Progress and Prospects in Parkinson's Research/Symptoms/Paradoxical kinesia

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Paradoxical kinesia
Sometimes referred to as 'Kinesia paradoxa'

Unexpected reversal of motor symptoms"Many PD patients find that the daily onset of movement disorders is inconsistent and unpredictable and varies according to the type of activity they undertake, their emotional state and social circumstances. For example it may seem easier to walk across uneven ground rather than on a flat, hard surface, or it may seem easier to climb stairs or a slope than progress on the level. This gives a pointer to alternative neural  pathways which could be exploited to ameliorate PD symptoms."

Faith 'Cures'
The earliest reference to this phenomenon is to be found in Chapter 2 of the Gospel of St. Mark, where Jesus is at Capernaum and is faced with a bedridden man who is "sick of the palsy".

"10 But ye may know that the Son of man hath power on earth to forgive sins,(he saith to the sick of the palsy.)""11. I say unto thee, Arise, and take up thy bed, and go thy way""t12. And immediately he arose, took up the bed, and went forth before them all; insomuch that they were all amazed, and glorified God, saying, We never saw it on this fashion."

This account begs the questions as to whether the palsy as described equates with PD and whether the observable benefits were permanent or temporary.

In modern times the most documented "miracle" cure is that of Sister Marie Simon-Pierre, who attested that she had been cured of Parkinson's Disease after praying to the late Pope John Paul II.[who himself manifested advanced symptoms of PD]

"ROME, APRIL 30, 2011 .- Here is a [part of]translation of the testimony of Sister Marie Simon-Pierre of the Congregation of the Little Sisters of Catholic Motherhood, regarding her miraculous cure from Parkinson's that she attributes to the intercession of Pope John Paul II. The testimony, written in 2006, formed part of John Paul II's case for beatification. Reports of medical and legal experts on the French nun's healing were submitted to the dicastery for scientific examination last October. The phenomenon was recognized by the Vatican as a miracle attributed to the intercession of John Paul II"

"In June 2001, I was diagnosed with Parkinson's disease. The disease had affected the whole left side of my body, creating great difficulties for me as I am left-handed. After three years, the initial phase of the disease, slow but progressive, was followed by an aggravation of the symptoms: accentuation of the trembling, rigidity, pain, insomnia."" From April 2, 2005, I began to worsen week by week, I grew worse day by day, I was unable to write (I repeat that I am left-handed), and if I attempted it, what I wrote was unintelligible. I could drive only for short trips because my left leg would stiffen sometimes, and my rigidity would have impeded my driving. Moreover, to do my work in a hospital, it took more time than usual. I was exhausted......."

{{blockquote|text=''......On May 13 [2005}, feast of Our Lady of Fatima, Benedict XVI announced the special dispensation to initiate the cause of beatification of John Paul II. Beginning the following day, the sisters of all the French and African communities began to pray for my cure through the intercession of John Paul II. They prayed incessantly until the news arrived of my cure. At that time I was on vacation. On May 26, my time of rest being at an end, I re-turned totally exhausted by the disease. "If you believe, you will see the glory of God": this phrase of St. John's Gospel accompanied me from May 14 onward. On June 1, I was finished; I struggled to stand and to walk.''}}

" On June 2 in the afternoon. With effort, I wrote: 'John Paul II.' We remained in silence before the il-legible letters, then the day continued as usual. At the end of the evening prayer, at 9 o'clock at night, I went to my office before going to my room. I felt the need to pick up the pen and to write, just as if someone within me was saying: 'Pick up the pen and write.' It was between 9:30 and 9:40 at night. To my great surprise I saw that the writing was clearly legible. Not understanding anything, I went to bed. Two months exactly had gone by since John Paul II's departure to the House of the Father. I woke up at 4:30 a.m., surprised that I was able to sleep and I leapt out of bed: my body was no longer insensitive, rigid, and interiorly I was not the same....... "

" ......Ten months have passed now since I interrupted all types of treatment. I am working normally again, I have no difficulty in writing and I also drive long distances. It feels as if I have been reborn: a new life, because nothing is as it was before....."

It is not possible to evaluate these events without a sight of the report of the panel of medical experts set up by the Vatican to evaluate claims of cures.

(1921)
Souques observed the phenomenon and coined the term 'Paradoxical kinesia' to describe it.

(1976)
Marshall et al  Activation-induced restoration of sensorimotor functions in rats with dopamine-depleting brain lesions  succeeded in reproducing Kinesia Paradoxica by exposing Parkinsonian rats to potentially life-threatening situations.

"They began to move and respond appropriately to environmental stimuli when placed in a sink of water, in a shallow ice bath, or among a colony of cats or rats. A reversal of the sensorimotor dysfunctions was still apparent shortly after the animals were removed from each activating situation. However, the therapeutic effects dissipated rapidly, and by 4 hr after an exposure the rats responded as poorly as they had prior to activation."

(1989)
Keefe et al  Dopamine ReleaseStudies in an Animal Model  found that by inducing PK they could switch Parkinson symptoms on and off in rats.

Rats were given brain lesions to inhibit their dopamine production capacity by 98% and they became Parkinsonian. They were placed in deep water and managed to swim effectively. They also escaped from shallow ice baths.

" These behaviors were not abolished by pretreating the animals with the dopamine antagonists haloperidol and SCH-23390. In contrast, haloperidol completely blocked the brain-damaged animals' behavioral responses to amphetamine. These results suggest that the paradoxical kinesia of dopamine-depleted rats is not a consequence of dopamine release from residual dopaminergic fibers."

(2007)
Schlesinger et al interviewed 50 PD patients, who had been exposed to life-threatening situations in war. Two had experiened PK.

(2009)
Robottom et al < noted that symptoms varied when PD patients were placed under emotional or physical stress.

(2009)
At 03.32 Central European Summer Time on the night of 6th April 2009 the city of L'Aquila, which is the capital of the Abruzzo region in Italy, was devastated by a sudden earthquake with a strength of 5.8 on the Richter  Scale. There was considerable damage to property, 308 people lost their lives and some 1,500 were injured.However there is a long history of earth tremors in the region and the majority of citizens evacuated their properties forthwith and survived.

It so happened that 70km. away was a Movement Disorder clinic, operated by the University G.D. Annunzio Chieti-Pescari, which had neen monitoring the symptoms of 14 patients in the city with parkinsonism and dementia. The movemnt disorders of all of them were at Hoehn and Yahr stages 3 to 5.

Measurements taken 3 months after the earthquake showed an unaccountable significant improvement in their UPDRS motor rating. There was also considerable anecdotal evidence of their performmance at the moment when the earthquake struck:-

"He ran like hell out of the two storey building pushing his two children (17 and 15 years old) and his wife" relates to a 59 year old retired chemical engineer in his tenth year since being diagnosed with PD.

"During the earthquake hit he ran from his house." describes a 58 year old retired truck driver five years after PD diagnosis.

'' "During the night time earthquake, she rose from her bed and hurried out of her apartment at the third floor.  When she was examined, 15 days after the earthquake, she walked to the office assisted by her daughter (in the previous visit she had been carried on a wheelchair)." ''Describes a 90 year old woman with both PD and dementia.

 "During the night time earthquake hit he ran away from his second floor apartment." relates to a 77 year od retired public employee.

 "During the earthquake, he jumped out of bed and ran through three flights of stairs, carrying and pushing his 72 year old wife (she reported he practically lifted her up through the collapsing apartment and floors)." Part of an acount of a 77 year old retired engineer who had experienced PD symptoms for three year.

After 5 months the patients had regressed to their pre-earthquake state. A full account was published by Bonanni et al(2010)  Protracted benefit from paradoxical kinesia in typical and atypical parkinsonisms

Oliver Sacks
PK can occur without the need for divine intervention or geological catastrophes. “Awakenings”, by Oliver Sacks, is one of the most lucid and closely observed accounts of PD symptoms. It is based on the case notes of a series of encounters that he had with patients as a result of the PD pandemic called Encephalitis Lethargica. In the 1920’s. This form of the disease is characterised by its rapid onset and progression and its pronounced symptoms. For example bradykinesia progresses to the point where the patient becomes catatonic.

Sacks noted a number of occurrences of Pardoxical kinesia:-"Thus one may see such patients rigid, motionless, seemingly lifeless as statues, abruptly called into normal life and action by some sudden exigency which catches their attention (in one famous case, a drowning man was saved by a Parkinsonian patient who leapt from his wheelchair into the breakers.)"

In the 1950s there was a PD patient at the Highlands Hospital, London, who:- would often sit frozen and motionless unless he were thrown a ball. This would instantly call him to life and he would leap to his feet, swerving, running, dribbling he ball……If thrown a match box he would catch it on the tip of one foot, kick it up, catch it, kick it up again, and in this fashion, juggling the matchbox on one foot, hop the entire length of the ward. 

At the same hospital were two PD patients who shared a room for 20 years. Both were motionless and mute, but one evening:-

" Dr. Stern heard a terrific noise coming from this room of perpetual silence. Rushing to it with a couple of nurses, he found its inmates in the midst if a violent fight, throwing each other around and houting obscenities. The moment they were separated they became motionless and mute again and have remained so ever since."

Another patient at Mount Carmel Hospital would sit completely motionless unless she was suddenly thrown three (or more) oranges.

"Instantly she starts juggling them – she can juggle up to seven, in a manner incredible to see – and can continue doing so for half an hour on end, But if she drops one, or is interrupted for a moment, she suddenly becomes motionless again. "

Another Mount Carmel patient seemed totally incapable of movement until one day when:-

"he suddenly took up my ophthalmoscope, a most intricate one, unscrewed it, put it together again, and gave a stunning imitation of me examining an eye. The entire performance, which was flawless and brilliant, occupied no more than a few seconds. "

(1989)
Morris et al evaluated the factors influencing gait in PD patients.

"Through bypassing the defective basal ganglia and instead using the frontal cortex to regulate movement size or timing by consciously thinking about the desired movement, people with PD arguably compensate for the neurotransmitter imbalance in the basal ganglia. Other strategies include visualizing walking with long steps, mentally rehearsing the desired movement pattern before the action is performed, breaking down long or complex motor sequences into parts and focusing on the performance of each individual segment (segmentation), avoiding dual task performance, reading instructions on a cue card, and verbally reciting phrases such as “think big” or “long steps.”This model is based on the theory that the ability to move normally is not lost in PD. Instead, there is an activation problem that can be overcome through targeted physical therapy together with optimal pharmacotherapy. "

(1991)
Glickstein and Stein

"The stimuli that often elicit paradoxical movements are similar to those that relay visual information to the cerebellum. We suggest that many instances of paradoxical movement may be explained by the fact that the pathways relaying those visual stimuli can bypass the damaged basal ganglia and allow an intact cerebellar circuit to be used for visuomotor control."

(2009)
Schlesimger et al (Ibid) advanced three possible hypotheses to explain PK.

Basal Ganglia Reserves

This assumes that reserves of dopamine are held in the basal ganglia and are released in emergencies.

Compensatory cerebellar circuitry

This assumes that dormant alternative cerebellar circuitry can be activated by reward-seeking behaviour.

Noradrenic augmentation

This assumes that a primitive, latent system of movement can be stimulated into use by the secretion of the neurotransmitter noradrenaline acting upon the '''sympathetic nervous system. ''' This is also known as the "fight-or-flight response"

Visual Cueing
Visual cueing is a form of PK which can be activated, and controlled by an indvidual as an alternative form of locomotion.

Morris et al evaluated cadence control for slow to medium walking speeds in PD patients and showed that an increase in step frequency was a compensation for reduced stride length. They concluded:-

" The findings indicated that cadence control remains unaffected throughout its entire range in Parkinson's disease and that gait hypokinesia is directly attributable to an inability to internally generate sufficiently large steps."