on the unaffected side may only seem unusual in juxtaposition to anhidrosis on the affected side.

  • Gustatory Hyperhidrosis

Ingesting highly spiced foods stimulates physiologic gustatory sweating in most people. This trigeminovascular reflex typically occurs symmetrically on the scalp or face and predominantly over the forehead, lips, and nose.[50] Pathologic facial gustatory sweating, in contrast, is usually asymmetrical and occurs independently of the nature of the ingested food. This phenomenon frequently occurs after injury or surgery in the region of the parotid gland (Frey syndrome).[51] The mechanism is ascribed to post-traumatic misdirection of regenerating parasympathetic fibers destined for the salivary glands to postganglionic sympathetic nerve fibers in the auriculotemporal nerve innervating the preauricular sweat glands and blood vessels.

Aberrant gustatory sweating follows up to 73% of surgical sympathectomies[52] and is particularly common after bilateral procedures.[53] Gustatory responses may be accompanied by facial flushing, gooseflesh, vasoconstriction, and paresthesia.[52,53] Facial sweating during salivation has also been described in diabetes mellitus,[54] cluster headache,[55,56] following chorda tympani injury,[57] and following facial herpes zoster.[58] Intradermal botulinum toxin has proven safe and effective in treating this condition.[54,59]

  • Cold-Induced Hyperhidrosis

Two sibships have been reported in whom exposure to cold ambient temperatures induced nuchal and truncal hyperhidrosis. Associated signs included a marfanoid appearance in two sisters[60] and orthostatic hypotension, cold-induced distal cyanosis, achalasia, and motor peripheral neuropathy in another two sisters.[61]

  • Hyperhidrosis with Cutaneous Disease

Several cutaneous disorders have been associated with localized hyperhidrosis. Increased sweating may occur in the region of organoid nevi, nevus sudoriferus, eccrinepilar angiomatous hamartoma, glomus tumor, and blue rubber bleb nevus. Hyperhidrosis also occurs in association with the polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome as well as over the palms and soles of patients with pachydermoperiostosis, dyskeratosis congenita, and symmetrical lividity of palms and soles.[20,21]

Box 1. Causes of Hyperhidrosis

Generalized hyperhidrosis

1- Hyperhidrosis with systemic illness

2- Nocturnal diaphoresis

3- Episodic hyperhidrosis

4- Medication-induced hyperhidrosis

Focal hyperhidrosis

1- Essential palmar hyperhidrosis

2- Hyperhidrosis with spinal cord disease

3- Gustatory hyperhidrosis

4- Hyperhidrosis with peripheral neuropathy

5- Idiopathic unilateral circumscribed hyperhidrosis

6- Hyperhidrosis associated with intrathoracic neoplasms

7- Hyperhidrosis with cerebrovascular disease

8- Cold-induced hyperhidrosis

9- Hyperhidrosis with cutaneous lesions

Box 2. Treatment of Hyperhidrosis


  • Aluminum chloride hexahydrate (6-25%) in anhydrous alcohol

  • Tap water iontophoresis for palmar hyperhidrosis


  • Anticholinergic agents such as glycopyrrolate (1-2 mg up to three times a day)

  • Clonidine (0.1-0.3 mg up to three times a day)

  • Benzodiazepines such as diazepam (5 mg as needed)


  • Botulinum toxin for focal hyperhidrosis


  • Second and third thoracic ganglionic sympathotomy for palmar hyperhidrosis

  • Excision of sweat glands for axillary hyperhidrosis


  1. Cabanac M. Temperature regulation. Annu Rev Physiol 1975;37:415-439
  2. Nathan PW, Smith MC. The location of descending fibres to sympathetic preganglionic vasomotor and sudomotor neurons in man. J Neurol Neurosurg Psychiatry 1987;50:1253-1262
  3. Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. I. Normal sweat gland function. J Am Acad Dermatol 1989;20:537-563
  4. Quinton PM. Sweating and its disorders. Annu Rev Med 1983;34:429-452
  5. List CF, Peet M. Sweat secretion in man. I. Sweating responses in normal persons. Arch Neurol Psychiatry 1938;39:1228-1237
  6. List CF, Peet MM. Sweat secretion in man. II. Anatomic distribution of disturbances in sweating associated with lesions of the sympathetic nervous system. Arch Neurol Psychiatry 1938;40:27-43
  7. Fealey RD. Thermoregulatory failure. In: Appenzeller O, ed. Autonomic Nervous System. Amsterdam: Elsevier Press; 2000:53-84
  8. Freeman R, Waldorf HA, Dover JS. Autonomic neurodermatology (Part II): Disorders of sweating and flushing. Semin Neurol 1992;12:394-407
  9. Penfield W. Diencephalic epilepsy. Arch Neurol Psychiatry 1929;22:358-374
  10. Bullard DE. Diencephalic seizures: responsiveness to bromocriptine and morphine. Ann Neurol 1987;21:609-611
  11. Boeve BF, Wijdicks EF, Benarroch EE, Schmidt KD. Paroxysmal sympathetic storms ("diencephalic seizures") after severe diffuse axonal head injury. Mayo Clin Proc 1998;73:148-152
  12. Solomon GE. Diencephalic autonomic epilepsy caused by a neoplasm. J Pediatr 1973;83:277-280
  13. Engel GL, Aring CD. Hypothalamic attacks with thalamic lesion. I. Physiologic and psychologic considerations. Arch Neurol Psychiatry 1945;54:37-43
  14. Fox RH, Wilkins DC, Bell JA, et al. Spontaneous periodic hypothermia: diencephalic epilepsy. BMJ 1973;2:693-695
  15. Shapiro WR, Williams GH, Plum F. Spontaneous recurrent hypothermia accompanying agenesis of the corpus callosum. Brain 1969;92:423-436
  16. Walker BR, Anderson JA, Edwards CR. Clonidine therapy for Shapiro’s syndrome. Q J Med 1992;82:235-245
  17. Klein CJ, Silber MH, Halliwill JR, Schreiner SA, Suarez GA, Low PA. Basal forebrain malformation with hyperhidrosis and hypothermia: variant of Shapiro’s syndrome. Neurology 2001;56:254-256
  18. Gilman AG, ed. The Pharmacological Basis of Therapeutics. New York: Pergamon Press; 1990
  19. Sato K, Kang WH, Sato KT. Biology of sweat glands and their disorders. II. Disorders of sweat gland function. J Am Acad Dermatol 1989;20:713-726
  20. Chan P, Kao GF, Pierson DL, Rodman OG. Episodic hyperhidrosis on the dorsum of hands. J Am Acad Dermatol 1985; 12:937-942
  21. Stolman LP. Treatment of excess sweating of the palms by iontophoresis. Arch Dermatol 1987;123:893-896
  22. Saadia D, Voustianiouk A, Wang AK, Kaufmann H. Botulinum toxin type A in primary palmar hyperhidrosis: randomized, single-blind, two-dose study. Neurology 2001;57:2095-2099
  23. Schnider P, Binder M, Kittler H, et al. A randomized, double-blind, placebo-controlled trial of botulinum A toxin for severe axillary hyperhidrosis. Br J Dermatol 1999;140:677-680
  24. Schnider P, Moraru E, Kittler H, et al. Treatment of focal hyperhidrosis with botulinum toxin type A: long-term follow-up in 61 patients. Br J Dermatol 2001;145:289-293
  25. Wollina U, Karamfilov T, Konrad H. High-dose botulinum toxin type A therapy for axillary hyperhidrosis markedly prolongs the relapse-free interval. J Am Acad Dermatol 2002;46:536-540
  26. Gossot D, Galetta D, Pascal A, et al. Long-term results of endoscopic thoracic sympathectomy for upper limb hyperhidrosis. Ann Thorac Surg 2003;75:1075-1079
  27. Lin TS, Kuo SJ, Chou MC. Uniportal endoscopic thoracic sympathectomy for treatment of palmar and axillary hyperhidrosis: analysis of 2000 cases. Neurosurgery 2002;51:84-87
  28. Atkinson JL, Fealey RD. Sympathotomy instead of sympathectomy for palmar hyperhidrosis: minimizing postoperative compensatory hyperhidrosis. Mayo Clin Proc 2003;78:167-172
  29. Low PA. Autonomic neuropathies. Curr Opin Neurol 2002; 15:605-609
  30. Slaugenhaupt SA, Blumenfeld A, Gill SP, et al. Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet 2001; 68:598-605
  31. Van De Kerkhof PCM, Den Arend JAJC, Bousema MT, Stolz E. Localized unilateral hyperhidrosis. Br J Dermatol 1987;117:779-782
  32. White JW. Treatment of primary hyperhidrosis. Mayo Clin Proc 1986;61:951-956
  33. Weaver LC. What causes autonomic dysreflexia after spinal cord injury? Clin Auton Res 2002;12:424-426
  34. Sudo K, Fujiki N, Tsuji S, et al. Focal (segmental) dyshidrosis in syringomyelia. J Neurol Neurosurg Psychiatry 1999;67:106-108
  35. Stanworth PA. The significance of hyperhidrosis in patients with post-traumatic syringomyelia. Paraplegia 1982;20:282-287
  36. Walsh JC, Low PA, Allsop JL. Localized sympathetic overactivity: an uncommon complication of lung cancer. J Neurol Neurosurg Psychiatry 1976;39:93-95
  37. McEvoy M, Ryan E, Neale G, Prichard J. Unilateral hyperhydrosis—an unusual presentation of bronchial carcinoma. Ir J Med Sci 1982;151:51-52
  38. Lindsay DC, Freeman JG, Record CO. Unilateral hyperhidrosis associated with underlying intrathoracic neoplasia. Thorax 1986;41:814-815
  39. Slabbynck H, Bedert L, De Deyn PP, Galdermans D, Coolen D. Unilateral segmental hyperhidrosis associated with pulmonary adenocarcinoma. Chest 1998;114:1215-1217
  40. Pleet DL, Mandel S, Neilan B. Paroxysmal unilateral hyperhidrosis and malignant mesothelioma. Arch Neurol 1983;40:256
  41. Lambert M, Kanyinda JM, Richard F, Sindic C. Unilateral hyperhidrosis associated with intrathoracic IgD lambda myelomatous tumour. Clin Oncol (R Coll Radiol) 1993;5:65-66
  42. Seline PC, Jaskierny DJ. Cutaneous metastases from a chondroblastoma initially presenting as unilateral palmar hyperhidrosis. J Am Acad Dermatol 1999;40:325-327
  43. Telford ED. Cervical rib and hyperhidrosis. BMJ 1942;2:96
  44. Korpelainen JT, Sotaniemi KA, Myllyla VV. Hyperhidrosis as a reflection of autonomic failure in patients with acute hemispheral brain infarction. An evaporimetric study. Stroke 1992; 23:1271-1275
  45. Labar DR, Mohr JP, Nichols FT, Tatemichi TK. Unilateral hyperhidrosis after cerebral infarction. Neurology 1988;38:1679-1682
  46. Rousseaux M, Hurtevent JF, Benaim C, Cassim F. Late contralateral hyperhidrosis in lateral medullary infarcts. Stroke 1996;27:991-995
  47. Awada A, Ammar A, Al-Rajeh S, Borollosi M. Excessive sweating: an uncommon sign of basilar artery occlusion. J Neurol Neurosurg Psychiatry 1991;54:277-278
  48. Smith CD. A hypothalamic stroke producing recurrent hemihyperhidrosis. Neurology 2001;56:1394-1396
  49. Kim BS, Kim YI, Lee KS. Contralateral hyperhidrosis after cerebral infarction. Clinicoanatomic correlations in five cases. Stroke 1995;26:896-899
  50. Lee TS. Physiological gustation sweating in a warm climate. J Physiol 1954;124:528-542
  51. Drummond PD. Mechanism of gustatory flushing in Frey’s syndrome. Clin Auton Res 2002;12:144-146
  52. Kurchin A, Adar R, Zweig A, Mozes M. Gustatory phenomena after upper dorsal sympathectomy. Arch Neurol 1977;34:619-623
  53. Bloor K. Gustatory sweating and other responses after cervicothoracic sympathectomy. Brain 1969;92:137-146
  54. Restivo DA, Lanza S, Patti F, et al. Improvement of diabetic autonomic gustatory sweating by botulinum toxin type A. Neurology 2002;59:1971-1973
  55. Sjaastad O. Cluster headache: on the inadequacy of existing hypotheses concerning the origin of the autonomic phenomena. Cephalalgia 1988;8:133-137
  56. Drummond PD. Autonomic disturbances in cluster headache. Brain 1988;111:1199-1209
  57. Young AG. Unilateral sweating of the submental region after eating (chorda tympani syndrome). Br Med J 1956;12:976-979
  58. Drummond PD, Boyce GM, Lance JW. Postherpetic gustatory flushing and sweating. Ann Neurol 1987;21:559-563
  59. Laskawi R, Rohrbach S. Frey’s syndrome. Treatment with botulinum toxin. Curr Probl Dermatol 2002;30:170-177
  60. ohar E, Shoenfeld Y, Udassin R, Magazanik A, Revach M. Cold-induced profuse sweating on back and chest. Lancet 1978; 2:1073-1074
  61. Lisker R, Garcia-Ramos G, de la Rosa-Laris C, Diaz-Mitoma F. Peripheral motor neuropathy associated with autonomic dysfunction in two sisters: new hereditary syndrome? Am J Med Genet 1981;9:255-259

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