Acetylcholine: Neurotransmitter present in both central (brain and spinal cord) and peripheral nervous systems. In the brain, acetylcholine helps modulate attention, memory, and motivation. In the peripheral nervous system, acetylcholine is the primary neurotransmitter of the parasympathetic division (rest, repair, and regeneration) and is released at the neuromuscular junction of both smooth and skeletal muscles to stimulate contraction.
Advance directive: A legal document through which a person dictates the kind of medical care that should be provided in the event that he or she becomes incapable of making those decisions. A living will is a type of advance directive in which the patient details the types of care he or she wishes to receive or not receive. The patient can also name an individual and grant legal authority to that person to make healthcare decisions, known as durable power-of-attorney.
Agonist: A chemical or drug that activates a neurotransmitter receptor. Agonists closely mimic the actions of neurotransmitters but are generally less specific and less effective. Examples of dopamine agonists include pramipexole, ropinirole, bromocriptine, and apomorphine.
Aggregate: A clump or tangle of protein molecules, such as alpha-synuclein or tau proteins within neurons in Parkinson’s related diseases.
Akinesia: Lack of ability to move or difficulty initiating voluntary movements.
Alpha-synuclein: Protein found mainly at the ends of nerve processes in the brain and muscles and thought to control release and recycling of neurotransmitters. Alpha-synuclein accumulates in Multiple System Atrophy (MSA), Parkinson’s and in Lewy Body Disease, and appears to play a key role in disease pathology.
Alexander Technique: This technique is a form of complementary therapy, pioneered at the turn of the century by FM Alexander. The principal aim is to teach people to stand and move more efficiently by improving movement awareness. Some MSA use it as a form of physical therapy.
Amantadine: An antiviral drug that also improves mild parkinsonian symptoms. Thought to stimulate release of dopamine or inhibit acetylcholine. Used as a single therapy or with L-DOPA and other medications. It has both an anti-Parkinson’s effect and an anti-dyskinesia effect. It is usually not effective for MSA.
Anticholinergics: Drugs that block the action of acetylcholine. In MSA patients, anticholinergics are typically used to treat muscle spasms and bladder control problems. Examples include benzotropine, biperidin, procyclidine, and scopolamine.
Antiparkinsonian medication: Drugs used for treating symptoms of parkinsonism; mainly levodopa, dopamine agonists, and MAO-B inhibitors.
Anosmia: Total loss of sense of smell. More common in Parkinson’s than MSA. Occurs due to accumulation of Lewy bodies.
Antagonist: A chemical or drug that blocks a neurotransmitter receptor. Dopamine antagonists can worsen parkinsonian symptoms and can cause drug-induced Parkinsonism. Virtually all antipsychotic drugs have dopamine antagonist activity.
Apathy: Lack of interest, enthusiasm, or concern. In MSA, can arise from damage to parts of the basal ganglia that relay with emotional centers in the brain.
Apomorphine: A type of dopamine agonist; highly powerful and effective but also causes a range of unpleasant effects, such as nausea, chest pain, dizziness, and fatigue.
Artane (trihexyphenidyl HCL): An anticholinergic drug that is often effective at reducing parkinsonian tremor. The most common side effects include anxiety, blurry vision, dry mouth, and nausea. It may also cause confusion.
Astrocytes: Support cells in the brain that assist neuron growth and repair, regulate communication between neurons, and detect and regulate glucose levels and blood flow in the brain. Also referred to as astroglia.
Ataxia: Inability to coordinate voluntary muscle movements, characterized by unsteady movements and staggering gait.
Athetosis: Slow, repetitive, involuntary movements, especially in the hands.
Autonomic Nervous System (ANS): Component of the peripheral nervous system that controls involuntary actions such as the heartbeat, the digestive and glandular systems, and smooth muscles of the bladder, bowel, and blood vessels. Consists of two divisions: sympathetic and parasympathetic.
Autonomic Dysfunction: Any abnormal functioning of the autonomic nervous system resulting in problems with bodily functions such as bowel and bladder control, blood pressure control, sweating, drooling, and so forth.
Autophagy: Process whereby cells recycle or dispose of aged or damaged cellular components. Increases when cells are stressed or deprived of nutrients and/or growth factors as a way to regenerate needed substrates. Excessive autophagy can result in production of dysfunctional organelles and misfolded protein molecules.
Autosomes/autosomal: All the chromosomes excluding the sex-related X and Y chromosomes.
Autosomal recessive: Passing on of a genetic trait or disease via transmission of two copies of a mutated gene to the offspring, one from each parent. Autosomal recessive inheritance guarantees that the offspring will manifest the trait or disease. MSA typically occurs in individuals with no family history is not associated with inheritance patterns.
Axon: A nerve fiber that carries electrical impulses from the nerve cell body to other neurons or muscles.
Basal Ganglia: Clusters of neurons that include the caudate nucleus, putamen, globus pallidus and substantia nigra which are located deep in the brain and play an important role in movement. Cell death in the substantia nigra contributes to Parkinsonian signs.
Big data: A system of data analysis that devises ways to accommodate data sets that are too large or complex for traditional methods.
Bilateral surgery: Surgery performed on both sides of the brain.
Biomarker: A chemical substance or imaging finding that is used as an early indicator that a person may have a disease. A biomarker, if present, could indicate that the person has a disease before symptoms of that disease appear. Currently, no biomarkers have been identified for MSA; however, some researchers have suggested that a characteristic thinning of the retinal nerve fiber layer in MSA patients may qualify as a biomarker.
Bilevel positive airway pressure (BIPAP): A machine that assists patients with sleep-related breathing disorders. Uses a mask-like device that is placed over the nose and mouth. A motor near the patient’s bed sends pressurized air through a tube connected to the mask to keep the patient’s airways open. The inhalation air pressure delivered by a BIPAP machine can be set to a different level from the exhalation pressure, which improves removal of CO2 compared to that from a CPAP (continuous positive airway pressure) machine, which uses uniform pressure on both phases of respiration. See also CPAP.
Blood brain barrier: A selective, semi-permeable membrane consisting of capillary cells and astocyte nerve endings that filters the blood as it enters the brain and protects the brain from being exposed to potentially harmful substances.
Braak Staging: A method to classify the degree of pathology in parkinsonian conditions on brain autopsy. Based on the idea that more brain regions contain alpha-synuclein pathology as diseases progresses over time. There is also a (different) Braak staging for Alzheimer’s disease.
Bradykinesia: Slowness of movement. It is commonly (but erroneously) used synonymously with akinesia and hypokinesia. Bradykinesia is a clinical hallmark of parkinsonism.
Bradyphrenia: Slowness of thought or information processing common to many brain disorders.
Brain stem: The posterior portion of the brain between the cerebral hemispheres and the spinal cord, comprising three sections: medulla oblongata, pons, and midbrain. The brain stem contains centers that command vital functions such as heart and breathing rates, relays information between the brain and spinal cord, maintains consciousness, and regulates sleep and wakefulness cycles. The substantia nigra, which is damaged in MSA, is located in the midbrain of the brain stem.
Bromocriptine: The generic name of a dopamine agonist drug that can alleviate Parkinson’s symptoms. The most common brand name is Parlodel.
C-Abl: A gene involved in the processes of cell differentiation, cell division, cell adhesion, and stress response. Is over-active in parkinsonian diseases and implicated in loss of dopamine-producing neurons.
Calcium: An essential mineral. Calcium is important for neurological “signaling” and is involved in many chemical reactions within neurons and in mitochondria function. Calcium overload in substantia nigra has been postulated as one mechanism that could contribute to death of these neurons.
Carbidopa: A drug given in conjunction with levodopa to increase levodopa’s effectiveness. Carbidopa blocks the enzyme that converts levodopa to dopamine in the peripheral tissues, thereby allowing more levodopa to reach the brain. Carbidopa also reduces levodopa’s unpleasant side effects such as nausea.
Carer/Care Partner: A name used to describe anyone who provides help or support of any kind to a relative or friend.
Caudate nucleus: A nucleus located in the basal ganglia important in learning and memory as well as motor function. It is one component of the basal ganglia called the striatum. The other component is the putamen. Studies have shown that the caudate nucleus is spared relative to the putamen in MSA.
Central Nervous System (CNS): A term referring to the brain and spinal cord.
Cerebellum: Part of the hindbrain; coordinates movement. Damage to the cerebellum results in ataxia. In some MSA patients, cerebellar symptoms are more prevalent than parkinsonian symptoms and this type of MSA is designated MSA-C.
Cerebrospinal fluid (CSF): A watery fluid generated within the brain’s ventricles. CSF cushions the brain and spinal cord from physical impact and removes waste products as part of the brain’s lymphatic system. Small amounts can be harvested in humans by lumbar puncture to measure chemicals coming from the brain.
Chemokines: Signaling proteins that are part of the cytokine family and an mportant component of the inflammatory response. Their activity has been found to be altered in MSA.
Chorea: A general term for nervous disorders characterized by involuntary, random, jerking movements of muscles in the body, face, or extremities. A type of dystonia.
Chronic: (opposite: acute) Chronic diseases are of long-term duration, typically with subtle onset. The term does not imply anything about the severity of a disease.
Clinical Trials: Refers to those research studies that involve human volunteers and are conducted to add to our understanding of certain diseases or to determine whether a drug may be effective in treating a disease.
Central Nervous System (CNS): consists of the brain, brain stem and spinal cord.
Coenzyme Q10: Antioxidant enzyme involved in cellular energy production. Protects nerve cells against oxidative stress and protects against loss of dopamine. Several clinical trials have been completed showing effectiveness for Parkinson’s disease. A phase 2 trial for MSA is currently underway.
Cognition: Mental processes including attention, memory, producing and understanding language, solving problems and making decisions.
Cognitive: Relating to cognition. Cognitive impairment occurs in some MSA patients, with recent statistics showing a greater prevalence than previously thought.
Cogwheeling: Also referred to as cogwheel rigidity. Stiffness of the muscles characterized by ratchetlike movements when arms and legs are moved against a resistance.
Complementary therapies: These are non-medical treatments, which many people use in addition to conventional medical treatments; examples include Alexander technique, acupuncture, aromatherapy, music and art therapies, reflexology, and osteopathy.
Computed tomography (CT or CAT Scan): A medical imaging method that uses computer processing to produce two-dimensional images seen as slices through the tissue. This presentation of images is known as tomography. The term CAT scan (computed axial tomography) refers to a specific orientation of images.
COMT Inhibitor: A drug that increases dopamine levels and is used to treat Parkinson’s symptoms. It works by inhibiting catechol-o-methyl transferase, COMT, an enzyme that breaks down dopamine.
COMT (catechol-O-methyltransferase): One of the enzymes that break down dopamine, adrenaline (also called epinephrine) and noradrenaline (also called norepinephrine).
Continuous Dopaminergic Stimulation (CDS): A therapeutic concept for the management of Parkinson’s disease and MSA that proposes that continuous (as opposed to discontinuous or pulsatile) stimulation of striatal dopamine receptors will delay or prevent the onset of levodopa-related motor complications. May also be effective for some MSA patients.
Continuous Positive Airway Pressure (CPAP): A machine that assists patients with sleep apnea and other conditions in which breathing is impaired during sleep. Uses a mask-like device that is placed over the nose and mouth. A motor near the patient’s bed sends pressurized air through a tube connected to the mask to keep the patient’s airways open. See also BIPAP.
Controlled Release Drugs: Drug delivery system whereby the drug is released into the body slowly and steadily rather than all at once. Controlled release maintains a steadier level of the drug in the bloodstream than the ‘ordinary’ version of the same drug.
CoQ10 (CoenzymeQ10): Compound produced by the body and found in all cells; vital for energy production and also functions as an antioxidant.
Cytokines: A family of small proteins that are secreted by specific cells of the immune system and carry signals locally between cells. Some cytokines are “pro-inflammatory, which is beneficial against infections but may also cause death of the body’s own cells whereas other cytokines are “anti-inflammatory”. MSA patients tend to have higher levels of pro-inflammatory cytokines.
DaTscan: a type of neuroimaging that evaluates the brain’s dopamine system using a radioactive tracer that attaches to the dopamine transporter molecule in the brain. Can be used to differentiate between parkinsonian syndromes,
Deep Brain Stimulation (DBS): A surgical treatment that involves the implantation of a medical device (electrical stimulator) that acts as a brain pacemaker sending electrical impulses to the specific area in which the electrode was inserted. In Parkinson’s patients, the device is typically inserted in either the subthalamic nucleus or the globus pallidus, depending upon the specific problem.
Dementia: A decline in cognitive function due to damage or disease in the brain beyond what might be expected from normal aging. Areas particularly affected include memory, attention, judgment, language, planning and problem solving.
Dendrites: (from Greek meaning, “tree”) Highly branched nerve fibers that project from the nerve cell body and receive incoming signals from other neurons and convert these chemical signals into electrical ones that travel to the nerve cell body.
Deprenyl: The generic name of the drug that inhibits the enzyme monoamine oxidase type B (MAO-B), thereby increasing the level of dopamine in the brain. The most common side effects include nausea, dizziness, insomnia, agitation, and confusion.
Depression: Feelings of sadness and/or a loss of interest in activities once enjoyed. It can decrease one’s ability to function in daily activities. Depression can be a clinical symptom of MSA due to cognitive impairment and/or emotional stresses imposed by the disease.
Diagnosis: Identification or naming of a disease by its signs and symptoms.
Disease modification: Treatments or interventions that affect the underlying pathological processes of a disease and have a beneficial outcome on the course of the disease.
Disequilibrium: Unsteadiness or balance problems.
DJ-1: A protein that inhibits alpha-synuclein aggregation and reduces oxidative stress. Mutations in the gene that codes for DJ-1 cause an autosomal recessive form of Parkinson’s disease.
Dopamine: One of the brain’s neurotransmitters that is involved in motivation, learning, and motor function. Produced by cells within the substantia nigra. These cells project to the striatum in the basal ganglia. Deficiency of dopamine in the striatum due to the death of cells in the substantia nigra causes symptoms of parkinsonism.
Dopamine agonist: A compound other than dopamine that activates dopamine receptors. Examples include drugs such as bromocriptine mesylate (Parlodel), pergolide (Permax), pramipexole (Mirapex), ropinirole hydrochloride (Requip), piribedil, cabergoline, apomorphine (Apokyn), rotigotine (Neupro patch) and lisuride. Dopamine agonists are the second most powerful type of anti-Parkinson medication after levodopa. They can cause side effects such as sleepiness, sleep attacks, ankle swelling, hallucinations and impulse control problems, more commonly than levodopa does.
Dopaminergic pathways: Neural pathways in the brain which utilize dopamine as their neurotransmitter. There are four major groups:
Drug Repurposing: Application of drugs for potential use with conditions other than those they were originally approved to treat.
Dysarthria: Impaired speech function.
Dysautonomia (autonomic disorder): A disorder affecting the function of the autonomic division of the nervous system, which controls automatic functions necessary for life, such as heart and respiratory rate, blood pressure, and bowel and bladder function. Symptoms include dizziness, difficulty swallowing, blurred vision, orthostatic hypotension, constipation, and urinary incontinence. Dysautonomia is a defining characteristic of MSA and is present to varying degrees in Parkinson’s disease and numerous other conditions.
Dyskinesia: An involuntary movement disorder, also sometimes called hyperkinesia. Characterized by lurching, dance-like or jerky movements that are distinct from the rhythmic tremor commonly associated with Parkinson’s disease. Often occurs as a side effect of long-term levodopa therapy and can affect a single body part or the entire body. In MSA, dyskinesias often occur in the face, neck, or limbs.
Dysphagia: Difficulty in swallowing.
Dystonia: Persistent or sudden intermittent muscle contractions causing abnormal posture and/or rigid or twisting movements. Dystonias associated with MSA include antecollis – a forward flexion of the neck, diurnal laryngeal stridor, which affects the vocal cords, and dystonias of the mouth and face.
Eldepryl:. The brand name for the version of deprenyl, also known as selegiline, an MAO-B inhibitor used to treat Parkinson’s disease and MSA. Manufactured by Somerset Pharmaceuticals.
Embryonic stem (ES) cell: See stem cell.
Enzyme: A protein that catalyzes or speeds up chemical reactions.
Encephalitis: Inflammation of the brain. See neuroinflammation.
Essential tremor: A rapid tremor (about eight cycles per second) that is most pronounced when performing an action such as writing or bringing a hand to a target.
Exosome: Small spherical structures consisting of proteins, lipids, DNA, enclosed in cellular membrane. Exosomes are released by cells into surrounding tissues and bodily fluids such as blood, urine, and CSF. They may serve as a means of intercellular communication and molecular transport.
Executive Dysfunction: A deficit in executive functioning that may occur in Parkinson’s dementia. Executive functioning allows the completion of tasks using higher level mental skills such as planning, organization, memory, flexible thinking, and self-regulation.
Extraordinary means: Ways of continuing human life that go beyond simple nutrition and hydration (even if that nutrition or hydration is provided via a feeding tube and the like. See ordinary means.
Festination: An involuntary quickening of the gait; characterized by short, accelerated steps combined with forward flexion of the torso; literally means “chasing the center of gravity”.
Freezing of Gait (FOG): The sudden brief inability of Parkinson’s patients to walk or to continue walking; frequently occurs at a boundary such as a door or when exiting a car.
Functional magnetic resonance imaging (fMRi): An imaging technique designed specifically for the brain. It measures the rate at which oxygen is removed from the blood to the cells, therefore suggesting the activity of a particular area of the brain.
GABA (gamma amino butyric acid): The principal inhibitory neurotransmitter in human brain. GABA-producing neurons are concentrated in the basal ganglia, substantia nigra and cerebellum.
GBA (Glucocerebrosidase): An enzyme involved in maintaining cell membrane stability, cellular immune response, and intercellular bonds. Mutations in the GBA gene are associated with Parkinson’s disease and MSA.
GDNF: Glial Cell line derived nerve growth factor. See growth factors.
Gene therapy: The insertion of genes into an individual’s cells and tissues to treat hereditary diseases where deleterious mutant alleles can be replaced with functional ones. The genes are usually placed within a non-pathogenic virus, which serves as the vector to penetrate the cells. Gene therapy can also be used to correct non-genetic deficiencies such as the loss of dopamine in MSA, to modify the function of a group of cells (e.g. convert an excitatory structure to one that is inhibitory) or to provide a source of growth factors.
Genetic: Referring to genes, the inherited code (“DNA”) for human structure and function.
Genetic predisposition: The inherited genetic pattern that may make some individuals more prone to certain conditions than others with a different genetic makeup.
Genotype: The collection of genetic material in an organism that gives rise to its characteristics.
Glia: Non-neural cells, commonly called neuroglia or simply glia (Greek for “glue”), that maintain homeostasis, form myelin, and provide support and protection for the brain’s neurons. Astrocytes are one kind of glial cells.
Globus pallidus: A component of the basal ganglia involved in movement control. It is split into two main parts: the internal globus pallidus (GPi), which, seems to be more affected, as evidenced by lower neuronal firing rates, in MSA than in Parkinson’s disease and the external globus pallidus (GPe), which is equally affected in the two conditions.
Glucose: A simple sugar that is an important energy source in living organisms and is a component of many carbohydrates.
Glutamate: An amino acid and the main excitatory neurotransmitter in the human brain. The major input to the striatum is from the cerebral cortex and uses glutamate as a neurotransmitter. Excess glutamate is toxic to neurons and if the neurotransmitter is not well regulated can result in neuronal cell death.
Glycation: The bonding of a sugar molecule to a protein or lipid molecule without enzymatic regulation causing the bonded molecules to be non-functional. Glycation products accumulate in cells and cause damage.
Glycosylceramide: A type of cerebroside. Cerebrosides are important components of muscle and nerve cell membranes.
Growth factors: Naturally occurring substances (usually proteins) that help maintain the health of neurons and encourage cell growth, proliferation and differentiation. Some growth factors are being looked at to try to promote the survival of the neural cells that are affected in MSA and Parkinson’s.
Gut microbiome: The complex community of microorganisms that live in the digestive tracts of humans and other animals. Alterations in the gut microbiome have been noted in MSA patients and may be associated with increased inflammation and intestinal permeability, leading to absorption of neurotoxins.
Heterogeneity: Lacking uniformity in composition or character (as opposed to homogeneity, which is uniformity in composition or character).
Hippocampus: A complex neural structure (shaped like a sea horse) located in the temporal lobes of the brain; involved in memory storage, motivation and emotion as part of the limbic system.
Hospice: A type of non-curative, palliative approach to care given to terminally ill patients for whom there are no further viable options for long-term disease management. Hospice care is meant to reduce suffering as well as address a patient’s emotional and spiritual needs.
Hyperkinesia: An abnormal increase in movement and/or muscle activity; sometimes used synonymously with dyskinesia.
Hypokinesia: Literally means reduced amplitude of movement. It is commonly used synonymously (but erroneously) with akinesia and bradykinesia.
Hypomimia: Immobile, expressionless face with reduced blinking.
Hypothalamic pituitary adrenal axis (HPA): A network of feedback loops within three components of the endocrine system: the hypothalamus, pituitary gland and the adrenal cortex. The HPA has a wide range of functions from stimulating the stress response to controlling digestion, the immune system, mood, sexuality and energy storage and consumption.
Hypothalamus: A component of the brain that acts as a relay between the nervous system and the endocrine system. Important in maintaining hormone balance, body temperature, sleep cycles, and other aspects of homeostasis.
Idiopathic: Arising from an unknown cause.
Impulse control disorder (ICD): A set of psychiatric disorders characterized by an inability to control one’s actions, in particular those that might bring harm to oneself or others. Common ICDs in patients receiving dopamine agonists are pathologic gambling, compulsive eating, compulsive shopping and hypersexuality.
Interdisciplinary care: Multiple healthcare professionals collaborating to provide care with a common perspective, often involving joint consultations.
iPS Cells: Stem cells that can be generated directly from adult cells. See stem cells.
Learned voluntary movements: Movements that we learn to do, like walking and talking.
Lesion: An area of cell damage or cell death.
Levodopa (L-DOPA): A precursor to dopamine that can pass through the blood-brain barrier (whereas dopamine cannot) and help restore dopamine levels in the brain. Levodopa is the most commonly administered drug for treating Parkinson’s symptoms.
Lewy bodies: Aggregates of alpha-synuclein proteins in several brain regions, including the substantia nigra and locus ceruleus. A pathologic hallmark and distinguishing feature among parkinsonian conditions. In Parkinson’s disease and dementia with Lewy bodies the deposits accumulate within dopamine-producing nerve cells, while in MSA, the deposits occur in glial cells.
Linked clinical trials (LCT): An international initiative to find potential drugs for treating Parkinson’s disease from among existing drugs that are approved for other diseases. A designated scientific committee meets annually to choose which drugs to recommend for fast-tracking into clinical trials.
Magnetic resonance imaging (MRI): A noninvasive medical imaging technique to visualize detailed internal structure and function of the body. MRI provides much greater contrast between the different soft tissues of the body than computed tomography (CT), making it especially useful in neurological (brain), musculoskeletal, cardiovascular and oncological (cancer-related) imaging.
Masking: Also known as facial masking. A symptom in Parkinsonian conditions caused by loss of control of the facial muscles leading to a mask-like expression.
MAO (monoamine oxidase): A family of enzymes that catalyze the breakdown of amine molecules, including some neurotransmitters. There are two MAO subtypes, with groups of drugs that target each:
MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine): A precursor of the neurotoxin known as MPP+ that is taken up in dopamine nerve terminals and damages dopamine-producing cells. MPTP is catalyzed to MPP+ by MAO-B. MPTP is widely used to create an animal model of Parkinsonism by depleting substantia nigra dopamine neurons.
Microbiome: The collection of microbes (bacteria, viruses, fungi) and their genetic material that live in or on the human body. See gut microbiome.
Microelectrodes: Thin metallic tubes inserted into the brain and guided stereotactically (surgically) to the target location. They are connected to the operating room computer and used to measure the electrical signal from brain cells during surgical procedures, such as pallidotomy.
Microglia: A type of glial cell; provides the first immune defense mechanism in the brain and central nervous system. Widespread activation of microglia is associated with neuroinflammatory changes in the early stages of MSA.
Micrographia: The tendency to have very small handwriting due to difficulty with fine motor movements in Parkinson’s disease.
Mild Cognitive Impairment (MCI): A decline in memory or intellectual functioning that is not as severe as that found in dementia.
Mirapex: The brand name of a dopamine agonist, pramipexole, made by Pharmacia; has been used in MSA patients who do not respond well to levodopa.
Mitochondria: A specialized cell structure that contains genetic material and many enzymes important for metabolism, including those responsible for the conversion of food to usable energy.
Mitophagy: The selective degradation of mitochondria by autophagy. See Mitochondria and Autophagy.
Monoamine oxidase inhibitors: Drugs that enhance the effect of dopamine by inhibiting the enzymes that break them down. See MAO.
Motor skills: The degree of control or coordination provided by brain control of the skeletal muscles.
Motor symptoms: Symptoms that involve movement, coordination, physical tasks or mobility. These include, among others: resting tremor, bradykinesia, rigidity, postural instability, freezing, micrographia, mask-like expression, unwanted accelerations, stooped posture, dystonia, impaired motor dexterity and coordination, speech problems, difficulty swallowing, muscle cramping, and drooling of saliva. See also non-motor symptoms.
Movement disorders: Refers to several conditions, many of them neurodegenerative, that prevent normal movement. Some are characterized by either lack of movement (bradykinesia, hypokinesia, etc) or excessive movement (chorea, athetosis, dystonia, tremor). Besides Parkinson’s, other conditions often defined as movement disorders include essential tremor, multiple system atrophy, progressive supranuclear palsy, Huntington’s disease, Tourette’s syndrome and cerebral palsy.
Movement Disorder Specialist (MDS): A neurologist who has special training and experience with movement disorders such as MSA.
Multidisciplinary care: Care given by multiple healthcare professionals each approaching the patient from their professional perspective, often involves separate, individual consultations.
Multiple System Atrophy (MSA): Formerly known as Shy-Drager syndrome, a progressive neurodegenerative disorder of dopamine-producing cells that affects autonomic (involuntary) and motor functions. Considered a form of parkinsonism, symptoms of MSA typically manifest between the ages of 50-60 years. Common autonomic symptoms include postural hypotension, irregular heartbeat, bowel and bladder incontinence, inability to control body temperature, sleep disorders, sexual dysfunction, and loss of emotional control.
Two forms are recognized depending on the symptom pattern:
Neurodegenerative: Refers to conditions such as MSA that are characterized by the progressive loss of neurons, particularly those in the brain.
Neuroinflammation: Swelling of the tissue of the nervous system. May be initiated in response to a number of triggers including infection, traumatic brain injury, toxic metabolites, or autoimmunity. Microglia are the immune cells of the nervous system that are activated in response to these cues.
Neurology: A branch of medicine dealing with the diagnosis and treatment of disorders of the nervous system.
Neurologist: A physician specializing in diseases and disorders of the brain, spinal cord, nerves, and muscles, including stroke, Parkinson’s disease, epilepsy and Alzheimer’s disease.
Neuromodulator: A chemical substance other than a neurotransmitter, released by a neuron at a synapse (juncture) with another neuron and either enhances or dampens the activity of the target neuron.
Neurological conditions: Disorders caused by damage to or malfunctioning of the brain or nervous system.
Neurologist: A doctor who specializes in the diagnosis, care, and treatment of disorders of the brain or nervous system.
Neuron: A nerve cell used to transmit information to other cells. Consists of a cell body, dendrites that convey information from other nerves toward the cell body, and an axon that conveys information away from the cell body.
Neuroplasticity: The ability of the brain to change and form new connections even with aging. Involves neurons regenerating anatomically or functionally after partial injury, or changing (such as by making more numerous or more effective connections) in response to training and experience.
Neuron: A nerve cell transmits information through electrochemical signals to other nerve cells or to muscles. The fundamental unit of the brain and nervous system.
Neuroprotection: Mechanisms within the nervous system that would protect neurons from dying due to a degenerative disease or from other types of injury.
Neuroprotective: Serving to protect neurons from injury or degeneration or an effect that may result in salvage, recovery or regeneration of the nervous system, its cells, structure and function.
Neuropsychology: The study of how the structure and function of the brain influence behavior and cognition.
Neuroscience: The scientific study of the nervous system that deals with the anatomy, biochemistry, molecular biology, and physiology of neurons and neural circuits.
Neurosurgeon: A doctor who specializes in surgical treatment of the nervous system.
Neurotransmitter: A chemical messenger in the nervous system that permits communication between two neuronal cells, often but not always across a synapse. The neurotransmitter is usually released from the nerve terminals on the axons. Examples of neurotransmitters include dopamine, acetylcholine, adrenaline, noradrenaline, serotonin, glutamate, and GABA.
Neurotrophic factors: A family of biomolecules that support the growth, survival, and differentiation of both developing and mature neurons.
Non-motor symptoms: Symptoms that do not involve movement, coordination, physical tasks or mobility. May include impaired sense of smell, constipation, sleep disturbances, mood disorders, orthostatic hypotension, bladder problems, sexual problems, excessive saliva, weight loss or gain, vision and dental problems, fatigue, depression, fear and anxiety, skin problems, and cognitive issues.
Objective measurements: The repetition of a unit amount that maintains its size, within an allowable range of error, no matter which instrument, intended to measure the variable of interest, is used and no matter who or what relevant person or thing is measured.
Occupational therapist (OT): An allied health professional trained to assess a person’s home or work environment and devise ways to make them more manageable and less hazardous. OT’s also work with patients to improve fine motor skills, as needed, as they apply to everyday activities such as dressing, writing, computer use.
Olfactory dysfunction: An impaired ability to detect odors, impaired sense of smell. Thought to be an early sign of MSA but can occur in many situations not related to MSA.
On-Off Phenomenon: Sudden loss of activity of levodopa lasting minutes to hours after a brief period of effectiveness. The term also sometimes refers to a cyclical response to medication where the patient can function adequately at times but is too stiff and immobile to function at other times.
Ordinary means: Methods of preserving life that are commonly accessible, subject to widely accepted social norms for moral and obligatory measures, and in which there is reasonable expectation of successful outcome. Nutrition and hydration, are considered by some to be ordinary means. For Catholics, the church requires members to provide nutrition and hydration, even by way of a feeding tube as along as the patient can assimilate such nutrition or hydration.
Orthostatic hypotension: A sudden drop in blood pressure (>20 mm Hg systolic) when a person goes from lying down to sitting or from sitting to standing and accompanied by symptoms such as dizziness, fatigue and syncope. Can occur as a complication of certain medications, but can sometimes be due to MSA itself.
Oxidative stress: Accumulation of free radicals (reactive molecules that form from the oxidation, or breakdown, of other molecules) within a cell, leading to cell damage.
Palliative care: A collaborative approach to care involving healthcare professionals from multiple specialty areas to minimize pain and suffering and maximize quality of life for patients with life-threatening illnesses.
Pallidotomy: A surgical procedure in which lesions are produced in the globus pallidus region of the brain in an effort to lessen Parkinson’s symptoms such as tremors, rigidity, and bradykinesia. Generally associated with poor clinical outcomes in MSA patients.
Palsy: Antiquated term referring to paralysis or an uncontrollable shaking of the body. Parkinson’s disease was originally called the “shaking palsy”.
Paradoxical kinesia: A characteristic of parkinsonian conditions in which an individual who experiences difficulty performing a simple movement may be able to perform a more complex movement.
Paralysis agitans: Antiquated name for Parkinson’s disease
Parkinson-plus syndromes: A group of neurodegenerative diseases featuring the classical features of Parkinsonism (rigidity, akinesia/ bradykinesia, postural instability and less commonly tremor) with additional features that distinguish them from typical Parkinson’s disease. Parkinson-plus syndromes include MSA, progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).
Parkinsonism: A group of neurological diseases whose features include slowness and paucity of spontaneous movement (bradykinesia), resting tremors, rigidity of the muscles, loss of postural reflexes, flexed posture and freezing of gait. Several conditions cause these signs and symptoms, including Parkinson’s disease, dementia with Lewy bodies, progressive supranuclear palsy, and multiple system atrophy. A number of medications are also associated with Parkinson-like side effects.
Parkinsonian gait: A slow, short paced gait with a tendency to shuffle, associated with decreased arm swing.
Parlodel: The brand name for the dopamine agonist bromocriptine that is made by Novartis.
Pathogenesis: The underlying biologic mechanism responsible for a disease.
Peripheral Nervous System: The nervous system outside the brain and spinal cord, comprising two divisions:
PD: Abbreviation for Parkinson’s disease.
PEG (percutaneous endoscopic gastrostomy): A procedure in which a feeding tube is passed into the stomach through the abdominal wall.
PEG-tube: Feeding tube used in a percutaneous endoscopic gastrostomy.
Permax: The brand name for the dopamine agonist pergolide that is made by Eli Lilly.
PET scan: An acronym for “positron emission tomography,” an imaging technique used to monitor and produce pictures of metabolic or biochemical activity in the brain.
Phenotype: The observable characteristics of an organism or person, such as appearance, development and behavior. Determined by the interaction between the genotype and the environment.
Phosphorylation: A process that modifies proteins by adding one or more phosphate groups. For proteins that function as enzymes, this results in activating or deactivating their function.
Pill-rolling tremor: A characteristic tremor in Parkinson’s, uncommon in MSA patients, in which the thumb and forefinger involuntarily move in a way that resembles rolling a small object such as a pill.
Physiotherapist (PT): An allied health professional trained to use physical means such as exercise and manipulation to help prevent or reduce stiffness in joints and restore muscle strength. PT’s can also advise on aids and equipment to help with movement problems.
Placebo: A simulated or inert form of treatment used in clinical trials along with the active drug being tested. Health professionals and/or participants involved in the trial do not know who receives the placebo or the drug. The difference in responses between the placebo and the drug is considered the true effect of the active drug. It is thought that benefits experienced from placebos, termed the placebo effect, may, in part, be associated with release of dopamine in the brains of patients who believe that they have received an active drug.
Positron emission tomography (PET): A medical imaging technique in which radioactive isotopes are incorporated into a chemically active compound utilized by an organ in the body. The isotopes emit gamma rays that are detected by a special camera/scanner. A computer then generates an image to illustrate the location of the active compound in the organ being studied.
In PET scans of the brain, the compound fluorodeoxyglucose (FDG), is used to measure regional glucose metabolism. F-DOPA, a radioactive form of L-DOPA is another compound used in PET scans of the brain. F-DOPA is taken up in dopamine nerve terminals. The amount of uptake serves as a measure of the integrity of these nerve terminals.
Postural instability: Difficulty with balance and inability to maintain stability while standing. One of the major motor symptoms of Parkinson’s disease and MSA.
Prodromal: Referring to early signs or symptoms of a disease that manifest before the development of definitive diagnostic signs and symptoms. In MSA, prodromal non-motor symptoms, such as sleep problems, respiratory problems, and other signs of autonomic failure may appear months to years before the onset of motor symptoms.
Prognosis: The expected future course of an illness.
Progressive Supranuclear Palsy (PSP): A rare degenerative brain disorder that causes progressive problems with control of gait and balance, along with complex eye movement and cognitive problems. A classic manifestation of the disease is the inability to move the eyes properly, particularly with looking up and down. PSP is one of the Parkinson-plus syndromes and is not helped consistently by levodopa.
Proteostatis: The concept that there are biological pathways within cells that compete for control of the creation, folding, transporting, and degradation of proteins present within and outside the cell. A combination of the words protein and homeostasis. Loss of proteostasis can lead to misfolding and degradation of proteins.
Proteasomes: Protein complexes which degrade unneeded or damaged proteins. Proteasome dysfunction is implicated as one of the contributing factors in the disease process of MSA.
Protein: 1. A class of food necessary for the growth and repair of the body tissues—sources of proteins include fish, meat, eggs and milk. 2. Large biomolecules or macromolecules consisting of long chains of amino acid residues. Within organisms, proteins catalyze metabolic reactions (enzymes), replicate DNA, and transport molecules.
Receptor: A protein structure typically embedded in the cell membrane with which neurotransmitters and drugs interact.
REM (rapid eye movement) REM behavior disorder (RBD): A sleep disorder that involves abnormal behavior during the sleep phase characterized by rapid eye movements – the stage of sleep in which dreaming occurs. In normal sleep, muscles are paralyzed during dreaming, except for the eye movements. In RBD, muscles are not paralyzed so that the dreamer acts out his or her dreams. RBD is common in people with Parkinson’s disease or Multiple System Atrophy.
Restless leg syndrome (RLS): A neurological disorder characterized by unpleasant sensations in the legs, often described as the feeling of ants crawling underneath the skin with the urge to move the legs to alleviate the sensations, hence the term “restless legs.” RLS usually occurs in the late evening and during sleep. The condition interferes with sleep and is common in people with MSA and PD. Medications, such as dopamine agonists, levodopa and opioids, can be effective treatments.
Rigidity: A type of muscle stiffness in which the muscles tend to pull against each other instead of working smoothly together. It is most apparent when an examiner moves a patient’s limb — as in a form known as cogwheeling. A type of rigidity in MSA patients affects the cervical spine muscles causing a forward or backward head posture known as torticollis.
Schwab and England Activities of Daily Living (ADL) Scale: An estimation of the abilities of a person’s degree of independence. The person (or a family member) can self-assess this as:
Second opinion: The process of consulting with a second medical specialist in order to confirm a diagnosis, receive a new or more precise diagnosis, or discuss alternative options for treating a health condition. When a potential diagnosis includes a rare condition or where symptoms overlap considerably with other conditions, for example with MSA, a second opinion is important in order to avoid a possible misdiagnosis. A second opinion is also useful if symptoms persist following a course of treatment, or when a recommended treatment is especially risky.
Senescence: A natural aging process in cells that stops them from dividing. Can become activated when certain types of damage occur.
Sepsis: A systemic inflammatory response to an infection. Sepsis is life threatening and can lead to organ damage and septic shock, a condition in which impaired blood flow due to sepsis results in low blood pressure that does not respond to fluid replacement. Occurs most often in the very young, the elderly, and in people with compromised immune systems.
Serotonin: A neurotransmitter that regulates mood, appetite, and sleep. It also has some cognitive functions, including memory and learning. The serotonin-producing neurons are located in the brain stem. Serotonin has a relaxing effect on smooth (non-voluntary) muscles and serotonin-enhancing drugs have been used to manage cerebellar ataxia and to alleviate chronic constipation and sleep apnea in MSA patients.
Shaking palsy: Prior term for Parkinson’s disease.
Shy-Drager Syndrome: An antiquated name for multiple system atrophy.
Side effects: A secondary reaction to a drug, usually adverse, that is additional to the intended therapeutic actions. Side effects vary in severity from person to person and can range from mild and/or tolerable to life-threatening.
Sinemet: The brand name of the most commonly prescribed version of the drug levodopa, made by Du Pont Pharmaceuticals
Single photon emission computed tomography (SPECT): A nuclear medicine imaging technique using gamma rays and able to provide 3D information via tomography, or imaging in sections. Commonly used to detect areas of reduced blood flow in the brain.
Sleep apnea: A sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing during sleep.
Sodium channel: Voltage gated channels in nerve cell membranes that allow the generation of nerve impulses via the flow of positively charged sodium ions into a cell. After sodium enters the cell, it needs to be pumped back out. This process happens through the sodium-pump mechanism, which requires the expenditure of cellular energy. Sodium channel blocking drugs are used to control pain and treat epilepsy and may be a target for new drugs in Parkinson’s and MSA.
Stem cells: Biological cells found in all multicellular organisms; can divide and differentiate into diverse specialized cell types and self-renew to produce more stem cells. Stem cells are a potential line of treatment in MSA and Parkinson’s, either by directly replacing the old nigrostriatal neuronal cells or by creating growth factor releasing cells. Problems have arisen due to the inability to stop growth, which may cause tumor development.
There are four types of stem cells:
Stereotactic: A minimally invasive surgery technique, guided by images from CAT or MRI scans, usually involving a metallic frame bolted to a patient’s head to prevent any movement.
Striatum: A large cluster of nerve cells that are part of the basal ganglia. The striatum controls movement, balance, and walking. It consists of two sectors: the caudate nucleus and the putamen. The striatum receives nerve inputs from many parts of the brain including dopamine neurons from the substantia nigra and glutamate neurons from the cerebral cortex. Acetylcholine and GABA neurons arelocated within the striatum. The striatum contains the largest concentrations of dopamine and acetylcholine in the brain.
Substantia nigra: (Latin for black substance). A brain structure located in the midbrain that plays an important role in movement. Parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopamine-producing neurons. The substantia nigra is the site of the brain’s major collection of dopamine neurons, which project their axons to the striatum, the so-called nigrostriatal pathway. These neurons slowly die in PD and MSA. The substantia nigra is part of the basal ganglia, along with the striatum (caudate nucleus, putamen), globus pallidus, and subthalamic nucleus.
Subthalamic Nucleus (STN): A nerve center near the substantia nigra and part of the basal ganglia. The STN may be targeted for deep brain stimulation (DBS) to reduce Parkinson’s symptoms. Is relatively unaffected in MSA.
Shuffling gait: Refers to short, slow steps, with feet close to the ground or dragging along the ground. This gait is often seen in people with advanced Parkinson’s disease and MSA-P.
Suprapubic Catheter: A permanent catheter inserted into the bladder above the pubic bone.
Synapse: The narrow space between two neurons (axon to dendrite) or between a neuron and a muscle. Axons release neurotransmitters at the nerve terminal. The neurotransmitter crosses the synapse to activate or inhibit another nerve cell by acting on a receptor on the dendrite of the receiving cell.
Synaptic plasticity: The ability of synaptic activity to modify and adapt to changes in activity levels. Particularly important for learning and memory.
Syndrome: A group of symptoms that tend to occur together and which reflect the presence of a specific disorders or diseases. Parkinson syndrome, also called parkinsonism, comprises a group of disorders with symptoms and signs in common, such as bradykinesia, rigidity, tremor, loss of postural reflexes, flexed posture and freezing of gait. A person with parkinsonism does not need to have all of these but must have bradykinesia according to one diagnostic criterion. Disorders that fall within parkinson syndrome include Parkinson’s disease, atypical parkinsonism, Parkinson-plus Syndromes, drug-induced parkinsonism, and normal pressure hydrocephalus.
Synucleinopathy: A class of neurodegenerative disease resulting from pathological accumulation of alpha-synuclein in neurons (Parkinson’s, Lewy Body Dementia) or in a kind of glial cell called oligodendrocytes (Multiple System Atrophy).
Tasmar: The brand name of the COMT inhibitor tolcapone, that is made by Roche Laboratories.
Tau proteins: Proteins that stabilize microtubules, which are structural entities in axons. They are abundant in neurons in the central nervous system and are less common elsewhere. When tau proteins are defective and no longer stabilize microtubules properly, they can result in dementia (including Alzheimer’s disease).
Tauopathies: A class of neurodegenerative diseases resulting from the pathological aggregation of tau protein in so-called neurofibrillary tangles (NFT) in the human brain. Besides Alzheimer’s, this is commonly seen in Pick’s disease, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Tau pathology is relatively rare in MSA.
Thalamotomy: A now uncommon surgical procedure used to treat Parkinson’s tremor in which a small portion of the brain area called the thalamus is destroyed. Thalamotomy is associated with significant secondary complications. The procedure has been replaced by medical and therapies, such as l-DOPA and deep brain stimulation surgery.
Thalamus: A midline paired symmetrical structure situated between the cerebral cortex and brain stem. The thalamus acts as a relay and processing center for sensory information to reach higher brain centers for interpretation and for coordination of regulatory commands among areas of the cerebral cortex. Its functions also include regulating sleep, wakefulness, and consciousness.
Tolcapone: A drug in the COMT inhibitor class that is sometimes prescribed in tandem with levodopa. The drug has been known to cause serious liver problems and has been withdrawn from the Canadian and European markets.
Toxicity: The degree to which a chemical substance or a particular mixture of substances can damage an organism.
Transcranial Magnetic Stimulation (TMS): A method in which a changing magnetic field is used to cause electric current to flow to a small region of the brain. Some initial clinical trials have reported improvements in motor control in MSA patients with the use of TMS.
Transcription factors: Proteins that regulate the transcription (i.e. the expression) of genes.
Translation: Also known as gene expression. The process by which protein molecules are assembled in accordance with a specific, corresponding genetic code. The process is preceded by transcription of the DNA into messenger RNA (mRNA).
Tremor: Involuntary rhythmic movements (may be fast or slow) that may affect the hands, head, voice or other body parts.
Trigger Event: An external or environmental factor such as head trauma, exposure to a toxin, or stress that contributes to the development of a condition or disease.
Tyramine-induced hypertension: High blood pressure caused by an increase in tyramine, an amine compound that promotes blood pressure elevation which forces noradrenaline/norepinephrine into circulation. This is the so-called “cheese effect” because some fermented cheeses (and other foods) contain high concentrations of tyramine. Normally, tyramine is broken down in the gut by MAO-A. When this enzyme is inhibited, as with a category of drugs called MAO inhibitors, the tyramine in food is able to enter the blood stream, resulting in a hypertensive crisis. MAO inhibitors are used in parkinsonian conditions because, in addition to preventing the breakdown of tyramine they also prevent the breakdown of dopamine.
Tyrosine: An amino acid used by cells to synthesize proteins. It is also the precursor of dopamine.
Ubiquitin: A small regulatory protein found ubiquitously in most tissues, hence its name. Ubiquitin is involved in the degradation of damaged proteins. Mutated forms have been found in MSA patients.
UMSARS (Unified MSA Rating Scale) – A four-part rating scale for MSA comprising:
Ventral Tegmental Area (VTA): A group neurons located in the midbrain next to the substantia nigra and involved in cognition and motivation, including reward and addiction. Contains the cell bodies of dopamine-producing cells and one of the major dopamine producing centers in the brain.
Vesicle: An organelle in a cell that separates some molecules from the rest of the cell. In nerve cells, neurotransmitters are stored in vesicles at the terminal ends of axons, called synaptic vesicles, and are released by the vesicles into the synapse when the nerve fires.
Wearable devices: Devices worn on the body, incorporating computers, electronics, software and/or sensors, often used to measure some aspect of function or physical manifestation, for example: activity trackers, accelerometers, gyroscopes, etc.
Wearing Off: The loss of the effectiveness of Parkinson’s medication between doses resulting in the return of symptoms.
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