Overview

Definition

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder affecting the CNS with cardinal features of restingtremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies,rigidityRigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Megacolon, bradykinesia, and postural instability.

Epidemiology

• One of the most common neurodegenerative disorders
• AnnualincidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency: 4.5–21 cases per 100,000 population
• MeanMeanMean is the sum of all measurements in a data set divided by the number of measurements in that data set.Measures of Central Tendency and Dispersion age at onset: approximately 60 years
• Lifetime risk: approximately 2% for men and 1.3% for women

Etiology

The etiology of PD is unclear but depends on various genetic and environmental factors. 

Risk factors

• Environmental and nongenetic risk factors: 
  • Exposure to pesticides
  • Exposure tonitrogenNitrogenAn element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.Urea Cycle dioxide
  • History oftraumatic brain injuryTraumatic brain injuryA form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.Le Fort Fractures
  • Exposure to hydrocarbon solvents
  • Living in a rural environment
  • Living in proximity to industrialplantsPlantsCell Types: Eukaryotic versus Prokaryotic or quarries
  • Drinking well water
  • Use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to cause irreversibleparkinsonismParkinsonismWest Nile Virus.
  • Excess body weight
  • Type 2Type 2Spinal Muscular AtrophydiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus
• GeneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics mutations associated with PD:
  • Alpha-synuclein (SNCA)geneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics
  • Leucine-rich repeat kinase 2 (LRRK2)geneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics loci
  • Parkin (PARK2)geneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics mutations
  • Phosphatase and tensin homologPhosphatase and TENsin homologA lipid phosphatase that contains a C2 domain and acts on phosphatidylinositol-3, 4, 5-trisphosphate to regulate various signal transduction pathways. It modulates cell growth processes; cell migration; and apoptosis. Mutations in pten are associated with cowden disease and proteus syndrome as well as neoplastic cell transformation.Cowden Syndrome (PTEN)–induced putative kinase 1 (PINK1)geneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics loci

Pathophysiology

Compensatory mechanisms in thebrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification may temporarily decrease the effects ofdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS depletion until these mechanisms are overpowered by the progression of PD.

• Depletion of dopaminergicneuronsNeuronsThe basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.Nervous System: Histology in thesubstantia nigraSubstantia nigraThe black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis.Basal Ganglia: Anatomy pars compacta → depletion ofdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS in thenigrostriatal pathwayNigrostriatal pathwayBasal Ganglia: Anatomy → development ofmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology symptoms
• Overactivity of theindirect pathwayIndirect PathwayHuntington Disease functionally disables functioning of thesubstantia nigraSubstantia nigraThe black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis.Basal Ganglia: Anatomy. 
• Lewy bodies (the pathologic hallmark of PD):
  • Round, eosinophilic, intracytoplasmic neuronal inclusions
  • Contain abnormal alpha-synucleinproteinsProteinsLinear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein.Energy Homeostasis 
  • Seen in:
    • Substantia nigraSubstantia nigraThe black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis.Basal Ganglia: Anatomy
    • LocusLocusSpecific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease.Basic Terms of Genetics coeruleus
    • Cerebral cortexCerebral cortexThe cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum.Cerebral Cortex: Anatomy
    • Sympathetic ganglia
• The pathologic changes in PD start in theolfactory bulbOlfactory bulbOvoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here.Olfaction: Anatomy → progress over many years to thecerebral cortexCerebral cortexThe cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum.Cerebral Cortex: Anatomy in 6 stages, called BraakstagingStagingMethods which attempt to express in replicable terms the extent of the neoplasm in the patient.Grading, Staging, and Metastasis:
  • Presymptomatic stages 1 and 2: pathologic changes are found in:
    • Olfactory bulbOlfactory bulbOvoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here.Olfaction: Anatomy
    • Medulla oblongataMedulla OblongataThe lower portion of the brain stem. It is inferior to the pons and anterior to the cerebellum. Medulla oblongata serves as a relay station between the brain and the spinal cord, and contains centers for regulating respiratory, vasomotor, cardiac, and reflex activities.Brain Stem: Anatomy 
  • Stages 3 and 4: symptoms start appearing as the pathology migrates to:
    • Substantia nigraSubstantia nigraThe black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis.Basal Ganglia: Anatomy pars compacta 
    • Structures of themidbrainMidbrainThe middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems.Brain Stem: Anatomy
  • Stages 5 and 6: pathologic process reaches:
    • Temporal lobeTemporal lobeLower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the occipital lobe.Cerebral Cortex: Anatomy
    • Frontal lobeFrontal lobeThe part of the cerebral hemisphere anterior to the central sulcus, and anterior and superior to the lateral sulcus.Cerebral Cortex: Anatomy

Clinical Presentation

The signs of PD are progressive and gradually appear over a long period of years to decades.

CardinalmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology manifestations

• Bradykinesia = slowness of movements:
  • Seen in about 80% of individuals with PD
  • Decreased manual dexterity of the fingers 
  • Progresses proximally
  • Difficulty in completing simple tasks such as tying shoelaces, buttoning clothes, and picking up small objects. 
  • Shortshuffling gaitShuffling GaitNormal Pressure Hydrocephalus 
  • Loss ofcoordinationCoordinationCerebellar Disorders of movements as the disease progresses
  • Advanced stages: Freezing of movements may occur.
• TremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies: 
  • RestingtremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies described as a “pill-rolling”tremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies
  • Intermittent in the early stages
  • Decreases with voluntary action
  • Can involve the hands, legs,lipsLipsThe lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves.Lips and Tongue: Anatomy,jawJawThe jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food.Jaw and Temporomandibular Joint: Anatomy, andtongueTongueThe tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves.Lips and Tongue: Anatomy
  • Exacerbated byanxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder, emotional excitement, and stressful situations
  • Initially unilateral involvement → progresses to bilateral
• RigidityRigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Megacolon:
  • Seen in 70%–90% of individuals with PD
  • Described as increasedresistanceResistancePhysiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Ventilation: Mechanics of Breathing to passive movement
  • Begins unilaterally → progresses to the contralateral side; remains asymmetrical throughout the course of the disease.
  • CogwheelrigidityRigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Megacolon = a pattern ofresistanceResistancePhysiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Ventilation: Mechanics of Breathing and relaxation in passive movement
  • “Lead pipe”rigidityRigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Megacolon may also be seen in a few individuals = tonicresistanceResistancePhysiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Ventilation: Mechanics of Breathing that is smooth in passive movement 
• RigidityRigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Megacolon affecting the face: characteristic “masked” expression
• Postural instability = impairment of postural reflexes resulting in a feeling of imbalance and a tendency to fall: 
  • Usually occurs in advanced stages of PD 
  • In the “pull test,” the examiner stands behind the individual and pulls the individual by their shoulders; those with PD are likely to take a few steps back or fall.

OthermotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology manifestations

• Speech impairment
• Laryngeal dysfunction anddysphagiaDysphagiaDysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical.Dysphagia
• Blurred visionBlurred VisionRetinal Detachment
• Micrographia
• Stooped posture
• MyoclonusMyoclonusInvoluntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous system diseases; (e.g., epilepsy-myoclonic). Nocturnal myoclonus is the principal feature of the nocturnal myoclonus syndrome.Neurological Examination
• GaitGaitManner or style of walking.Neurological Examination abnormalities:
  • Shuffling, short-steppedgaitGaitManner or style of walking.Neurological Examination
  • Freezing ingaitGaitManner or style of walking.Neurological Examination
  • FestinatinggaitGaitManner or style of walking.Neurological Examination = pattern described as small, increasingly quick steps

Nonmotor symptoms

• Autonomic dysfunctionAutonomic DysfunctionAnterior Cord Syndrome presenting as:
  • Orthostasis
  • ConstipationConstipationConstipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency< 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic.Constipation
  • Diaphoresis
  • Urinary difficulties
  • Sexual dysfunctionSexual dysfunctionPhysiological disturbances in normal sexual performance in either the male or the female.Sexual Physiology
• Olfactory dysfunction:anosmiaAnosmiaComplete or severe loss of the subjective sense of smell. Loss of smell may be caused by many factors such as a cold, allergy, olfactory nerve diseases, viral respiratory tract infections (e.g., COVID-19), aging and various neurological disorders (e.g., Alzheimer disease).Cranial Nerve Palsies
• Mood disorders, including depression andanxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder
• PainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways andsensorySensoryNeurons which conduct nerve impulses to the central nervous system.Nervous System: Histology disturbances
• Cognitive dysfunction anddementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders
  • Psychosis 
  • HallucinationsHallucinationsSubjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders.Schizophrenia
• SleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disturbances:
  • InsomniaInsomniaInsomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking.Insomnia
  • Daytime sleepinessDaytime sleepinessNarcolepsy
  • REM sleepREM sleepA stage of sleep characterized by rapid movements of the eye and low voltage fast pattern eeg. It is usually associated with dreaming.Physiology of Sleep behavior disorder (RBD)

Diagnosis

The diagnosis of PD is made by clinical history and neurologic examination.

Diagnosis requires 4 things:

1. MotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: HistologyparkinsonismParkinsonismWest Nile Virus
2. No absolute exclusion criteria
3. At least 2 supportive criteria
4. No red flags

MotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: HistologyparkinsonismParkinsonismWest Nile Virus, an essential criterion of PD, requires bradykinesia and at least 1 of the following:

• RestingtremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies
• RigidityRigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Megacolon
• Postural instability

Absolute exclusion criteria (incompatible with a diagnosis of PD):

• Cerebellar abnormalities such as cerebellargaitGaitManner or style of walking.Neurological Examination or limbataxiaAtaxiaImpairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions.Ataxia-telangiectasia
• Downward vertical supranuclear gazepalsyPalsyparalysis of an area of the body, thus incapable of voluntary movementCranial Nerve Palsies or selective slowing of downward vertical saccades
• Diagnosis of frontotemporaldementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders within the 1st 5 years after disease onset
• Parkinsonian features restricted to the lower limbs for > 3 years
• Treatment in the past year with adopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNSreceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors blocker that may be associated with drug-inducedparkinsonismParkinsonismWest Nile Virus
• Lack of response to high-doselevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs in (at least) moderate disease
• CorticalsensorySensoryNeurons which conduct nerve impulses to the central nervous system.Nervous System: Histology loss (e.g., agraphesthesia, astereognosis), ideomotorapraxiaApraxiaA group of cognitive disorders characterized by the inability to perform previously learned skills that cannot be attributed to deficits of motor or sensory function. The two major subtypes of this condition are ideomotor and ideational apraxia, which refers to loss of the ability to mentally formulate the processes involved with performing an action. For example, dressing apraxia may result from an inability to mentally formulate the act of placing clothes on the body. Apraxias are generally associated with lesions of the dominant parietal lobe and supramarginal gyrus.Cranial Nerve Palsies, and/or progressiveaphasiaAphasiaA cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia.Ischemic Stroke
• FunctionalneuroimagingNeuroimagingNon-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities.Febrile Infant of the presynaptic dopaminergic system is normal.

Supportive criteria:

• Dramatic improvement of symptoms with dopaminergic drugs
• Levodopa-induced dyskinesia
• RestingtremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies of a limb (unilateral or bilateral)
• Either olfactory loss or cardiac sympathetic denervation onnuclear medicineNuclear medicineA specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds.Nuclear Imaging imaging

Red flags (signs of alternative pathology that point toward another diagnosis):

• Rapid progression ofgaitGaitManner or style of walking.Neurological Examination impairment requiring the use of a wheelchair
• Absence of progression ofmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology symptoms or signs > 5 years
• Early bulbar dysfunction within the 1st 5 years after onset:
  • SeveredysphoniaDysphoniaDifficulty and/or pain in phonation or speaking.Epiglottitis
  • SeveredysarthriaDysarthriaDisorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition.Wilson Disease
  • SeveredysphagiaDysphagiaDysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical.Dysphagia
• InspiratorystridorStridorLaryngomalacia and Tracheomalacia ordyspneaDyspneaDyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary).Dyspnea
• Severe autonomic failure in the 1st 5 years after disease onset:
  • Orthostatic dysfunction
  • Severeurinary retentionUrinary retentionInability to empty the urinary bladder with voiding (urination).Delirium
• Recurrent falls due to impaired balance within 3 years after onset
• InvoluntaryflexionFlexionExamination of the Upper Limbs of theneckNeckThe part of a human or animal body connecting the head to the rest of the body.Peritonsillar Abscess orcontracturesContracturesProlonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint.Wound Healing ofhandHandThe hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves.Hand: Anatomy or feet 
• Absence of the common nonmotor symptoms in the 1st 5 years after disease onset
• Unexplained pyramidal tract signs:
  • Pyramidal weakness
  • Clear pathologic hyperreflexia
• Bilateral symmetricparkinsonismParkinsonismWest Nile Virus

There are no physiologic, radiologic, or blood tests to confirm the clinical diagnosis of PD:

• Imaging may be needed to rule out other causes ofparkinsonismParkinsonismWest Nile Virus (e.g., stroke):
  • MRI
  • DaTscan: a type ofSPECTSPECTAn imaging technique using a device which combines tomography, emission-computed, single-photon and tomography, x-ray computed in the same session.Nuclear Imaging that can visualizebrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and ClassificationdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS transporter levels
• Olfactory andnuclear medicineNuclear medicineA specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds.Nuclear Imaging tests for autonomic testing for cardiac sympathetic denervation are helpful in distinguishing PD from other causes ofparkinsonismParkinsonismWest Nile Virus (supportive criteria as above).

Parkinson disease is confirmed with the finding of Lewy bodies on postmortem analysis.

Management

The goal of management is to treat the symptomaticmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology and nonmotor features of the disorder to improvequalityQualityActivities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps.Quality Measurement and Improvement of life.

Treatment

General measures:

• Physical therapyPhysical TherapyBecker Muscular Dystrophy
• Occupational therapyOccupational TherapySkilled treatment that helps individuals achieve independence in all facets of their lives. It assists in the development of skills needed for independent living.Fetal Alcohol Spectrum Disorder 
• Emotional support

Medical therapy:

• LevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs is the drug of choice in individuals of any age with moderate or severe symptoms:
  • AdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS precursor converted intodopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS after crossing theblood–brain barrierBlood–Brain BarrierMeningitis in Children 
  • Normally combined with carbidopa, which enhances CNSbioavailabilityBioavailabilityPharmacokinetics and Pharmacodynamics 
• MonoamineoxidaseOxidaseNeisseria type B (MAO-B) inhibitors (selegilineSelegilineA selective, irreversible inhibitor of type B monoamine oxidase that is used for the treatment of newly diagnosed patients with parkinson disease, and for the treatment of depressive disorders.Monoamine Oxidase Inhibitors,rasagilineRasagilineMonoamine Oxidase Inhibitors,safinamideSafinamideParkinson’s Disease Drugs): 
  • Inhibit the enzyme MAO from breaking downdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS,serotoninSerotoninA biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity.Receptors and Neurotransmitters of the CNS,norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS, and tyramine in thebrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification 
  • Effective as an early symptomatic treatment for PD
  • Monotherapy or in combination withlevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs/carbidopa
• Non-ergotdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS agonists (pramipexolePramipexoleA benzothiazole derivative and dopamine agonist with antioxidant properties that is used in the treatment of parkinson disease and restless legs syndrome.Parkinson’s Disease Drugs,ropiniroleRopiniroleParkinson’s Disease Drugs,apomorphineApomorphineA derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.Parkinson’s Disease Drugs):
  • Indicated in younger individuals to postpone use oflevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs/carbidopa and avoid long-term side effects 
  • Monotherapy or in conjunction withlevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs/carbidopa
  • Should notbe stopped abruptly

DeepbrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification stimulation:

• NeurosurgicalimplantationImplantationEndometrial implantation of embryo, mammalian at the blastocyst stage.Fertilization and First Week of stimulatingelectrodesElectrodesElectric conductors through which electric currents enter or leave a medium, whether it be an electrolytic solution, solid, molten mass, gas, or vacuum.Electrocardiogram (ECG) in thesubstantia nigraSubstantia nigraThe black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis.Basal Ganglia: Anatomy
• Exact mechanism of action is unknown. 
• Best candidates are individuals who:
  • Are younger
  • Have a short course of illness
  • Have a good response tolevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs 
• Not recommended for those with atypicalparkinsonismParkinsonismWest Nile Virus

Side effects ofdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS therapy

• NauseaNauseaAn unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Antiemetics
• Orthostasis: worsened by dopaminergic therapy 
  • May need to stop antihypertensive medication 
  • May need to taperdopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS agonists and MAO-B inhibitors 
• Drug-induced dyskinesia (abnormal involuntary movements can occur with long-term use oflevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs)
• Confusion andhallucinationsHallucinationsSubjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders.Schizophrenia
• Impulse control disorders →dopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS agonist therapy must be reduced
• DopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS dysregulation syndrome: 
  • Cyclical mood disorder characterized byhypomaniaHypomaniaBipolar Disorder or manic psychosis 
  • Prevention of the excessive use of dopaminergic drugs is imperative.

Differential Diagnosis

• EssentialtremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies: most common neurologic cause of actiontremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies. EssentialtremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies usually affects both hands and arms and is apparent when the arms are held outstretched or when they are engaged in activities. EssentialtremorTremorCyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease.Myotonic Dystrophies is most oftensymmetricalSymmetricalDermatologic Examination.
• DementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders with Lewy bodies: characterized clinically bydementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders with visualhallucinationsHallucinationsSubjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders.Schizophrenia, fluctuating cognition, RBD, andparkinsonismParkinsonismWest Nile Virus.DementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders occurs before the development of signs ofparkinsonismParkinsonismWest Nile Virus.CholinesteraseCholinesteraseLiver Function Tests inhibitors,atypical antipsychoticsAtypical AntipsychoticsAntiemetics, andregularRegularInsulin exercise are used for treatment. 
• Corticobasal degenerationCorticobasal DegenerationAtypical Parkinsonian Syndromes: distinctive form ofparkinsonismParkinsonismWest Nile Virus that is a progressive asymmetric movement disorder. Cognitive features ofcorticobasal degenerationCorticobasal DegenerationAtypical Parkinsonian Syndromes includeaphasiaAphasiaA cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia.Ischemic Stroke,apraxiaApraxiaA group of cognitive disorders characterized by the inability to perform previously learned skills that cannot be attributed to deficits of motor or sensory function. The two major subtypes of this condition are ideomotor and ideational apraxia, which refers to loss of the ability to mentally formulate the processes involved with performing an action. For example, dressing apraxia may result from an inability to mentally formulate the act of placing clothes on the body. Apraxias are generally associated with lesions of the dominant parietal lobe and supramarginal gyrus.Cranial Nerve Palsies, behavioral changes, loss of executive function, and visuospatial dysfunction. Asymmetrical corticalatrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation is seen on imaging. 
• Progressive supranuclearpalsyPalsyparalysis of an area of the body, thus incapable of voluntary movementCranial Nerve Palsies:clinically presents as postural instability with a history of multiple falls. Progressive supranuclearpalsyPalsyparalysis of an area of the body, thus incapable of voluntary movementCranial Nerve Palsies is the most common degenerative form ofparkinsonismParkinsonismWest Nile Virus. The disorder includesdysarthriaDysarthriaDisorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition.Wilson Disease,dysphagiaDysphagiaDysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical.Dysphagia,rigidityRigidityContinuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.Megacolon, and cognitive symptoms. MRI shows the “hummingbird signHummingbird SignAtypical Parkinsonian Syndromes” or prominentmidbrainMidbrainThe middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems.Brain Stem: AnatomyatrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation without pontineatrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation. Management is supportive, with both pharmacologic and nonpharmacologic measures.
• Multiple systematrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation (MSAMSAA syndrome complex composed of three conditions which represent clinical variants of the same disease process: striatonigral degeneration; shy-drager syndrome; and the sporadic form of olivopontocerebellar atrophies. Clinical features include autonomic, cerebellar, and basal ganglia dysfunction. Pathologic examination reveals atrophy of the basal ganglia, cerebellum, pons, and medulla, with prominent loss of autonomic neurons in the brain stem and spinal cord.Atypical Parkinsonian Syndromes): group of rare, fatal neurodegenerative symptoms. Multiple systematrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation presents with akinetic rigidparkinsonismParkinsonismWest Nile Virus, autonomic and urogenital dysfunction,cerebellar ataxiaCerebellar ataxiaIncoordination of voluntary movements that occur as a manifestation of cerebellar diseases. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention tremor), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and gait ataxia.Cerebellar Disorders, and pyramidal signs. Lack of response tolevodopaLevodopaThe naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Parkinson’s Disease Drugs can help distinguishMSAMSAA syndrome complex composed of three conditions which represent clinical variants of the same disease process: striatonigral degeneration; shy-drager syndrome; and the sporadic form of olivopontocerebellar atrophies. Clinical features include autonomic, cerebellar, and basal ganglia dysfunction. Pathologic examination reveals atrophy of the basal ganglia, cerebellum, pons, and medulla, with prominent loss of autonomic neurons in the brain stem and spinal cord.Atypical Parkinsonian Syndromes from PD, andMSAMSAA syndrome complex composed of three conditions which represent clinical variants of the same disease process: striatonigral degeneration; shy-drager syndrome; and the sporadic form of olivopontocerebellar atrophies. Clinical features include autonomic, cerebellar, and basal ganglia dysfunction. Pathologic examination reveals atrophy of the basal ganglia, cerebellum, pons, and medulla, with prominent loss of autonomic neurons in the brain stem and spinal cord.Atypical Parkinsonian Syndromes progresses more rapidly than PD. Diagnosis is clinical and management is symptomatic, as there are no disease-modifying treatments available.

References

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