SEM 1 Tiama, Leslie Vidal, Regine Parkinsons Disease (PD) Definition: Parkinsons Disease (PD) is a chronic, slow progressive

disease of the nervous system characterized by the cardinal features of rigidity, bradykinesia, tremor, and postural instability. PD was first described as paralysis agitans or shaking paralysis by James Parkinson in 1817. There are 2 major neuropathologic findings: the loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. One of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. Although the cause of Parkinson's disease is unknown, environmental and genetic factors have been implicated in its etiology. Etiology: Parkinsonism Refers to a group of disorders that produce abnormalities of basal ganglia (BG) function. - An umbrella term that describes many conditions which share some of the symptoms of Parkinson's. 3 Groups: 1. Idiopathic Parkinsonism - Most common - M=F - Unknown etiology - Peak onset between 6th 8th decade - Subclinical period of 20 30 years 2. Secondary or Acquired Parkinsonism a. Hereditary / Familial Parkinsonism b. Infectious Parkinsonism Ex. Encephalitis Lethargica c. Toxic Parkinsonism Symptoms occur in individuals exposed to certain industrial poisons and chemicals. Ex. Manganese (most common), carbon disulfide, carbon monoxide, cyanide, methanol.

 Occupational hazards. d. Pharmacologic Parkinsonism / Drug-Induced Parkinsonism A variety of drugs can produce extrapyramidal dysfunction that imitates the signs of PD. Example: Neuroleptic drugs Antidepressant drugs Antihypertensive drugs e. Metabolic Causes Parkinsonism can be caused in rare cases by metabolic conditions, including disorders of calcium metabolism that result in BG calcification. These include hypothyroidism, hyperparathyroidism, hypoparathyroidism, and Wilsons disease. f. Vascular Causes Due to repeated head trauma. Ex. Dementia Pugilistica (a.k.a. boxers encephalopathy) 3. Parkinson-Plus Syndrome / Atypical Parkinsonism - A group of neurodegenerative diseases can affect the substancia nigra and produce parkinsonian symptoms along with other neurological signs. - These diseases include: a. Multiple System Atrophy - Striatonigral Degeneration - Shy-Drager syndrome - Olivopontocerebellar atrophy b. Progressive Supranuclear Palsy c. Steele Richardson Olszewski Disease d. Cortical-basal ganglionic degeneration. - Parkinsonian symptom can be exhibited in patients with: a. Multi-infarct vascular disease b. Alzheimers disease c. Diffuse Lewy body disease d. Wilsons Disease e. Juvenile Huntingtons Disease Epidemiology: Affects 1% in those over 60 years of age. Affects 4% of the population over 80 y/o. Average age of onset is 50 60 y/o but may occur as early as 20 40 y/o. Mean age of onset: 58 62 y/o Peak onset: 6th decade of life

M=F Young onset: before the age of 40. PD is the second most common neurodegenerative disorder after Alzheimer's disease. Anatomy and Pathophysiology: Normal voluntary motor control depends on an intricately balanced relationship between cortical, subcortical (including the extrapyramidal system and cerebellum), spinal, and peripheral mechanisms. Extrapyramidal system comprises those motor centers that are not part of the pyramidal cortex and tract. These centers includes: - Basal Ganglia (BG), including the caudate, putamen, and globus pallidus; subthalamic nucleus; substancia nigra, red nucleus; and the reticular formation of the upper brain stem. Basal ganglia - A group of nuclei situated at the base of the forebrain. - Play an important role in the planning and programming of movement by selecting and inhibiting specific motor synergies. - Also play a role in some cognitive processes, primarily the caudate nucleus, including awareness of body orientation in space, ability to adapt behavior as task requirements changes, and motivation. - the most seriously affected brain areas in PD - Components: Caudate & putamen (collectively termed the striatum) Globus pallidus Subthalamic nucleus Substancia nigra Pars compacta Pars reticulata Dopamine - a naturally occurring sympathetic nervous system neurotransmitter. - It is produce in the substancia nigra and transmitted to the putamen and caudate nucleus. - It has an inhibitory effect on movement. - a chemical messenger responsible for exchanging signals from our brains to our muscles. - a neurotransmitter that helps control the brain's reward and pleasure centers. Dopamine also helps regulate movement and emotional responses, and it enables us not only to see rewards, but to take action to move toward them. - ability to experience pleasure and pain. o Dopaminergic pathways: a. Mesocortical pathway

malfunction in this pathway might be the cause of some of the symptoms of schizophrenia, such as hallucinations and disordered thinking. essential to the normal cognitive function believed to be involved in motivational and emotional responses. b. Mesolimbic pathway important for memory and for motivating behaviours. "reward" pathway. By blocking this pathway, antipsychotic drugs reduce the intense emotions caused by conditions such as schizophrenia. c. Nigrostriatal pathway Substancia nigra to striatum. For motor control Death of neurons in this pathway can result in Parkinson's Disease. d. Tuberoinfundibular pathway Hypothalamus to Pituitary gland Hormonal regulation Maternal behavior (nurturing) Pregnancy Sensory processes

PD results from degeneration of dopamine-producing neurons within the pars compacta of the substacia nigra and the locus ceruleus in the brain-stem. This deficiency is secondary to a degeneration of striatal neurons that terminate in the caudate nucleus and putamen. As the disease progresses and neurons degenerate, they develop eosinophilic cytoplasmic inclusion bodies, called Lewy bodies (microscopic protein deposits found/develops in deteriorating nerve cells). The pathologic hallmark of PD is the presence of Lewy bodies, within many of the surviving neurons. When symptoms become clinically evident, 30% - 60% of dopaminergic neurons in the substancia nigra have been lost, and the basal ganglia (striatal) dopamine level has decreased by 80%. The cause of degeneration of dopaminergic cells within the substancia nigra is unknown. Prognosis: Pd is a neurodegenerative disorder that worsens slowly with time. Prior to the introduction of levodopa, PD caused severe disability or death in 25% of patients within 5 years of onset, in 65% in the nest 5 years, and 89% of those who survived for 15 years.

With the introduction of levodopa, the mortality rate dropped approximately 50%, and longevity was extended by several years.

Sign and Symptoms: Cardinal Features: 1. Tremor - It is an involuntary oscillation of a body part occurring at a slow frequency of 4 6 Hz (cycles/second). - It is the most common initial symptom of PD in about 70% of patients. - Parkinsonian tremor is describe as resting tremor, because it is typically present at rest and disappears with voluntary movement and sleep. And is intensified by stress or fatigue. - A feature of tremor is "pill-rolling", a term used to describe the tendency of the index finger of the hand to get into contact with the thumb and perform together a circular movement. The term derives from the similarity between the movement in PD patients and the earlier pharmaceutical technique of manually making pills. - It affects to a greater extent the most distal part of the limb. At onset, typically appears in only one limb for months or years and may over time generalize to all limbs. - Although resting tremor usually involves distal limbs, it may also affect the muscles of the face, tongue, jaw, neck, and trunk. - Tremor in the lower limbs is most apparent while the patient is supine. Tremor of the head and trunk, postural tremor, can be seen when muscles are used to maintain an upright position against gravity. - In the early stages, tremor is usually unilateral, quite mild and occurs for only short periods, whereas in later stages tremor can become severe, interfering with daily function. - EMG: rhythmic alternating bursts in agonist and antagonist muscles. 2. Bradykinesia - Slowness of movement. Another characteristic feature of PD, and is associated with difficulties along the whole course of the movement process, from planning to initiation and finally execution of a movement. Movements are typically reduced in speed, range, and amplitude. - Most disabling symptom of PD, with the slowness and prolonged movement leading to increased dependence in daily tasks. - Reduction of the rotatory component of movement results in one plane of motion. - Accounts or many disabling characteristic of PD: Hypomimia loss of facial expression Staring expression due to loss of blinking (5 10 blinks/min. [normal: 20 blinks/min.]) Slight widening of the palpebral fissures (Stelwag sign) Micrographia small cramped handwriting Slow speech and low volume (hypophonia) Difficulty rising from a chair and turning in bed Difficulties with ambulation Reduced arm swing when walking

Dysarthria Drooling Hypokinesia (reduce amplitude of movement) is most evident with repetitive movements such as finger and toe tapping. Akinesia inablitity to move Kinesia paradoxical ability to make rapid movement when experiencing surge of emotional energy (e.g. patient is able to catch a ball when thrown to him but is not able to do so when asked to do so) - All aspects of movement are affected: Initiation Execution Ability to stop movement once initiated - EMG: delayed motor unit recruitment, pauses once recruited, inability to increase firing rate. 3. Rigidity - Stiffness and resistance to limb movement caused by increased muscle tone, an excessive and continuous contraction of muscles. - Patients frequently complain of heaviness and stiffness of their limbs. - Two types: Cogwheel Rigidity Is a jerky, ratchetlike resistance to passive movement as muscles alternately tense and relax. Leadpipe rigidity Is more sustained resistance to passive movement, with no fluctuations. A smooth resistance to passive movement that is independent of velocity. - It is felt uniformly in both agonist and antagonist muscles and in movements in both directions. - Affects proximal muscles first, especially the shoulders and neck, and it progresses to involve muscles of the face and extremities. - Rigidity decreases the ability to move easily. For example, loss of bed mobility or loss of reciprocal arm swing during gait are often related to the degree of truncal rigidity. - Active movement, mental concentration, or emotional stress may all increase rigidity. - Prolonged rigidity results in decreased range of motion and serious secondary complications of contracture and postural deformity - Rigidity also has a direct impact on increasing resting energy expenditure and fatigue levels. - In early stages of Parkinson's disease, rigidity is often asymmetrical and it tends to affect the neck and shoulder muscles prior to the muscles of the face and extremities. With the progression of the disease, rigidity typically affects the whole body and reduces the ability to move. 4. Postural Instability

Is typical in the late stages of the disease, leading to impaired balance and frequent falls, and secondarily to bone fractures. Loss of righting reflexes. Contributing factors: Rigidity Decreased muscle torque production Loss of available ROM particularly of trunk motions Weakness Frequent falls and fall injury are the result of progressive loss of balance, with about two thirds of patients with PD experiencing falls and 13 percent falling more than once a week. Disease severity includes: Freezing Poor gait Balance impairments

EMG: motor unit recruitment is delayed and that once initiated is characterized by asynchronization; that is, pauses and an inability to smoothly increase firing rate as contraction continues.

Secondary Manifestations of PD: 1. Sweating 2. Sleep disturbance 3. Mood changes (depression, dysphoric mood) 4. Anxiety 5. Constipation 6. Urinary bladder dysfunction 7. Panic attacks 8. Changes in sensation (paresthesias, pain, akathisia) 9. Cognition deficits (dementia, bradyphrenia , visuospatial deficits, 10.Feeling of warmth or coldness 11.Discomfort in abdomen usu. during wearing off. 12.Fatigue 13.Seborrhea (too much oil) 14.Sialorrhea (drooling, or excessive salivation) 15.Kyphosis 16.Loss of libido 17.Blepharospasm 18.Blurred vision Medical Management/ Laboratory Procedures: Early diagnosis at onset of PD is difficult with accurate diagnosis possible only with continued observation of evolving clinical signs and symptoms. There is no single definitive test or group of test used to diagnose the disease. The diagnosis is made on the basis of history and clinical examination.

1. Pharmacological Management - Symptomatic Therapy a. Levodopa (L-dopa) Is the most potent agent for the symptomatic treatment of PD. It is a metabolic precursor of dopamine that is able to cross the bloodbrain-barrier and raise the level of striatal dopamine in the basal ganglia. In early, mild PD the cardinal motor symptoms are effectively abolished, leading to the notion that clinical response to levodopa is diagnostic. The therapeutic window for levodopa is 5 7 years before optimal benefit wears off. Common disturbances/side effects: Gastrointestinal (anorexia, nausea, vomiting, constipation) Cognitive (confusion and hallucinations) Cardiovascular (hypotension, arryhthmias) Genitourinary (dysuria) Neuromuscular (motor fluctuations and dyskinesias) Sleep disturbances (insomnia, sleep fragmentation) Indication for starting levodopa: Postural instability Falling Freezing Festination Retropulsion Inability to carry out ADL No effect from dopamine agonist PD patients <70 y/o with cognitive decline L-dopa is commonly administered with carbidopa (a decarboxylase inhibitors that allows a higher percentage of L-dopa to enter the CNS). Carbidopa is a peripheral dopa-decarboxylase inhibitor. It increases therapeutic potency and decreases gastrointestinal side effects of levodopa Sinemet is the most common carbidopa/L-dopa medication. 2 types: Sinemet Immediate-release (IR) short half-life requiring multiple oral dosing throughout the day. Sinemet Controlled-release (CR) long-acting, sustained release preparation. **both are equally effective. Side effects: dystonia, abnormal/involuntary movements, nausea, vomiting, confusion, dreams, hallucinations b. Dopamine Agonist (DA) Are synthetic compounds that stimulate striatal dopamine receptors. Although initially used as add-on therapy in patients receiving levodopa, the agonist are now commonly used as primary monotherapy in patients with mild PD.

 All dopamine agonists should be started at very low doses and increased gradually to reduce the risk of adverse affects. Benefits: reduce rigidity, bradykinesia and motor fluctuations. Side effects: nervousness, dyskinesias, insomnia, hallucinations, nausea, confusion, erythromelalgia, fatigue, crams, constipation, confusion. c. Anticholinergic agents Used in early, untreated PD or as an add-on for patients on levodopa. They block cholinergic function and have the most benefit moderating tremor and rigidity. Amantidine (Symmetrel) is an antiviral agent that has anti-Parkinson effects. Side effects: dry mouth, dizziness, blurred vision, tachycardia, nausea, vomiting, confusion. - Neuroprotective Therapy a. Monoamine Oxidase Inhibitors (MAOs) Improve metabolism of intracerebral dopamine. Provide mild symptomatic benefit, have excellent adverse effect profiles, and may improve long-term outcomes. Side effects: nausea, dreams, hallucinations, confusion, dyskinesias. 2. Nutritional Management - High- calorie, low-protein diet. - Take dietary supplements - Increase intake of water and dietary fiber to alleviate problems of constipation. 3. Surgical Management - Ablative surgery a. Stereotactic surgery the surgical lesioning of the brain. This technique uses images of the brain to guide the surgeon to a target within the brain. b. Pallidotomy a surgical procedure in which part of the globus pallidus, an area of the brain located within the basal ganglia, is damaged so that it cannot function. Dyskinesias, rigidity, tremor, gait disturbances, freezing, hypophonia are less responsive. c. Thalamotomy Involves producing a destructive lesion within the ventral intermediate nucleus of the thalamus. Reduce tremor, improvement of rigidity. Bilateral surgical lesions are not recommended because of a high rate of motor complications. - Deep Brain Stimulation (DBS) Involves the implantation of electrodes into the brain where they block nerve signals that cause symptoms.

Neural Transplantation Transplantation of cells capable of surviving and delivering dopamine into the striatum of patients with advanced PD is an experimental treatment and currently under investigation.

4. Rehabilitation may not reverse the progressive nature of the disease but: - Teach patient compensatory mechanism - Helps prevent complication - Enhances the quality of patients life. - Physical Therapy Rehabilitation Relaxation exercises Gentle rocking can be used to produce generalized relaxation of excessive muscle tension due to rigidity. Rocking chair can be used to temporarily reduce rigidity and enhance sit-to-stand transfers. During therapy, slow, rhythmic, rotational movements of the trunk can be considered and should precede interventions such as ROM, stretching and functional training. PNF technique (rhythmic initiation) specifically designed to help overcome the effects of rigidity in PD. Stress management Flexibility exercises AROM and PROM exercises are used to improve flexibility Focus on strengthening the weak, elongated extensor muscles, while lengthening the shortened, tight flexor muscles. Strength training Functional training Improving mobility function with specific emphasis on improving mobility of axial structures, the head, trunk, hips, and shoulders. Moving in bed are essential skills. Sidelying rolling activities should be practice Sitting posture can be facilitated through exercises designed to improve pelvic mobility as the patient with PD typically sits with a stiff and posteriorly tilted pelvis. Anterior and posterior tilts, side-to-side tilts, pelvic clock exercises can be practiced while sitting on a therapy ball. Sit-to-stand transitions are also very difficult for PD patients. Initial rocking forward and backward can be used to promote relaxation and enhance the ability to move weight forward. Mobilizing facial muscles. Massage, stretch, manual contacts and verbal cueing. Balance training Begin with low intensity weight shifting, sitting and standing. Sit-to-stand, stepping and walking to challenge on the postural system. Gait training

Patient is trained to walk proper posture, look up, widen the base of gait (12 15 inch apart), use a high-step pattern and take long strides. Arm swinging is encouraged. Scales used in evaluating a patient - Hoehn Yahr Scale Developed in 1967 by the physicians Margaret Hoehn and Melvin Yahr commonly used system for describing how the symptoms of Parkinson's disease progress this scale primarily assesses mobility and motor function. Stage 0: No signs of disease. Stage 1: Unilateral symptoms only. Stage 1.5: Unilateral and axial involvement. Stage 2: Bilateral symptoms. No impairment of balance. Stage 2.5: Mild bilateral disease with recovery on pull test. Stage 3: Balance impairment. Mild to moderate disease. Physically independent. Stage 4: Severe disability, but still able to walk or stand unassisted. Stage 5: Needing a wheelchair or bedridden unless assisted. - United Parkinsons rating Scale Rating tool to follow the longitudinal course of Parkinson's disease. It is made up of the 1) Mentation, Behavior, and Mood, 2) ADL and 3) Motor sections These are evaluated by interview A total of 199 points are possible. 199 represents the worst (total) disability), 0--no disability.