The dark glasses he wears lie on the physician's desk in front of him; he had cataracts removed from both eyes, but he still suffers from macular degeneration- a condition where retina gradually thins and results in blindness.  He carries a large magnificying glass which he holds close to his nose as he peers at his list of medications.  The purpose of the visit is to seek another opinion regarding the tentative diagnosis of Parkinsonism.  He has already seen several physicians who have conflicting opinions about his tremor.
 

Losing his hearing, the patient asks the doctor to speak up, interrupting him, as he speaks. The doctor repeats himself, with abbreviated thoughts.  The patient holds his palm up towards the doctor, interrupting, telling him to let him speak. His hands are big, his finger long. Several of the fingernails on his left hand are cropped off, midway through the nail. He is 88 years old and states with a serious expression that he expects to live to 120.  An American chess champion in the over 75-year division, he visits Florida once a year to compete. He claims in his youth he could play ten games blindfolded, now he can play only one game this way; his short term memory is not what it was. But it is the tremor in his hands that bothers him, especially when eating soup. Three years ago, he noticed his handwriting became larger and shakier. He comments also he has lost the bounce in his step; he no longer rises up onto his forefoot when he walks. Balancing is tricky.

The doctor stands and takes the man's hand, and folds it inward towards his shoulder and out. He tells the patient his upper body is supple, without rigidity. The patient concedes he was a magician, and takes a packet of cards from a small leather case in his trouser pocket. He describes a trick he was able to do with one hand, holding the deck of cards divided into two bundles, he was able to shuffle them with one hand. Standing, he positions the cards in his left hand, and then nothing happens. The doctor follows his actions, and nods, understanding dexterity is gone from his hands. With a tuning fork, the doctor assesses the patient's reflexes and notes whether the patient can sense the vibration of the fork, when applied to the bony prominences of his feet and legs. Noteworthy, the patient fails to feel vibration applied to the right leg. The physician explains it is a cheap way of assessing the integrity of the long nerves in the body, and states the lack of sensation explains some of the change in his walking style, as he appears to have a mild sensory neuropathy. The cause, the physician guesses is from compression of the nerve roots in the spine. The doctor explains we rely on three mechanisms to keep us upright in space; position sense derived from the sensory nerves in our limbs that pick up vibration, fine touch and temperature; our vestibular system and our vision.

When the physician summarizes his findings, he notes the patient has a mild action tremor, and a mild sensory abnormality in the right leg and foot. He would like an MRI to look at the blood vessels of the brain. However, the patient leaves on Thursday to his home state, he'd prefer to have the testing performed there. The doctor agrees to send notes to the physicians involved in his care and the conversation shifts to what sort of cutting edge therapies exist in the field of Parkinson's and Alzheimer's disease. Sitting behind the desk, the physician explains a study in which people with Alzheimer's are getting GCSF(granulocyte- colony stimulating factor) to remove the amyloid plaques from the brain and improve cognition. The patient voices some interest in undergoing the same treatment, and the doctor wonders whether that would be ethical, or even practical, as the patient lacks the symptoms of those with the illness. He also notes when the amyloid is removed it can get stuck in small blood vessels, and result in micro-hemorrhages. He is unsure of the consequences of such trauma in the brain of a healthy, yet older individual. The man, wearing a woolen red sweater over a collared shirt, reaches into a file and withdraws the list of therapies he receives regularly from a physician whose specialty is aging. In the second or third line is a product called Neupogen, the same substance used in the research study for patients with Alzheimer's.

Alot can happen in seventy-six years; twenty years of hypertension, seven years of diabetes, a quadruple bypass for the heart, three transient ischemic attacks, two strokes, thyroid imbalance, and Parkinson's disease brings the patient in to see the specialist in movement disorders. The patient was diagnosed only three months prior, and yet he is in stage three of the illness (according to the H&Y scale), evident with bilateral symptoms and impairment of balance and equilibrium. His dose of Sinemet is high, 25/250 three times per day, and yet he experienced no nausea when he began the medication.

The patient wears a freshly starched short sleeve linen shirt. He is balding and he wears glasses, yet he takes them off when the doctor examines his eye movements. The spouse comments the way her husband holds his lips and jaw have changed. He admits he grinds his teeth now, the doctor comments some of the jaw clenching may be an involuntary movement caused by relatively high doses of Sinemet.

The patient has several atypical symptoms that may be reason to consider whether he suffers from Shy Dragers Syndrome, currently called multiple system atrophy.

Doctors classify the disorder into 3 types:

• the Parkinsonian-type: symptoms of Parkinson's disease- slow movement, stiff muscles, and tremor

• the cerebellar-type:  causes problems with coordination and speech

• the combined-type: symptoms of both parkinsonism and cerebellar failure. Problems with urinary incontinence, constipation, and sexual impotence in men happen early in the course of the disease. Other symptoms include generalized weakness, double vision or other vision disturbances, difficulty breathing and swallowing, sleep disturbances, and decreased sweating.1

Patients with the disease respond less favorably to medications aimed to treat PD symptoms, though they may derive a general feeling of well- being. The wife of the patient reports he has dramatically improved with the medication. He lacked any facial expression, his arm failed to swing when he walked, and the tremor in his hands and feet was nearly constant. All of these symptoms have changed for the better with medication.

The loose ends hang about, unresolved. For example, when he is not speaking the patient lapses easily into a pattern of hyperventilation. Could this quirky behavior be the result of ischemia, or a lack of oxygen, to the vessels in the brainstem that govern the rate of breathing? What can account for a sudden fainting spell, besides a sudden drop in blood pressure, which commonly occurs in Shy Dragers? What can be said for the need to urinate every two hours?

The doctor recommends the patient stay on the current level of medication, though it may behoove him to add coenzyme Q10 to his daily intake, at levels between 300 and 900 mg per day. The specialist advocates aerobic exercise, beginning at thirty minutes, three times per week, and notes he would like to see them again in four months, to check on him.

Difficulty writing was the first symptom of his illness. Then his wife noted his walking was slower, and his face more fixed and rigid. Since diagnosis in 2001, he has taken a very light dose of medications: three doses of 25/100 daily and Mirapex. The doctor comments he has had a long honeymoon period; fortunate man. He sits without expression in the office chair, yet he asks questions. He wonders about the frequent hallucinations his is having.  The doctor tells him that hallucinations are very common in PD patients.  He relates a story of an older man who sees a young naked woman get into bed between him and his dozing wife. The physician asks the patient whether he reached out to see whether the woman was a hallucination, and he replied he didn't dare move, for fear he would wake his sleeping spouse. That dream the patient comments, is one he would like to have. Instead, the dog hallucination visits him nightly.

When the honeymoon period runs out, patients begin to experience lapses in the effectiveness of medication. These periods, commonly known as "off" periods become more pronounced as illness progresses. The doctor notes the dopamine- rich cells in the brain lose their ability to store excess dopamine, their buffering capacity wanes and patients begin to vary in their levels of function according to the level of medication that reaches the brain. Here, the physician begins speaking about the importance of avoiding proteins, especially milk proteins in the morning meal. Milk proteins compete strongly with the morning levodopa (Sinemt) for passage into the brain; their presence in the diet inhibits the ability of levodopa to get through the blood- brain barrier.  This is the reason for having a non-dairy creamer like Cremora instead of milk in coffee and cereal. Dopamine agonists, like Mirapex do not have this problem.

The physician dips into a discussion of sleep and PD, noting the disease ruins normal sleep architecture, causing sleep to fragment. Patients may doze during the day.  Excessive daytime napping impedes sleeping ability during night hours, and works to further weaken normal sleep cycles. The body requires a certain amount of rapid eye movement sleep, when not acquired at night, the person with PD becomes susceptible to hallucinations, which are essentially waking dreams. In a study the physician conducted, he found 26% of patients with PD hallucinated; all 26% had fragmented sleep. Novel tranquilizers, such as Seroquel and Clozaril, when given in small doses in the evening counteract fragmented sleep patterns and encourage slumber. The physician prefers patients have a solid length of time given to sleep, as it is more likely they will acquire the needed amount of dreamtime. With a fixed sleep schedule, patients are less likely to hallucinate.

The practitioner- researcher informs the patient and family about a clinical research study he's involved in, asking whether the patient would be willing to provide a sample of blood. The aim is to find out whether an agent or biomarker exists in the blood that changes with progression of illness. By identifying such an entity, it would be possible to gauge whether medications can truly inhibit the progression of disease.

                Yenta, was the word she used to describe her brother in law. He has a lot wrong with him; the high blood pressure was discovered when he was in his thirties.  Diabetes; he uses an insulin pump, and has a neuropathy in the left leg and foot, as a consequence of the illness. He underwent cardiac ablation, had a triple by pass surgery to his heart, and wears a pacemaker. The pacemaker for his heart makes an MRI of the brain impossible. He is sometimes incontinent, has difficulty rising from a chair, and has fallen and injured his right shoulder; doctors think he has a torn labrum and will need surgery. The toes of his left foot curl up in dystonic spasms he cannot control. Some time ago, he worked as an architect, and he retains the ability to draw well, though his handwriting has succumbed to illness.

                They come for another opinion of what they can do for their family member. The patient has had speech and physical therapy. The specialist reads the notes from other physicians and the differential diagnosis; the list of possible diagnoses the patient may suffer from. Over the course of several months, the wife has seen her spouse decline in function. She contends he has lost a lot of drive.  He was a Type- A personality and now lacks the motivation for common things. His personality has become more emotional, and he admits he cries easily. The physician listening comments to the medical student sitting next to him that it sounds as though the frontal lobes are affected, as the area on both sides of the brain, dampens emotional expression.

                The specialist performs the physical examination and notes the patient's eye movements are full. The women mention the patient usually has his eyes closed, and frequently walks into objects when using his walker. This makes some sense to the specialist, as other neurologists have noted he may suffer from Supranuclear Palsy, which usually results in the patient having difficulty looking downwards,  though this is not his problem right now. Botox injections to the muscles of the foot helped relieve the uncontrollable spasms on the right. When given to the muscles around the orbit of the eyes, they have been less effective.

                The specialist is concerned the patient may suffer from normal pressure hydrocephalus, which can mimic vascular, or lower body parkinsonism. He requests a CT of the brain, which will show whether the ventricles are enlarged. If so, a neurosurgeon can place a shunt in the brain, allowing the excess cerebral spinal fluid to drain out of the brain and into the body.

                The doctor recommends the family have a consultation with a fellow neurologist trying to assemble a group of patients for a study on progressive supranuclear palsy. The colleague intends to do a drug study to discover whether a certain medication is useful in that population. At the very least, they will get another opinion from a movement disorder specialist, who will have the results of the CT of the brain to possibly to rule out normal pressure hydrocephalus.               

About five years ago she noticed the tremor in her right hand. Now as she sits in the examination room, her slightly swollen hand vacillates steadily as she rests it on the arm of the chair. She feels the muscles cramping and shortening and uses her other hand to straighten the fingers. Gradually she has lost most of the strength, dexterity and the ability to write legibly. She states she has taken Azilect for two years and sees little improvement.

Ah, but that's good, the doctor states. It means progression of your illness is slow; the other side of the body may be affected with disease, within that time. The comment buoys the patient's sentiments, somewhat. The specialist in movement disorders asks about her prior medical history and learns the patient underwent heart surgery to amend a leaking heart valve, seven months prior. Surgeons removed her thyroid two years ago and she suffers from high blood pressure, and high cholesterol. She states she is healthy, otherwise; comments from an optimist.

As the specialist dives into a description of how and who implicated dopamine as the neurotransmitter depleted in Parkinson's disease, the steady murmur of his voice and the quality of the fluorescent overhead lights lulls the listeners into a stupor. The patient has brought a cup of coffee with her, remarking it's decaffeinated, and the doctor remarks smoking and drinking coffee are two habits that are negatively correlated with illness and PD; the more one smokes and drinks coffee, the smaller the likelihood one will acquire PD.

On physical examination of the patient, the specialist discovers brisk reflexes; probably a byproduct of high blood pressure he comments. He inquires whether she has had an MRI of the brain, as people with long-standing high blood pressure commonly have a multitude of small white spots scattered just under the cortex of the brain. The neurologist feels the fluidity of movement from the left elbow and wrist and senses some rigidity in the muscles of the biceps. When he asks her to walk in the hallway, her gait is regular, with wide steps though she tends to hold the right arm and hand at her side, while she swings the left.

Sitting again in the examination room the patient asks about exercise. The doctor encourages the patient to discover when her cardiologist feels it safe to increase her heart rate, and then describes a clinical experiment in which researchers trained monkeys  to jog on a tread mill six hours a day. Those mokeys that underwent an experimental unilateral injection of a toxin that destroys dopamine neurons to one side of the brain, recuperated much faster, while those that did no exercise remained disabled. He states exercise, especially aerobic activity, enhances repair in the brain and provides a neuroprotective benefit. The patient confides she had to end her membership to the gym, as the temptation to get on the aerobic machines was overwhelming. She states she has always been an active person, and not allowing her heart rate to climb has been difficult. Yoga and Tai Chi are also helpful for those with PD, the physician states.

The doctor creates a chart for the patient, detailing how to increase the dosage of Sinemet. She should aim for the smallest dose that eliminates the stiffness and rigidity in her hand. He also encourages her to seek physical therapy for her hand, to regain strength and extensibility in the muscles. The doctor states he would like to see her again in three months time to see whether the transition to Sinemet has gone smoothly.

Before leaving, the patient reveals she lived in Alaska for sixteen years raising four children. The darkness of the winters never bothered her, or made her feel blue; an unusual blessing for a person with PD, where depression affects 70% of the patient population.