A Multidisciplinary Approach to Manage Gait Difficulty in Parkinson Patients
Summary
The study team proposes to treat Parkinson's patients with gait difficulty with multidisciplinary approach of medications. Single medication treatment, such as the use of cholinergic-boosting anti-dementia medication targeting cholinergic deficiency to improve executive dysfunction and attention deficit, or the use of medication boosting the norepinephrine system, have not proven effective so far in treating the gait difficulty. Anti-anxiety medications, particularly the SNRI (serotonin and norepinephrine reuptake inhibitor) medications, which also ameliorate the norepinephrinergic deficiency, have not been studied except for one successful case report using duloxetine to treat primary progressive freezing of gait. Targeting multiple mechanisms at same time, such as the combination of a SNRI antianxiety medication (also boosting the norepinephrine system, such as duloxetine) with an anti-dementia medication correcting the cholinergic deficiency (such as donepezil), or targeting a new mechanism, such as the use of anti-GABAergic medication targeting the area responsible for gait and sleep cycle (pedunculopontine nucleus area, PPNa) should be tried. Therefore, a collaboration of multidisciplinary teams among the neurology movement disorder team and cognition and sleep team, and psychiatry team is essential, which has not been tried before in studying and treating the challenging gait difficulty in Parkinson patients.
Timeline
- Start
- 2016-11
- Primary completion
- 2017-11
- Completion
- 2017-11
Publications
- Background Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011 Aug;10(8):734-44. doi: 10.1016/S1474-4422(11)70143-0.
- Background Shine JM, Matar E, Ward PB, Frank MJ, Moustafa AA, Pearson M, Naismith SL, Lewis SJ. Freezing of gait in Parkinson's disease is associated with functional decoupling between the cognitive control network and the basal ganglia. Brain. 2013 Dec;136(Pt 12):3671-81. doi: 10.1093/brain/awt272. Epub 2013 Oct 18.
- Background Fasano A, Herman T, Tessitore A, Strafella AP, Bohnen NI. Neuroimaging of Freezing of Gait. J Parkinsons Dis. 2015;5(2):241-54. doi: 10.3233/JPD-150536.
- Background Bohnen NI, Frey KA, Studenski S, Kotagal V, Koeppe RA, Scott PJ, Albin RL, Muller ML. Gait speed in Parkinson disease correlates with cholinergic degeneration. Neurology. 2013 Oct 29;81(18):1611-6. doi: 10.1212/WNL.0b013e3182a9f558. Epub 2013 Sep 27.
- Background Lewitt PA. Norepinephrine: the next therapeutics frontier for Parkinson's disease. Transl Neurodegener. 2012 Jan 13;1(1):4. doi: 10.1186/2047-9158-1-4.
- Background Pagano G, Rengo G, Pasqualetti G, Femminella GD, Monzani F, Ferrara N, Tagliati M. Cholinesterase inhibitors for Parkinson's disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):767-73. doi: 10.1136/jnnp-2014-308764. Epub 2014 Sep 15.
- Background Morgante F, Fasano A. Improvement with duloxetine in primary progressive freezing gait. Neurology. 2010 Dec 7;75(23):2130-2. doi: 10.1212/WNL.0b013e318200d7a3. No abstract available.
- Background Nandi D, Jenkinson N, Stein J, Aziz T. The pedunculopontine nucleus in Parkinson's disease: primate studies. Br J Neurosurg. 2008;22 Suppl 1:S4-8. doi: 10.1080/02688690802448350.
- Background Xie T, Vigil J, MacCracken E, Gasparaitis A, Young J, Kang W, Bernard J, Warnke P, Kang UJ. Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. Neurology. 2015 Jan 27;84(4):415-20. doi: 10.1212/WNL.0000000000001184. Epub 2014 Dec 24.
- Background Plaha P, Gill SS. Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson's disease. Neuroreport. 2005 Nov 28;16(17):1883-7. doi: 10.1097/01.wnr.0000187637.20771.a0.
- Background Mazzone P, Lozano A, Stanzione P, Galati S, Scarnati E, Peppe A, Stefani A. Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson's disease. Neuroreport. 2005 Nov 28;16(17):1877-81. doi: 10.1097/01.wnr.0000187629.38010.12.
- Background Acar F, Acar G, Bir LS, Gedik B, Oguzhanoglu A. Deep brain stimulation of the pedunculopontine nucleus in a patient with freezing of gait. Stereotact Funct Neurosurg. 2011;89(4):214-9. doi: 10.1159/000326617. Epub 2011 May 20.
- Background Garcia-Rill E, Kezunovic N, Hyde J, Simon C, Beck P, Urbano FJ. Coherence and frequency in the reticular activating system (RAS). Sleep Med Rev. 2013 Jun;17(3):227-38. doi: 10.1016/j.smrv.2012.06.002. Epub 2012 Oct 6.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Donepezil | Small molecule | 10 mg | — |
| Subject | Duloxetine | Small molecule | 120 mg | — |
| Subject | Modafinil | Small molecule | 200 mg | — |