Annals of Movement Disorders

: 2019  |  Volume : 2  |  Issue : 2  |  Page : 39--47

Sweating and other thermoregulatory abnormalities in Parkinson’s disease: A review

Valentina Leta1, Daniel J van Wamelen2, Katarina Rukavina3, Elina Jaakkola4, Carolina Sportelli5, Yi-Min Wan6, Aleksandra M Podlewska1, Miriam Parry1, Vinod Metta1, Kallol Ray Chaudhuri1,  
1 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London, UK; Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
2 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London, UK; Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands, UK
3 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London, UK; Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK; Klinik für Gerontopsychiatrie, Asklepios Klinik Nord–Ochsenzoll, Hamburg, Germany, UK
4 Division of Clinical Neurosciences, University of Turku, Turku, Finland
5 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London, UK
6 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London, UK; Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK; Department of Psychiatry, Ng Teng Fong General Hospital, 1 Jurong East Street 21, Singapore, UK

Correspondence Address:
Dr. Valentina Leta
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, SE5 8AF


Thermoregulatory abnormalities, especially sweating disorders, are very common in Parkinson’s disease (PD). The estimated prevalence of sweating abnormalities ranges from 5.5% to 12.9% in de novo, newly diagnosed patients with PD and up to 64% during later stages of the disease. The range of thermoregulatory abnormalities in PD is broad, and includes hyperhidrosis, hypohidrosis, and hypothermia. In addition, the way in which these symptoms present themselves varies between patients and they can be chronic or fluctuating, local or generalized affecting the whole body, and related to motor complications or medication. Often there is a strong link to other autonomic symptoms, yet the exact pathogenesis behind these overlapping symptoms remains largely elusive, although current evidence points toward both central and peripheral involvement. Treatment remains difficult because of the lack of understanding of pathophysiology as well as specific clinical trials needed for evidence base. In this review, we have identified 43 studies in English language assessing sweating disorders in idiopathic PD. Here, we summarize knowledge gleaned from these reports and discuss current understanding of thermoregulatory dysfunction in PD, its phenomenology, pathophysiology, and management options.

How to cite this article:
Leta V, van Wamelen DJ, Rukavina K, Jaakkola E, Sportelli C, Wan YM, Podlewska AM, Parry M, Metta V, Chaudhuri KR. Sweating and other thermoregulatory abnormalities in Parkinson’s disease: A review.Ann Mov Disord 2019;2:39-47

How to cite this URL:
Leta V, van Wamelen DJ, Rukavina K, Jaakkola E, Sportelli C, Wan YM, Podlewska AM, Parry M, Metta V, Chaudhuri KR. Sweating and other thermoregulatory abnormalities in Parkinson’s disease: A review. Ann Mov Disord [serial online] 2019 [cited 2023 Mar 28 ];2:39-47
Available from:

Full Text


Sweating disorders represent one of the least studied non-motor dysfunctions in Parkinson’s disease (PD) despite the fact that its prevalence is reported by some authors to be as high as 64% compared to 12.5% in healthy controls.[1],[2],[3] Sweating disorders in PD consist of hyperhidrosis, and to a lesser extent, hypohidrosis, which can occur as local or generalized complaints. In addition, sweating disorders can be chronic or fluctuating, the latter frequently related to motor complications, such as dyskinesia and wearing off.[4],[5] Most of these complaints appear not to correlate with disease severity because of conflicting results, but there is a strong correlation with other autonomic dysfunction symptoms.[1] In PD, hyperhidrosis appears to be mainly axial and associated with decreased activation of sweat glands in the palms of the hands, suggesting that axial hyperhidrosis could be a compensatory phenomenon for reduced sympathetic function in the extremities.[6] Sweating disorders may have a profound impact on the quality of life in patients with PD. Indeed, heat intolerance and the need to frequently change clothing or bedding may influence social activity.[1] Also, temperature intolerance or night sweats may impact on sleep.[1]

In this review, we will address the symptomatology of sweating dysfunction in PD, its pathogenesis, related autonomic symptoms, and treatment options.


We performed a systematic literature search, using the PubMed database, encompassing all articles published between 1966 and 1 January 2019. To identify appropriate studies, we used two terms: term A was “Parkinson” or “Parkinson’s” and Term B was “sweating” or “hyperhidrosis” or “diaphoresis” “hypohidrosis” or “dyshidrosis” or “hypothermia” or “thermoregulatory.” We also used the reference lists of each publication to identify further papers. The following inclusion and exclusion criteria were used for each of the articles identified in the search: (1) original papers, (2) human subjects, (3) studies that address idiopathic PD, and (4) written in the English language (articles with at least an abstract written in English were retained). An initial screen returned 324 results from the PubMed database. After excluding articles not written in English and after revision for relevance, 43 studies were retained for the final review and data extraction [Figure 1].{Figure 1}


In de novo PD, sweating abnormalities seem to occur in only a minority of patients, with prevalence figures ranging from 5.5% to 12.9%.[7],[8],[9] These numbers increase rapidly, however, during the first few years after formal PD diagnosis. For example, Giorelli et al.[7] showed that 1 year after diagnosis of PD, the prevalence of sweating problems was 12.9%, which increased to 25.8% after 1-year follow-up. Similarly, Ou et al.[10] reported that at 3.9 years disease duration, the prevalence of sweating disorders was 28.2%, increasing to 35.3% after 2 years of follow-up. After approximately 10 years, almost 40% of patients are affected by sweating disorders.[11] Several older studies have reported more conflicting results with sweating disturbances occurring in 30%–80% of patients[1],[3],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25] [Table 1]. In these patients, hyperhidrosis affected 10%–100%, whereas hypohidrosis was present in 0%–40%.{Table 1}

 Clinical Phenomenology

Thermoregulatory problems, including sweating disorders such as hyperhidrosis and hypohidrosis, have already been described in PD as far back as 1893 by Gower[26] in his Manual of Diseases of the Nervous System: “In a few cases, . . . there is an abnormal sensation of cold; the patient always feels chilly, or there is a special sense of coldness in the affected limbs. Such patients like warmth, and may shake more when cold, as the disease progressed, the occasional sensations of cold gradually yield to an enduring sense of warmth, but the alternation may persist even until late stage; at one time the patient feels cold, and another bursts into perspiration . . . one patient could not dictate the simplest letter, even in winter, without first having his coat taken off, so intense was the perspiration caused. Sometimes sweating is local, corresponding to the sense of heat. In one patient, with left-sided agitation, the left axilla was always wet with perspiration, while the right was always dry.”


Hyperhidrosis or diaphoresis is a condition characterized by abnormally increased sweating. Hyperhidrosis can be local or generalized, symmetric or asymmetric, chronic or fluctuating, related or not to motor complications such as wearing off and dyskinesia, and related to medication [Figure 2]. In patients with PD, hyperhidrosis is usually fluctuating in nature, but it can be generalized or even local with an asymmetric distribution,[20],[27] frequently affecting the side of maximal motor deficit.[28],[29] Fluctuating hyperhidrosis is often associated with motor complications including dyskinesia and motor fluctuations.[5],[29]{Figure 2}

Hyperhidrosis can also be the result of dopamine agonist withdrawal syndrome in PD. Although hyperhidrosis is not an isolated feature of this syndrome,[30] it occurs very commonly. When patients, in whom recent changes in dopaminergic medication have been made, present with excessive sweating the possibility of a withdrawal should be considered. Symptoms, which are often associated with withdrawal syndrome, include anxiety, panic attacks, depression, agitation, nausea, orthostatic hypotension, and insomnia.[30] Similar symptoms in PD, including hyperhidrosis, may occur in serotonin syndrome and neuroleptic malignant syndrome.[31],[32]


Although less common than hyperhidrosis, hypohidrosis (abnormally decreased sweating) is still frequently reported by patients with PD and evidence suggests that it occurs more frequently in them than that in the healthy population.[1] It may be reported by the patient as heat intolerance, and frequently involves the distal extremities, in particular, the lower limbs.[1],[33],[34] Similar to hyperhidrosis, hypohidrosis can be local or generalized, and in the latter, it may be related to treatment with anticholinergic medication.


Another common thermoregulatory disorder is hypothermia, which refers to a body temperature of 35°C (95°F) or less, although some patients with PD may have a body temperature of as low as 30.9°C. Episodes of hypothermia are often associated with worsening bradykinesia and rigidity and changes in mental state, ranging from somnolence to coma.[35],[36],[37],[38] In addition, other features may be present such as myoclonus[38] and cardiac arrhythmia, requiring cardiac monitoring.[39] These latter changes include bradycardia that resolves after a return of the normal body temperature.[37],[38] Mortality in these cases, on the contrary, appears to be linked to comorbid conditions rather than exact body temperature.[40] Whether or not hypothermia episodes in PD are precipitated by any triggers remained unclear in the aforementioned studies.


Sweating has a thermal and mental aspect. Mental sweating, mainly seen in the palms and soles of the feet, develops with psychological stress and it is not associated with disorders in thermoregulation.[24] A variety of other factors may lead to sweating abnormalities in PD.[31] It has been observed that hyperhidrosis episodes frequently occur together with dyskinesia.[5] It is likely that excessive movements may, in part, lead to increased sweating[1]; however, the pathological mechanism underlying dyskinesia-related sweating is still poorly understood. On the contrary, the multiplicity of autonomic symptoms occurring during off periods suggests that “off sweating” may result from sympathetic dysfunction.[28],[30] Indeed, evidence suggests that thermoregulatory dysfunction, and subsequently, thermal sweating, are intrinsic features of PD [Figure 3].{Figure 3}

Normal thermoregulatory responses (involving both central and peripheral mechanisms) are crucial in maintaining a set body temperature, which in most individuals is around 37°C. The central regulation is driven by the hypothalamus. Here, heat conservation and production are triggered by temperature-sensing neurons located within the preoptic area in response to heat loss. This system is modulated by several neurotransmitters, for example, stimulation of D2 and 5-HT1 receptors by dopamine and serotonin, respectively, induces hypothermia, whereas stimulation of 5-HT2 receptors induces hyperthermia.[41],[42] The output of the hypothalamic system involved in thermoregulation includes projections to the rostral raphe pallidus area.[41],[43] From here, projections run down to sympathetic and motor neurons in the spinal cord, which when activated, modulate skin vasomotor tone and induce shivering.[42] Dyshidrosis may be explained by alterations in dopaminergic neurotransmission, supported both by the fact that changes in dopaminergic medication may improve dyshidrosis[5] and by the observation that sweating attacks in PD are more prevalent during the motor off-state.[29] It is recognized that the hypothalamus in patients with PD shows Lewy pathology[44] and alpha-synuclein deposits,[45] although in the latter studies, no correlation was reported between the amount of alpha-synuclein and non-motor symptoms (NMS) burden, including autonomic symptoms. This suggests that hypothalamic functional deficits rather than Lewy pathology contribute to NMS, supported by the observation that hypothalamic functional connectivity is disturbed in autonomic dysfunction in PD.[46]

In addition to the central mechanisms, peripheral thermoregulatory processes also are involved to maintain body temperature. These pathways are mainly cholinergic (to the sweat glands) and noradrenergic (responsible for vasoconstriction). Furthermore, there are several vasodilator outputs (including nitric oxide).[47] Combined, these systems support the central process of heat conservation. Sudomotor output to sweat glands, resulting in sweating, is the most important way for humans to reduce body temperature. Sweat glands consist of two types: eccrine, which are cholinergic and distributed over almost the entire body, and apocrine glands, mainly in the palms and soles and are activated by emotional responses. The pattern of dyshidrosis in PD appears to differ from the general population, and axial hyperhidrosis in PD is associated with decreased activation of sweat glands in the palms of the hands suggesting that axial hyperhidrosis could be a compensatory phenomenon for reduced sympathetic function in the extremities.[8] Moreover, alpha-synuclein can be found in the cutaneous autonomic nerves innervating sweat glands and arterioles in patients with PD.[48],[49]

 Related Autonomic Symptoms and PD Endophenotypes

Sweating abnormalities in PD are frequently linked to other autonomic features. These features often aggregate in patients with PD, and several authors have proposed specific non-motor subtypes in PD, analogs to the better-known motor subtypes. One of these phenotypes is an autonomic phenotype, with adrenergic/cholinergic dysfunctions, such as orthostatic hypotension and gastrointestinal symptoms overlapping with sleep dysfunction and levodopa-induced dyskinesia.[4],[50],[51] In a recent study, it was shown that hyperhidrosis was associated with a dysautonomia dominant subtype in patients with PD, including sleep disorders and a higher rate of dyskinesia. Conditions, which were related to hyperhidrosis in this study, included orthostatic hypotension, fatigue, somnolence, restless legs, apathy, double vision, sialorrhea, constipation, urinary urgency and frequency, and unexplained pain.[52] Others have also shown the link between dyshidrosis and sialorrhea as well as constipation.[1] These symptoms often correlate with disease severity as measured by motor impairment.[53],[54],[55],[56] Whether or not this was related to dopaminergic medication in these studies remains unclear.


Treatment of sweating abnormalities in patients with PD remains challenging because of the lack of validated and evidence-based algorithms.[57] First, it is recommended to adopt non-pharmacological measures, such as avoiding hot and humid environments, as well as food and drinks that may trigger sweating (e.g., alcoholic drinks and spicy food), maintaining a good hydration status, and wearing well-ventilating clothes made of natural fibers.

Pharmacological treatment

A detailed history of thermoregulatory symptoms and particularly their fluctuations, according to the administration of dopaminergic medication, is essential for the management of sweating abnormalities in patients with PD. Indeed, motor complications-related sweating can be managed by optimizing dopaminergic treatment [Figure 4]. Although advanced therapies are not indicated for the treatment of sweating dysfunctions, a few observational studies suggest that infusion therapies, such as subcutaneous apomorphine[58] and intrajejunal levodopa infusion,[59] may have a positive effect on sweating.{Figure 4}

Despite the fact that anticholinergics are often considered in the treatment of sweating disorders, evidence for their use is very limited. In fact, no studies have been performed in PD and only a few studies have investigated the effect of anticholinergics on sweating in other disorders, including the use of topical glycopyrrolate, oral oxybutynin, and oral methantheline bromide. Glycopyrrolate wipes, compared to placebo, appear to have a beneficial effect on axillary and facial sweating.[60],[61] Another study looked at glycopyrrolate spray and compared it to botulinum toxin (BoNT) injections for axillary hyperhidrosis and no effect was noticed.[62] Three placebo-controlled studies evaluated the effectiveness of oral oxybutynin for axillary, plantar, and palmar hyperhidrosis, and generalized hyperhidrosis.[63],[64],[65] Two additional placebo-controlled studies investigated oral methantheline bromide for axillary and palmar hyperhidrosis.[66],[67] None of the studies showed a clear benefit and probably all studies were biased for treatment outcomes.[68] Overall, the use of anticholinergic medication in PD should be approached with caution, especially in older patients, given the high rate of side effects (including cognitive effects).

The efficacy of BoNT injections has not been studied in PD. There is, however, evidence for its efficacy in essential/primary hyperhidrosis.[69],[70] Future research is needed to validate the efficacy and safety of BoNT therapy for hyperhidrosis related to PD.

No studies have yet focused on the drug treatment of hypothermia; however, it is advised to carefully perform external rewarming rather than the use of invasive rewarming methods. Indeed, faster rewarming has not been proven to reduce mortality.[71]

Treatment of medical emergencies, including the treatment of serotonin syndrome, dopamine agonist withdrawal syndrome, and neuroleptic malignant syndrome, is not the merit of these reviews, and as such, the treatment for these syndromes will not be discussed here.

Non-pharmacological treatment

Several authors have reported improvement of (severe) hyperhidrosis after deep brain stimulation (DBS) to the bilateral subthalamic nucleus (STN),[72] and also improvement of sympathetic skin responses in 19 patients who received bilateral STN DBS.[73] In a recent cohort of 67 patients with PD who underwent bilateral STN DBS, a significant improvement of hyperhidrosis was reported as measured by the NMS scale. This improvement was persistent after 24 months of follow-up.[58] In addition, others have reported an improvement on hyperhidrosis using a structured interview with improvement of this symptom in 34 of 35 patients after 1 year of bilateral STN DBS.[74] It may be argued that the reduction in hyperhidrosis may have been due to reduction in the dose of dopaminergic medication; however, a recent publication has shown a differential effect on specific NMS, including hyperhidrosis, based on the exact location of the DBS leads within the STN.[75]


Sweating disorders are one of the many non-motor expressions of PD with a clinical prevalence as high as 64% during later stages of the disease. The range of sweating disorders and thermoregulatory abnormalities in PD is broad, and includes hyperhidrosis, hypohidrosis, and hypothermia. These conditions can be chronic, fluctuating, related to motor complications, and related to medication. Interestingly, these complaints are not always correlated to the severity of the disease but there is a strong link with other autonomic symptoms. The pathogenesis remains largely elusive; however, there is emerging evidence to suggest that several levels of the sympathetic outflow pathways are affected in PD, including the hypothalamus and the sweat glands. Further, the treatment of thermoregulatory abnormalities in PD remains understudied and the available evidence is largely biased. On the basis of mainly essential hyperhidrosis, current treatment options include BoNT injections, anticholinergic drugs, and although not indicated for the treatment of thermoregulatory disorders, advanced treatments may reduce hyperhidrosis.

Financial support and sponsorship

This article represents independent collaborative research part funded by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London.

Conflicts of interest

There are no conflicts of interest.


1Swinn L, Schrag A, Viswanathan R, Bloem BR, Lees A, Quinn N Sweating dysfunction in Parkinson’s disease. Mov Disord 2003;18:1459-63.
2Chaudhuri KR, Healy DG, Schapira AH; National Institute for Clinical Excellence. Non-motor symptoms of Parkinson’s disease: Diagnosis and management. Lancet Neurol 2006;5:235-45.
3Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, MacPhee G, et al. Prevalence of nonmotor symptoms in Parkinson’s disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 2007;22:1623-9.
4Marras C, Chaudhuri KR Nonmotor features of Parkinson’s disease subtypes. Mov Disord 2016;31:1095-102.
5Coon EA, Low PA Thermoregulation in Parkinson disease. Handb Clin Neurol 2018;157:715-25.
6Appenzeller O, Goss J Autonomic dysfunction in Parkinson’s syndrome. Trans Am Neurol Assoc 1970;95:200-3.
7Giorelli M, Bagnoli J, Consiglio L, Difazio P, Zizza D, Zimatore GB Change in non-motor symptoms in Parkinson’s disease and essential tremor patients: A one-year follow-up study. Tremor Other Hyperkinet Mov (N Y) 2014;4:216.
8Picillo M, Erro R, Amboni M, Longo K, Vitale C, Moccia M, et al. Gender differences in non-motor symptoms in early Parkinson’s disease: A 2-years follow-up study on previously untreated patients. Parkinsonism Relat Disord 2014;20:850-4.
9Erro R, Picillo M, Vitale C, Amboni M, Moccia M, Santangelo G, et al. The non-motor side of the honeymoon period of Parkinson’s disease and its relationship with quality of life: A 4-year longitudinal study. Eur J Neurol 2016;23:1673-9.
10Ou R, Yang J, Cao B, Wei Q, Chen K, Chen X, et al. Progression of non-motor symptoms in Parkinson’s disease among different age populations: A two-year follow-up study. J Neurol Sci 2016;360:72-7.
11Guo X, Song W, Chen K, Chen X, Zheng Z, Cao B, et al. Disease duration-related differences in non-motor symptoms: A study of 616 Chinese Parkinson’s disease patients. J Neurol Sci 2013;330:32-7.
12Aminoff MJ, Wilcox CS Assessment of autonomic function in patients with a parkinsonian syndrome. Br Med J 1971;4:80-4.
13Uono K Parkinsonism and Autonomic Failure. Jiritsu Skinkei (Autonomic Nerves) 1993;10:163-170.
14Rajput AH, Rozdilsky B Dysautonomia in parkinsonism: A clinicopathological study. J Neurol Neurosurg Psychiatry 1976;39:1092-100.
15Saito H, Kogure K [Thermal sudomotor deficits in Parkinson’s disease]. Rinsho Shinkeigaku 1989;29:734-40.
16Sandroni P, Ahlskog JE, Fealey RD, Low PA Autonomic involvement in extrapyramidal and cerebellar disorders. Clin Auton Res 1991;1:147-55.
17Wang SJ, Fuh JL, Shan DE, Liao KK, Lin KP, Tsai CP, et al. Sympathetic skin response and R-R interval variation in Parkinson’s disease. Mov Disord 1993;8:151-7.
18Sasaki I, Takeuchi H, Deguchi K, Yamada A, Nishioka M, Sakamoto H [Autonomic nervous function in progressive supranuclear palsy—Comparison with Parkinson’s disease and healthy controls]. Rinsho Shinkeigaku 1994;34:975-9.
19Choi BO, Bang OY, Sohn YH, Sunwoo IN Sympathetic skin response and cardiovascular autonomic function tests in Parkinson’s disease. Yonsei Med J 1998;39:439-45.
20De Marinis M, Argenta G, Mele D, Carbone A, Baffigo G, Agnoli A Evaluation of vesico-urethral and sweating function in disorders presenting with parkinsonism. Clin Auton Res 1993;3:125-30.
21Fischer M, Gemende I, Marsch WC, Fischer PA Skin function and skin disorders in Parkinson’s disease. J Neural Transm (Vienna) 2001;108:205-13.
22Zakrzewska-Pniewska B, Jamrozik Z Are electrophysiological autonomic tests useful in the assessment of dysautonomia in Parkinson’s disease? Parkinsonism Relat Disord 2003;9:179-83.
23Riley DE, Chelimsky TC Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:56-60.
24Hirayama M Sweating dysfunctions in Parkinson’s disease. J Neurol 2006;253:VII42-7.
25Schestatsky P, Valls-Solé J, Ehlers JA, Rieder CR, Gomes I Hyperhidrosis in Parkinson’s disease. Mov Disord 2006;21:1744-8.
26Gowers W A Manual of Diseases of the Nervous System. 2nd ed. London, UK: J. & A. Churchill; 1893.
27De Marinis M, Stocchi F, Testa SR, De Pandis F, Agnoli A Alterations of thermoregulation in Parkinson’s disease. Funct Neurol 1991;6:279-83.
28Goetz CG, Lutge W, Tanner CM Autonomic dysfunction in Parkinson’s disease. Neurology 1986;36:73-5.
29Pursiainen V, Haapaniemi TH, Korpelainen JT, Sotaniemi KA, Myllylä VV Sweating in parkinsonian patients with wearing-off. Mov Disord 2007;22:828-32.
30Yu XX, Fernandez HH Dopamine agonist withdrawal syndrome: A comprehensive review. J Neurol Sci 2017;374:53-5.
31Chaudhuri K, Ondo, W Movement Disorders in Clinical Practice. London, UK: Springer-Verlag; 2010.
32Kwei K, Frucht S Acute presentation of nonmotor symptoms in Parkinson’s disease. Int Rev Neurobiol 2017;134:973-86.
33Lipp A, Sandroni P, Ahlskog JE, Fealey RD, Kimpinski K, Iodice V, et al. Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch Neurol 2009;66:742-50.
34Kimpinski K, Iodice V, Burton DD, Camilleri M, Mullan BP, Lipp A, et al. The role of autonomic testing in the differentiation of Parkinson’s disease from multiple system atrophy. J Neurol Sci 2012;317:92-6.
35Gubbay SS, Barwick DD Two cases of accidental hypothermia in Parkinson’s disease with unusual EEG findings. J Neurol Neurosurg Psychiatry 1966;29:459-66.
36Hama K, Miwa H, Kondo T Life-threatening hypothermia in Parkinson’s disease. Mov Disord 2009;24:945-6.
37Sehara Y Hypothermia with Osborn waves in Parkinson’s disease. Intern Med 2009;48:615-8.
38Li BY, Lou M Severe hypothermia in Parkinson’s disease. CNS Neurosci Ther 2012;18:864-6.
39Biem J, Koehncke N, Classen D, Dosman J Out of the cold: Management of hypothermia and frostbite. CMAJ 2003;168:305-11.
40Muszkat M, Durst RM, Ben-Yehuda A Factors associated with mortality among elderly patients with hypothermia. Am J Med 2002;113:234-7.
41Benarroch EE Thermoregulation: Recent concepts and remaining questions. Neurology 2007;69:1293-7.
42Romanovsky AA Thermoregulation: Some concepts have changed. Functional architecture of the thermoregulatory system. Am J Physiol Regul Integr Comp Physiol 2007;292:R37-46.
43Dimicco JA, Zaretsky DV The dorsomedial hypothalamus: A new player in thermoregulation. Am J Physiol Regul Integr Comp Physiol 2007;292:R47-63.
44Langston JW, Forno LS The hypothalamus in Parkinson disease. Ann Neurol 1978;3:129-33.
45De Pablo-Fernandez E, Courtney R, Holton JL, Warner TT Hypothalamic α-synuclein and its relation to weight loss and autonomic symptoms in Parkinson’s disease. Mov Disord 2017;32:296-8.
46Dayan E, Sklerov M, Browner N Disrupted hypothalamic functional connectivity in patients with PD and autonomic dysfunction. Neurology 2018;90:e2051-8.
47Charkoudian N Skin blood flow in adult human thermoregulation: How it works, when it does not, and why. Mayo Clin Proc 2003;78:603-12.
48Wang N, Gibbons CH, Lafo J, Freeman R α-Synuclein in cutaneous autonomic nerves. Neurology 2013;81:1604-10.
49Donadio V, Incensi A, Leta V, Giannoccaro MP, Scaglione C, Martinelli P, et al. Skin nerve α-synuclein deposits: A biomarker for idiopathic Parkinson disease. Neurology 2014;82:1362-9.
50Sauerbier A, Jenner P, Todorova A, Chaudhuri KR Non motor subtypes and Parkinson’s disease. Parkinsonism Relat Disord 2016;22:S41-6.
51Titova N, Martinez-Martin P, Katunina E, Chaudhuri KR Advanced Parkinson’s or “complex phase” Parkinson’s disease? Re-evaluation is needed. J Neural Transm (Vienna) 2017;124: 1529-37.
52van Wamelen DJ, Leta V, Podlewska AM, Wan YM, Krbot K, Jaakkola E, et al. Exploring hyperhidrosis and related thermoregulatory symptoms as a possible clinical identifier for the dysautonomic subtype of Parkinson’s disease. J Neurol 2019;266:1736-1742.
53Turkka JT, Myllylä VV Sweating dysfunction in Parkinson’s disease. Eur Neurol 1987;26:1-7.
54Kihara M, Kihara Y, Tukamoto T, Nishimura Y, Watanabe H, Hanakago R, et al. Assessment of sudomotor dysfunction in early Parkinson’s disease. Eur Neurol 1993;33:363-5.
55Mano Y, Nakamuro T, Takayanagi T, Mayer RF Sweat function in Parkinson’s disease. J Neurol 1994;241:573-6.
56Magalhães M, Wenning GK, Daniel SE, Quinn NP Autonomic dysfunction in pathologically confirmed multiple system atrophy and idiopathic Parkinson’s disease—A retrospective comparison. Acta Neurol Scand 1995;91:98-102.
57Seppi K, Ray Chaudhuri K, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, et al; Collaborators of the Parkinson’s Disease Update on Non-Motor Symptoms Study Group on behalf of the Movement Disorders Society Evidence-Based Medicine Committee. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov Disord 2019;34:180-98.
58Dafsari HS, Silverdale M, Strack M, Rizos A, Ashkan K, Mahlstedt P, et al. Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson’s disease. Mov Disord 2018;33:421-30.
59Pursiainen V, Lyytinen J, Pekkonen E Effect of duodenal levodopa infusion on blood pressure and sweating. Acta Neurol Scand 2012;126:e20-4.
60Hyun MY, Son IP, Lee Y, Choi HG, Park KY, Li K, et al. Efficacy and safety of topical glycopyrrolate in patients with facial hyperhidrosis: A randomized, multicentre, double-blinded, placebo-controlled, split-face study. J Eur Acad Dermatol Venereol 2015;29:278-82.
61Mehrotra S, Schmith VD, Dumitrescu TP, Gobburu J Pharmacometrics-guided drug development of antihyperhidrosis agents. J Clin Pharmacol 2015;55:1256-67.
62Baker D Topical glycopyrrolate spray 2% reduces axillary hyperhidrosis to a similar extent as Botox injections 2013;169:4.
63Wolosker N, de Campos JR, Kauffman P, Puech-Leão P A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis. J Vasc Surg 2012;55:1696-700.
64Costa AaS, Leão LE, Succi JE, Perfeito JA, Filho Castelo A, Rymkiewicz E, et al. Randomized trial—Oxybutynin for treatment of persistent plantar hyperhidrosis in women after sympathectomy. Clinics (Sao Paulo) 2014;69:101-5.
65Schollhammer M, Brenaut E, Menard-Andivot N, Pillette-Delarue M, Zagnoli A, Chassain-Le Lay M, et al. Oxybutynin as a treatment for generalized hyperhidrosis: A randomized, placebo-controlled trial. Br J Dermatol 2015;173:1163-8.
66Hund M, Sinkgraven R, Rzany B [Randomized, placebo-controlled, double blind clinical trial for the evaluation of the efficacy and safety of oral methantheliniumbromide (vagantin) in the treatment of focal hyperhidrosis]. J Dtsch Dermatol Ges 2004;2:343-9.
67Müller C, Berensmeier A, Hamm H, Dirschka T, Reich K, Fischer T, et al. Efficacy and safety of methantheline bromide (Vagantin®) in axillary and palmar hyperhidrosis: Results from a multicenter, randomized, placebo-controlled trial. J Eur Acad Dermatol Venereol 2013;27:1278-84.
68Wade R, Llewellyn A, Jones-Diette J, Wright K, Rice S, Layton AM, et al. Interventional management of hyperhidrosis in secondary care: a systematic review. Br J Dermatol 2018;179:599-608.
69Mills R, Bahroo L, Pagan F An update on the use of botulinum toxin therapy in Parkinson’s disease. Curr Neurol Neurosci Rep 2015;15:511.
70Jocson A, Lew M Use of botulinum toxin in Parkinson’s disease. Parkinsonism Relat Disord 2019;59:57-64.
71Kempainen RR, Brunette DD The evaluation and management of accidental hypothermia. Respir Care 2004;49:192-205.
72Sanghera MK, Ward C, Stewart RM, Mewes K, Simpson RK, Lai EC Alleviation of drenching sweats following subthalamic deep brain stimulation in a patient with Parkinson’s disease—A case report. J Neurol Sci 2009;285:246-9.
73Trachani E, Constantoyannis C, Sirrou V, Kefalopoulou Z, Markaki E, Chroni E Effects of subthalamic nucleus deep brain stimulation on sweating function in Parkinson’s disease. Clin Neurol Neurosurg 2010;112:213-7.
74Witjas T, Kaphan E, Azulay JP, Blin O, Ceccaldi M, Pouget J, et al. Nonmotor fluctuations in Parkinson’s disease: Frequent and disabling. Neurology 2002;59:408-13.
75Dafsari HS, Petry-Schmelzer JN, Ray-Chaudhuri K, Ashkan K, Weis L, Dembek TA, et al; EUROPAR; IPMDS Non Motor PD Study Group. Non-motor outcomes of subthalamic stimulation in Parkinson’s disease depend on location of active contacts. Brain Stimul 2018;11:904-12.