Progress and Prospects in Parkinson's Research/Therapy/Symptomatic Relief/Tremor
Tremor is defined as the rhythmic involuntary oscillatory movement of a body part, and resting tremor is one of the signature symptoms of Parkinson’s Disease. Its precise nature remains unexplained. It is experienced by many, but not all, P.D. patients. It can affect any limb, and frequently all four. Sometimes the jaw is affected and more rarely the eyelids. It is socially demeaning, it can make it almost impossible to relax and it often inhibits sleep.
This tremor, present predominantly at rest, appears early on in the disease course and causes a significant amount of life distress. It presents in up to 75% of individuals with PD, and has been shown to occur in a frequency range of 3–7Hz, a range distinct from that seen in dyskinesias (1–2Hz), essential tremor (8Hz), and postural tremors (8–12Hz)
Collins-Praino et al font color="maroon">2011 
Frequently patients report that it is less responsive to dopamine replacement therapy. It is more closely associated with their emotional state than where they are on their levadopa on/off cycle. This leads to the suspicion that other metabolic processes are involved and separate therapies might be possible.
Isaias et al font color="maroon">(2012) (2012) state:-
The tremor in PD is remarkable for several features:-
(1) It is neither a consistent or homogeneous feature across patients or within an individual patient’s disease course.
(2) It may diminish in the end stage of PD.
(3) It occurs predominantly at rest and is reduced or disappears by action
(4) It increases in amplitude or can be triggered by manoeuvres such as walking or psychological states as anxiety or stress (specific tasks, like simple arithmetic calculation may induce stress-related tremor).
(5) It is not present during sleep.
(6) It may be the predominant or the only clinical sign for years before the appearance of akinesia.
(7) It poorly correlates with nigrostriatal dopaminergic deficits.
The PD tremor can be mirrored by other conditions leading to occasional misdiagnoses and these have been evaluated by Schwingenschuh et al (2005) who reviewed diagnostic methods of distinguishing PD tremors from other movement disorders.
Approximately 10% of subjects thought clinically to have early Parkinson’s disease (PD) have normal dopaminergic functional imaging (SWEDDs – Scans Without Evidence of Dopaminergic Deficit).
The difficulties in determining the root causes of resting tremors have been analysed by Hallett & Deuschl (2010)
Mure et al (2010) used a series of imaging techniques to map those areas of the brain that were active when the resting tremor was present in PD patients. They found that the tremor was:-
characterized by network-related increases in the metabolic activity of the cerebellum/dorsal pons and primary motor cortex, and to a lesser degree in the caudate/putamen. The expression of this pattern in individual patients correlated with independent clinical ratings for tremor, but not akinesia-rigidity.
This section requires information on other treatments, drug and non-drug, for tremor.
Relaxation Guided Imagery (RGI)
In 2009 the Rambam Health Care Campus at Haifa in Israel ran a series of physiotherapy clinics for PD patients with a view to maintaining their mobility.
On one occasion a group of patients arrived for the clinic but the physiotherapist rang in to say that she was unable to make it. The nurse in charge decided to make up for the shortfall by trying out a technique, which she had been taught, called Relaxation Guided Imagery. She was amazed to find that this had a dramatic effect on the patients’ resting tremor: switching it off completely. This was the first recorded instance of a therapy which reversed this symptom and the nurse duly reported the result to the hospital doctors. Subsequently a group of them organised a controlled test and described the results in a paper Schlesinger et al (2009)  and posted a video to an on-line site.
In order to conduct the test they assembled a cohort of 20 tremulous patients with a mixture of age range and gender. The patients were not told the objective of the test and were divided into small groups, sitting on reclining chairs with their forearms supported by arm rests. They each wore a device called an accelerometer, which recorded the incidence of tremor. The two hour session was divided into four parts.
Initially patients were given nothing to do for half an hour apart from talking to one another and the tremor measurements taken constituted a baseline. Then for 15 minutes relaxing background music was played and this was continued for the remainder of the session.
For the following 15 minutes the patients were invited to use any effective relaxation method which they had learned from experience. There followed 15 minutes of RGI.
The session concluded with a 30 minute period during which no therapy took place but the tremor continued to be measured.
Relaxation music and self-relaxation techniques resulted in a moderate diminution of tremor, but the effect of the RGI was much more dramatic, switching off the tremor completely. The beneficial effects persisted after the RGI was terminated. All patients reported this follow-on benefit for periods from 2 to 14 hours.
During the procedure the patients appeared to go into a totally relaxed state, which raised the issue as to whether they were simply falling asleep. To validate this, three of them were retested while attached to an EEG machine, which showed that they were fully awake during the procedure. Relaxation Guided Imagery is a form of self hypnosis involving the imagination of structured scenarios. There are a number of variations of this technique and it is not clear which was used in the Israeli experiment.
Bhidayasiri, R. (2005) Postgrad. Med. J. 81 (982) 756-782 Differential diagnosis of common tremor syndromes http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1743400/?tool=pmcentrez
Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits? Helmich,Rick C.;Hallett, Mark; Deuschl, Gunther; Toni1, Ivan and Bloem, Bastiaan R.Cerebral (2012) BrainCerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?http://brain.oxfordjournals.org/content/early/2012/03/01/brain.aws023.full.pdf+html
- Collins-Praino, Lyndsey E.; Paul, Nicholas E.; Rychalsky.Krisren L.; Hinman, James R.; Chrobak, James J.; Senatus, Patrick B. And Salamone, John D. font color="maroon">201 Front. Syst. Neurosc. 5 49 Pharmacological and Physiological Characterization of the Tremulous Jaw Movement Model of Parkinsonian Tremor: Potential Insights into the Pathophysiology of Tremor http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131529/?tool=pmcentrez
- Isaias, Ioannis U.; Marzegan, Alberto; Pezzoli, Gianni; Marotta, Giorgio: Canesi, Margherita; Biella, Gabriele M.E.; Volkmann, Jens and Cvallari, Paolo font color="maroon"><2012> (2012)font color="maroon">date Front Hum. Neurosc. 5: A role for the locus coelruleus in Parkinson tremor.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250076/
- Schwingenshuh, Petra: Ruge, Diane: Edwards, Mark J.; Terranova, Carmen; Karschnig, Petra; Carrillo, Fatima; Sileira-Moriyama, Laura; Schneider, Susanne A.; Kagi, George; Dickson, John; Lees, Andrew J.; Quinn, Niall, Mir, Pablo: Rockwell, John D. and Bhatia, Kailash B. (2010) Movement Disorders 25 (5) 580-589 Adult onset asymmetric upper limb tremor misdiagnosed as Parkinson’s Disease: a clinical and electrophysiological study. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996567/?tool=pmcentrez
- Hallett, Mark and Deuschl, Gunther (2010) Ann. Neurol. 68 (6) 780-781 Are we making progress in the understanding of tremor in Parkinson’s disease? http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058743/?tool=pmcentrez
- Mure, Hideo; Hirano, Shigeki; Tang, Chris.c.; Isaias Ioannis U.; Antonini, Angelo; Ma,Yilong; Dhawan, Vijay and Eidelberg, David (2011) Neuroimage 54 (2) 1244-1253 Parkinson’s Disease Tremor-Related Metabolic Network,; Characterization, Progression and Treatment Effects http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997135/?tool=pmcentrez
- Schlesinger, I.; Benyakov, O.; Erikh, O.; Sureiya, S. and Schiller, Y. 2009) Movement Disorders 24(14) 2059-62. Parkinson’s Disease tremor is diminished with relaxation guided imagery