Key Points
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Autonomic failure can occur in isolation, in association with peripheral neuropathy, or as a manifestation of a neurodegenerative disorder
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Disorders associated with autonomic failure can be classified according to the type and severity of autonomic manifestations, associated neurological symptoms, and temporal profile
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Acute or subacute autonomic failure suggests an autoimmune autonomic ganglionopathy, which may be paraneoplastic
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In patients with parkinsonism and autonomic failure, early onset and progression of orthostatic hypotension or urogenital dysfunction, urinary incontinence, generalized anhidrosis, and/or laryngeal stridor are highly suggestive of multiple system atrophy
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Autonomic failure can occur with any type of diabetic or amyloid neuropathy
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Important causes of painful neuropathy associated with autonomic failure include Sjögren syndrome, HIV infections, Fabry disease, and sodium channelopathies
Abstract
Central or peripheral neurological disorders can manifest with autonomic failure or autonomic hyperactivity, which may affect the sympathetic, parasympathetic and/or enteric nervous systems. Disorders causing autonomic failure can be classified according to the presence or absence of associated neurological manifestations, such as peripheral neuropathy or parkinsonism, and their temporal profile (acute or subacute, chronic progressive, static, or episodic). A systematic approach allows focused evaluation to detect treatable, potentially disabling or life-threatening conditions. Subacute isolated autonomic failure affecting sympathetic, parasympathetic and enteric nervous system function, in various combinations, occurs in autoimmune autonomic ganglionopathy, which might be the first manifestation of an underlying neoplasm. Autonomic failure can be an important feature of several types of peripheral neuropathy, including sensorimotor peripheral neuropathies, sensory ganglionopathy, and distal painful peripheral neuropathies. Progressive autonomic failure occurs in neurodegenerative synucleinopathies such as multiple system atrophy and Lewy body disorders. Autonomic failure may also occur in hereditary leukoencephalopathies or prion disorders. This Review outlines the clinical approach to patients with generalized autonomic failure, focusing predominantly on classification and diagnosis, but also touching briefly on treatment and management.
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References
Stefanova, N., Bucke, P., Duerr, S. & Wenning, G. K. Multiple system atrophy: an update. Lancet Neurol. 8, 1172–1178 (2009).
Cersosimo, M. G. & Benarroch, E. E. Autonomic involvement in Parkinson's disease: pathology, pathophysiology, clinical features and possible peripheral biomarkers. J. Neurol. Sci. 313, 57–63 (2012).
Vernino, S. Autoimmune and paraneoplastic channelopathies. Neurotherapeutics 4, 305–314 (2007).
Muppidi, S. & Vernino, S. Autoimmune autonomic failure. Handb. Clin. Neurol. 117, 321–327 (2013).
Freeman, R. Autonomic peripheral neuropathy. Lancet 365, 1259–1270 (2005).
Freeman, R. et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Auton. Neurosci. 161, 46–48 (2011).
Mathias, C. J. et al. Differential blood pressure and hormonal effects after glucose and xylose ingestion in chronic autonomic failure. Clin. Sci. (Lond.) 77, 85–92 (1989).
Mathias, C. J., Mallipeddi, R. & Bleasdale-Barr, K. Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple system atrophy. J. Neurol. 246, 893–898 (1999).
Freeman, R. Clinical practice. Neurogenic orthostatic hypotension. N. Engl. J. Med. 358, 615–624 (2008).
Benarroch, E. E. The arterial baroreflex: functional organization and involvement in neurologic disease. Neurology 71, 1733–1738 (2008).
Cheshire, W. P. & Freeman, R. Disorders of sweating. Semin. Neurol. 23, 399–406 (2003).
Fowler, C. J., Griffiths, D. & de Groat, W. C. The neural control of micturition. Nat. Rev. Neurosci. 9, 453–466 (2008).
Holstege, G. Micturition and the soul. J. Comp. Neurol. 493, 15–20 (2005).
Panicker, J. N. & Fowler, C. J. The bare essentials: uro-neurology. Pract. Neurol. 10, 178–185 (2010).
Travagli, R. A., Hermann, G. E., Browning, K. N. & Rogers, R. C. Brainstem circuits regulating gastric function. Annu. Rev. Physiol. 68, 279–305 (2006).
Furness, J. B. The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol. 9, 286–294 (2012).
Kyle, R. A. & Bayrd, E. D. Amyloidosis: review of 236 cases. Medicine (Baltimore) 54, 271–299 (1975).
Vernino, S. et al. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N. Engl. J. Med. 343, 847–855 (2000).
McKeon, A., Lennon, V. A., Lachance, D. H., Fealey, R. D. & Pittock, S. J. Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments. Arch. Neurol. 66, 735–741 (2009).
Goldstein, D. S. Catecholamines 101. Clin. Auton. Res. 20, 331–352 (2010).
Robertson, D. et al. Isolated failure of autonomic noradrenergic neurotransmission. Evidence for impaired β-hydroxylation of dopamine. N. Engl. J. Med. 314, 1494–1497 (1986).
Fealey, R. D., Low, P. A. & Thomas, J. E. Thermoregulatory sweating abnormalities in diabetes mellitus. Mayo Clin. Proc. 64, 617–628 (1989).
Low, P. A. Autonomic nervous system function. J. Clin. Neurophysiol. 10, 14–27 (1993).
Gibbons, C. H., Illigens, B. M., Centi, J. & Freeman, R. QDIRT: quantitative direct and indirect test of sudomotor function. Neurology 70, 2299–2304 (2008).
Bennett, T. et al. Assessment of vagal control of the heart in diabetes. Measures of R–R interval variation under different conditions. Br. Heart J. 39, 25–28 (1977).
Booth, R. W. & Ryan, J. M. The clinical use of the Valsalva maneuver. Heart Bull. 10, 111–113 (1961).
Sandroni, P., Benarroch, E. E. & Low, P. A. Pharmacological dissection of components of the Valsalva maneuver in adrenergic failure. J. Appl. Physiol. 71, 1563–1567 (1991).
Cooke, J. et al. Sitting and standing blood pressure measurements are not accurate for the diagnosis of orthostatic hypotension. QJM 102, 335–339 (2009).
Low, P. A. Testing the autonomic nervous system. Semin. Neurol. 23, 407–421 (2003).
Freeman, R. Assessment of cardiovascular autonomic function. Clin. Neurophysiol. 117, 716–730 (2006).
Hilz, M. J. & Dutsch, M. Quantitative studies of autonomic function. Muscle Nerve 33, 6–20 (2006).
Lauria, G. et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur. J. Neurol. 17, 903–912, e44–e49 (2010).
Donadio, V. et al. Peripheral autonomic neuropathy: diagnostic contribution of skin biopsy. J. Neuropathol. Exp. Neurol. 71, 1000–1008 (2012).
Gibbons, C. H., Illigens, B. M., Wang, N. & Freeman, R. Quantification of sweat gland innervation: a clinical-pathologic correlation. Neurology 72, 1479–1486 (2009).
Nolano, M. et al. Quantification of pilomotor nerves: a new tool to evaluate autonomic involvement in diabetes. Neurology 75, 1089–1097 (2010).
Libbey, C. A., Skinner, M. & Cohen, A. S. Use of abdominal fat tissue aspirate in the diagnosis of systemic amyloidosis. Arch. Intern. Med. 143, 1549–1552 (1983).
Kyle, R. A. & Greipp, P. R. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin. Proc. 58, 665–683 (1983).
Klein, C. J. et al. Mass spectrometric-based proteomic analysis of amyloid neuropathy type in nerve tissue. Arch. Neurol. 68, 195–199 (2011).
Gilman, S. et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71, 670–676 (2008).
Wenning, G. K., Ben Shlomo, Y., Magalhaes, M., Daniel, S. E. & Quinn, N. P. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 117, 835–845 (1994).
Kollensperger, M. et al. Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry. Mov. Disord. 25, 2604–2612 (2010).
Kaufmann, H. & Biaggioni, I. Autonomic failure in neurodegenerative disorders. Semin. Neurol. 23, 351–363 (2003).
Chaudhuri, K. R. & Schapira, A. H. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 8, 464–474 (2009).
Graham, J. G. & Oppenheimer, D. R. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J. Neurol. Neurosurg. Psychiatry 32, 28–34 (1969).
Papp, M. I., Kahn, J. E. & Lantos, P. L. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy–Drager syndrome). J. Neurol. Sci. 94, 79–100 (1989).
Iodice, V. et al. Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests. J. Neurol. Neurosurg. Psychiatry 83, 453–459 (2012).
Multiple-System Atrophy Research Collaboration. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N. Engl. J. Med. 369, 233–244 (2013).
Tada, M. et al. Early development of autonomic dysfunction may predict poor prognosis in patients with multiple system atrophy. Arch. Neurol. 64, 256–260 (2007).
O'Sullivan, S. S. et al. Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain 131, 1362–1372 (2008).
Wenning, G. K. et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol. 12, 264–274 (2013).
Wenning, G. K. et al. Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study. J. Neurol. Neurosurg. Psychiatry 67, 620–623 (1999).
Oppenheimer, D. R. Lateral horn cells in progressive autonomic failure. J. Neurol. Sci. 46, 393–404 (1980).
Benarroch, E. E., Smithson, I. L., Low, P. A. & Parisi, J. E. Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure. Ann. Neurol. 43, 156–163 (1998).
Winge, K. & Fowler, C. J. Bladder dysfunction in Parkinsonism: mechanisms, prevalence, symptoms, and management. Mov. Disord. 21, 737–745 (2006).
Benarroch, E. E. & Schmeichel, A. M. Depletion of corticotrophin-releasing factor neurons in the pontine micturition area in multiple system atrophy. Ann. Neurol. 50, 640–645 (2001).
Kennedy, P. G. & Duchen, L. W. A quantitative study of intermediolateral column cells in motor neuron disease and the Shy–Drager syndrome. J. Neurol. Neurosurg. Psychiatry 48, 1103–1106 (1985).
Chalmers, D. & Swash, M. Selective vulnerability of urinary Onuf motoneurons in Shy–Drager syndrome. J. Neurol. 234, 259–260 (1987).
Kirchhof, K., Apostolidis, A. N., Mathias, C. J. & Fowler, C. J. Erectile and urinary dysfunction may be the presenting features in patients with multiple system atrophy: a retrospective study. Int. J. Impot. Res. 15, 293–298 (2003).
Sakakibara, R. et al. Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy. Mov. Disord. 19, 924–929 (2004).
Sandroni, P., Ahlskog, J. E., Fealey, R. D. & Low, P. A. Autonomic involvement in extrapyramidal and cerebellar disorders. Clin. Auton. Res. 1, 147–155 (1991).
Lipp, A. et al. Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch. Neurol. 66, 742–750 (2009).
Iranzo, A. Sleep and breathing in multiple system atrophy. Curr. Treat. Options Neurol. 9, 347–353 (2007).
Ghorayeb, I., Bioulac, B. & Tison, F. Sleep disorders in multiple system atrophy. J. Neural Transm. 112, 1669–1675 (2005).
Silber, M. H. & Levine, S. Stridor and death in multiple system atrophy. Mov. Disord. 15, 699–704 (2000).
Glass, G. A., Josephs, K. A. & Ahlskog, J. E. Respiratory insufficiency as the primary presenting symptom of multiple-system atrophy. Arch. Neurol. 63, 978–981 (2006).
Vetrugno, R. et al. Sleep-related stridor due to dystonic vocal cord motion and neurogenic tachypnea/tachycardia in multiple system atrophy. Mov. Disord. 22, 673–678 (2007).
Schwarzacher, S. W., Rub, U. & Deller, T. Neuroanatomical characteristics of the human pre-Bötzinger complex and its involvement in neurodegenerative brainstem diseases. Brain 134, 24–35 (2011).
Benarroch, E. E., Schmeichel, A. M., Low, P. A. & Parisi, J. E. Depletion of putative chemosensitive respiratory neurons in the ventral medullary surface in multiple system atrophy. Brain 130, 469–475 (2007).
Tada, M. et al. Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death. Brain 132, 1810–1819 (2009).
Braak, H. et al. Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered. Mov. Disord. 21, 2042–2051 (2006).
Dickson, D. W. et al. Evidence that incidental Lewy body disease is pre-symptomatic Parkinson's disease. Acta Neuropathol. 115, 437–444 (2008).
Jellinger, K. A. A critical reappraisal of current staging of Lewy-related pathology in human brain. Acta Neuropathol. 116, 1–16 (2008).
Beach, T. G. et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 119, 689–702 (2010).
Shishido, T. et al. α-Synuclein accumulation in skin nerve fibers revealed by skin biopsy in pure autonomic failure. Neurology 74, 608–610 (2010).
Wang, N., Gibbons, C. H., Lafo, J. & Freeman, R. α-Synuclein in cutaneous autonomic nerves. Neurology 81, 1604–1610 (2013).
Polinsky, R. J. Clinical autonomic neuropharmacology. Neurol. Clin. 8, 77–92 (1990).
Klein, C. M. et al. The spectrum of autoimmune autonomic neuropathies. Ann. Neurol. 53, 752–758 (2003).
Pfeiffer, R. F. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Relat. Disord. 17, 10–15 (2011).
Siddiqui, M. F., Rast, S., Lynn, M. J., Auchus, A. P. & Pfeiffer, R. F. Autonomic dysfunction in Parkinson's disease: a comprehensive symptom survey. Parkinsonism Relat. Disord. 8, 277–284 (2002).
Abbott, R. D. et al. Frequency of bowel movements and the future risk of Parkinson's disease. Neurology 57, 456–462 (2001).
Savica, R. et al. Medical records documentation of constipation preceding Parkinson disease: a case–control study. Neurology 73, 1752–1758 (2009).
Proulx, M., de Courval, F. P., Wiseman, M. A. & Panisset, M. Salivary production in Parkinson's disease. Mov. Disord. 20, 204–207 (2005).
Cersosimo, M. G. et al. Hyposialorrhea as an early manifestation of Parkinson disease. Auton. Neurosci. 150, 150–151 (2009).
Del Tredici, K., Hawkes, C. H., Ghebremedhin, E. & Braak, H. Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson's disease. Acta Neuropathol. 119, 703–713 (2010).
Edwards, L. L., Quigley, E. M., Harned, R. K., Hofman, R. & Pfeiffer, R. F. Characterization of swallowing and defecation in Parkinson's disease. Am. J. Gastroenterol. 89, 15–25 (1994).
Castell, J. A. et al. Manometric abnormalities of the oesophagus in patients with Parkinson's disease. Neurogastroenterol. Motil. 13, 361–364 (2001).
Wakabayashi, K., Takahashi, H., Takeda, S., Ohama, E. & Ikuta, F. Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses. Acta Neuropathol. 76, 217–221 (1988).
Sakakibara, R., Uchiyama, T., Yamanishi, T., Shirai, K. & Hattori, T. Bladder and bowel dysfunction in Parkinson's disease. J. Neural Transm. 115, 443–460 (2008).
Sharabi, Y. & Goldstein, D. S. Mechanisms of orthostatic hypotension and supine hypertension in Parkinson disease. J. Neurol. Sci. 310, 123–128 (2011).
Winge, K., Skau, A. M., Stimpel, H., Nielsen, K. K. & Werdelin, L. Prevalence of bladder dysfunction in Parkinsons disease. Neurourol. Urodyn. 25, 116–122 (2006).
Blackett, H., Walker, R. & Wood, B. Urinary dysfunction in Parkinson's disease: a review. Parkinsonism Relat. Disord. 15, 81–87 (2009).
Winge, K. & Nielsen, K. K. Bladder dysfunction in advanced Parkinson's disease. Neurourol. Urodyn. 31, 1279–1283 (2012).
Sakakibara, R., Uchiyama, T., Yamanishi, T. & Kishi, M. Sphincter EMG as a diagnostic tool in autonomic disorders. Clin. Auton. Res. 19, 20–31 (2009).
Seppi, K. et al. Progression of putaminal degeneration in multiple system atrophy: a serial diffusion MR study. Neuroimage 31, 240–245 (2006).
Feigin, A. et al. Tc-99m ethylene cysteinate dimer SPECT in the differential diagnosis of parkinsonism. Mov. Disord. 17, 1265–1270 (2002).
Kwon, K. Y., Choi, C. G., Kim, J. S., Lee, M. C. & Chung, S. J. Comparison of brain MRI and 18F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease. Mov. Disord. 22, 2352–2358 (2007).
Varrone, A., Marek, K. L., Jennings, D., Innis, R. B. & Seibyl, J. P. [123I]β-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson's disease and multiple system atrophy. Mov. Disord. 16, 1023–1032 (2001).
King, A. E., Mintz, J. & Royall, D. R. Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov. Disord. 26, 1218–1224 (2011).
Goldstein, D. S., Holmes, C., Cannon, R. O. 3rd, Eisenhofer, G. & Kopin, I. J. Sympathetic cardioneuropathy in dysautonomias. N. Engl. J. Med. 336, 696–702 (1997).
Treglia, G. et al. Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson's disease and multiple-system atrophy: a systematic review and a meta-analysis. Clin. Neurol. Neurosurg. 113, 823–829 (2011).
Nagayama, H. et al. Abnormal cardiac [123I]-meta-iodobenzylguanidine uptake in multiple system atrophy. Mov. Disord. 25, 1744–1747 (2010).
McKeith, I. G. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J. Alzheimers. Dis. 9, 417–423 (2006).
Stubendorff, K., Aarsland, D., Minthon, L. & Londos, E. The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson's disease with dementia. PLoS ONE 7, e45451 (2012).
Kanazawa, M. et al. An autopsy case of dementia with Lewy bodies showing autonomic failure and dementia as the initial symptoms. Mov. Disord. 22, 1212–1213 (2007).
Thaisetthawatkul, P. et al. Autonomic dysfunction in dementia with Lewy bodies. Neurology 62, 1804–1809 (2004).
Leehey, M. A. Fragile X-associated tremor/ataxia syndrome: clinical phenotype, diagnosis, and treatment. J. Investig. Med. 57, 830–836 (2009).
Guaraldi, P. et al. Isolated noradrenergic failure in adult-onset autosomal dominant leukodystrophy. Auton. Neurosci. 159, 123–126 (2011).
Mead, S. et al. A novel prion disease associated with diarrhea and autonomic neuropathy. N. Engl. J. Med. 369, 1904–1914 (2013).
Koike, H., Watanabe, H. & Sobue, G. The spectrum of immune-mediated autonomic neuropathies: insights from the clinicopathological features. J. Neurol. Neurosurg. Psychiatry 84, 98–106 (2013).
Suarez, G. A., Fealey, R. D., Camilleri, M. & Low, P. A. Idiopathic autonomic neuropathy: clinical, neurophysiologic, and follow-up studies on 27 patients. Neurology 44, 1675–1682 (1994).
Gibbons, C. H. & Freeman, R. Antibody titers predict clinical features of autoimmune autonomic ganglionopathy. Auton. Neurosci. 146, 8–12 (2009).
Vernino, S., Cheshire, W. P. & Lennon, V. A. Myasthenia gravis with autoimmune autonomic neuropathy. Auton. Neurosci. 88, 187–192 (2001).
Peltier, A. C. et al. Coexistent autoimmune autonomic ganglionopathy and myasthenia gravis associated with non-small-cell lung cancer. Muscle Nerve 41, 416–419 (2010).
Gibbons, C. H., Vernino, S. A. & Freeman, R. Combined immunomodulatory therapy in autoimmune autonomic ganglionopathy. Arch. Neurol. 65, 213–217 (2008).
Imrich, R., Vernino, S., Eldadah, B. A., Holmes, C. & Goldstein, D. S. Autoimmune autonomic ganglionopathy: treatment by plasma exchanges and rituximab. Clin. Auton. Res. 19, 259–262 (2009).
Iodice, V. et al. Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy. Neurology 72, 2002–2008 (2009).
Sandroni, P. et al. Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody. Arch. Neurol. 61, 44–48 (2004).
Lucchinetti, C. F., Kimmel, D. W. & Lennon, V. A. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 50, 652–657 (1998).
Winkler, A. S., Dean, A., Hu, M., Gregson, N. & Chaudhuri, K. R. Phenotypic and neuropathologic heterogeneity of anti-Hu antibody-related paraneoplastic syndrome presenting with progressive dysautonomia: report of two cases. Clin. Auton. Res. 11, 115–118 (2001).
Chinn, J. S. & Schuffler, M. D. Paraneoplastic visceral neuropathy as a cause of severe gastrointestinal motor dysfunction. Gastroenterology 95, 1279–1286 (1988).
De Giorgio, R. et al. Inflammatory neuropathies of the enteric nervous system. Gastroenterology 126, 1872–1883 (2004).
Colan, R. V., Snead, O. C. 3rd, Oh, S. J. & Kashlan, M. B. Acute autonomic and sensory neuropathy. Ann. Neurol. 8, 441–444 (1980).
Koike, H. et al. Clinicopathological features of acute autonomic and sensory neuropathy. Brain 133, 2881–2896 (2010).
Pavlakis, P. P. et al. Peripheral neuropathies in Sjögren syndrome: a new reappraisal. J. Neurol. Neurosurg. Psychiatry 82, 798–802 (2011).
Dawson, L., Tobin, A., Smith, P. & Gordon, T. Antimuscarinic antibodies in Sjögren's syndrome: where are we, and where are we going? Arthritis Rheum. 52, 2984–2995 (2005).
Nakamura, Y. et al. High prevalence of autoantibodies to muscarinic-3 acetylcholine receptor in patients with juvenile-onset Sjögren syndrome. Ann. Rheum. Dis. 67, 136–137 (2008).
Park, K., Park, S. & Jackson, M. W. The inhibitory effects of antimuscarinic autoantibodies in the sera of primary Sjogren syndrome patients on the gastrointestinal motility. Mol. Immunol. 56, 583–587 (2013).
Kondo, T. et al. Autoimmune autonomic ganglionopathy with Sjögren's syndrome: significance of ganglionic acetylcholine receptor antibody and therapeutic approach. Auton. Neurosci. 146, 33–35 (2009).
Tesfaye, S. et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33, 2285–2293 (2010).
Ziegler, D., Gries, F. A., Spuler, M. & Lessmann, F. The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group. J. Diabetes Complications 6, 49–57 (1992).
Low, P. A. et al. Autonomic symptoms and diabetic neuropathy: a population-based study. Diabetes Care 27, 2942–2947 (2004).
England, J. D. et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology 72, 177–184 (2009).
Vinik, A. I. & Ziegler, D. Diabetic cardiovascular autonomic neuropathy. Circulation 115, 387–397 (2007).
Maleki, D. et al. Gastrointestinal tract symptoms among persons with diabetes mellitus in the community. Arch. Intern. Med. 160, 2808–2816 (2000).
Lysy, J., Israeli, E. & Goldin, E. The prevalence of chronic diarrhea among diabetic patients. Am. J. Gastroenterol. 94, 2165–2170 (1999).
Schiller, L. R. et al. Pathogenesis of fecal incontinence in diabetes mellitus: evidence for internal-anal-sphincter dysfunction. N. Engl. J. Med. 307, 1666–1671 (1982).
Bradley, W. E. Diagnosis of urinary bladder dysfunction in diabetes mellitus. Ann. Intern. Med. 92, 323–326 (1980).
Kaplan, S. A., Te, A. E. & Blaivas, J. G. Urodynamic findings in patients with diabetic cystopathy. J. Urol. 153, 342–344 (1995).
Bacon, C. G. et al. Association of type and duration of diabetes with erectile dysfunction in a large cohort of men. Diabetes Care 25, 1458–1463 (2002).
Malavige, L. S. & Levy, J. C. Erectile dysfunction in diabetes mellitus. J. Sex. Med. 6, 1232–1247 (2009).
Watkins, P. J. Facial sweating after food: a new sign of diabetic autonomic neuropathy. Br. Med. J. 1, 583–587 (1973).
Gibbons, C. H. & Freeman, R. Treatment-induced diabetic neuropathy: a reversible painful autonomic neuropathy. Ann. Neurol. 67, 534–541 (2010).
Wang, A. K., Fealey, R. D., Gehrking, T. L. & Low, P. A. Patterns of neuropathy and autonomic failure in patients with amyloidosis. Mayo Clin. Proc. 83, 1226–1230 (2008).
Cappellari, M. et al. Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients. J. Peripher. Nerv. Syst. 16, 119–129 (2011).
Rajkumar, S. V., Gertz, M. A. & Kyle, R. A. Prognosis of patients with primary systemic amyloidosis who present with dominant neuropathy. Am. J. Med. 104, 232–237 (1998).
Gertz, M. A. et al. Stem cell transplantation for the management of primary systemic amyloidosis. Am. J. Med. 113, 549–555 (2002).
Planté-Bordeneuve, V. & Said, G. Familial amyloid polyneuropathy. Lancet Neurol. 10, 1086–1097 (2011).
Said, G. & Planté-Bordeneuve, V. TTR-familial amyloid polyneuropathy—neurological aspects. Amyloid 19 (Suppl. 1), 25–27 (2012).
Arruda-Olson, A. M. et al. Genotype, echocardiography, and survival in familial transthyretin amyloidosis. Amyloid 20, 263–268 (2013).
Yamashita, T. et al. Long-term survival after liver transplantation in patients with familial amyloid polyneuropathy. Neurology 78, 637–643 (2012).
Coelho, T. et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology 79, 785–792 (2012).
Robinson-Papp, J., Sharma, S., Simpson, D. M. & Morgello, S. Autonomic dysfunction is common in HIV and associated with distal symmetric polyneuropathy. J. Neurovirol. 19, 172–180 (2013).
Dutsch, M. et al. Small fiber dysfunction predominates in Fabry neuropathy. J. Clin. Neurophysiol. 19, 575–586 (2002).
Dib-Hajj, S. D., Cummins, T. R., Black, J. A. & Waxman, S. G. From genes to pain: Nav1.7 and human pain disorders. Trends Neurosci. 30, 555–563 (2007).
Faber, C. G. et al. Gain of function Nav1.7 mutations in idiopathic small fiber neuropathy. Ann. Neurol. 71, 26–39 (2012).
Rush, A. M. et al. A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc. Natl Acad. Sci. USA 103, 8245–8250 (2006).
Han, C. et al. Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. Brain 135, 2613–2628 (2012).
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Benarroch, E. The clinical approach to autonomic failure in neurological disorders. Nat Rev Neurol 10, 396–407 (2014). https://doi.org/10.1038/nrneurol.2014.88
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DOI: https://doi.org/10.1038/nrneurol.2014.88
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