What Is Parkinson’s Disease? When we hear the name “Muhammad Ali” we instantly picture a man with a sturdy physique, roaring at his opponent in the boxing ring with his eyes aimed firmly at the title. People could recognize Ali amidst crowds not only in a country or a region but across the globe. His fame was not confined to geographic boundaries. A man with a heart of gold, Muhammad Ali was a star, inside and outside of the boxing ring. He was a face of strength and terror to his opponents inside the ring. Outside the ring however, he was an epitome of wit, kindness and humanity.
Louisville Mayor Greg Fischer while paying homage to deceased boxing champion Muhammad Ali last Friday, had the following to say.
“The values of hard work, conviction and compassion that Muhammad Ali developed while growing up in Louisville helped him become a global icon. As a boxer, he became ‘The Greatest,’ though his most lasting victories happened outside the ring.
Muhammad leveraged his fame as a platform to promote peace, justice and humanitarian efforts around the world, while always keeping strong ties to his hometown. Today, Muhammad Ali’s fellow Louisvillians join the billions whose lives he touched worldwide in mourning his passing, celebrating his legacy and committing to continue his fight to spread love and hope.”
Born on January 17th 1942 as Cassius Marcellus Clay, the boxing legend Muhammad Ali bid us farewell on Friday, June 3rd 2016 at the age of 74.
Muhammad Ali’s funeral was held earlier today on June 10th in his hometown Louisville and was attended by international dignitaries and commoners alike.
Revenge To Champion — A Midas Touch
Muhammad Ali began his boxing career at the early age of 12. Young Cassius’s journey began when he rode his bicycle to a fair, where it was stolen. Furious, the youngster went to the police station to report the theft, telling police officers he would beat the thief up himself if he found him.
It was at that moment when Joe Martin, then a local police officer and boxing instructor, identified a gem that needed refinement. From that point on, Ali seriously began his journey from being an amateur to becoming the boxing legend who ruled the world.
At the age of 18, Ali qualified for the Olympic Games in Rome. Emerging as a new star in a galaxy already filled with stars, he won a gold medal in the light heavyweight category. In the same year of 1960, Ali stepped into his first ever professional bout against Henry Cooper. At the age of 22, he defeated the heavyweight champion Sonny Liston in Miami. Furthermore, he became the first man to win the glorious heavyweight titles three times.
In 1979, Muhammad Ali announced his retirement from a glorious boxing career. However, tempted by the glory of being a symbol of undefeated power in the ring, he returned to face Larry Holmes in the ring. This turned out to be a bad decision from the otherwise-intelligent boxer — Ali faced terrible defeats at the hands of Larry Holmes and later from Trevor Berbick.
Seeing his “unbeatable” streak steadily decline, Ali bid his final farewell to the boxing ring in 1981. The legend’s health was deteriorating day by day with his drooling, slurred speech and trembling hands becoming increasingly noticeable. However, it was not until 1984 that Ali was diagnosed with Parkinson’s disease at the age of 43.
Man Of Steel
Muhammad Ali was a man of faith — he believed in himself and never compromised on what paths he chose in life. His opinionated political views and voice against racism brought him in the spotlight outside the ring.
It was in 1964 when Ali joined the Nation of Islam that he first rose to fame outside the ring. In 1967, he refused to participate in the Vietnam War, putting his boxing career at risk. His license to box was stripped and the court sentenced him to three years of imprisonment. However, this temporary halt to his boxing career ended as he returned to the ring in 1970.
Ali converted to orthodox Islam in 1975. Despite strong opposition he stood firm on his decisions. Unsurprisingly, Ali’s name made its way to the headlines several times, some of them not always being about his boxing career.
Was Rope-a-Dope The Hidden Culprit Behind Star’s Ailment?
Known for his speed, agility and quick reflexes against his opponents in the ring, Muhammad Ali began to lose his signature traits with his comeback in the 1970s. In an encounter against Joe Frazier in 1974 Ali changed his tactics and adopted the “rope-a-dope” technique.
According to this strategy, Ali would face punches from his opponent until he was exhausted before counterattacking. This drastic change in game plan raised speculations suggesting that absorbing punches from his opponents caused Ali neurological damage that later resulted in Parkinson’s disease.
But was rope-a-dope the hidden culprit behind the star’s ailment? One cannot make a sweeping statement when it comes to the reasons leading to Parkinson’s diseases.
Parkinson’s disease is a complex disease embedded into even more complex multifactorial causes. The possible risk factors that increase the likelihood of developing Parkinson’s disease will be discussed as we move ahead.
Diagnosing Parkinson’s disease is not an easy task, as experts have not found a specific biological marker for it. MRI and PET scans are administered by neurologists but diagnoses accuracy and precision have not been fully attained.
In Ali’s case things were not different. Ten weeks before Ali’s match in 1980 against Larry Holmes, doctors at the Mayo Clinic submitted a medical report to the Nevada State Athletic Commission describing a small hole in his brain’s outer layer. They also took note of the boxer’s complaint about experiencing a tingling sensation in his hands and slurred speech. However, it wasn’t until 1984 when a diagnosis was made. As scientists believed that Parkinson’s disease has its roots in a person’s genetic makeup, they have found some genes that may contribute towards a person’s susceptibility of developing Parkinson’s disease.
Seven genes found to be contributing towards Parkinson’s disease have been identified. Dominant mutations in three known genes called SNCA (PARK1), UCHL1 (PARK 5), PARK3 and LRRK2 (PARK8) have been found. One the other hand, recessive mutations have been found in PARK2 (PARK2), PARK7 (PARK7), and PINK1 (PARK6).
Scientists are investigating into the occurrence of early onset of Parkinson’s disease and related genetic variations, however this research is still in its preliminary stages.
Genetic testing is now available for PARK7, SNCA and LRRK2 genes. PARK7 (Parkinsonism associated deglycase) encodes a protein that protects brain cells against oxidative stress caused by the accumulation of free radicals in cells. This causes damage to the brain cells, which are ultimately killed if the gene of this protein is mutated.
The SNCA gene encodes the alpha-synuclein protein, if the gene is flawed, this protein clumps up in the brain cells. Experts are trying to obtain an insight into the pathways involved with alpha-synuclein becoming a target for new Parkinson’s disease drugs.
The LRRK2 gene encodes a protein which has a kinase and hydrolysis activity. Involved in cell signaling, if flawed, this protein causes toxicity in brain cells leading to Parkinson’s disease symptoms. While scientists are not sure about the exact mechanism of this gene’s involvement in Parkinson’s disease, they are hopeful in finding substantial information soon. Better understanding of the contribution of this gene will eventually bring therapeutic improvements to the horizon.
Furthermore, experts firmly believe that genetic susceptibility towards Parkinson’s disease has to combine with environmental factors to cause the disease.
“In Parkinson’s disease, research has been pointing in the direction supporting the notion that genetics loads the gun, and the environment pulls the trigger,” says Dr. Michael S. Okun, Medical Director of the National Parkinson Foundation.
In a study from The Journal of the American Medical Association (JAMA), scientists have said that nothing can be accurately said about the factors causing neural cell deterioration but it is most likely to be caused by an interaction between a person’s genotype and the environment, which leads to the disease. In about 15-25% cases of Parkinson’s disease a family member suffers from the disease as well. The effect of the LRRK gene discussed above, is most prominent in familial Parkinson’s disease.
On the other hand, in about 75% of the occurrences of Parkinson’s disease, environmental exposure plays an essential role.
In this context, exposure to the man-made chemical known as trichloroethylene (TCE) is associated with increasing the risk of Parkinson’s by six folds altogether. To our surprise, TCE is a common organic contaminant which pollutes groundwater, soil and the air thereby increasing our risk of developing Parkinson’s disease.
Another compound known as 1-methyl-4-Phenyl-1,2,3,6 Tetrahydroppyridine (MPTP) is also found to be contributing to the disease onset. This chemical, found in illegal drug production, pesticides and certain metals, has a toxic activity specifically towards the neurons involved in Parkinson’s disease.
However, studies have shown that using foods rich in vitamins A, B, C and E, Omega-3 (DHA) and phytochemicals reduces the risk of developing Parkinson’s disease. Interestingly, nicotine-containing vegetables, moderate smoking, moderate alcohol consumption, caffeine intake through tea and coffee non-steroidal anti-inflammatory drugs are also found to be helpful against developing the disease.
What Is Parkinson’s Disease? Does Parkinson’s Disease Have A Cure?
Currently, Parkinson’s disease has no cure, but treatments are given which involve the symptoms of the disease. This involves physiotherapy, speech therapy and occupational therapy. Researchers have been working tirelessly for decades to find a treatment for Parkinson’s disease. Few medications have been formulated that have claimed to slow down the disease progression but no treatments have yet been developed that can reverse the changes to the brain cells caused by the disease.
Oral medicines are the first line of treatment for Parkinson’s disease, which work to optimize dopamine levels in the brain cells.
- Dopamine Replacement Therapy — a dopamine precursor, Levodopa is administered in combination with other drugs such as carbidopa or benserazide. This medication helps replenish normal dopamine levels in brain cells.
- Dopamine agonists — these medications are administered to stimulate dopamine receptors to mimic the action of dopamine. This class of medicines includes; bromocriptine, pergolide, cabergoline and apomorphine.
- Anticholinergics — these were the first medications to be used for Parkinson’s disease. Anticholinergics govern through the principle of blocking the effect of another neurotransmitter, acetylcholine to help rebalance chemical balance with dopamine. These drugs included benzotropine, biperidine, and some antihistamines. The benefits of these medications were outweighed by the side effects, due to which they are not used now.
- Amantadine (Symmetrel) — this class of drug has the properties of both anticholinergic and dopamine agonists which help drug-induced involuntary movement in Parkinson’s disease patients.
- Monamine Oxidase Type B Inhibitors — this class of medication prevents the breakdown of available dopamine to stop symptom deterioration. These inhibitors, if taken in combination with levodopa, can increase the medication efficacy.
- Cathechol-o-methyl Transferase Inhibitors — these medications include the use of entacapone and tolcapone. Either of these drugs is used with levodopa for better results. These inhibitors block the enzyme COMT that breaks down levodopa (dopamine precursor) in the intestines and the brain. By doing this, they help in the prolonged activity of levodopa.
Another treatment option for Parkinson’s disease is surgery. In a deep brain stimulation surgery, electrodes are inserted in targeted regions of the brain, mapped by MRI scan. With the help of neuroimaging, a device called an impulse generator is inserted under the collarbone. This device stimulates an electrical impulse in the region of the brain responsible for motor functioning. Currently, it is the most advanced treatment modality for treating Parkinson’s disease, however not everybody can benefit from this treatment.
To fight off the disease, scientists are working tirelessly to find novel treatments. In these efforts, the long-term function of transplanted dopamine neurons was examined in human fetal midbrain cellular transplants. The expression of dopamine transporters (DATs) and mitochondrial morphology was monitored. DAT was found to be robustly expressing itself after the transplant while neural morphology also remained normal.
Clinical findings showed that the fetal dopamine neuron transplants maintained normal activity for 15-18 years. These findings are critical in towards developing stem-cell-based dopamine neuronal replacement therapy.
From An Olympic Gold Medalist To Parkinson’s Kline Lighter
The first indicator of the disease showed a glimpse in 1978 when Ali’s speech began to slur. In the same year, he lost at the hands of Leon Spinks. But being the champion that he was, he avenged his defeat by winning defeating his opponent after seven months. When Ali hit back, he became the first man to win the title three times.
Talking of the disease which represented Ali’s biggest opponent, we need to stop and learn what Parkinson’s disease actually did to him.
According to an estimate, about 1 million Americans suffer from Parkinson’s disease. The onset of this neurodegenerative disease is commonly observed in people over the age of 50, however in Muhammad Ali’s case it began in his late 30s.
In Parkinson’s disease, the nerve cells responsible for carrying a neurotransmitter known as dopamine are damaged. Dopamine is a neurotransmitter which plays a vital role in controlling and coordinating the body movement.
As these dopaminergic neurons in the ventrolateral region of the substantia nigra pars compacta are degenerated, the amount of dopamine carried from one nerve cell to another via synapses is reduced.
The central process of dopaminergic neurons degeneration is followed by dopamine striatal deficit and accumulation of aggregated alpha-synuclein in undamaged neurons, brainstem nuclei, amyglada and cortical regions. Dopamine deficiency begins a change in the neural pathways in the basal ganglia circuits which results in the manifestation of symptoms of Parkinson’s disease.
However, the symptoms of Parkinson’s disease start to manifest only when 80% of these dopamine carrying nerve cell are lost. The disease is divided into five stages by means of the Hoehn and Yahr staging of Parkinson’s disease.
As a person who suffers from Parkinson’s disease progresses from one stage to the other, his symptoms worsen. The warning begins with minor tremors which penetrate the system as the disease enters advance stages, leaving a person with slurred speech, disrupted body balance, violent shaking of limbs, drooling, choking while eating, weak throat muscles and effected cognitive abilities.
To make the disease easier to understand for our readers, the following are the most prominent symptoms of Parkinson’s disease:
- Tremors — the uncontrollable shaking of arms and hands. This involuntary movement hinders the normal performance of routine tasks.
- Slowness of movement (bradykinesia) — in this condition, physical movements are slower than normal and the performance of everyday tasks is affected. A person’s walk is shuffled and they are only able to take small steps while walking.
- Muscles stiffness — Parkinson’s results in the tension and stiffness in the muscles which makes it difficult for a person to move around. Furthermore, facial expressions are severely affected, leaving a person with a flat face. This stiffness also results in painful muscle cramps.
- Some of the other symptoms include a loss of smell sense, balance problems, excessive sweating, dizziness, constipation and nerve pain.
Why Parkinson’s Was Ali’s Greatest Battle
It was in 1996 that Muhammad Ali received the honor of lighting the Olympic cauldron. Prior to the opening ceremony Ali couldn’t attend the rehearsals due to Parkinson’s. His capability to hold the torch seemed dubious.
But he was a fighter after all. The crowd held their breath when ‘The People’s Champion’ took hold of the Olympic torch. The sight of him carrying the cauldron was reflective of his strength in battling against Parkinson’s disease. However, at the same time, his ailing self broke the hearts of his fans. With awe, the crowd witnessed their champion triumph over his condition, their eyes welling up with tears seeing their hero in such indomitable suffering.
At this point, it is estimated that his condition had advanced from stage 1 which had been characterized by unilateral involvement with only minimal or no functional impairment. While he was holding the torch with his right hand, his left hand was violently shaking.
His condition was progressing to stage 2 which involved bilateral or midline involvement without balance impairment. This is accompanied by the onset of axial signs, which may include bilateral loss of facial expression widely known as masking, fading voice, slurring, speech abnormalities, decreased blinking and stiffness of truncal muscle.
We saw how stiff Ali’s body looked and how he couldn’t move his neck, eventually forcing him to make a U-turn. When in this condition, the patient suffers back and neck pains, postural abnormalities, stooping and slow movements and reflexes.
At the time of the 2012 Olympics, Ali made a guest appearance at the opening ceremony. By this point, the ailing champions condition had greatly deteriorated. With a hunched back and sunglasses over his eyes, Ali couldn’t even manage standing without support. But even with the will he had, the star didn’t shun the world but held his spirits high in his struggle against Parkinson’s disease.
The disease had penetrated Ali’s system and caused the most harm at this point. It seemed as though the acclaimed former boxer was at stage 5 of his ailment.
The disease at this stage is severely disabling; the person is confined to the bed or wheelchair unless he or she is aided. The patient shows an inability to get out of bed or to stand from a sitting position without help. Additionally, the patient is prone to freezing, stumbling or falling when standing or turning. Muhammad Ali’s appearance at the ceremony did reflect these symptoms but he was strong enough to get out of bed and face the world.
After the 2012 Olympics and the few public appearances he made afterwards, Ali’s sunglasses began to catch our attention. Why had he been wearing them all the time?
We learnt that as Parkinson’s disease progress, visual motor symptoms begin to appear as well — vision may be blurred or a person may see two images. The coordination between eye movements is severely disrupted which leads to eye staining. Eyelid spasms may occur; the eyes may become dry as the patient would blink 1-2 times in a minute with his or her perception of distance and depth also being greatly affected.
It is worth noting here that cognitive and intellectual impairment is collateral damage caused by Parkinson’s disease. However, Ali had not lost his cognitions due to the disease. His positivity and contentment towards life were so strong that his cognition did not slip from of his grip.
A Champion’s Final Evolution
Muhammad Ali was a fighter in every sense of the word. It is ironic that when he retired, wanting to take a break from fighting another fight was inflicted on him by nature. This time, his opponent didn’t fight him face-to-face but penetrated the ailing boxer’s nerve cells, making him vulnerable at a slow but steady pace.
Yet this fighter did not kneel before his crippling disease, but in fact became the new face of Parkinson’s disease, intending to raise awareness about the disease among Americans.
Leslie Chambers, President and CEO of the American Parkinson Disease Association while talking to New York Daily News said, “Selflessness and bravery — those are the two things he epitomized. He brought the average American’s attention to this disease. We’re so grateful for him. In the long run, he’s helped our community in a tremendous way.”
Ali made various public appearances after being diagnosed with Parkinson’s disease. With time, his fans saw him wither. Having witnessed Ali’s peak years with joy, seeing their long-time boxing idol ailing so badly pierced the hearts of fans.
But was Ali never afraid of Parkinson’s? Did he not feel shattered after being diagnosed with such a serious disease?
In 1991, Muhammad Ali was interviewed by Bryant Gumbel, when the star admitted that the disease initially made him fearful to speak and appear in public. But he quickly added that his fear did not win over him and he thought of Parkinson’s as a new challenge he had to overcome.
Ali said, “I realise my pride would make me say no, but it scares me to think I’m too proud to come on this show because of my condition.”
At another point, while talking to The New York Times, he said; “I’m in no pain. A slight slurring of my speech, a little tremor. Nothing critical. If I was in perfect health — if I had won my last two fights — if I had no problem, people would be afraid of me. Now they feel sorry for me. They thought I was Superman. Now they can go, ‘He’s human, like us. He has problems.”
With this ailment, philanthropy became the goal of Ali’s life. In 1997, Muhammad Ali, along with a few philanthropists, established the Muhammad Ali Parkinson Center on the campus of Dignity Health, St. Joseph’s Hospital and Medical Center in Phoenix.
The center aimed to help people suffering from this incurable neurodegenerative disease in the best possible way. Ali was very dedicated to this cause for which he would organize and attend fund raising activities. It was in April earlier this year, when the former boxer was glimpsed headed to a fund raiser dinner. With a hunched back and increasingly frail appearance, ‘The People’s Champ’ looked more fragile than ever.
The boxer who lived by his words influenced many lives across the globe. His wife Lonnie commented on her husband’s influence by saying, “Even though Muhammad has Parkinson’s and his speech isn’t what it used to be, he can speak to people with his eyes. He can speak to people with his heart, and they connect with him.”
In November last year, Ali’s close friend and former manager Gene Kilroy said that Ali was a prisoner in his own body and it was hard seeing him in such pain. But he added that the spirit of his friend amazes him every single time.
According to Kilroy, “He can just about walk and his speech is slurred. It takes a huge effort for him to make the simplest communication now, but when he does, every word is worthwhile”.
He added that, “But even now he has no fear. He says, I’ll stay here as long as God wants me to. When my time comes I’ll have no regrets. I have achieved a lot.”
Another of Ali’s close friends, Tim Shanahan recollected the memories of his courageous friend who defied the doctors for more than two decades.
He recalled Ali saying, ”Tim, do you remember in 1986 when the UCLA doctors told me that I had Parkinson’s and I had 10 years to live, maybe 15? Well, I am still in the fight 30 years on and I shook up the world again.”
However, Ali’s most famous quotes came in when he was still in the prime of his career.
The legend once replied to an interviewer when asked how he would want the world to remember him and he eloquently said, “I’d like for them to say, He took a few cups of love. He took one tablespoon of patience. One tablespoon, teaspoon of generosity. One pint of kindness. He took one quart of laughter. One pinch of concern. And then he mixed willingness with happiness. He added lots of faith. And he stirred it up well. Then he spread it over a span of a lifetime. And he served it to each and every deserving person he met.”
It’s been a week since Ali’s death and his memories show no signs of fading away any time soon. Fans across the world fled to his homeland to say goodbye to their star. The champion rests beneath the ground today, but he will live in our hearts, always.
Muhammad Ali is certainly here to stay — legends don’t die.