Welcome to BIDMC Neurology

BIDMC – Neurology Fellowship: Autonomic Disorders Selected Publications


  1. Gibbons CH, Garcia J, Wang N, Shi L, Freeman R The diagnostic discrimination of cutaneous alpha-synuclein deposition in Parkinson disease.  Neurology (In press)
  2. Ziegler D, Low P, Freeman R, Tritschler H, Vinik A.  Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4 years in the NATHAN 1 trial.  Journal of Diabetes and Its Complications (In press)
  3. Rao A, Bonyhay I, Dankwa, J; Baimas-George, M; Kneen, L; Ballatori, S; Freeman, R*; Adler, G*.  Baroreflex Sensitivity Impairment During Hypoglycemia – Implications for Cardiovascular Control.  Diabetes Diabetes. 2016; 65(1):209-15. PMID: 26438610 PMCID: PMC4686952
  4. Freeman R, Emir B, Parsons B.  Predictors of placebo response in peripheral neuropathic pain: insights from pregabalin clinical trials.  J Pain Res. 2015;8:257-68  [PMID: 26082659]
  5. Gibbons C, Freeman R.  Clinical implications of delayed orthostatic hypotension – a 10 year follow up study.  Neurology 2015;85:1362-1367. [PMID: 26400576]
  6. Biaggioni I, Freeman R, Mathias CJ, Low PA, Hewitt A, Kaufmann H.  Randomized-withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension. 2015;65:101-7. [PMID: 25350981]
  7. Gibbons C, Freeman R.  Treatment induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes.  Brain. 2015; 138:43-52. [PMID: 25392197]
  8. Freeman R. Wallace Mark S, Sweeney M, Backonja MM.  Relationships among pain quality, pain impact, and overall improvement in patients with postherpetic neuralgia treated with gastroretentive gabapentin.  Pain Medicine.  2015 (In press).  [PMID:26115203]
  9. Kaufmann H, Freeman R, Biaggioni I, Low PA, Pedder S, Hewitt A, Mauney J, Feirtag M, and Mathias CJ.  Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo- controlled Phase 3 trial.  Neurology 2014: 83:328-35. [PMCID:PMC4115605]
  10. Low PA, Robertson D, Gilman S, Kaufmann H, Singer W, Biaggioni I, Freeman R, Perlman S, Hauser RA, Cheshire W, Lessig S, Vernino S, Mandrekar J, Dupont WD, Chelimsky T, Galpern WR.  Efficacy and safety of rifampicin for multiple system atrophy: a randomised, double-blind, placebo-controlled trial.  Lancet Neurology.  2014;13:268-75.
  11. Gibbons CH, Bonyhay I, Benson A, Wang N, Freeman R.  Structural and Functional Small Fiber Abnormalities in the Neuropathic Postural Tachycardia Syndrome.  PLoS One 2013; 8(12): e84716. doi:10.1371/journal.pone.0084716 [PMCID:PMC3874039]
  12. Freeman R, Baron R, Bouhassira D, Cabrera J, Birol E.  Sensory profiles of patients with neuropathic pain based on the neuropathic pain symptoms and signs.  Pain 2014;155:367-76. [PMID: 244725]
  13. Wang N, Gibbons CH, Lafo J, Freeman R. Alpha-synuclein in cutaneous autonomic nerves.  Neurology. 2013; 81:1604-10. [PMCID: PMC3806913]
  14. Bonyhay I, Risk M, Freeman R.  High-Pass Filter Characteristics of the Baroreflex – A Comparison of Frequency Domain and Pharmacological Methods. PLoS One 2013; 8(11): e79513. doi:10.1371/journal.pone.0079513[PMCID: PMC3828383]
  15. Gibbons CH, Freeman R, Tecilazich F, Dinh T, Lyons TE, Gnardellis C, Veves A.  The evolving natural history of neurophysiologic function in patients with well-controlled diabetes.  J Peripher Nerv Syst. 2013; 18:153-61. [PMID:  23781962]
  16. Zhang L, Rainka M, Freeman R, Harden RN, Bell CF, Chen C, Graff O, Harding K, Hunter S, Kavanagh S, Laurijssens B, Schwartzbach C, Warren S, McClung C.  A randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of gabapentin enacarbil in subjects with neuropathic pain associated with postherpetic neuralgia (PXN110748).  Journal of Pain.  2013; 14:590-603. [PMID: 23602345]
  17. Harden RN, Freeman R, Rainka M, Zhang L, Bell C, Berges A et al.  A Phase 2a, randomized, crossover trial of gabapentin enacarbil for the treatment of postherpetic neuralgia in gabapentin inadequate responders.  Pain Medicine 2013; 12:1918-32. [PMID: 24102928]
  18. Gibbons CH, Adler GK, Bonyhay I, Freeman R.  Experimental hypoglycemia is a human model of stress-induced hyperalgesia.  Pain 2012; 153: 2204-2209 [PMCID:PMC356339]
  19. Siepmann T, Gibbons CH, Illigens B, Lafo JA, Brown CM, Freeman R.  Quantitative Pilomotor Axon-Reflex Test – A Novel Test of Pilomotor Function. Arch Neurol. 2012; 69:1488-92 [PMCID: PMC3563419].
  20. Kaufmann H, Malamut R; Norcliffe-Kaufmann L; Rosa R; Freeman R.  The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clinical Autonomic Research 2011; 1-12.
  21. Gibbons CH, Centi J, Vernino S, Freeman R.  Autoimmune autonomic ganglionopathy with reversible cognitive impairment. Arch Neurol. 2012;69:461-466 [PMCID: PMC3359761].
  22. Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schütte K, Dyck PJ.  Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: The NATHAN 1 Trial. Diabetes Care (epub 2011)
  23. Wang N, Gibbons CH, Freeman R.  Novel immunohistochemical techniques using discrete signal amplification systems for human cutaneous peripheral nerve fiber imaging. Journal of Histochemistry & Cytochemistry. 2011;59:382-90 [PMCID: PMC3201146].
  24. Gibbons C, Wang N, Freeman R.  Capsaicin induces degeneration of cutaneous autonomic nerve fibers.  Annals of Neurology 2010;68:888-98.
  25. Gibbons C, Freeman R, Veves A.  Diabetic Neuropathy: A cross sectional study of the relationships among test of neurophysiology.  Diabetes Care 2010;12:2629-34.
  26. Adler GK, Bonyhay I, Curren V, Waring E, Freeman R.  Hypoglycemia increases aldosterone in a dose-dependent fashion.  Diabetic Medicine 2010; 11:1250-5.
  27. Gibbons C, Freeman R.  Treatment Induced Diabetic Neuropathy: A reversible painful autonomic neuropathy.  Annals of Neurology. 2010; 67:534-41.
  28. Simpson DM, Schifitto, G, Clifford DB, Murphy, TK, Durso-De Cruz E, Glue P, Whalen E,  Emir E, Scott, G, Freeman R.  Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial.  2010;74:413-420
  29. Gibbons C, Illigens B, Wang N, Freeman R.  The quantification of sudomotor innervation: a comparison of 3 methods. Muscle and Nerve. 2010;42:112-9.
  30. Adler GK, Bonyhay I, Waring E, Failing HJ, Dotson S, Freeman R. Antecedent hypoglycemia impairs autonomic cardiovascular function – implications for rigorous glycemic control.  Diabetes 2009;58:1-8.


  1. Edwards RR, Dworkin R, Turk D, Angst M, Dionne R, Freeman R, Hansson P, Haroutounian S,  Arendt-Nielsen L, Attal N, MD et al.  Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations.  Pain 2016 (In Press)
  2. Taylor AM, Phillips K, Patel KV, Turk D, Dworkin RH, Beaton D, Clauw DJ, Gignac MAM, Markman JD, Williams DA, Bujanover S, Burke LB, Carr DB, Choy EH. et al. Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations.  Pain 2016 (In Press).
  3. Thakur S, Dworkin RH, Freeman R, Gorson KC, Herrmann DN, Pain in acquired inflammatory demyelinating polyneuropathies.  Pain 2016 (In Press) [PMID: 26945234]
  4. Finnerup NB, Haroutounian, S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja S, Rice ASC; Serra J, Smith BH, Treede R-D,; Jensen TS.  Neuropathic pain: An updated grading system for research and clinical practice.  Pain 2016 (In press)
  5. Dineen J.  Freeman R.  Autonomic Peripheral Neuropathy.  Seminars in Neurology 2015; 35: 458-468.
  6. Freeman R, Barosso F.  Familial amyloid polyneuropathy.  Current Opinion in Neurology 2016 (in Press)
  7. van Hecke O, Kamerman P, Attal N, Baron R, Bjornsdottir G, Bennett DL, Bennett MI, Bouhassira D, Diatchenko L, Freeman R, Freynhagenk R, Haanpääm M, Jensen TS, Raja SN, Rice ASC, Seltzer Z, Yarnitsky D, Smith BH.  Neuropathic pain phenotyping by international consensus (NeuroPPIC): a NeuPSIG systematic review, Delphi survey and expert panel recommendations.  Pain 2015;156:2337-53.PMID: 2646932
  8. Laurens B, Constantinescu R, Freeman R, Gerhard A, Jellinger K, Jeromin A, Krismer F, Mollenhauer B, Schlossmacher MG, Shaw LM, Verbeek MM, Wenning GK, Winge K, Zhang J, Meissner WG.  Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative.  Neurobiol Dis. 2015;80:29-41.  [PMID: 25982836]
  9. Freeman R.  Syncope.  In Harrison’s Principles of Internal Medicine. Nineteenth Edition.  McGraw Hill Medical.  2015.
  10. Freeman R.  The puzzle of orthostatic tolerance in hereditary sensory and autonomic neuropathy, type IV.  Ann Neurol. 2015; 77:741-2. [PMID: 25866260]
  11. Freeman R.  Diabetic autonomic neuropathy. Handbook of Clinical Neurology. 2014;126:63-79.  [PMID: 25410215]
  12. Höke A, Simpson DM, Freeman R.  Designing innovative therapies for neuropathic pain: preclinical and early clinical development challenges. J Peripher Nerv Syst. 2014: Suppl 2:S28-9. PMID:25269739
  13. Fillingim, R.B., Bruehl, S., Dworkin, R.H., Dworkin, S.F., Loeser, J.D., Turk, D.C., Widerstrom-Noga, E., Arnold, L., Bennett, R., Edwards, R.R., Freeman, R., Gewandter, J., Hertz, S., Hochberg, M., Krane, E., Mantyh, P.W., Markman, J., Neogi, T., Ohrbach, R., Paice, J., Porreca, F., Rappaport, B.A., Smith, S.M., Smith, T.J., Sullivan, M.D., Verne, G.N., Wasan, A.D. & Wesselmann, U.   The ACTTION-American Pain Society Pain Taxonomy (AAPT): An evidence-based and multi-dimensional approach to classifying chronic pain conditions.  J Pain. 2014;15:241-9.  [PMID: 2458163]
  14. Gibbons C, Cheshire W, Barboi A, Levine B, Olshansky B, Kinsella L, Claydon VE, Crandall C, Fink G, Joyner M, Macefield V, Norcliffe-Kaufmann L, Freeman R, Raj S, Stewart J, Sandroni P, Kaufmann H, Chelimsky T.  Endovascular procedures for the treatment of autonomic dysfunction.  Clin Auton Res. 2014;24:1-2. PMID:  24178965
  15. Höke A, Simpson DM, Freeman R.  Challenges in developing novel therapies for peripheral neuropathies.  J Peripher Nerv Syst. 2013; 18:1-6. [PMID:  23521637
  16. Freeman R.  New and developing drugs for the treatment of pain in diabetic peripheral neuropathy.   Curr Diab Rep. 2013;13:500-8 [PMID: 2377140]
  17. Emir B, Amaratunga D, Beltangady M, Cabrera J, Freeman R, Madigan D, Nguyen H, Whalen E.  Generating productive dialogue between consulting statisticians and their clients in the pharmaceutical and medical research settings.  Open Access Medical Statistics.  2013:3 51–56
  18. Schestatsky P, Simis M, Freeman R, Pascual-Leone A, Fregni F.  Non-invasive brain stimulation and the autonomic nervous system.  Clin Neurophysiol. 2013; 124:1716-28. [PMID: 23684898]
  19. Backonja MM, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck PJ, Edwards RR, Freeman R, Gracely R, Haanpaa MH, Hansson P, Hatem SM, Krumova EK, Jensen TS, Maier C, Mick G, Rice AS, Rolke R, Treede RD, Serra J, Toelle T, Tugnoli V, Walk D, Walalce MS, Ware M, Yarnitsky D, Ziegler D.  Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus.  Pain. 2013; 154:1807-19.
  20. Freeman R, Chapleau MW.  Testing the autonomic nervous system. Handbook of Clinical Neurology. 2013; 115: 115-36.
  21. Freeman R.  Objective evidence of autonomic dysfunction and the role of stress in the Gulf War syndrome.  JAMA Neurol. 2013;70:158-9. doi: 10.1001/jamaneurol.2013.1494. PMID: 23407742
  22. Freeman R. Pharmacotherapy of Neuropathic Pain.  In: Simpson DM, McArthur JCM, Dworkin R,  Editors. Neuropathic Pain: Mechanisms and Management. Oxford University Press. New York, NY. 2012.
  23. Freeman R.  Autonomic Peripheral Neuropathy.  In Donofrio PD (ed) .Textbook of Peripheral Neuropathy  Chapter 28 (421-438).  Demos Medical (New York) 2012.
  24. Gibbons CH, Freeman R.  Cutaneous autonomic innervation – Assessment by skin biopsy  In: Robertson D, , Biaggioni I, Burnstock G , Low PA, Paton JFR eds.  Primer on the Autonomic nervous system. 3nd Edition.  Academic Press, New York, 2011; 85:413-417.
  25. Gibbons CH, Freeman R.  Delayed orthostatic hypotension. In: Robertson D, , Biaggioni I, Burnstock G , Low PA, Paton JFR eds.  Primer on the Autonomic nervous system. 3nd Edition.  Academic Press, New York, 2011; 109:529-530.
  26. Kempler P, Amarenco G, Freeman R, Frontoni S, Horowitz M, Stevens M, Low P, Pop-Busui R, Tahrani A, Tesfaye S, Várkonyi T, Ziegler D, Valensi P; on behalf of the Toronto Consensus Panel on Diabetic Neuropathy.  Gastrointestinal autonomic neuropathy, erectile-, bladder- and sudomotor dysfunction in patients with diabetes mellitus: clinical impact, assessment, diagnosis, and management.  Diabetes Metab Res Rev. 2011 (Epub)
  27. Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, Stevens M, Kempler P, Hilsted J, Tesfaye S, Low P, Valensi P; on behalf of the Toronto Consensus Panel on Diabetic Neuropathy.  Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011 (Epub)
  28. Bernardi L, Spallone V, Stevens M, Hilsted J, Frontoni S, Pop-Busui R, Ziegler D, Kempler P, Freeman R, Low P, Tesfaye S, Valensi P; on behalf of the Toronto Consensus Panel on Diabetic Neuropathy.  Investigation methods for cardiac autonomic function in human research studies. Diabetes Metab Res Rev. 2011 (Epub)
  29. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.  Autonomic Neuroscience – Basic and Clinical 2011;161:46-8.
  30. Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group.  Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments.  Diabetes Care. 2010;33:2285-93.
  31. Freeman R.  Syncope. Chapter 20. In Harrison’s Principles of Internal Medicine.  Eighteenth Edition.  McGraw Hill Medical.  2011