A Woman’s Guide to the Brain: Part 3 – The Shaking Palsy
In 1817, the English doctor, James Parkinson, described what has become known as Parkinson’s disease in a report of six cases he titled, “An Essay on the Shaking Palsy.” To this day our understanding of the disease continues to evolve. When I learned neurology in the 1990’s we talked about Parkinson’s disease as a condition in which specialized dopamine-producing cells in the brainstem region called the substantia nigra pars compacta undergo premature death.
About the same time a brilliant neuroscientist named Dr. Mahlon DeLong became Chairman of the Department of Neurology at Emory University, and brought his research team from Johns Hopkins to study primates using a model in which the energy-producing engines of nerve cells, called mitochondria, were given a toxin called “MPTP” (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). This toxin caused the apes to develop Parkinson’s disease. DeLong believed that Parkinson’s disease resulted from mitochondrial demise, and the MPTP model gave him a way to study it.
Though centered in the brainstem Parkinson’s disease eventually affects the brain more widely. We called it a neurodegenerative condition, and still do. But the latest research suggests this nerve cell loss is the result of a variety of insults that trigger sustained, low-level inflammation starting not in the brain, but in the gut.
When Beth first presented to my office it was at the recommendation of a colleague whose practice focuses on helping women address the root causes and hormonal consequences of stress. She had been a runner, and at age 41, two years prior to her initial consultation, Beth had to stop because she noticed left foot weakness that would cause the limb to involuntarily “slam down” to the ground during races and regular training sessions. She was depressed and anxious. She had a jitteriness to her appearance. Over time the problem that had started in the left foot spread to affect the entire left side of her body, up to the back of her head. She hurt along the left arm, and described a sense that the arm and leg were “about to become numb.” It seemed as if that half of the body was not entirely under the control of her brain.
Her diagnosis was not immediately apparent. Neurologists are medical detectives. We take clues from the medical history and examination to determine where within the vast geography that is the nervous system the problem stems. In Beth’s case, she had symptoms from the back of her head to her foot on the left. Her arm and leg deep tendon reflexes (the response the doctor gets when he taps on the tendon in front of the knee, for example) were brisk, especially at the left ankle. This finding clues the physician that the problem is more likely within the brain or spinal cord, rather than the peripheral nerves or muscles. The left foot was positioned inward and downward flexed. In other words, she had trouble bringing her foot up or pushing it outward from the ankle.
My first concern, because of her relatively young age, gender, and the physical findings, was that she had multiple sclerosis. She had an MRI of the brain and neck portion of the spinal cord, but there was no evidence for the inflammatory plaques associated with that disease. To be thorough, I performed electromyography (EMG for short—a test of muscles and peripheral nerves), and ordered an MRI of her low back to evaluate for a lumbar disk problem that might be affecting the left foot. But they were normal. In retrospect, there was something on her brain MRI that was important.
Though a non-specific finding Beth’s brain showed a remarkable degree of shrinkage or atrophy, and this volume loss was out of proportion to her age. It appeared as if her brain was aging faster than her chronological age – an interesting finding, but not a diagnosis. The first chapter of Beth’s journey had taken me down a dead-end alley. She did not have multiple sclerosis, nor did she have a pinched nerve in her back. While she did have some depression and anxiety, was her emotional state the cause or the result of her problem?
With no immediate danger suggested by her tests the decision was made to send her for physical therapy and continue to monitor her status. I have always said that time is one of the best allies to help sort through a complicated diagnosis, and it was true in Beth’s case. After two months, I became aware that Beth’s balance was worse. She could not make fast movements with her left hand such as patting or tapping. She had an abnormal stride with a decreased arm swing on the left. She had a rounded back posture. Her facial appearance was flat or “masked.” Taken together, Beth appeared to have Parkinson’s disease.
But there were atypical aspects to her case. The average age of onset of Parkinson’s disease is 62 years old. At age 43 Beth would be considered to have “Early Onset Parkinson’s disease.” Also, Parkinson’s disease tends to affect men more than women. This contrasts other neurological conditions including Alzheimer’s, multiple sclerosis, and migraine. Beth did not have the classic “resting tremor” present in 76% or more of those affected. The left foot is explained in hindsight as “dystonic pseudo foot drop,” a finding described in 2015 by Dr. Anthony Lang and his team of neurology researchers from The Morton and Gloria Shulman Movement Disorder Center and the Edmond J. Safra Program in Parkinson’s Disease of Toronto Western Hospital, Toronto, Ontario. Here the word “dystonia” refers to abnormal muscle tone or movement involving a segment or region of the body. The dystonia gives the false appearance of a flaccid foot, classically known as “foot drop.” During Beth’s EMG, she would involuntary twitch her left foot, a sign of dystonia.
There is no single test specific for Parkinson’s disease. At best, we can distinguish Parkinson’s disease and a group of Parkinson’s-like degenerative disorders from isolated tremor using a nuclear medicine brain scan called a DaT (for dopamine transporter) scan. But response to treatment with the dopamine pre-cursor drug, levodopa, made famous in the book by physician-writer Dr. Oliver Sacks, and later portrayed in the movie by the same name, Awakenings, helps to confirm the diagnosis. (For accuracy, Dr. Sacks’ patients had post-encephalitic parkinsonism, not Parkinson’s disease.) Furthermore, gender differences in the characteristics of the disorder have been observed. Women tend to have more depression and while dystonias, such as those involving the foot, are more common presentations of Early-Onset Parkinson’s Disease, they may also be more common among women affected by the disorder. As part of her overall treatment program Beth was started on levodopa. While she had a difficult time tolerating the medication – it caused dizziness and headache – she did respond favorably though not with full resolution of symptoms. Determined to address the causes of her condition Beth decided to integrate a functional medicine approach into her treatment plan. The focus of functional medicine is the identification of the root causes of illness and how they interact with our unique genetic makeup. These include toxic body burden, hormone disruption, inadequate digestion and assimilation of nutrients, excessive oxidative stress, disruption of tissue integrity, infection, and imbalances in the number and diversity of the microbes that inhabit the gut as major contributing factors to chronic disease.
The human gut is a remarkable ecosystem. While its primary role is the digestion and absorption of nutrients necessary for cellular function and the proper elimination of waste, this could not be accomplished without the estimated 100 trillion bacteria and other microbes that live inside each of us. This is the Human Microbiome. These microbes produce signaling molecules such as hormones and neurotransmitters, and nutrients such as biotin, B12, folate, and thiamine. They also produce short-chain fatty acids involved in countering oxidative stress and inflammation, mediating normal movement of the colon, strengthening the blood-brain barrier, and energy metabolism. The cells lining the colon are the selective gateway to our internal world where nutrients and other important molecules can come in, and threats to the body are excluded. When this barrier is compromised, or “leaky,” systemic inflammation ensues. This poses a direct threat to the integrity of the brain. Besides commensal microbes there is a gut-associated immune system that acts as a sentinel to guard this internal world. It is the delicate balance between the important players of the intestinal tract that keeps us vital.
There are direct and indirect connections to the brain. The direct connection consists of the body’s longest nerve, cranial nerve X (Roman numeral for ‘ten’), called the Vagus Nerve, which runs from the base of the brain to the gut. Along the way, the vagus nerve connects to other tissue, including the lungs and heart. There are the blood vessels which form a circuitous route around the body, and indirectly connect the gut and the brain. The sustained intestinal inflammatory pattern in the gut that leads to Parkinson’s disease triggers the formation of an abnormal protein called “alpha synuclein” that not only accumulates in the gut, but travels to the brain along the vagus nerve where it accumulates and induces the destruction of dopamine-producing cells in the substantia nigra. Over time, Parkinson’s disease affects the whole brain, and results in the picture of premature aging – the diffuse atrophy identified in Beth’s MRI.
What happened to Beth? To help Beth we first had to address her gut. This involved removing the things that negatively affected her gastrointestinal tract while replenishing with those that support a healthy gut environment. By healing the gut the cycle of inflammation is curtailed at its source. For Beth, it was a matter of identifying where the imbalances existed, using a targeted therapeutic approach where necessary (like tightening a loose bolt), and giving simultaneous attention to all the lifestyle factors that support vitality. These are restorative sleep, proper nutrition, exercise, stress reduction, and nurturing relationships. In addition, her treatment triggered the brain’s ability to generate new nerve cells from progenitors, make new connections, and find new pathways where old ones had been lost. This is the principle of neuroplasticity. The last time I saw Beth she strolled down the hallway of my office with a straight posture, a smile on her face, a zip to her stride, and a fluid, nearly even arm swing. There was barely a hint of her Parkinson’s disease. Increasingly, evidence abounds that we can change the trajectory of diseases historically thought to be untreatable through a combination of targeted therapy and lifestyle intervention, especially if caught early. Now, more than ever, we must avoid the trap in thinking the only solution to illness is drugs or surgery. The appreciation that the human body has the power to heal, and that all the systems which govern function in the body are connected and influence one another gives functional medicine its power. Hippocrates is credited with the phrase, “All disease begins in the gut.” I wonder if he knew he could see the future?