Basal Ganglia 6 (2016) 75–78

Contents lists available at ScienceDirect

Basal Ganglia
journal homepage: www.elsevier.com/locate/baga

Review

Progressive supranuclear palsy treatment—A systematic review

Samah H. Hajjar* , James K. Cooper
Department of Medicine, School of Medicine and Health Sciences, George Washington University, 2150 Pennsylvania Avenue Northwest, Washington, DC
20037, USA

A R T I C L E I N F O A B S T R A C T

Article history: Progressive supranuclear palsy (PSP) is an uncommon neurodegenerative disease associated with
Received 23 October 2015 postural instability, falling, and memory loss. Different therapeutic approaches have been suggested for
Received in revised form 3 January 2016 PSP, but their efficacy is unclear. With our growing understanding of Parkinson’s-related syndromes, it is
Accepted 13 January 2016
likely that PSP will be increasingly diagnosed, so it is even more important now to know the usefulness of
Available online 16 January 2016
the possible therapies. To our knowledge, no systematic review of PSP therapy has been published.
Objective: To determine the effectiveness of published PSP treatments.
Keywords:
Evidence review: A systematic review of published literature was completed. We searched using PubMed,
Progressive supranuclear palsy
Therapeutics
Scopus, EMBASE, PsychInfo, Cochrane and CINAHL for related articles. To maximize sensitivity, we also
Parkinson-plus searched “gray” literature.
Steele–Richardson–Olszewski Standard exclusion criteria were used: no comparison group; no clear, defined interventions; outcome(s)
Treatment outcome that were not objective; and outcome assessors not blinded to the intervention.
Findings: The initial search obtained 1073 publications. Of these studies, 24 were relevant to the question
of therapy efficacy. Fifteen dealt with medications, 4 with intra- or transcranial procedures, 2 with
physical therapy, 1 dealt with ophthalmic treatment, and 2 dealt with two simultaneous types of
interventions, ophthalmic and physical rehabilitation. Of these studies, 13 remained after application of
our exclusion criteria.
In this final group, all either showed no benefit, or found changes that were not reflected in any benefit to
the subject’s quality of life or longevity.
Conclusion: At the patient level, effectiveness has not been established for any treatment for PSP.
ã 2016 Elsevier GmbH. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
2. Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
2.1. Statistical analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
4.1. Medication trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
4.2. Physical therapy/rehabilitation trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
4.3. Non-clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Funding source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Sponsor’s role . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Author contribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

1. Introduction

Progressive supranuclear palsy (PSP) is an uncommon neuro-

* Corresponding author. Fax: +1 202 741 2791.
E-mail addresses: [email protected], [email protected] degenerative disease that typically presents as postural instability
(S.H. Hajjar). with falls (often backward) and ophthalmological signs. The

http://dx.doi.org/10.1016/j.baga.2016.01.004
2210-5336/ ã 2016 Elsevier GmbH. All rights reserved.
76 S.H. Hajjar, J.K. Cooper / Basal Ganglia 6 (2016) 75–78

incidence rate among those 50–99 years old has been seen as 5 per In the final step, we determined if each of the remaining studies
100,000 per year [1]. PSP is probably underdiagnosed—one had demonstrated any direct benefit to the subjects’ quality of life,
estimate is that for every diagnosed patient, three people with such as reduced falls or fewer hospitalizations, or increased
PSP are misdiagnosed or undiagnosed [2]. longevity.
Many PSP therapeutic interventions have been investigated but
their effectiveness has not been clear. To examine the effectiveness 2.1. Statistical analyses
of studied therapies, we did a systematic review. To our knowledge,
this is the first systematic review of PSP therapeutic options. We were unable to do a meta-analysis due to an inadequate
number of suitable studies.
2. Methodology
3. Results
To search the published literature, we used the following
information resources: PubMed, Scopus, EMBASE, PsychInfo, From our initial search, we obtained 1073 articles. Only
Cochrane and CINAHL. The time frame was January 1, 1994 to 24 articles met inclusion criteria. Four articles apparently reported
June 1, 2015. Additionally we searched broader databases: on the same experiment (they had the same authors, patient
LexisNexis Database, Web of Science, and Google Scholar from numbers and protocols), however the investigators assessed
2011 to June2015. We used terms associated with progressive different variables and had different objectives and were counted
supranuclear palsy such as PSP, Steele–Richardson–Olszewski, and as separate trials. In the final set of included articles,15 dealt with
Richardson syndrome, as well as terms correlated to its clinical medications, 4 with intra- or transcranial procedures, 2 with
manifestation, e.g., progressive supranuclear ophthalmoplegia. For physical therapy, 1 dealt with ophthalmic treatment, and 2 dealt
therapeutic options, we used each possible expression that related with two simultaneous types of interventions, ophthalmic and
to treatment categories, medications, physical therapy/rehabilita- physical rehabilitation.
tion, ophthalmic procedures, and brain stimulation. Two medical Out of these 24 included articles, we excluded 11 articles due to
librarians independently helped in data extraction. absence of a control group. Thirteen articles remained. (Fig. 1).
We assessed articles for eligibility independently. Disagree- Eleven trials dealt with medication and 2 with combined
ments were resolved by consensus. This produced a pool of articles ophthalmic with rehabilitation interventions. All were double
that dealt with PSP therapy, and included reviews, single case blind randomized controlled trials.
reports, and discussions of pathophysiology. In the remaining 13 articles, we looked for efficacy of the
From the pool, we developed a working set (Fig.1). Our inclusion proposed PSP therapeutic interventions. We found no studies that
criteria were [1] articles that provided data on a PSP therapeutic presented efficacy of the studied intervention (Table 1).
intervention [2], English language and [3] human species. Articles
were excluded (removed) from the working set if they had any of 4. Discussion
the following exclusion criteria: [1] no comparison group [2], no
clearly defined intervention [3], outcome(s) that were not This study documents that, from a patient’s perspective, no
objective (we allowed opinion/observations recorded by the treatment has been shown to be of benefit to quality of life,
patient or a family member), [4] outcome assessors not blinded hospitalization rate, cost or life expectancy. While offering “hope”
to the intervention. If the intervention outcome could be affected may have treatment benefit, patients deserve to receive a realistic
by psychological factors, then the control group needed a sham assessment. Small functional improvements found in a few studies
intervention, and was excluded if that were absent. We categorized may be of interest, but do not establish that they have any
the potentially relevant articles according to the therapeutic meaningful impact on patients’ lives.
domain to facilitate the review. This review also highlights the importance of including quality
of life measures such as number of falls, hospitalization, or
improvement in activities of daily living (ADL) or instrumental
activities of daily living (IADL), or longevity in treatment studies
Records identified through database
searching and gray literature, duplicates
that are not pilot studies.
removed (n = 1073) While our review found no study that established treatment
efficacy, several treatment approaches were of interest.

4.1. Medication trials

Records screened in Records excluded
(n = 24) (n = 11) Cholinergic dysfunction has been reported in PSP as a
contributor to motor and cognitive signs [3]. It was postulated
that increasing brain cholinergic effect might produce benefit. To
determine if cholinergic enhancement could alleviate any PSP
clinical symptoms, a double blind randomized control trial was
Articles assessed for Articles excluded due done. Six subjects received a maximum tolerated dose of an
eligibility to efficacy not seen infused acetylcholine esterase inhibitor, physostigmine, and at
(n = 13) (n =13)
another time a placebo infusion. Under steady-state physostigmine
infusions, there were significant effects on brain glucose kinetics:
more glucose entered the brain circulation, but there was no
increase in uptake. There was an observed improvement in ocular
Studies included in movement (antisaccades). Neurocognitive testing showed a small
qualitative synthesis improvement in 2 tests but loss (more impairment) in 2, and no
(n = 0) significant difference in 3. No significant improvement in motor
performance was found [4]. Other investigators looked for the
Fig. 1. PRISMA flow diagram of selection process. effects of oral physostigmine on swallowing and oral motor
 S.H. Hajjar, J.K. Cooper / Basal Ganglia 6 (2016) 75–78 77

Table 1
Discussion of efficacy of the final pool of 13 articles.

Intervention Year Comment

Physostigmine (infusions) [4] 1995 Some ocular improvement (antisaccades); neurobehavioral tests were inconsistent; No motor function improvement; no defined
benefit to subjects
Efaroxan [9] 1998 No significant clinical improvement
Zolpidem [13] 1999 A pilot study; at low dose, zolpidem showed improvements in motor and eye (saccadic) movement. Quality of life elements were
not evaluated. Adverse effects were drowsiness and increased postural instability
Physostigmine (oral) [5] 1999 No significant improvement in oral motor and swallowing functions
Donepezil [6] 2001 Deterioration in activities of daily living and mobility scores regardless of treatment
Gabapentin [14] 2007 No functional improvement
Coenzyme Q10 [15] 2008 Mild clinical improvement in PSP Rating Scale scores. Phase 3 trial is ongoing
Balance and eye movement 2008 Between the treatment and control groups, no gait improvement was detected
training [18]
Riluzole [7] 2009 No significant effects in the survival and disease progression rate
Balance and eye movement 2009 Improvement in gaze control. General efficacy not evaluated
training [19]
Davunetide [10] 2014 Not an effective treatment
Tideglusib [11,12] 2014 No clinical efficacy

disturbances in PSP. Results failed to show any significant effects More evaluations are underway (NCT00382824 is the Trial Registry
[5]. Identification Number at http://www.clinicaltrials.gov).
A study of donepezil, another acetylcholine esterase inhibitor, We are aware that l-dopamine is sometimes used to treat PSP.
found no improvement in primary outcomes. Activities of daily Separately, we looked specifically for documentation (with no date
living and mobility scores showed deterioration with treatment. restriction), and found no clinical trials that demonstrated l-
The authors concluded, “In light of its deleterious effects on ADL/ dopamine efficacy. Results in one article found 6% of patients had
mobility, donepezil is not recommended for this patient popula- moderate benefit based on chart review of observations made by
tion” [6]. clinicians not blinded to the therapy and using no standard criteria,
Riluzole, a benzothiazole drug, inhibits glutamate release and so the results are unreliable [16]. Another article found “anti-
some sodium channels to inhibit excitatory neurotransmitters, and Parkinson drugs largely ineffective and caused frequent adverse
may have neuroprotective action. It is used in the treatment of effects” [17].
amyotrophic lateral sclerosis. A well designed trial examined the
potential efficacy of riluzole on PSP survival and disease 4.2. Physical therapy/rehabilitation trials
progression rates and did not find any significant positive effects
[7]. While medication interventions were the most commonly
An alpha-2 antagonist, idazoxan, had been investigated in a published treatment trials, rehabilitation strategies were the
small double blind randomized control trial that showed possible second. Two clinical trials investigated the effect of physical
benefit [8]. A more potent alpha-2 antagonist, efaroxan, was therapy (balance training) and eye movement rehabilitation
evaluated in a double blind randomized control trial. No valuable compared to balance training alone. Investigators found benefit
therapeutic benefits were found [9]. in gaze control and a trend (non-significant) for improvement in
Tau hyperphosphorylation is felt to be a major PSP pathological gait and general mobility. However, there was no adequate control
process. Davunetide and tideglusib can inhibit tau phosphoryla- group and the overall benefit to patients (falls, quality or length of
tion. Both were promising disease modifying agents but double life, hospitalization, etc.) was not evaluated [18,19].
blind randomized control trials showed davunetide and tideglusib A systematic review that evaluates the effectiveness of allied
as non-effective treatments for PSP [10,11]. In a related trial, health therapy in the symptomatic management of progressive
investigators evaluated the efficacy of tideglusib on brain atrophy. supranuclear palsy is currently ongoing [20].
They reported significant reduction in the progression of brain
atrophy without clinical correlation [12]. 4.3. Non-clinical trials
Zolpidem is a nonbenzodiazepine hypnotic drug (GABA agonist)
that was investigated in a pilot study in addition to two case In addition to clinical trials, there were some interesting reports
reports. A double blind randomized control trial of 10 patients that showed good results which may or may not be reproducible.
showed significant improvement in motor function and eye A recent report on a single patient was considered the first in
movement; however, no data on the overall effect on subjects' using intrathecal infusions of autologous adipose tissue-derived
quality of life was presented [13]. Drowsiness and postural mesenchymal stem cells. It showed improvements in cognitive
instability are restrictions for zolpidem use as a treatment for PSP. function and daily living activities [21]. Another report showed
A study of gabapentin as a potential treatment for PSP found an significant improvement in motor dysfunctions from amitriptyline
improvement in reflexive saccade inhibition (P < 0.048) that was administration. Two patients became able to feed themselves and
evaluated by blinded investigators, but reported no functional transferred independently [22].
benefit to subjects [14]. Many either intra- or transcranial electrical stimulation
Coenzyme Q10 trials showed improvement in mitochondrial procedures were published. An improvement in walking speed
energy metabolism and overall cerebral metabolism. There were was obtained in an intracranial stimulation report in which the
mild clinical improvements that led to improvement in the total patient was able to walk 4 times faster than before treatment [23].
PSP Rating Scale scores (PSP-RS is 28 items clinical prognostic scale Another report of transcranial alternating current pulsed applica-
and survival estimator) and Frontal Assessment Battery scores (a tions of weak electromagnetic fields on one patient showed
clinical score system with 6 subtests used to differentiate between significant improvements in freezing and falling rate (falling rate
dementia of frontal lobe dysfunction and Alzheimer’s disease) [15]. reduced from 3–4 times per day to 2–3 times per week) [24].
78 S.H. Hajjar, J.K. Cooper / Basal Ganglia 6 (2016) 75–78

Numerous reports described different rehabilitation strategies. in the treatment of progressive supranuclear palsy, Mov. Disord. 13 (4) (1998)
A rehabilitation program that combined a dynamic antigravity 673–676.
[10] A.L. Boxer, A.E. Lang, M. Grossman, D.S. Knopman, B.L. Miller, L.S. Schneider, R.
postural system and a vibration sound system on 10 patients S. Doody, A. Lees, L.I. Golbe, D.R. Williams, J.C. Corvol, A. Ludolph, D. Burn, S.
showed improvement of postural instability with positive impact Lorenzl, I. Litvan, E.D. Roberson, G.U. Hoglinger, M. Koestler, C.R. Jack, Jr. Van
on quality of life due at least in part to “the acquired notion of new Deerlin, V. Randolph, C. Lobach, I.V. Heuer, H.W. Gozes, I. Parker, L. Whitaker, S.
Hirman, J. Stewart, A.J. Gold, M. Morimoto, B.H. Investigators, Davunetide in
treatment options for a nosological entity (PSP) lacking for patients with progressive supranuclear palsy: a randomised, double-blind,
effective pharmacological therapies” [25]. placebo-controlled phase 2/3 trial, Lancet Neurol. 13 (7) (2014) 676–685, doi:
More cases of PSP may be identified as our understanding of http://dx.doi.org/10.1016/S1474-4422(14) 70088-2.
[11] E. Tolosa, I. Litvan, G.U. Hoglinger, D. Burn, A. Lees, M.V. Andres, B. Gomez-
Parkinson-like disorders increases, It is important to disseminate Carrillo, T. Leon, T. Del Ser, T. Investigators, A phase 2 trial of the GSK-
the finding that so far no effective therapy has been found, and 3 inhibitor tideglusib in progressive supranuclear palsy, Mov. Disord. 29 (4)
treatments appear to be futile. (2014) 470–478, doi:http://dx.doi.org/10.1002/mds.25824.
[12] G.U. Hoglinger, H.J. Huppertz, S. Wagenpfeil, M.V. Andres, V. Belloch, T. Leon, T.
Del Ser, T.M. Investigators, Tideglusib reduces progression of brain atrophy in
Conflict of interest progressive supranuclear palsy in a randomized trial, Mov. Disord. 29 (4)
(2014) 479–487, doi:http://dx.doi.org/10.1002/mds.25815.
Both authors state they have no conflict of interests. [13] A. Daniele, E. Moro, A.R. Bentivoglio, Zolpidem in progressive supranuclear
palsy, N. Engl. J. Med. 341 (7) (1999) 543–544, doi:http://dx.doi.org/10.1056/
NEJM199908123410721.
Funding source [14] A. Poujois, M. Vidailhet, J.M. Trocello, F. Bourdain, B. Gaymard, S. Rivaud-
Pechoux, Effect of gabapentin on oculomotor control and parkinsonism in
patients with progressive supranuclear palsy, Eur. J. Neurol. 14 (9) (2007)
Taibah University, Saudi Arabia. 1060–1062 ENE1687[pii].
[15] M. Stamelou, A. Reuss, U. Pilatus, J. Magerkurth, P. Niklowitz, K.M. Eggert, A.
Sponsor’s role Krisp, T. Menke, C. Schade-Brittinger, W.H. Oertel, G.U. Hoglinger, Short-term
effects of coenzyme Q10 in progressive supranuclear palsy: a randomized,
placebo-controlled trial, Mov. Disord. 23 (7) (2008) 942–949, doi:http://dx.
The sponsor had no role in this study, except to provide some doi.org/10.1002/mds.22023.
salary support for Dr. Hajjar. [16] K.A. Nieforth, L.I. Golbe, Retrospective study of drug response in 87 patients
with progressive supranuclear palsy, Clin. Neuropharmacol. 16 (4) (1993)
338–346 Epub 1993/08/01. PubMed PMID: 8374914.
Author contribution [17] K. Kompoliti, C.G. Goetz, I. Litvan, K. Jellinger, M. Verny, Pharmacological
therapy in progressive supranuclear palsy, Arch. Neurol. 55 (8) (1998)
1099–1102.
Each author participated in literature review, evaluation and
[18] C. Zampieri, R.P. Di Fabio, Balance and eye movement training to improve gait
writing. in people with progressive supranuclear palsy: quasi-randomized clinical trial,
Phys. Ther. 88 (12) (2008) 1460–1473, doi:http://dx.doi.org/10.2522/
References ptj.20070302.
[19] C. Zampieri, R.P. Di Fabio, Improvement of Gaze control after balance and eye
movement training in patients with progressive supranuclear palsy: a quasi-
[1] J.H. Bower, D.M. Maraganore, S.K. McDonnell, W.A. Rocca, Incidence of randomized controlled trial, Arch. Phys. Med. Rehabil. 90 (2) (2009) 263–270.
progressive supranuclear palsy and multiple system atrophy in Olmsted [20] E. Tilley, S. White, M. Peters, S.A. Koblar, J. McLoughlin, The effectiveness of
County, Minnesota, 1976 to 1990, Neurology 49 (5) (1997) 1284–1288. allied health therapy in the symptomatic management of progressive
[2] L.I. Golbe, Progressive supranuclear palsy, Semin. Neurol. 34 (2) (2014) supranuclear palsy: a systematic review protocol, JBI Database Syst. Revi.
151–159. Implement. Rep. 12 (7) (2014) 119–137, doi:http://dx.doi.org/10.11124/jbisrir-
[3] N.M. Warren, M.A. Piggott, E.K. Perry, D.J. Burn, Cholinergic systems in 2014-1633 PubMed PMID: 2012733894. Language: English. Entry Date:
progressive supranuclear palsy, Brain: J. Neurol. 128 (Part 2) (2005) 239–249 20141003. Revision Date: 20141024. Publication Type: journal article.
PubMed PMID: 2009157531. Language: English. Entry Date: 20060505. [21] S.W. Choi, K.B. Park, S.K. Woo, S.K. Kang, J.C. Ra, Treatment of progressive
Publication Type: journal article.. supranuclear palsy with autologous adipose tissue-derived mesenchymal
[4] J. Blin, P. Mazetti, B. Mazoyer, S. Rivaud, S. Ben Ayed, C. Malapani, B. Pillon, Y. stem cells: a case report, J. Med. Case Rep. 8 (1) (2014) 87, doi:http://dx.doi.org/
Agid, Does the enhancement of cholinergic neurotransmission influence brain 10.1186/1752-1947-8-87 PubMed PMID: 2012539507. Language: English.
glucose kinetics and clinical symptomatology in progressive supranuclear Entry Date: In Process. Revision Date: 20140418. Publication Type: journal
palsy? Brain: J. Neurol. 118 (Pt 6) (1995) 1485–1495. article. Journal Subset: Biomedical.
[5] C.M. Frattali, B.C. Sonies, G. Chi-Fishman, I. Litvan, Effects of physostigmine on [22] P.A. Engel, Treatment of progressive supranuclear palsy with amitriptyline:
swallowing and oral motor functions in patients with progressive therapeutic and toxic effects, J. Am. Geriatr. Soc. 44 (9) (1996) 1072–1074
supranuclear palsy: a pilot study, Dysphagia 14 (3) (1999) 165–168. PubMed PMID: 1997009898. Language: English. Entry Date: 19970301.
[6] I. Litvan, M. Phipps, V.L. Pharr, M. Hallett, J. Grafman, A. Salazar, Randomized Publication Type: journal article.
placebo-controlled trial of donepezil in patients with progressive [23] N. Tani, Y. Saitoh, H. Kishima, S. Oshino, J. Hatazawa, K. Hashikawa, T.
supranuclear palsy, Neurology 57 (3) (2001) 467–473. Yoshimine, Motor cortex stimulation for levodopa-resistant akinesia: case
[7] G. Bensimon, A. Ludolph, Y. Agid, M. Vidailhet, C. Payan, P.N. Leigh, Group NS. report, Mov. Disord. 22 (11) (2007) 1645–1649, doi:http://dx.doi.org/10.1002/
Riluzole treatment, survival and diagnostic criteria in Parkinson plus mds.21593.
disorders: the NNIPPS study, Brain: J. Neurol. 132 (Pt 1) (2009) 156–171, doi: [24] R. Sandyk, Transcranial AC pulsed applications of weak electromagnetic fields
http://dx.doi.org/10.1093/brain/awn291. reduces freezing and falling in progressive supranuclear palsy: a case report,
[8] J. Ghika, M. Tennis, E. Hoffman, D. Schoenfeld, J. Growdon, Idazoxan treatment Int. J. Neurosci. 94 (1-2) (1998) 41–54.
in progressive supranuclear palsy, Neurology 41 (7) (1991) 986–991 Epub [25] L. Di Pancrazio, R.G. Bellomo, R. Franciotti, P. Iodice, V. Galati, A.
1991/07/01. PubMed PMID: 1676832. D’Andreagiovanni, S. Bifolchetti, A. Thomas, M. Onofrj, L. Bonanni, L. Bonanni,
[9] O. Rascol, K. Sieradzan, H. Peyro-Saint-Paul, C. Thalamas, C. Brefel-Courbon, J. Combined rehabilitation program for postural instability in progressive
M. Senard, P. Ladure, J.L. Montastruc, A. Lees, Efaroxan, an alpha-2 antagonist, supranuclear palsy, NeuroRehabilitation 32 (4) (2013) 855–860.